Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia.

PubMed

Dempsey, Jerome A; Powell, Frank L; Bisgard, Gerald E; Blain, Gregory M; Poulin, Marc J; Smith, Curtis A

2014-04-01

During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of "sleep high-train low"!

Association between sensitization to Aureobasidium pullulans (Pullularia sp) and severity of asthma.

PubMed

Niedoszytko, Marek; Chełmińska, Marta; Jassem, Ewa; Czestochowska, Eugenia

2007-02-01

Recent data indicate that fungi may contribute to increased severity of asthma. To determine the prevalence of allergy to 15 mold allergens among patients hospitalized because of exacerbation of asthma and to evaluate the relationship between the severity of the disease and allergy to particular molds. Skin prick tests with standard aeroallergens of airborne allergens, including grass, tree, Dermatophagoides pteronyssinus, Dermatophagoides farinae, feather, and cat and dog fur, and a panel of mold allergens, including Alternaria, Cladosporium, Aspergillus, Penicillium, Trichothecium, Chaetomium globosum, Epicoccum, Epidermophyton, Helminthosporium, Aureobasidium pullulans, Rhizopus nigricans, Fusarium, Mucor, Merulius lacrymans, and yeast mix, were performed in 105 asthmatic patients and 30 controls. Positive skin prick test results were found in 98% of asthmatic patients and 66% of controls. Sensitivity to A pullulans was significantly associated with more severe asthma (odds ratio, 1.4; 95% confidence interval, 1.09-1.75; P = .006). Sensitization to Helminthosporium was associated with an increased number of asthma exacerbations that required hospitalization (17% vs 38%; chi2 test P = .03). Sensitization to A pullulans is a risk factor for severe asthma. Sensitization to Helminthosporium may be related to asthma exacerbation that requires hospitalization.

Occupational sensitization to epoxy resins in Northeastern Italy (1996–2010)

PubMed Central

Prodi, Andrea; Rui, Francesca; Fortina, Anna Belloni; Corradin, Maria Teresa; Filon, Francesca Larese

2015-01-01

Background: One of the main health concerns of epoxy resins is their role as skin sensitizer. This sensitization is not uncommon, because the prevalence ranges around 1–12% of the general population. Objectives: Perform a cross sectional study in a patch test population from Northeastern Italy to investigate the prevalence of epoxy resins sensitization among patients with suspected contact dermatitis. Subsequently, relate findings to patients’ occupation and evaluate time trend of prevalence. Methods: The final study database included 19 088 consecutive patients, tested from 1996 to 2010 in Northeastern Italy. Results: The overall prevalence of epoxy resins sensitization was 0·89%. Dermatitis most frequently involved hands (40·25%). In both sexes, we find a significant correlation in mechanics, woodworkers, and chemical industry workers; and in males only, among farmers and fishers, construction workers, and unemployed. We found significant increase of sensitization in construction workers in the analyzed period. Conclusions: The overall prevalence of sensitization to epoxy resins in Northeastern Italy is in line with other European countries, but we found an increased risk of sensitization in some professions and an increasing trend of prevalence in construction workers. Better preventive actions are strongly advised in higher risk professions, with particular attentions towards building sector. PMID:25633931

An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

PubMed

Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

2015-01-01

Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. © The Author(s) 2015.

The BCL2 antagonist of cell death pathway influences endometrial cancer cell sensitivity to cisplatin.

PubMed

Chon, Hye Sook; Marchion, Douglas C; Xiong, Yin; Chen, Ning; Bicaku, Elona; Stickles, Xiaomang Ba; Bou Zgheib, Nadim; Judson, Patricia L; Hakam, Ardeshir; Gonzalez-Bosquet, Jesus; Wenham, Robert M; Apte, Sachin M; Lancaster, Johnathan M

2012-01-01

To identify pathways that influence endometrial cancer (EC) cell sensitivity to cisplatin and to characterize the BCL2 antagonist of cell death (BAD) pathway as a therapeutic target to increase cisplatin sensitivity. Eight EC cell lines (Ishikawa, MFE296, RL 95-2, AN3CA, KLE, MFE280, MFE319, HEC-1-A) were subjected to Affymetrix Human U133A GeneChip expression analysis of approximately 22,000 probe sets. In parallel, endometrial cell line sensitivity to cisplatin was quantified by MTS assay, and IC(50) values were calculated. Pearson's correlation test was used to identify genes associated with response to cisplatin. Genes associated with cisplatin responsiveness were subjected to pathway analysis. The BAD pathway was identified and subjected to targeted modulation, and the effect on cisplatin sensitivity was evaluated. Pearson's correlation analysis identified 1443 genes associated with cisplatin resistance (P<0.05), which included representation of the BAD-apoptosis pathway. Small interfering RNA (siRNA) knockdown of BAD pathway protein phosphatase PP2C expression was associated with increased phosphorylated BAD (serine-155) levels and a parallel increase in cisplatin resistance in Ishikawa (P=0.004) and HEC-1-A (P=0.02) cell lines. In contrast, siRNA knockdown of protein kinase A expression increased cisplatin sensitivity in the Ishikawa (P=0.02) cell line. The BAD pathway influences EC cell sensitivity to cisplatin, likely via modulation of the phosphorylation status of the BAD protein. The BAD pathway represents an appealing therapeutic target to increase EC cell sensitivity to cisplatin. Copyright © 2011 Elsevier Inc. All rights reserved.

Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men

PubMed Central

Buxton, Orfeu M.; Pavlova, Milena; Reid, Emily W.; Wang, Wei; Simonson, Donald C.; Adler, Gail K.

2010-01-01

OBJECTIVE Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness. RESEARCH DESIGN AND METHODS This 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20–35 years and BMI 20–30 kg/m2). Subjects spent 10 h/night in bed for ≥8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured. RESULTS IVGTT-derived insulin sensitivity was reduced by (means ± SD) 20 ± 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 11 ± 5.5% (P < 0.04) after sleep restriction. Glucose tolerance and the disposition index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51 ± 8% with sleep restriction, P < 0.02), urinary catecholamines, or slow wave sleep. CONCLUSIONS Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance. PMID:20585000

Comparison of the diagnostic ability of Moorfield’s regression analysis and glaucoma probability score using Heidelberg retinal tomograph III in eyes with primary open angle glaucoma

PubMed Central

Jindal, Shveta; Dada, Tanuj; Sreenivas, V; Gupta, Viney; Sihota, Ramanjit; Panda, Anita

2010-01-01

Purpose: To compare the diagnostic performance of the Heidelberg retinal tomograph (HRT) glaucoma probability score (GPS) with that of Moorfield’s regression analysis (MRA). Materials and Methods: The study included 50 eyes of normal subjects and 50 eyes of subjects with early-to-moderate primary open angle glaucoma. Images were obtained by using HRT version 3.0. Results: The agreement coefficient (weighted k) for the overall MRA and GPS classification was 0.216 (95% CI: 0.119 – 0.315). The sensitivity and specificity were evaluated using the most specific (borderline results included as test negatives) and least specific criteria (borderline results included as test positives). The MRA sensitivity and specificity were 30.61 and 98% (most specific) and 57.14 and 98% (least specific). The GPS sensitivity and specificity were 81.63 and 73.47% (most specific) and 95.92 and 34.69% (least specific). The MRA gave a higher positive likelihood ratio (28.57 vs. 3.08) and the GPS gave a higher negative likelihood ratio (0.25 vs. 0.44).The sensitivity increased with increasing disc size for both MRA and GPS. Conclusions: There was a poor agreement between the overall MRA and GPS classifications. GPS tended to have higher sensitivities, lower specificities, and lower likelihood ratios than the MRA. The disc size should be taken into consideration when interpreting the results of HRT, as both the GPS and MRA showed decreased sensitivity for smaller discs and the GPS showed decreased specificity for larger discs. PMID:20952832

Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism

PubMed Central

Vandell, Alexander G; Walker, Joseph; Brown, Karen S; Zhang, George; Lin, Min; Grosso, Michael A; Mercuri, Michele F

2017-01-01

Objective The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. Methods Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes. An exploratory analysis was also conducted comparing normal responders to pooled sensitive responders (ie, sensitive and highly sensitive responders). Results The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time overanticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252). Conclusion In this study, CYP2C9 and VKORC1 genotypes identified patients with VTE at increased bleeding risk with warfarin. Trial registration number NCT00986154. PMID:28689179

Increased sensitivity to proactive and retroactive interference in amnestic mild cognitive impairment: new insights.

PubMed

Hanseeuw, Bernard J; Seron, Xavier; Ivanoiu, Adrian

2012-10-01

Increased sensitivity to proactive (PI) and retroactive (RI) interference has been observed in amnestic mild cognitive impairment (aMCI). PI and RI are often explained as being the result of a response competition mechanism. However, patients with aMCI are supposed to suffer mostly from encoding deficits. We hypothesized that in aMCI interference may occur at encoding and not only at the retrieval stage. We developed an original paradigm enabling PI and RI to be tested with and without response competitors. Eighteen young controls (YC), 16 elderly controls (EC) and 15 aMCI participated in the study. The YC and EC groups presented interference effects only in conditions that included a direct response competitor. In contrast, aMCI had interference effects in all conditions including the one without response competitor. Increased sensitivity to interference in aMCI appears to occur at the encoding/consolidation stage and not only at the retrieval stage, as is the case in healthy subjects. This result is discussed in the context of the associative encoding deficits characterizing aMCI. Copyright © 2012 Elsevier Inc. All rights reserved.

Serine Protease Zymography: Low-Cost, Rapid, and Highly Sensitive RAMA Casein Zymography.

PubMed

Yasumitsu, Hidetaro

2017-01-01

To detect serine protease activity by zymography, casein and CBB stain have been used as a substrate and a detection procedure, respectively. Casein zymography has been using substrate concentration at 1 mg/mL and employing conventional CBB stain. Although ordinary casein zymography provides reproducible results, it has several disadvantages including time-consuming and relative low sensitivity. Improved casein zymography, RAMA casein zymography, is rapid and highly sensitive. RAMA casein zymography completes the detection process within 1 h after incubation and increases the sensitivity at least by tenfold. In addition to serine protease, the method also detects metalloprotease 7 (MMP7, Matrilysin) with high sensitivity.

Dedicated training program for shoulder sonography: the results of a quality program reverberate with everyone.

PubMed

Delzell, Patricia B; Boyle, Alex; Schneider, Erika

2015-06-01

The purpose of this study was to define and report on the effect of a comprehensive musculoskeletal sonography training program to improve accuracy (sensitivity and specificity) for the diagnosis of rotator cuff tears in relatively inexperienced operators. Before the training program was implemented, radiologists (n = 12) had a mean of 2 years (range, <1-12 years) of experience performing and interpreting musculoskeletal sonography. Pre- and post-training shoulder sonographic results were compared to surgical reports or, in their absence, to shoulder magnetic resonance imaging or computed tomographic arthrographic results if within 2 months of the sonographic examination. A total of 82 patients were included in the pre-training group (January 2010-December 2011), and 50 patients were included in the post-training group (January 2012-June 2013). The accuracy, sensitivity, specificity, and positive and negative predictive values were determined for the presence or absence of supraspinatus and infraspinatus tendon tears. After implementation of the training program, the sensitivity of sonography for detecting full-thickness rotator cuff tears increased by 14%, and the sensitivity for detecting partial-thickness rotator cuff tears increased by 3%. Quality improvement programs and acquisition standardization along with ongoing, focused case conferences for the entire care team increased the sensitivity of shoulder sonography for diagnosing both full- and partial-thickness rotator cuff tears, independent of the years of operator experience. © 2015 by the American Institute of Ultrasound in Medicine.

Efficacy of high-fiber diets in the management of type 2 diabetes mellitus.

PubMed

Wolfram, Taylor; Ismail-Beigi, Faramarz

2011-01-01

To review outcomes of randomized controlled clinical trials exploring the efficacy of different types of diets containing various amounts of fiber in the management of type 2 diabetes mellitus. We searched PubMed, Medline, and Google Scholar for published data from the past decade (through December 2009) on dietary patterns and risk of type 2 diabetes mellitus. Only randomized controlled trials investigating the effect of whole grains, fiber, or vegetarian diets on type 2 diabetes were included. Search criteria included whole grain, fruit, vegetable, fiber, and meat intake regarding insulin sensitivity and glycemic responses in healthy, prediabetic, and diabetic persons. A total of 14 randomized clinical trials were included. Addition of insoluble or soluble fiber to meals, increased consumption of diets rich in whole grains and vegetables, and vegan diets improve glucose metabolism and increase insulin sensitivity. The greatest improvement in blood lipids, body weight, and hemoglobin A(1c) level occurred in participants following low-fat, plant-based diets. Increased consumption of vegetables, whole grains, and soluble and insoluble fiber is associated with improved glucose metabolism in both diabetic and nondiabetic individuals. Improvements in insulin sensitivity and glucose homeostasis were more evident in participants following a plant-based diet compared with other commonly used diets.

Aberrant semantic and affective processing in people at risk for psychosis.

PubMed

Kerns, J G; Berenbaum, H

2000-11-01

Semantic and affective processing were examined in people at risk for psychosis. The participants were 3 groups of college students: 41 people with elevated Perceptual Aberration and Magical Ideation (PerMag) scores, 18 people with elevated Social Anhedonia (SocAnh) scores, and 100 control participants. Participants completed a single-word, continuous presentation pronunciation task that included semantically related words, affectively valenced words, and semantically unrelated and affectively neutral words. PerMag participants exhibited increased semantic priming and increased sensitivity to affectively valenced primes. SocAnh participants had increased sensitivity to affectively valenced targets.

Individual differences in personality as a function of degree of handedness: consistent-handers are less sensation seeking, more authoritarian, and more sensitive to disgust.

PubMed

Christman, Stephen

2014-01-01

Prior research indicates that consistent-handedness is associated with decreased access to right hemisphere processing and consequent decreased cognitive flexibility. Handedness differences on three dimensions of personality related to cognitive flexibility were investigated. Experiment 1 found that consistent-handedness was associated with decreased sensation seeking. Experiment 2 found that consistent-handedness was associated with increased Right Wing Authoritarianism. Experiment 3 found that consistent-handedness was associated with increased sensitivity to disgust. Prior research has shown associations between decreased sensation seeking, increased authoritarianism, and increased disgust sensitivity, and consistent-handedness appears to underlie all of these associations. Personality researchers are encouraged to include handedness as a factor in analyses, as failure to do so can lead to systematic mis-estimation of sex differences due to the over-representation of females among consistent-handers.

Sickle cell mice exhibit mechanical allodynia and enhanced responsiveness in light touch cutaneous mechanoreceptors

PubMed Central

2012-01-01

Background Sickle cell disease (SCD) is associated with both acute vaso-occlusive painful events as well as chronic pain syndromes, including heightened sensitivity to touch. We have previously shown that mice with severe SCD (HbSS mice; express 100% human sickle hemoglobin in red blood cells; RBCs) have sensitized nociceptors, which contribute to increased mechanical sensitivity. Yet, the hypersensitivity in these neural populations alone may not fully explain the mechanical allodynia phenotype in mouse and humans. Findings Using the Light Touch Behavioral Assay, we found HbSS mice exhibited increased responses to repeated application of both innocuous punctate and dynamic force compared to control HbAA mice (100% normal human hemoglobin). HbSS mice exhibited a 2-fold increase in percent response to a 0.7mN von Frey monofilament when compared to control HbAA mice. Moreover, HbSS mice exhibited a 1.7-fold increase in percent response to the dynamic light touch “puffed” cotton swab stimulus. We further investigated the mechanisms that drive this behavioral phenotype by focusing on the cutaneous sensory neurons that primarily transduce innocuous, light touch. Low threshold cutaneous afferents from HbSS mice exhibited sensitization to mechanical stimuli that manifested as an increase in the number of evoked action potentials to suprathreshold force. Rapidly adapting (RA) Aβ and Aδ D-hair fibers showed the greatest sensitization, each with a 75% increase in suprathreshold firing compared to controls. Slowly adapting (SA) Aβ afferents had a 25% increase in suprathreshold firing compared to HbAA controls. Conclusions These novel findings demonstrate mice with severe SCD exhibit mechanical allodynia to both punctate and dynamic light touch and suggest that this behavioral phenotype may be mediated in part by the sensitization of light touch cutaneous afferent fibers to suprathreshold force. These findings indicate that Aβ fibers can be sensitized to mechanical force and should potentially be examined for sensitization in other tissue injury and disease models. PMID:22963123

Identifying Candidate Genes that Underlie Cellular pH Sensitivity in Serotonin Neurons Using Transcriptomics: A Potential Role for Kir5.1 Channels

PubMed Central

Puissant, Madeleine M.; Mouradian, Gary C.; Liu, Pengyuan; Hodges, Matthew R.

2017-01-01

Ventilation is continuously adjusted by a neural network to maintain blood gases and pH. Acute CO2 and/or pH regulation requires neural feedback from brainstem cells that encode CO2/pH to modulate ventilation, including but not limited to brainstem serotonin (5-HT) neurons. Brainstem 5-HT neurons modulate ventilation and are stimulated by hypercapnic acidosis, the sensitivity of which increases with increasing postnatal age. The proper function of brainstem 5-HT neurons, particularly during post-natal development is critical given that multiple abnormalities in the 5-HT system have been identified in victims of Sudden Infant Death Syndrome. Here, we tested the hypothesis that there are age-dependent increases in expression of pH-sensitive ion channels in brainstem 5-HT neurons, which may underlie their cellular CO2/pH sensitivity. Midline raphe neurons were acutely dissociated from neonatal and mature transgenic SSePet-eGFP rats [which have enhanced green fluorescent protein (eGFP) expression in all 5-HT neurons] and sorted with fluorescence-activated cell sorting (FACS) into 5-HT-enriched and non-5-HT cell pools for subsequent RNA extraction, cDNA library preparation and RNA sequencing. Overlapping differential expression analyses pointed to age-dependent shifts in multiple ion channels, including but not limited to the pH-sensitive potassium ion (K+) channel genes kcnj10 (Kir4.1), kcnj16 (Kir5.1), kcnk1 (TWIK-1), kcnk3 (TASK-1) and kcnk9 (TASK-3). Intracellular contents isolated from single adult eGFP+ 5-HT neurons confirmed gene expression of Kir4.1, Kir5.1 and other K+ channels, but also showed heterogeneity in the expression of multiple genes. 5-HT neuron-enriched cell pools from selected post-natal ages showed increases in Kir4.1, Kir5.1, and TWIK-1, fitting with age-dependent increases in Kir4.1 and Kir5.1 protein expression in raphe tissue samples. Immunofluorescence imaging confirmed Kir5.1 protein was co-localized to brainstem neurons and glia including 5-HT neurons as expected. However, Kir4.1 protein expression was restricted to glia, suggesting that it may not contribute to 5-HT neuron pH sensitivity. Although there are caveats to this approach, the data suggest that pH-sensitive Kir5.1 channels may underlie cellular CO2/pH chemosensitivity in brainstem 5-HT neurons. PMID:28270749

Developmental Programming: Impact of Prenatal Testosterone Excess on Insulin Sensitivity, Adiposity, and Free Fatty Acid Profile in Postpubertal Female Sheep

PubMed Central

Veiga-Lopez, A.; Moeller, J.; Patel, D.; Ye, W.; Pease, A.; Kinns, J.

2013-01-01

Prenatal T excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested whether increases in visceral adiposity, adipocyte size, and total free fatty acids underlie the insulin resistance seen in prenatal T-treated female sheep. At approximately 16 months of age, insulin resistance and adipose tissue partitioning were determined via hyperinsulinemic euglycemic clamp and computed tomography, respectively, in control and prenatal T-treated females. Three months later, adipocyte size and free fatty acid composition were determined. Results revealed that at the postpubertal time points tested, insulin sensitivity was increased, visceral adiposity and adipocyte size in both the sc and the visceral compartments were reduced, and circulating palmitic acid was increased in prenatal T-treated females relative to controls. In parallel studies, 20-month-old prenatal T-treated females tended to have increased basal insulin to glucose ratio. Relative to earlier findings of reduced insulin sensitivity of prenatal T-treated females during early life and adulthood, these findings of increased insulin sensitivity and reduced adiposity postpubertally are suggestive of a period of developmental adaptation. The disruption observed in free fatty acid metabolism a few months later correspond to a time point when the insulin sensitivity indices of prenatal T-treated animals appear to shift toward insulin resistance. In summary, current findings of improved insulin sensitivity and reduced visceral adiposity in postpubertal prenatal T-treated sheep relative to our earlier findings of reduced insulin sensitivity during early postnatal life and adulthood are indicative of a period of developmental adaptation. PMID:23525243

Recyclability of mixed office waste papers containing pressure sensitive adhesives and silicone release liners

Treesearch

Julie Hess; Roberta Sena-Gomes; Lisa Davie; Marguerite Sykes

2001-01-01

Increased use of pressure sensitive adhesives for labels and stamps has introduced another contaminant into the office paper stream: silicone- coated release liners. This study examines methods and conditions for removal of contaminants, including these liners, from a typical batch of discarded office papers. Removal of contaminants contained in the furnish were...

Bilirubin Increases Insulin Sensitivity in Leptin-Receptor Deficient and Diet-Induced Obese Mice Through Suppression of ER Stress and Chronic Inflammation

PubMed Central

Dong, Huansheng; Huang, Hu; Yun, Xinxu; Kim, Do-sung; Yue, Yinan; Wu, Hongju; Sutter, Alton; Chavin, Kenneth D.; Otterbein, Leo E.; Adams, David B.; Kim, Young-Bum

2014-01-01

Obesity-induced endoplasmic reticulum (ER) stress causes chronic inflammation in adipose tissue and steatosis in the liver, and eventually leads to insulin resistance and type 2 diabetes (T2D). The goal of this study was to understand the mechanisms by which administration of bilirubin, a powerful antioxidant, reduces hyperglycemia and ameliorates obesity in leptin-receptor-deficient (db/db) and diet-induced obese (DIO) mouse models. db/db or DIO mice were injected with bilirubin or vehicle ip. Blood glucose and body weight were measured. Activation of insulin-signaling pathways, expression of inflammatory cytokines, and ER stress markers were measured in skeletal muscle, adipose tissue, and liver of mice. Bilirubin administration significantly reduced hyperglycemia and increased insulin sensitivity in db/db mice. Bilirubin treatment increased protein kinase B (PKB/Akt) phosphorylation in skeletal muscle and suppressed expression of ER stress markers, including the 78-kDa glucose-regulated protein (GRP78), CCAAT/enhancer-binding protein (C/EBP) homologous protein, X box binding protein (XBP-1), and activating transcription factor 4 in db/db mice. In DIO mice, bilirubin treatment significantly reduced body weight and increased insulin sensitivity. Moreover, bilirubin suppressed macrophage infiltration and proinflammatory cytokine expression, including TNF-α, IL-1β, and monocyte chemoattractant protein-1, in adipose tissue. In liver and adipose tissue of DIO mice, bilirubin ameliorated hepatic steatosis and reduced expression of GRP78 and C/EBP homologous protein. These results demonstrate that bilirubin administration improves hyperglycemia and obesity by increasing insulin sensitivity in both genetically engineered and DIO mice models. Bilirubin or bilirubin-increasing drugs might be useful as an insulin sensitizer for the treatment of obesity-induced insulin resistance and type 2 diabetes based on its profound anti-ER stress and antiinflammatory properties. PMID:24424052

Highly Sensitive GMO Detection Using Real-Time PCR with a Large Amount of DNA Template: Single-Laboratory Validation.

PubMed

Mano, Junichi; Hatano, Shuko; Nagatomi, Yasuaki; Futo, Satoshi; Takabatake, Reona; Kitta, Kazumi

2018-03-01

Current genetically modified organism (GMO) detection methods allow for sensitive detection. However, a further increase in sensitivity will enable more efficient testing for large grain samples and reliable testing for processed foods. In this study, we investigated real-time PCR-based GMO detection methods using a large amount of DNA template. We selected target sequences that are commonly introduced into many kinds of GM crops, i.e., 35S promoter and nopaline synthase (NOS) terminator. This makes the newly developed method applicable to a wide range of GMOs, including some unauthorized ones. The estimated LOD of the new method was 0.005% of GM maize events; to the best of our knowledge, this method is the most sensitive among the GM maize detection methods for which the LOD was evaluated in terms of GMO content. A 10-fold increase in the DNA amount as compared with the amount used under common testing conditions gave an approximately 10-fold reduction in the LOD without PCR inhibition. Our method is applicable to various analytical samples, including processed foods. The use of other primers and fluorescence probes would permit highly sensitive detection of various recombinant DNA sequences besides the 35S promoter and NOS terminator.

Effects of inflammation on social processes and implications for health.

PubMed

Moieni, Mona; Eisenberger, Naomi I

2018-05-28

Although at first glance inflammation and social behavior may appear unrelated, research points to an important role for inflammation in shaping social processes. This review summarizes findings in this field, specifically highlighting work that provides support for the idea that inflammation can lead to (1) increases in sensitivity to negative, threatening social experiences and (2) increases in sensitivity to positive, socially rewarding experiences. These diverging sensitivities in response to inflammation may depend on context and be adaptive for recuperation and recovery from illness. This review also discusses the implications of these findings for health and future research, including implications for depression, loneliness, and inflammatory disorders. © 2018 New York Academy of Sciences.

Hydrogen-related challenges for the steelmaker: the search for proper testing

NASA Astrophysics Data System (ADS)

Thiessen, R. G.

2017-06-01

The modern steelmaker of advanced high-strength steels has always been challenged with the conflicting targets of increased strength while maintaining or improving ductility. These new steels help the transportation sector, including the automotive sector, to achieve the goals of increased passenger safety and reduced emissions. With increasing tensile strengths, certain steels exhibit an increased sensitivity towards hydrogen embrittlement (HE). The ability to characterize the material's sensitivity in an as-delivered condition has been developed and accepted (SEP1970), but the complexity of the stress states that can induce an embrittlement together with the wide range of applications for high-strength steels make the development of a standardized test for HE under in-service conditions extremely challenging. Some proposals for evaluating the material's sensitivity give an advantage to materials with a low starting ductility. Despite this, newly developed materials can have a higher original elongation with only a moderate reduction in elongation due to hydrogen. This work presents a characterization of new materials and their sensitivity towards HE. This article is part of the themed issue 'The challenges of hydrogen and metals'.

Hydrogen-related challenges for the steelmaker: the search for proper testing.

PubMed

Thiessen, R G

2017-07-28

The modern steelmaker of advanced high-strength steels has always been challenged with the conflicting targets of increased strength while maintaining or improving ductility. These new steels help the transportation sector, including the automotive sector, to achieve the goals of increased passenger safety and reduced emissions. With increasing tensile strengths, certain steels exhibit an increased sensitivity towards hydrogen embrittlement (HE). The ability to characterize the material's sensitivity in an as-delivered condition has been developed and accepted (SEP1970), but the complexity of the stress states that can induce an embrittlement together with the wide range of applications for high-strength steels make the development of a standardized test for HE under in-service conditions extremely challenging. Some proposals for evaluating the material's sensitivity give an advantage to materials with a low starting ductility. Despite this, newly developed materials can have a higher original elongation with only a moderate reduction in elongation due to hydrogen. This work presents a characterization of new materials and their sensitivity towards HE.This article is part of the themed issue 'The challenges of hydrogen and metals'. © 2017 The Author(s).

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care.

PubMed

Cherry, Simon R; Jones, Terry; Karp, Joel S; Qi, Jinyi; Moses, William W; Badawi, Ramsey D

2018-01-01

PET is widely considered the most sensitive technique available for noninvasively studying physiology, metabolism, and molecular pathways in the living human being. However, the utility of PET, being a photon-deficient modality, remains constrained by factors including low signal-to-noise ratio, long imaging times, and concerns about radiation dose. Two developments offer the potential to dramatically increase the effective sensitivity of PET. First by increasing the geometric coverage to encompass the entire body, sensitivity can be increased by a factor of about 40 for total-body imaging or a factor of about 4-5 for imaging a single organ such as the brain or heart. The world's first total-body PET/CT scanner is currently under construction to demonstrate how this step change in sensitivity affects the way PET is used both in clinical research and in patient care. Second, there is the future prospect of significant improvements in timing resolution that could lead to further effective sensitivity gains. When combined with total-body PET, this could produce overall sensitivity gains of more than 2 orders of magnitude compared with existing state-of-the-art systems. In this article, we discuss the benefits of increasing body coverage, describe our efforts to develop a first-generation total-body PET/CT scanner, discuss selected application areas for total-body PET, and project the impact of further improvements in time-of-flight PET. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Accuracy of screening women at familial risk of breast cancer without a known gene mutation: Individual patient data meta-analysis.

PubMed

Phi, Xuan-Anh; Houssami, Nehmat; Hooning, Maartje J; Riedl, Christopher C; Leach, Martin O; Sardanelli, Francesco; Warner, Ellen; Trop, Isabelle; Saadatmand, Sepideh; Tilanus-Linthorst, Madeleine M A; Helbich, Thomas H; van den Heuvel, Edwin R; de Koning, Harry J; Obdeijn, Inge-Marie; de Bock, Geertruida H

2017-11-01

Women with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program. An individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI. There were 2226 women (median age: 41 years, interquartile range 35-47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3-14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P < 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P < 0.01 compared with mammography alone). In this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the Exploitation of Sensitivity Derivatives for Improving Sampling Methods

NASA Technical Reports Server (NTRS)

Cao, Yanzhao; Hussaini, M. Yousuff; Zang, Thomas A.

2003-01-01

Many application codes, such as finite-element structural analyses and computational fluid dynamics codes, are capable of producing many sensitivity derivatives at a small fraction of the cost of the underlying analysis. This paper describes a simple variance reduction method that exploits such inexpensive sensitivity derivatives to increase the accuracy of sampling methods. Three examples, including a finite-element structural analysis of an aircraft wing, are provided that illustrate an order of magnitude improvement in accuracy for both Monte Carlo and stratified sampling schemes.

Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism.

PubMed

Vandell, Alexander G; Walker, Joseph; Brown, Karen S; Zhang, George; Lin, Min; Grosso, Michael A; Mercuri, Michele F

2017-11-01

The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes. An exploratory analysis was also conducted comparing normal responders to pooled sensitive responders (ie, sensitive and highly sensitive responders). The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time overanticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252). In this study, CYP2C9 and VKORC1 genotypes identified patients with VTE at increased bleeding risk with warfarin. NCT00986154. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Drought sensitivity changes over the last century at the North American savanna-forest boundary

NASA Astrophysics Data System (ADS)

Heilman, K.; McLachlan, J. S.

2017-12-01

Future environmental changes can affect the sensitivity of tree growth to climate. Theses changes are of particular concern at biome boundaries where tree distribution could shift as a result of changes in both drought and drought sensitivity. One such region is the North American savanna-forest boundary, where increased CO2 and droughts could alter savanna and forest ecosystem distributions in two contrasting ways: 1). More severe droughts may increase drought sensitivity, favoring open savanna ecosystems or, 2). Increases in water use efficiency resulting from higher atmospheric CO2 may decrease drought sensitivity, promoting forest expansion. This study sought to understand whether the past 100 years of climate and CO2 changes have impacted regional tree growth-climate sensitivity. To test for these climate sensitivity changes, we measured the sensitivity of Quercus spp. radial growth to Palmer Drought Severity Index (PDSI). Tree growth sensitivity to climate can vary according to many factors, including: stand structure, available moisture, and tree age. To control for these factors, we sampled tree growth-climate responses at sites in both open and closed forests, and at both low and high annual precipitation. Within each site, we compared growth responses to climate between trees established under high CO2 conditions after 1950 (high CO2 young), and tree established before 1950 under low CO2 levels (low CO2 young). At most sites, low CO2 young have a higher drought sensitivity than higher CO2 young. These changes in the sensitivity to drought are consistent with CO2 enhancement of water use efficiency. Furthermore, these differences in drought sensitivity are higher at sites with high temperature and low precipitation, suggesting that the alleviation of drought is more likely in hot and dry regions. Thus, if CO2 enhancement is indeed occurring in these systems, lower growth sensitivity to drought in hot and dry regions could favor increased forest growth. If changes in drought sensitivity scale to ecosystem level, decreased drought sensitivity may have helped promote regional forest expansion.

Age Dependent Variability in Gene Expression in Fischer 344 ...

EPA Pesticide Factsheets

Recent evidence suggests older adults may be a sensitive population with regard to environmental exposure to toxic compounds. One source of this sensitivity could be an enhanced variability in response. Studies on phenotypic differences have suggested that variation in response does increase with age. However, few reports address the question of variation in gene expression as an underlying cause for increased variability of phenotypic response in the aged. In this study, we utilized global analysis to compare variation in constitutive gene expression in the retinae of young (4 mos), middle-aged (11 mos) and aged (23 mos) Fischer 344 rats. Three hundred and forty transcripts were identified in which variance in expression increased from 4 to 23 mos of age, while only twelve transcripts were found for which it decreased. Functional roles for identified genes were clustered in basic biological categories including cell communication, function, metabolism and response to stimuli. Our data suggest that population stochastically-induced variability should be considered in assessing sensitivity due to old age. Recent evidence suggests older adults may be a sensitive population with regard to environmental exposure to toxic compounds. One source of this sensitivity could be an enhanced variability in response. Studies on phenotypic differences have suggested that variation in response does increase with age. However, few reports address the question of variation in

Proteasome phosphorylation regulates cocaine-induced sensitization.

PubMed

Gonzales, Frankie R; Howell, Kristin K; Dozier, Lara E; Anagnostaras, Stephan G; Patrick, Gentry N

2018-04-01

Repeated exposure to cocaine produces structural and functional modifications at synapses from neurons in several brain regions including the nucleus accumbens. These changes are thought to underlie cocaine-induced sensitization. The ubiquitin proteasome system plays a crucial role in the remodeling of synapses and has recently been implicated in addiction-related behavior. The ATPase Rpt6 subunit of the 26S proteasome is phosphorylated by Ca 2+ /calmodulin-dependent protein kinases II alpha at ser120 which is thought to regulate proteasome activity and distribution in neurons. Here, we demonstrate that Rpt6 phosphorylation is involved in cocaine-induced locomotor sensitization. Cocaine concomitantly increases proteasome activity and Rpt6 S120 phosphorylation in cultured neurons and in various brain regions of wild type mice including the nucleus accumbens and prefrontal cortex. In contrast, cocaine does not increase proteasome activity in Rpt6 phospho-mimetic (ser120Asp) mice. Strikingly, we found a complete absence of cocaine-induced locomotor sensitization in the Rpt6 ser120Asp mice. Together, these findings suggest a critical role for Rpt6 phosphorylation and proteasome function in the regulation cocaine-induced behavioral plasticity. Copyright © 2017 Elsevier Inc. All rights reserved.

Including Effects of Water Stress on Dead Organic Matter Decay to a Forest Carbon Model

NASA Astrophysics Data System (ADS)

Kim, H.; Lee, J.; Han, S. H.; Kim, S.; Son, Y.

2017-12-01

Decay of dead organic matter is a key process of carbon (C) cycling in forest ecosystems. The change in decay rate depends on temperature sensitivity and moisture conditions. The Forest Biomass and Dead organic matter Carbon (FBDC) model includes a decay sub-model considering temperature sensitivity, yet does not consider moisture conditions as drivers of the decay rate change. This study aimed to improve the FBDC model by including a water stress function to the decay sub-model. Also, soil C sequestration under climate change with the FBDC model including the water stress function was simulated. The water stress functions were determined with data from decomposition study on Quercus variabilis forests and Pinus densiflora forests of Korea, and adjustment parameters of the functions were determined for both species. The water stress functions were based on the ratio of precipitation to potential evapotranspiration. Including the water stress function increased the explained variances of the decay rate by 19% for the Q. variabilis forests and 7% for the P. densiflora forests, respectively. The increase of the explained variances resulted from large difference in temperature range and precipitation range across the decomposition study plots. During the period of experiment, the mean annual temperature range was less than 3°C, while the annual precipitation ranged from 720mm to 1466mm. Application of the water stress functions to the FBDC model constrained increasing trend of temperature sensitivity under climate change, and thus increased the model-estimated soil C sequestration (Mg C ha-1) by 6.6 for the Q. variabilis forests and by 3.1 for the P. densiflora forests, respectively. The addition of water stress functions increased reliability of the decay rate estimation and could contribute to reducing the bias in estimating soil C sequestration under varying moisture condition. Acknowledgement: This study was supported by Korea Forest Service (2017044B10-1719-BB01)

Comparison of patterns of allergen sensitization among inner-city Hispanic and African American children with asthma.

PubMed

Rastogi, Deepa; Reddy, Mamta; Neugebauer, Richard

2006-11-01

Among Hispanics, the largest minority ethnic group in the United States, asthma prevalence is increasing, particularly in inner-city neighborhoods. Although allergen sensitization among asthmatic African Americans has been extensively studied, similar details are not available for Hispanic children. To examine patterns of allergen sensitization, including the association with illness severity, in asthmatic children overall and in Hispanic and African American children living in a socioeconomically disadvantaged area of New York City. A retrospective medical record review of asthmatic children attending a community hospital in the South Bronx area of New York City was performed. Information abstracted included demographics, asthma severity classification, reported exposures to indoor allergens, and results of allergy testing. Among 384 children in the analysis, 270 (70.3%) were Hispanic and 114 (29.7%) were African American. Sensitization to indoor and outdoor allergens, respectively, did not differ between Hispanic (58.5% and 27.0%) and African American (58.8% and 32.6%) children. Allergen sensitization exhibited a direct, significant association with asthma severity for indoor allergens for the 2 ethnic groups combined and for Hispanics separately but not between asthma severity and outdoor allergens (P < .01). No correlation was found between self-reported allergen exposure and sensitization. Patterns of allergen sensitization among inner-city Hispanic asthmatic children resemble those among African American children, a finding that is likely explained by the similarity in levels of environmental exposures. With the increasing prevalence of asthma among inner-city Hispanic children, skin testing should be used frequently for objective evaluation of asthma in this ethnic group.

Lead exposure and increased food allergic sensitization in U.S. children and adults.

PubMed

Mener, David J; Garcia-Esquinas, Esther; Navas-Acien, Ana; Dietert, Rodney R; Shargorodsky, Josef; Lin, Sandra Y

2015-03-01

Whether blood lead levels are associated with sensitization to food allergens in adults and children is unclear. Prior studies have shown that exposure to lead is associated with atopic sensitization and modulation of several cytokines (eg, interleukin [IL]-12, IL-10, interferon [IFN]-γ, and IL-4 production) and with T-cell dysregulation and bias toward T helper 2 (Th2) activity. The objective of this work was to assess whether exposure to lead is independently associated with allergic symptoms and sensitizations in a large nationally representative sample of children and adults. We studied 2712 children and 4333 adults enrolled in the 2005-2006 cycle of the National Health and Nutritional Examination Surveys (NHANES). Participants were tested for serum-specific immunoglobulin E (IgE) levels to food allergens as well as blood lead levels. Food allergens tested included shrimp, egg, peanut, and milk. Logistic regression models adjusted for demographic factors, body mass index, history of asthma, smoking, housing characteristics, and current exposure to animals in the home, to assess the association of blood lead levels with sensitization to food allergens. Median (interquartile range [IQR]) for serum blood was 0.87 μg/L (0.61 to 1.31) in children and 1.48 μg/L (0.92 to 2.34) in adults. At baseline, 672 (24.7%) of children participants and 719 (16.6%) of adult participants tested positive for increased sensitization to food allergens. A 2-fold increase in blood lead levels in adult participants was associated with increased sensitization to food allergens (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.02 to 1.22). Blood lead was not associated with sensitization to food allergens among pediatric participants (OR, 0.95; 95% CI, 0.82 to 1.10). Exposure to lead was associated with increased odds of sensitization to food allergens in adult but not children participants. © 2014 ARS-AAOA, LLC.

Correcting the MoCA for education: effect on sensitivity.

PubMed

Gagnon, Genevieve; Hansen, Kevin T; Woolmore-Goodwin, Sarah; Gutmanis, Iris; Wells, Jennie; Borrie, Michael; Fogarty, Jennifer

2013-09-01

The goal of this study was to quantify the impact of the suggested education correction on the sensitivity and specificity of the Montreal Cognitive Assessment (MoCA). Twenty-five outpatients with dementia and 39 with amnestic mild cognitive impairment (aMCI) underwent a diagnostic evaluation, which included the MoCA. Thirty-seven healthy controls also completed the MoCA and psychiatric, medical, neurological, functional, and cognitive difficulties were ruled out. For the total MoCA score, unadjusted for education, a cut-off score of 26 yielded the best balance between sensitivity and specificity (80% and 89% respectively) in identifying cognitive impairment (people with either dementia or aMCI, versus controls). When applying the education correction, sensitivity decreased from 80% to 69% for a small specificity increase (89% to 92%). The cut-off score yielding the best balance between sensitivity and specificity for the education adjusted MoCA score fell to 25 (61% and 97%, respectively). Adjusting the MoCA total score for education had a detrimental effect on sensitivity with only a slight increase in specificity. Clinically, this loss in sensitivity can lead to an increased number of false negatives, as education level does not always correlate to premorbid intellectual function. Clinical judgment about premorbid status should guide interpretation. However, as this effect may be cohort specific, age and education corrected norms and cut-offs should be developed to help guide MoCA interpretation.

Glycine and GABAA Ultra-Sensitive Ethanol Receptors as Novel Tools for Alcohol and Brain Research

PubMed Central

Naito, Anna; Muchhala, Karan H.; Asatryan, Liana; Trudell, James R.; Homanics, Gregg E.; Perkins, Daya I.; Alkana, Ronald L.

2014-01-01

A critical obstacle to developing effective medications to prevent and/or treat alcohol use disorders is the lack of specific knowledge regarding the plethora of molecular targets and mechanisms underlying alcohol (ethanol) action in the brain. To identify the role of individual receptor subunits in ethanol-induced behaviors, we developed a novel class of ultra-sensitive ethanol receptors (USERs) that allow activation of a single receptor subunit population sensitized to extremely low ethanol concentrations. USERs were created by mutating as few as four residues in the extracellular loop 2 region of glycine receptors (GlyRs) or γ-aminobutyric acid type A receptors (GABAARs), which are implicated in causing many behavioral effects linked to ethanol abuse. USERs, expressed in Xenopus oocytes and tested using two-electrode voltage clamp, demonstrated an increase in ethanol sensitivity of 100-fold over wild-type receptors by significantly decreasing the threshold and increasing the magnitude of ethanol response, without altering general receptor properties including sensitivity to the neurosteroid, allopregnanolone. These profound changes in ethanol sensitivity were observed across multiple subunits of GlyRs and GABAARs. Collectively, our studies set the stage for using USER technology in genetically engineered animals as a unique tool to increase understanding of the neurobiological basis of the behavioral effects of ethanol. PMID:25245406

Detection of low-level environmental chemical allergy by a long-term sensitization method.

PubMed

Fukuyama, Tomoki; Ueda, Hideo; Hayashi, Koichi; Tajima, Yukari; Shuto, Yasufumi; Saito, Toru R; Harada, Takanori; Kosaka, Tadashi

2008-07-30

Multiple chemical sensitivity (MCS) is characterized by various signs, including neurological disorders and allergy. Exposure may occur through a major event, such as a chemical spill, or from long-term contact with chemicals at low levels. We are interested in the allergenicity of MCS and the detection of low-level chemical-related hypersensitivity. We used long-term sensitization followed by low-dose challenge to evaluate sensitization by well-known Th2 type sensitizers (trimellitic anhydride (TMA) and toluene diisocyanate (TDI)) and a Th1 type sensitizer (2,4-dinitrochlorobenzene (DNCB)). After topically sensitizing BALB/c mice (9 times in 3 weeks) and challenging them with TMA, TDI or DNCB, we assayed their auricular lymph nodes (LNs) for number of lymphocytes, surface antigen expression of B cells, and local cytokine production, and measured antigen-specific serum IgE levels. TMA and TDI induced marked increases in levels of antigen-specific serum IgE and of Th2 cytokines (IL-4, IL-5, IL-10, and IL-13) produced by ex vivo restimulated lymph node cells. DNCB induced a marked increase in Th1 cytokine (IL-2, IFN-gamma, and TNF-alpha) levels, but antigen-specific serum IgE levels were not elevated. All chemicals induced significant increases in number of lymphocytes and surface antigen expression of B cells. Our mouse model enabled the identification and characterization of chemical-related allergic reactions at low levels. This long-term sensitization method would be useful for detecting environmental chemical-related hypersensitivity.

Automatic detection of ECG cable interchange by analyzing both morphology and interlead relations.

PubMed

Han, Chengzong; Gregg, Richard E; Feild, Dirk Q; Babaeizadeh, Saeed

2014-01-01

ECG cable interchange can generate erroneous diagnoses. For algorithms detecting ECG cable interchange, high specificity is required to maintain a low total false positive rate because the prevalence of interchange is low. In this study, we propose and evaluate an improved algorithm for automatic detection and classification of ECG cable interchange. The algorithm was developed by using both ECG morphology information and redundancy information. ECG morphology features included QRS-T and P-wave amplitude, frontal axis and clockwise vector loop rotation. The redundancy features were derived based on the EASI™ lead system transformation. The classification was implemented using linear support vector machine. The development database came from multiple sources including both normal subjects and cardiac patients. An independent database was used to test the algorithm performance. Common cable interchanges were simulated by swapping either limb cables or precordial cables. For the whole validation database, the overall sensitivity and specificity for detecting precordial cable interchange were 56.5% and 99.9%, and the sensitivity and specificity for detecting limb cable interchange (excluding left arm-left leg interchange) were 93.8% and 99.9%. Defining precordial cable interchange or limb cable interchange as a single positive event, the total false positive rate was 0.7%. When the algorithm was designed for higher sensitivity, the sensitivity for detecting precordial cable interchange increased to 74.6% and the total false positive rate increased to 2.7%, while the sensitivity for detecting limb cable interchange was maintained at 93.8%. The low total false positive rate was maintained at 0.6% for the more abnormal subset of the validation database including only hypertrophy and infarction patients. The proposed algorithm can detect and classify ECG cable interchanges with high specificity and low total false positive rate, at the cost of decreased sensitivity for certain precordial cable interchanges. The algorithm could also be configured for higher sensitivity for different applications where a lower specificity can be tolerated. Copyright © 2014 Elsevier Inc. All rights reserved.

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

Microperimetric correlations of autofluorescence and optical coherence tomography imaging in dry age-related macular degeneration.

PubMed

Querques, Lea; Querques, Giuseppe; Forte, Raimondo; Souied, Eric H

2012-06-01

To investigate the microperimetric correlations of autofluorescence imaging and optical coherence tomography (OCT) in dry age-related macular degeneration (AMD). Retrospective, observational, cross-sectional study. Consecutive patients with dry AMD underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), blue fundus autofluorescence (FAF), near-infrared autofluorescence, and spectral-domain (SD)-OCT with integrated microperimetry. A total of 58 eyes of 29 patients (21 women; mean age 73 ± 9 years) were included. Mean BCVA was 0.28 ± 0.3 logarithm of the minimal angle of resolution (logMAR). Overall, 2842 points were analyzed as regards FAF and near-infrared autofluorescence patterns, the status of inner segment/outer segment (IS/OS) interface, and retinal sensitivity. We observed a good correlation between the FAF and near-infrared autofluorescence patterns for all the points graded (increased FAF/near-infrared autofluorescence, Pearson rho = 0.6, P = .02; decreased FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01; normal FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01). Mean retinal sensitivity was significantly reduced in cases of decreased FAF (4.73 ± 2.23 dB) or increased FAF (4.75 ± 2.39 dB) compared with normal FAF (7.44 ± 2.34 dB) (P = .001). Mean retinal sensitivity was significantly reduced in case of decreased near-infrared autofluorescence (3.87 ± 2.28 dB), compared with increased near-infrared autofluorescence (5.76 ± 2.44 dB) (P = .02); mean retinal sensitivity in case of increased near-infrared autofluorescence was significantly reduced compared with normal near-infrared autofluorescence (7.15 ± 2.38 dB) (P = .002). On SD-OCT, there was a high inverse correlation between retinal sensitivity and rate of disruptions in IS/OS interface (Pearson rho = -0.72, P = .001). A reduced retinal sensitivity consistently correlates with decreased FAF/near-infrared autofluorescence and a disrupted IS/OS interface. Increased near-infrared autofluorescence may represent a useful method for detection of retinal abnormalities early in dry AMD development. Copyright © 2012 Elsevier Inc. All rights reserved.

Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development.

PubMed

Xu, Siguang; Liu, Cui; Ma, Yana; Ji, Hong-Long; Li, Xiumin

2016-01-01

The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC) and acid sensitive ionic channel (ASIC). ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na(+)) across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

Longitudinal Effects of Embryonic Exposure to Cocaine on Morphology, Cardiovascular Physiology, and Behavior in Zebrafish.

PubMed

Mersereau, Eric J; Boyle, Cody A; Poitra, Shelby; Espinoza, Ana; Seiler, Joclyn; Longie, Robert; Delvo, Lisa; Szarkowski, Megan; Maliske, Joshua; Chalmers, Sarah; Darland, Diane C; Darland, Tristan

2016-05-31

A sizeable portion of the societal drain from cocaine abuse results from the complications of in utero drug exposure. Because of challenges in using humans and mammalian model organisms as test subjects, much debate remains about the impact of in utero cocaine exposure. Zebrafish offer a number of advantages as a model in longitudinal toxicology studies and are quite sensitive physiologically and behaviorally to cocaine. In this study, we have used zebrafish to model the effects of embryonic pre-exposure to cocaine on development and on subsequent cardiovascular physiology and cocaine-induced conditioned place preference (CPP) in longitudinal adults. Larval fish showed a progressive decrease in telencephalic size with increased doses of cocaine. These treated larvae also showed a dose dependent response in heart rate that persisted 24 h after drug cessation. Embryonic cocaine exposure had little effect on overall health of longitudinal adults, but subtle changes in cardiovascular physiology were seen including decreased sensitivity to isoproterenol and increased sensitivity to cocaine. These longitudinal adult fish also showed an embryonic dose-dependent change in CPP behavior, suggesting an increased sensitivity. These studies clearly show that pre-exposure during embryonic development affects subsequent cocaine sensitivity in longitudinal adults.

The phosphoenolpyruvate:sugar phosphotransferase system is involved in sensitivity to the glucosylated bacteriocin sublancin.

PubMed

Garcia De Gonzalo, C V; Denham, E L; Mars, R A T; Stülke, J; van der Donk, W A; van Dijl, J M

2015-11-01

The mode of action of a group of glycosylated antimicrobial peptides known as glycocins remains to be elucidated. In the current study of one glycocin, sublancin, we identified the phosphoenolpyruvate:sugar phosphotransferase system (PTS) of Bacillus species as a key player in bacterial sensitivity. Sublancin kills several Gram-positive bacteria, such as Bacillus species and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). Unlike other classes of bacteriocins for which the PTS is involved in their mechanism of action, we show that the addition of PTS-requiring sugars leads to increased resistance rather than increased sensitivity, suggesting that sublancin has a distinct mechanism of action. Collectively, our present mutagenesis and genomic studies demonstrate that the histidine-containing phosphocarrier protein (HPr) and domain A of enzyme II (PtsG) in particular are critical determinants for bacterial sensitivity to sublancin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

PubMed

Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

2008-02-01

Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

An in vitro human skin test for assessing sensitization potential.

PubMed

Ahmed, S S; Wang, X N; Fielding, M; Kerry, A; Dickinson, I; Munuswamy, R; Kimber, I; Dickinson, A M

2016-05-01

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. Copyright © 2015 John Wiley & Sons, Ltd.

Two-step sensitivity testing of parametrized and regionalized life cycle assessments: methodology and case study.

PubMed

Mutel, Christopher L; de Baan, Laura; Hellweg, Stefanie

2013-06-04

Comprehensive sensitivity analysis is a significant tool to interpret and improve life cycle assessment (LCA) models, but is rarely performed. Sensitivity analysis will increase in importance as inventory databases become regionalized, increasing the number of system parameters, and parametrized, adding complexity through variables and nonlinear formulas. We propose and implement a new two-step approach to sensitivity analysis. First, we identify parameters with high global sensitivities for further examination and analysis with a screening step, the method of elementary effects. Second, the more computationally intensive contribution to variance test is used to quantify the relative importance of these parameters. The two-step sensitivity test is illustrated on a regionalized, nonlinear case study of the biodiversity impacts from land use of cocoa production, including a worldwide cocoa products trade model. Our simplified trade model can be used for transformable commodities where one is assessing market shares that vary over time. In the case study, the highly uncertain characterization factors for the Ivory Coast and Ghana contributed more than 50% of variance for almost all countries and years examined. The two-step sensitivity test allows for the interpretation, understanding, and improvement of large, complex, and nonlinear LCA systems.

Insulin Sensitivity and Inflammation Mediate the Impact of Fitness on Cerebrovascular Health in Adolescents.

PubMed

Yau, Po Lai; Ross, Naima; Tirsi, Andrew; Arif, Arslan; Ozinci, Zeynep; Convit, Antonio

2017-06-01

To investigate in adolescents the relationships between retinal vessel diameter, physical fitness, insulin sensitivity, and systemic inflammation. We evaluated 157 adolescents, 112 with excessive weight and 45 lean, all without type 2 diabetes mellitus. All received detailed evaluations, including measurements of retinal vessel diameter, insulin sensitivity, levels of inflammation, and physical fitness. Overweight/obese adolescents had significantly narrower retinal arteriolar and wider venular diameters, significantly lower insulin sensitivity, and physical fitness. They also had decreased levels of anti-inflammatory and increased levels of proinflammatory markers as well as an overall higher inflammation balance score. Fitness was associated with larger retinal arteriolar and narrower venular diameters and these relationships were mediated by insulin sensitivity. We demonstrate that inflammation also mediates the relationship between fitness and retinal venular, but not arterial diameter; insulin sensitivity and inflammation balance score jointly mediate this relationship with little overlap in their effects. Increasing fitness and insulin sensitivity and reducing inflammation among adolescents carrying excess weight may improve microvascular integrity. Interventions to improve physical fitness and insulin function and reduce inflammation in adolescents, a group likely to benefit from such interventions, may reduce not only cardiovascular disease in middle age, but also improve cerebrovascular function later in life.

Time-dependent climate sensitivity and the legacy of anthropogenic greenhouse gas emissions

PubMed Central

Zeebe, Richard E.

2013-01-01

Climate sensitivity measures the response of Earth’s surface temperature to changes in forcing. The response depends on various climate processes that feed back on the initial forcing on different timescales. Understanding climate sensitivity is fundamental to reconstructing Earth’s climatic history as well as predicting future climate change. On timescales shorter than centuries, only fast climate feedbacks including water vapor, lapse rate, clouds, and snow/sea ice albedo are usually considered. However, on timescales longer than millennia, the generally higher Earth system sensitivity becomes relevant, including changes in ice sheets, vegetation, ocean circulation, biogeochemical cycling, etc. Here, I introduce the time-dependent climate sensitivity, which unifies fast-feedback and Earth system sensitivity. I show that warming projections, which include a time-dependent climate sensitivity, exhibit an enhanced feedback between surface warming and ocean CO2 solubility, which in turn leads to higher atmospheric CO2 levels and further warming. Compared with earlier studies, my results predict a much longer lifetime of human-induced future warming (23,000–165,000 y), which increases the likelihood of large ice sheet melting and major sea level rise. The main point regarding the legacy of anthropogenic greenhouse gas emissions is that, even if the fast-feedback sensitivity is no more than 3 K per CO2 doubling, there will likely be additional long-term warming from slow climate feedbacks. Time-dependent climate sensitivity also helps explaining intense and prolonged warming in response to massive carbon release as documented for past events such as the Paleocene–Eocene Thermal Maximum. PMID:23918402

Time-dependent climate sensitivity and the legacy of anthropogenic greenhouse gas emissions.

PubMed

Zeebe, Richard E

2013-08-20

Climate sensitivity measures the response of Earth's surface temperature to changes in forcing. The response depends on various climate processes that feed back on the initial forcing on different timescales. Understanding climate sensitivity is fundamental to reconstructing Earth's climatic history as well as predicting future climate change. On timescales shorter than centuries, only fast climate feedbacks including water vapor, lapse rate, clouds, and snow/sea ice albedo are usually considered. However, on timescales longer than millennia, the generally higher Earth system sensitivity becomes relevant, including changes in ice sheets, vegetation, ocean circulation, biogeochemical cycling, etc. Here, I introduce the time-dependent climate sensitivity, which unifies fast-feedback and Earth system sensitivity. I show that warming projections, which include a time-dependent climate sensitivity, exhibit an enhanced feedback between surface warming and ocean CO2 solubility, which in turn leads to higher atmospheric CO2 levels and further warming. Compared with earlier studies, my results predict a much longer lifetime of human-induced future warming (23,000-165,000 y), which increases the likelihood of large ice sheet melting and major sea level rise. The main point regarding the legacy of anthropogenic greenhouse gas emissions is that, even if the fast-feedback sensitivity is no more than 3 K per CO2 doubling, there will likely be additional long-term warming from slow climate feedbacks. Time-dependent climate sensitivity also helps explaining intense and prolonged warming in response to massive carbon release as documented for past events such as the Paleocene-Eocene Thermal Maximum.

Cardiac amyloidosis

MedlinePlus

... beta-blockers may be used in people with atrial fibrillation. However, the drugs must be used with caution, ... Complications may include: Atrial fibrillation or ventricular ... ( ascites ) Increased sensitivity to digoxin Low blood pressure ...

Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

PubMed

Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

2013-01-01

Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

Accuracy of the ECG for differential diagnosis between hypertrophic cardiomyopathy and athlete's heart: comparison between the European Society of Cardiology (2010) and International (2017) criteria.

PubMed

Zorzi, Alessandro; Calore, Chiara; Vio, Riccardo; Pelliccia, Antonio; Corrado, Domenico

2018-05-01

Interpretation of the athlete's ECG is based on differentiation between benign ECG changes and potentially pathological abnormalities. The aim of the study was to compare the 2010 European Society of Cardiology (ESC) and the 2017 International criteria for differential diagnosis between hypertrophic cardiomyopathy (HCM) and athlete's heart. The study populations included 200 patients with HCM and 563 athletes grouped as follows: 'group 1', including normal ECG and isolated increase of QRS voltages, which are considered non-pathologic according to ESC and International criteria; 'group 2', including left atrial enlargement or left axis deviation in isolation and Q-waves with an amplitude ≥4 mm but <25% of the ensuing R-wave and a duration <0.04 s which are considered pathologic according to the ESC but not according to the International criteria; and 'group 3', including abnormalities which are considered pathologic according to ESC and International criteria. Overall, the 2010 ESC criteria showed a sensitivity of 95.5% and a specificity of 86.9%. Considering group 2 ECG changes as normal according to the International criteria led to a statistically significant (p<0.001) increase of specificity to 95.9%, associated with a non-significant (p=0.47) reduction of sensitivity to 93%. Among patients with HCM, there was a significant increase of maximal left ventricular wall thickness from group 1 to 3 (p=0.02). The use of 2017 International criteria is associated with a substantial increase in specificity and a marginal decrease in sensitivity for differential diagnosis between HCM and athlete's heart. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The microbial temperature sensitivity to warming is controlled by thermal adaptation and is independent of C-quality across a pan-continental survey

NASA Astrophysics Data System (ADS)

Berglund, Eva; Rousk, Johannes

2017-04-01

Climate models predict that warming will result in an increased loss of soil organic matter (SOM). However, field experiments suggest that although warming results in an immediate increase in SOM turnover, the effect diminishes over time. Although the use and subsequent turnover of SOM is dominated by the soil microbial community, the underlying physiology underpinning warming responses are not considered in current climate models. It has been suggested that a reduction in the perceived quality of SOM to the microbial community, and changes in the microbial thermal adaptation, could be important feed-backs to soil warming. Thus, studies distinguishing between temperature relationships and how substrate quality influences microbial decomposition are a priority. We examined microbial communities and temperature sensitivities along a natural climate gradient including 56 independent samples from across Europe. The gradient included mean annual temperatures (MAT) from ca -4 to 18 ˚ C, along with wide spans of environmental factors known to influence microbial communities, such as pH (4.0 to 8.8), nutrients (C/N from 7 to 50), SOM (from 4 to 94%), and plant communities, etc. The extensive ranges of environmental conditions resulted in wide ranges of substrate quality, indexed as microbial respiration per unit SOM, from 5-150 μg CO2g-1 SOM g-1 h-1. We hypothesised microbial communities to (1) be adapted to the temperature of their climate, leading to warm adapted bacterial communities that were more temperature sensitive (higher Q10s) at higher MAT; (2) have temperature sensitivities affected by the quality of SOM, with higher Q10s for lower quality SOM. To determine the microbial use of SOM and its dependence on temperature, we characterized microbial temperature dependences of bacterial growth (leu inc), fungal growth (ac-in-erg) and soil respiration in all 56 sites. Temperature dependences were determined using brief (ca. 1-2 h at 25˚ C) laboratory incubation experiments including temperatures from 0 to 35˚ C. Temperature relationships were modelled using the Ratkowsky model, and cardinal points including minimum temperature (Tmin) for growth and respiration along with temperature sensitivity (Q10) values were used as indices to compare sites. Microbial communities were cold-adapted in cold sites and warm-adapted in warm sites, as shown by Tmin values ranging from ca. -20 ˚ C to 0 ˚ C. For every 1˚ C rise in MAT, Tmin increased by 0.22˚ C and 0.28˚ C for bacteria and fungi, respectively. Soil respiration was less dependent on MAT, increasing 0.16 ˚ C per 1˚ C. Temperature dependence analyses grew stronger when regressed against summer temperatures, and weaker when regressed against winter temperatures. Hence, microbial communities adjusted their temperature dependence for growth more than for respiration, and higher temperatures had more impact than low temperatures did. The correlation between Tmin and MAT resulted in Q10s increasing with MAT, showing that microorganisms from cold regions were less temperature sensitive than those from warmer regions. For every 1˚ C increase in MAT, Q10 increased with 0.04 and 0.03 units for bacterial and fungal growth respectively, and 0.08 units for soil respiration. In contrast to previous studies, we found no relationship between temperature sensitivity and substrate quality. We demonstrate that the strongest driver of variation in microbial temperatures sensitivities (Q10s) is the microbial adaptation to its thermal environment. Surprisingly, the quality of SOM had no influence on the temperature sensitivity. This calls for a revision of the understanding for how microbial decomposers feed-back to climate warming. Specifically, the thermal adaptation of microbial communities need to be incorporated into climate models to capture responses to warming, while the quality of SOM can be ignored.

The association of noise sensitivity with music listening, training, and aptitude.

PubMed

Kliuchko, Marina; Heinonen-Guzejev, Marja; Monacis, Lucia; Gold, Benjamin P; Heikkilä, Kauko V; Spinosa, Vittoria; Tervaniemi, Mari; Brattico, Elvira

2015-01-01

After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician's auditory system also develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein's Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person's life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual's noise sensitivity.

An oxidized metabolite of linoleic acid increases intracellular calcium in rat adrenal glomerulosa cells.

PubMed

Payet, Marcel D; Goodfriend, Theodore L; Bilodeau, Lyne; Mackendale, Cherilu; Chouinard, Lucie; Gallo-Payet, Nicole

2006-12-01

EKODE, an epoxy-keto derivative of linoleic acid, was previously shown to stimulate aldosterone secretion in rat adrenal glomerulosa cells. In the present study, we investigated the effect of exogenous EKODE on cytosolic [Ca(2+)] increase and aimed to elucidate the mechanism involved in this process. Through the use of the fluorescent Ca(2+)-sensitive dye Fluo-4, EKODE was shown to rapidly increase intracellular [Ca(2+)] ([Ca(2+)](i)) along a bell-shaped dose-response relationship with a maximum peak at 5 microM. Experiments performed in the presence or absence of Ca(2+) revealed that this increase in [Ca(2+)](i) originated exclusively from intracellular pools. EKODE-induced [Ca(2+)](i) increase was blunted by prior application of angiotensin II, Xestospongin C, and cyclopiazonic acid, indicating that inositol trisphosphate (InsP(3))-sensitive Ca(2+) stores can be mobilized by EKODE despite the absence of InsP(3) production. Accordingly, EKODE response was not sensitive to the phospholipase C inhibitor U-73122. EKODE mobilized a Ca(2+) store included in the thapsigargin (TG)-sensitive stores, although the interaction between EKODE and TG appears complex, since EKODE added at the plateau response of TG induced a rapid drop in [Ca(2+)](i). 9-oxo-octadecadienoic acid, another oxidized derivative of linoleic acid, also increases [Ca(2+)](i), with a dose-response curve similar to EKODE. However, arachidonic and linoleic acids at 10 microM failed to increase [Ca(2+)](i) but did reduce the amplitude of the response to EKODE. It is concluded that EKODE mobilizes Ca(2+) from an InsP(3)-sensitive store and that this [Ca(2+)](i) increase is responsible for aldosterone secretion by glomerulosa cells. Similar bell-shaped dose-response curves for aldosterone and [Ca(2+)](i) increases reinforce this hypothesis.

Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive Detection of Gaseous HF.

PubMed

Wallace, Ryan A; Sepaniak, Michael J; Lavrik, Nickolay V; Datskos, Panos G

2017-06-06

Sensitive detection of harmful chemicals in industrial applications is pertinent to safety. In this work, we demonstrate the use of a sensitive silicon microcantilever (MC) system with a porous silicon oxide layer deposited on the active side of the MCs that have been mechanically manipulated to increase sensitivity. Included is the evaluation of porous silicon oxide present on different geometries of MCs and exposed to varying concentrations of hydrogen fluoride in humid air. Profilometry and the signal generated by the stress-induced porous silicon oxide (PSO) coating and bending of the MC were used as methods of evaluation.

Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive Detection of Gaseous HF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallace, Ryan A.; Sepaniak, Michael J.; Lavrik, Nickolay V.

Sensitive detection of harmful chemicals in industrial applications is pertinent to safety. In this paper, we demonstrate the use of a sensitive silicon microcantilever (MC) system with a porous silicon oxide layer deposited on the active side of the MCs that have been mechanically manipulated to increase sensitivity. Included is the evaluation of porous silicon oxide present on different geometries of MCs and exposed to varying concentrations of hydrogen fluoride in humid air. Finally, profilometry and the signal generated by the stress-induced porous silicon oxide (PSO) coating and bending of the MC were used as methods of evaluation.

Evaluation of Porous Silicon Oxide on Silicon Microcantilevers for Sensitive Detection of Gaseous HF

DOE PAGES

Wallace, Ryan A.; Sepaniak, Michael J.; Lavrik, Nickolay V.; ...

2017-05-10

Sensitive detection of harmful chemicals in industrial applications is pertinent to safety. In this paper, we demonstrate the use of a sensitive silicon microcantilever (MC) system with a porous silicon oxide layer deposited on the active side of the MCs that have been mechanically manipulated to increase sensitivity. Included is the evaluation of porous silicon oxide present on different geometries of MCs and exposed to varying concentrations of hydrogen fluoride in humid air. Finally, profilometry and the signal generated by the stress-induced porous silicon oxide (PSO) coating and bending of the MC were used as methods of evaluation.

Climate Sensitivity in the Anthropocene

NASA Technical Reports Server (NTRS)

Previdi, M.; Liepert, B. G.; Peteet, Dorothy M.; Hansen, J.; Beerling, D. J.; Broccoli, A. J.; Frolking, S.; Galloway, J. N.; Heimann, M.; LeQuere, C.;

Advanced X-ray Imaging Crystal Spectrometer for Magnetic Fusion Tokamak Devices

NASA Astrophysics Data System (ADS)

Lee, S. G.; Bak, J. G.; Bog, M. G.; Nam, U. W.; Moon, M. K.; Cheon, J. K.

2008-03-01

An advanced X-ray imaging crystal spectrometer is currently under development using a segmented position sensitive detector and time-to-digital converter (TDC) based delay-line readout electronics for burning plasma diagnostics. The proposed advanced XICS utilizes an eight-segmented position sensitive multi-wire proportional counter and supporting electronics to increase the spectrometer performance includes the photon count-rate capability and spatial resolution.

Birth weight, current anthropometric markers, and high sensitivity C-reactive protein in Brazilian school children.

PubMed

Boscaini, Camile; Pellanda, Lucia Campos

2015-01-01

Studies have shown associations of birth weight with increased concentrations of high sensitivity C-reactive protein. This study assessed the relationship between birth weight, anthropometric and metabolic parameters during childhood, and high sensitivity C-reactive protein. A total of 612 Brazilian school children aged 5-13 years were included in the study. High sensitivity C-reactive protein was measured by particle-enhanced immunonephelometry. Nutritional status was assessed by body mass index, waist circumference, and skinfolds. Total cholesterol and fractions, triglycerides, and glucose were measured by enzymatic methods. Insulin sensitivity was determined by the homeostasis model assessment method. Statistical analysis included chi-square test, General Linear Model, and General Linear Model for Gamma Distribution. Body mass index, waist circumference, and skinfolds were directly associated with birth weight (P < 0.001, P = 0.001, and P = 0.015, resp.). Large for gestational age children showed higher high sensitivity C-reactive protein levels (P < 0.001) than small for gestational age. High birth weight is associated with higher levels of high sensitivity C-reactive protein, body mass index, waist circumference, and skinfolds. Large for gestational age altered high sensitivity C-reactive protein and promoted additional risk factor for atherosclerosis in these school children, independent of current nutritional status.

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans

PubMed Central

Stanhope, Kimber L.; Schwarz, Jean Marc; Keim, Nancy L.; Griffen, Steven C.; Bremer, Andrew A.; Graham, James L.; Hatcher, Bonnie; Cox, Chad L.; Dyachenko, Artem; Zhang, Wei; McGahan, John P.; Seibert, Anthony; Krauss, Ronald M.; Chiu, Sally; Schaefer, Ernst J.; Ai, Masumi; Otokozawa, Seiko; Nakajima, Katsuyuki; Nakano, Takamitsu; Beysen, Carine; Hellerstein, Marc K.; Berglund, Lars; Havel, Peter J.

2009-01-01

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults. PMID:19381015

Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging

PubMed Central

O’Donovan, Aoife; Slavich, George M; Epel, Elissa S.; Neylan, Thomas C

2015-01-01

Anxiety disorders increase risk for the early development of several diseases of aging. Elevated inflammation, a common risk factor across diseases of aging, may play a key role in the relationship between anxiety and physical disease. However, the neurobiological mechanisms linking anxiety with elevated inflammation remain unclear. In this review, we present a neurobiological model of the mechanisms by which anxiety promotes inflammation. Specifically we propose that exaggerated neurobiological sensitivity to threat in anxious individuals may lead to sustained threat perception, which is accompanied by prolonged activation of threat-related neural circuitry and threat-responsive biological systems including the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS), and inflammatory response. Over time, this pattern of responding can promote chronic inflammation through structural and functional brain changes, altered sensitivity of immune cell receptors, dysregulation of the HPA axis and ANS, and accelerated cellular aging. Chronic inflammation, in turn, increases risk for diseases of aging. Exaggerated neurobiological sensitivity to threat may thus be a treatment target for reducing disease risk in anxious individuals. PMID:23127296

Positron emission tomography with α-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy.

PubMed

Rubí, Sebastià; Costes, Nicolas; Heckemann, Rolf A; Bouvard, Sandrine; Hammers, Alexander; Martí Fuster, Berta; Ostrowsky, Karine; Montavont, Alexandra; Jung, Julien; Setoain, Xavier; Catenoix, Hélène; Hino, Keiko; Liger, François; Le Bars, Didier; Ryvlin, Philippe

2013-12-01

Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy. We reevaluated whether increased uptake of α-[(11) C]methyl-l-tryptophan (AMT) in cerebral tubers is associated with tuber epileptogenicity. We included 12 patients (six male, 4-53 years old) with TSC and refractory seizures who were evaluated for epilepsy surgery in our center, including video-electroencephalographic (EEG) monitoring, fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI), and positron emission tomography (PET) with α-[(11) C]methyl-l-tryptophan (AMT-PET). Nine of these 12 patients also underwent intracerebral EEG recording. AMT uptake in each tuber was visually evaluated on PET coregistered with MRI. An AMT uptake index based on lesional/healthy cortex ratio was also calculated. Sensitivity and specificity values of AMT-PET in the detection of epileptogenic lesions were obtained, using the available electroclinical and neuroimaging evidence as the gold standard for epileptogenicity. A total of 126 tubers were identified. Two of 12 patients demonstrated a tuber with clearly increased AMT uptake, one of whom also showed a subtle increased AMT uptake in another contralateral tuber. Four other patients showed only subtle increased AMT uptake. The only two tubers with clearly increased AMT uptake proved to be epileptogenic based on intracerebral EEG data, whereas none of the tubers associated with subtle increased AMT uptake were involved at ictal onset. In a per-patient approach, this yielded a sensitivity of clearly increased AMT uptake in detecting tuber epileptogenicity of 17% (2/12 patients), whereas the per-lesion sensitivity and specificity were 12% (95% confidence interval [CI]: 3-34%) and 100% (95% CI: 97-100%), respectively. AMT-PET is a specific neuroimaging technique in the identification of epileptogenic tubers in TSC. Despite its low sensitivity, the clinical usefulness of AMT-PET still deserves to be considered according to the challenging complexity of epilepsy surgery in tuberous sclerosis. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Determining Regional Sensitivity to Energy-Related Water Withdrawals in Minnesota

NASA Astrophysics Data System (ADS)

McCulloch, A.; Brauman, K. A.

2015-12-01

Minnesota has abundant freshwater resources, yet concerns about water-impacts of energy and mining development are increasing. Statewide, total annual water withdrawals have increased, and, in some watersheds, withdrawals make up a large fraction of available water. The energy and mining sectors play a critical role in determining water availability, as water is used to irrigate biofuel feedstock crops, cool thermoelectric plants, and process and transport fuels and iron ore. We evaluated the Minnesota Department of Natural Resources (DNR) Water and Reporting System (MPARS) dataset (1988-2014) to identify regions where energy and mining-related water withdrawals are high or where they are increasing. The energy and mining sectors account for over 65 percent of total water extractions in Minnesota, but this percentage is greater in some regions. In certain southern and northeastern Minnesota watersheds, these extractions account for 90 percent of total water demand. Sensitivity to these demands is not dependent on total water demand alone, and is also not uniform among watersheds. We identified and evaluated factors influencing sensitivity, including population, extraction type (surface water or groundwater), percentage of increased demand, and whether withdrawals are consumptive or not. We determined that southern Minnesota is particularly sensitive to increased water demands, because of growing biofuel and sand extraction industries (the products of which are used in hydraulic fracturing). In the last ten years, ethanol production in Minnesota has increased by 440 percent, and over fifteen refineries (each with a capacity over 1.1 billion gallons), have been built. These users primarily extract from surface water bodies within a few watersheds, compromising local supplies. As these energy-related industries continue to grow, so will the demand for freshwater resources. Determining regional sensitivity to increased demands will allow policy-makers to manage the increased competition for Minnesota's future water supplies.

Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia.

PubMed

Stanhewicz, Anna E; Jandu, Sandeep; Santhanam, Lakshmi; Alexander, Lacy M

2017-08-01

Women who have had preeclampsia have increased cardiovascular disease risk; however, the mechanism(s) responsible for this association remain unclear. Microvascular damage sustained during a preeclamptic pregnancy may persist postpartum. The putative mechanisms mediating this dysfunction include a reduction in NO-dependent dilation and an increased sensitivity to angiotensin II. In this study, we evaluated endothelium-dependent dilation, angiotensin II sensitivity, and the therapeutic effect of angiotensin II receptor blockade (losartan) on endothelium-dependent dilation in vivo in the microvasculature of women with a history of preeclampsia (n=12) and control women who had a healthy pregnancy (n=12). We hypothesized that preeclampsia would have (1) reduced endothelium-dependent dilation, (2) reduced NO-mediated dilation, and (3) increased sensitivity to angiotensin II. We further hypothesized that localized losartan would increase endothelium-dependent vasodilation in preeclampsia. We assessed microvascular endothelium-dependent vasodilator function by measurement of cutaneous vascular conductance responses to graded infusion of acetylcholine (acetylcholine; 10 -7 -102 mmol/L) and a standardized local heating protocol in control sites and sites treated with 15 mmol/L L-NAME ( N G -nitro-l-arginine methyl ester; NO-synthase inhibitor) or 43 µmol/L losartan. Further, we assessed microvascular vasoconstrictor sensitivity to angiotensin II (10 -20 -10 -4 mol/L). Preeclampsia had significantly reduced endothelium-dependent dilation (-0.3±0.5 versus -1.0±0.4 log EC50 ; P <0.001) and NO-dependent dilation (16±3% versus 39±6%; P =0.006). Preeclampsia also had augmented vasoconstrictor sensitivity to angiotensin II (-10.2±1.3 versus -8.3±0.5; P =0.006). Angiotensin II type I receptor inhibition augmented endothelium-dependent vasodilation and NO-dependent dilation in preeclampsia but had no effect in healthy pregnancy. These data suggest that women who have had preeclampsia have persistent microvascular dysfunction postpartum, mediated, in part, by increased sensitivity to angiotensin II. © 2017 American Heart Association, Inc.

Intravesical PAC1 Receptor Antagonist, PACAP(6–38), Reduces Urinary Bladder Frequency and Pelvic Sensitivity in NGF-OE Mice

PubMed Central

Girard, Beatrice M.; Malley, Susan E.; Mathews, Morgan M.; May, Victor

2017-01-01

Chronic NGF overexpression (OE) in the urothelium, achieved through the use of a highly urothelium-specific uroplakin II promoter, stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency and non-voiding contractions, and referred somatic sensitivity. Additional NGF-mediated pleiotropic changes might contribute to increased voiding frequency and pelvic hypersensitivity in NGF-OE mice such as neuropeptide/receptor systems including PACAP(Adcyap1) and PAC1 receptor (Adcyap1r1). Given the presence of PAC1-immunoreactive fibers and the expression of PAC1 receptor expression in bladder tissues, and PACAP-facilitated detrusor contraction, whether PACAP/receptor signaling contributes to increased voiding frequency and somatic sensitivity was evaluated in NGF-OE mice. Intravesical administration of the PAC1 receptor antagonist, PACAP(6–38) (300 nM), significantly (p ≤ 0.01) increased intercontraction interval (2.0-fold) and void volume (2.5-fold) in NGF-OE mice. Intravesical instillation of PACAP(6–38) also decreased baseline bladder pressure in NGF-OE mice. PACAP(6–38) had no effects on bladder function in WT mice. Intravesical administration of PACAP(6–38) (300 nM) significantly (p ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in WT mice. PACAP/receptor signaling contributes to the increased voiding frequency and pelvic sensitivity observed in NGF-OE mice. PMID:27146136

VARS-TOOL: A Comprehensive, Efficient, and Robust Sensitivity Analysis Toolbox

NASA Astrophysics Data System (ADS)

Razavi, S.; Sheikholeslami, R.; Haghnegahdar, A.; Esfahbod, B.

2016-12-01

VARS-TOOL is an advanced sensitivity and uncertainty analysis toolbox, applicable to the full range of computer simulation models, including Earth and Environmental Systems Models (EESMs). The toolbox was developed originally around VARS (Variogram Analysis of Response Surfaces), which is a general framework for Global Sensitivity Analysis (GSA) that utilizes the variogram/covariogram concept to characterize the full spectrum of sensitivity-related information, thereby providing a comprehensive set of "global" sensitivity metrics with minimal computational cost. VARS-TOOL is unique in that, with a single sample set (set of simulation model runs), it generates simultaneously three philosophically different families of global sensitivity metrics, including (1) variogram-based metrics called IVARS (Integrated Variogram Across a Range of Scales - VARS approach), (2) variance-based total-order effects (Sobol approach), and (3) derivative-based elementary effects (Morris approach). VARS-TOOL is also enabled with two novel features; the first one being a sequential sampling algorithm, called Progressive Latin Hypercube Sampling (PLHS), which allows progressively increasing the sample size for GSA while maintaining the required sample distributional properties. The second feature is a "grouping strategy" that adaptively groups the model parameters based on their sensitivity or functioning to maximize the reliability of GSA results. These features in conjunction with bootstrapping enable the user to monitor the stability, robustness, and convergence of GSA with the increase in sample size for any given case study. VARS-TOOL has been shown to achieve robust and stable results within 1-2 orders of magnitude smaller sample sizes (fewer model runs) than alternative tools. VARS-TOOL, available in MATLAB and Python, is under continuous development and new capabilities and features are forthcoming.

Basal plasma insulin and homeostasis model assessment (HOMA) are indicators of insulin sensitivity in cats.

PubMed

Appleton, D J; Rand, J S; Sunvold, G D

2005-06-01

The objective of this study was to compare simpler indices of insulin sensitivity with the minimal model-derived insulin sensitivity index to identify a simple and reliable alternative method for assessing insulin sensitivity in cats. In addition, we aimed to determine whether this simpler measure or measures showed consistency of association across differing body weights and glucose tolerance levels. Data from glucose tolerance and insulin sensitivity tests performed in 32 cats with varying body weights (underweight to obese), including seven cats with impaired glucose tolerance, were used to assess the relationship between Bergman's minimal model-derived insulin sensitivity index (S(I)), and various simpler measures of insulin sensitivity. The most useful overall predictors of insulin sensitivity were basal plasma insulin concentrations and the homeostasis model assessment (HOMA), which is the product of basal glucose and insulin concentrations divided by 22.5. It is concluded that measurement of plasma insulin concentrations in cats with food withheld for 24 h, in conjunction with HOMA, could be used in clinical research projects and by practicing veterinarians to screen for reduced insulin sensitivity in cats. Such cats may be at increased risk of developing impaired glucose tolerance and type 2 diabetes mellitus. Early detection of these cats would enable preventative intervention programs such as weight reduction, increased physical activity and dietary modifications to be instigated.

Sensitivity and Specificity of Biochemical Tests for Diagnosis of Intrahepatic Cholestasis of Pregnancy.

PubMed

Jurate, Kondrackiene; Rimantas, Zalinkevicius; Jolanta, Sumskiene; Vladas, Gintautas; Limas, Kupcinskas

2017-01-01

Intrahepatic cholestasis of pregnancy (ICP) is linked with increased risk of fetal complications. An accurate diagnostic test is needed to diagnose this disorder on time. We aimed to assess sensitivity and specificity of laboratory tests used for diagnosis of intrahepatic cholestasis of pregnancy and determine more reliable cut-off values of transaminases. Sixty one symptomatic patients with ICP and 29 healthy pregnant women were included in the retrospective analysis. ICP patients had higher total bile acids (TBA) levels than healthy women (32 vs. 6; P < 0.0001) due to increase in cholic acid (CA) and chenodeoxycholic acid (CDCA). CA/CDCA ratio was significantly higher in ICP patients compared to healthy pregnant women (1.13 vs. 0.68; P < 0.00002). TBA, CA, CDCA and CA/CDCA ratio demonstrate the following sensitivity (94%, 96%, 89%, 71.9%) and specificity (63%, 63%, 59%, 79.3%, respectively) for ICP diagnosis. Lowering cut-off values for ALT (31 U/L) and AST (30 U/L) resulted only in minimal increase of sensitivity to 92.2% vs. 90.1% for ALT and to 92.2%, vs. 90.6% for AST. The present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP. Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP.

Bioplastic made from corn starch as an effective biological delivery vehicle for control of agricultural pests

USDA-ARS?s Scientific Manuscript database

In recent years, increasing consumer sensitivity to environmental sustainability and favorable legislation has resulted in a rising demand for renewable and bio-based products, including biodegradable plastic. A recent market research report has projected a 15% annual increase in the demand of biode...

Resilience and rejection sensitivity mediate long-term outcomes of parental divorce.

PubMed

Schaan, Violetta K; Vögele, Claus

2016-11-01

Increasing divorce rates leave more and more children to deal with the separation of their parents. Recent research suggests that children of divorced parents more often experience psychological and physical symptoms than children of non-divorced parents. The processes that mediate the relationship between parental divorce and ill-health, however, are still elusive. This study investigated the mediating role of psychological factors such as resilience and rejection sensitivity on the long-term consequences of parental divorce in young adults. One hundred and ninety-nine participants (mean age 22.3 years) completed an online survey, including measures of mental health, childhood trauma, resilience, and rejection sensitivity. Participants with divorced parents (33 %) reported increased levels of psychological symptoms, childhood trauma, rejection sensitivity, and lower levels of resilience. The association between parental divorce and mental health was fully mediated by resilience, rejection sensitivity, and childhood trauma. The mediation model explained up to 44 % of the total variance in mental health symptoms. Resilience and rejection sensitivity are crucial factors for successful coping with the experience of parental separation. Prevention programs that help to boost children's resilience might help to reduce the long-term effects of parental divorce on their attachment style (e.g., rejection sensitivity), thereby improving their mental health on the long run. Furthermore, the results call for parental awareness and counseling to target and reduce the observed increased level of childhood trauma. Limitations concern the cross-sectional and retrospective design of the study.

Interpreting IgE sensitization tests in food allergy.

PubMed

Chokshi, Niti Y; Sicherer, Scott H

2016-01-01

Food allergies are increasing in prevalence, and with it, IgE testing to foods is becoming more commonplace. Food-specific IgE tests, including serum assays and prick skin tests, are sensitive for detecting the presence of food-specific IgE (sensitization), but specificity for predicting clinical allergy is limited. Therefore, positive tests are generally not, in isolation, diagnostic of clinical disease. However, rationale test selection and interpretation, based on clinical history and understanding of food allergy epidemiology and pathophysiology, makes these tests invaluable. Additionally, there exist highly predictive test cutoff values for common allergens in atopic children. Newer testing methodologies, such as component resolved diagnostics, are promising for increasing the utility of testing. This review highlights the use of IgE serum tests in the diagnosis of food allergy.

Theoretical Study on Stress Sensitivity of Fractal Porous Media with Irreducible Water

NASA Astrophysics Data System (ADS)

Lei, Gang; Dong, Zhenzhen; Li, Weirong; Wen, Qingzhi; Wang, Cai

The couple flow deformation behavior in porous media has drawn tremendous attention in various scientific and engineering fields. However, though the coupled flow deformation mechanism has been intensively investigated in the last decades, the essential controls on stress sensitivity are not determined. It is of practical significance to use analytic methods to study stress sensitivity of porous media. Unfortunately, because of the disordered and extremely complicated microstructures of porous media, the theoretical model for stress sensitivity is scarce. The goal of this work is to establish a novel and reasonable quantitative model to determine the essential controls on stress sensitivity. The predictions of the theoretical model, derived from the Hertzian contact theory and fractal geometry, agree well with the available experimental data. Compared with the previous models, our model takes into account more factors, including the influence of the water saturation and the microstructural parameters of the pore space. The proposed models can reveal more mechanisms that affect the coupled flow deformation behavior in fractal porous media. The results show that the irreducible water saturation increases with the increase of effective stress, and decreases with the increased rock elastic modulus (or increased power law index) at a given effective stress. The effect of stress variation on porosity is smaller than that on permeability. Under a given effective stress, the normalized permeability (or the normalized porosity) becomes smaller with the decrease of rock elastic modulus (or the decrease of power law index). And a lower capillary pressure will correspond to an increased rock elastic modulus (or an increased power law index) under a given water saturation.

Comparison of Heidelberg Retina Tomograph-3 glaucoma probability score and Moorfields regression analysis of optic nerve head in glaucoma patients and healthy individuals.

PubMed

Caglar, Çagatay; Gul, Adem; Batur, Muhammed; Yasar, Tekin

2017-01-01

To compare the sensitivity and specificity of Moorfields regression analysis (MRA) and glaucoma probability score (GPS) between healthy and glaucomatous eyes with Heidelberg Retinal Tomograph 3 (HRT-3). The study included 120 eyes of 75 glaucoma patients and 138 eyes of 73 normal subjects, for a total of 258 eyes of 148 individuals. All measurements were performed with the HRT-3. Diagnostic test criteria (sensitivity, specificity, etc.) were used to evaluate how efficiently GPS and MRA algorithms in the HRT-3 discriminated between the glaucoma and control groups. The GPS showed 88 % sensitivity and 66 % specificity, whereas MRA had 71.5 % sensitivity and 82.5 % specificity. There was 71 % agreement between the final results of MRA and GPS in the glaucoma group. Excluding borderline patients from both analyses resulted in 91.6 % agreement. In the control group the level of agreement between MRA and GPS was 64 % including borderline patients and 84.1 % after excluding borderline patients. The accuracy rate is 92 % for MRA and 91 % for GPS in the glaucoma group excluding borderline patients. The difference was nor statistically different. In both cases, agreement was higher between MRA and GPS in the glaucoma group. We found that both sensitivity and specificity increased with disc size for MRA, while the sensitivity increased and specificity decreased with larger disc sizes for GPS. HRT is able to quantify and clearly reveal structural changes in the ONH and RNFL in glaucoma.

Synthetic Modifications In the Frequency Domain for Finite Element Model Update and Damage Detection

DTIC Science & Technology

2017-09-01

Sensitivity-based finite element model updating and structural damage detection has been limited by the number of modes available in a vibration test and...increase the number of modes and corresponding sensitivity data by artificially constraining the structure under test, producing a large number of... structural modifications to the measured data, including both springs-to-ground and mass modifications. This is accomplished with frequency domain

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair.

PubMed

Ford, James B; Baturin, Dmitry; Burleson, Tamara M; Van Linden, Annemie A; Kim, Yong-Mi; Porter, Christopher C

2015-09-29

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine and that mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia.

AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair

PubMed Central

Burleson, Tamara M.; Van Linden, Annemie A.; Kim, Yong-Mi; Porter, Christopher C.

2015-01-01

While some children with acute lymphoblastic leukemia (ALL) have excellent prognoses, the prognosis for adults and children with T cell ALL is more guarded. Treatment for T-ALL is heavily dependent upon antimetabolite chemotherapeutics, including cytarabine. Targeted inhibition of WEE1 with AZD1775 has emerged as a strategy to sensitize cancer cells to cytarabine and other chemotherapeutics. We sought to determine if this strategy would be effective for T-ALL with clinically relevant anti-leukemia agents. We found that AZD1775 sensitizes T-ALL cells to several traditional anti-leukemia agents, acting synergistically with cytarabine by enhancing DNA damage and apoptosis. In addition to increased phosphorylation of H2AX at serine 139 (γH2AX), AZD1775 led to increased phosphorylation of H2AX at tyrosine 142, a signaling event associated with promotion of apoptosis over DNA repair. In a xenograft model of T-ALL, the addition of AZD1775 to cytarabine slowed leukemia progression and prolonged survival. Inhibition of WEE1 with AZD1775 sensitizes T-ALL to several anti-leukemia agents, particularly cytarabine. Mechanistically, AZD1775 promotes apoptosis over DNA repair in cells treated with cytarabine. These data support the development of clinical trials including AZD1775 in combination with conventional chemotherapy for acute leukemia. PMID:26334102

Nanophotonics of biomaterials and inorganic nanostructures

NASA Astrophysics Data System (ADS)

Petrik, P.; Agocs, E.; Kalas, B.; Fodor, B.; Lohner, T.; Nador, J.; Saftics, A.; Kurunczi, S.; Novotny, T.; Perez-Feró, E.; Nagy, R.; Hamori, A.; Horvath, R.; Hózer, Z.; Fried, M.

2017-01-01

Optical methods have been used for the sensitive characterization of surfaces and thin films for more than a century. The first ellipsometric measurement was conducted on metal surfaces by Paul Drude in 1889. The word ‘ellipsometer’ was first used by Rothen in a study of antigen-antibody interactions on polished metal surfaces in 1945. The ‘bible’ of ellipsometry has been published in the second half of the ‘70s. The publications in the topic of ellipsometry started to increase rapidly by the end of the ‘80s, together with concepts like surface plasmon resonance, later new topics like photonic crystals emerged. These techniques find applications in many fields, including sensorics or photovoltaics. In optical sensorics, the highest sensitivities were achieved by waveguide interferometry and plasmon resonance configurations. The instrumentation of ellipsometry is also being developed intensively towards higher sensitivity and performance by combinations with plasmonics, scatterometry, imaging or waveguide methods, utilizing the high sensitivity, high speed, non-destructive nature and mapping capabilities. Not only the instrumentation but also the methods of evaluation show a significant development, which leads to the characterization of structures with increasing complexity, including photonic, porous or metal surfaces. This article discusses a selection of interesting applications of photonics in the Centre for Energy Research of the Hungarian Academy of Sciences.

Theoretical study on the phenylpropanolamine drug interaction with the pristine, Si and Al doped [60] fullerenes

NASA Astrophysics Data System (ADS)

Moradi, Morteza; Nouraliei, Milad; Moradi, Reza

2017-03-01

Phenylpropanolamine (PPA) is a popular drug of abuse and its detection is of great importance for police and drug communities. Herein, we investigated the electronic sensitivity and reactivity of pristine, Al and Si doped C60 fullerenes to the PPA drug, using density functional theory calculations. Two adsorption mechanisms were predicted for PPA on the pristine C60 including cycloaddition and adsorption via -NH2 group. It was found that the pristine C60 has a good sensitivity to this drug but suffers from a weak interaction (adsorption energy -0.1 kcal/mol) because of structural deformation and aromaticity break. The PPA is adsorbed on the Al or Si doped C60 from its -OH or -NH2 groups. The Al-doping significantly improves the reactivity of C60 but decreases its electronic sensitivity. Unlike the Al-doping, the Si-doping increases both the reactivity and electronic sensitivity to the PPA drug. At the presence of PPA drug, the conductivity of the Si-doped C60 considerably increases due to the HOMO-LUMO gap reduction by about 30.3%. Different analyses were used to obtain the results including nucleus independent chemical shift (NICS), density of states (DOS), molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), etc.

Gamma ray irradiated AgFeO{sub 2} nanoparticles with enhanced gas sensor properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiuhua, E-mail: xhwang@mail.ahnu.edu.cn; Shi, Zhijie; Yao, Shangwu

2014-11-15

AgFeO{sub 2} nanoparticles were synthesized via a facile hydrothermal method and irradiated by various doses of gamma ray. The products were characterized with X-ray powder diffraction, UV–vis absorption spectrum and transmission electron microscope. The results revealed that the crystal structure, morphology and size of the samples remained unchanged after irradiation, while the intensity of UV–Vis spectra increased with irradiation dose increasing. In addition, gamma ray irradiation improved the performance of gas sensor based on the AgFeO{sub 2} nanoparticles including the optimum operating temperature and sensitivity, which might be ascribed to the generation of defects. - Graphical abstract: Gamma ray irradiationmore » improved the performance of gas sensor based on the AgFeO{sub 2} nanoparticles including sensitivity and optimum operating temperature, which might be ascribed to the generation of defects. - Highlights: • AgFeO{sub 2} nanoparticles were synthesized and irradiated with gamma ray. • AgFeO{sub 2} nanoparticles were employed to fabricate gas sensors to detect ethanol. • Gamma ray irradiation improved the sensitivity and optimum operating temperature.« less

The association of noise sensitivity with music listening, training, and aptitude

PubMed Central

Kliuchko, Marina; Heinonen-Guzejev, Marja; Monacis, Lucia; Gold, Benjamin P.; Heikkilä, Kauko V.; Spinosa, Vittoria; Tervaniemi, Mari; Brattico, Elvira

2015-01-01

After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician's auditory system also develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein's Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person's life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual's noise sensitivity. PMID:26356378

Photon energy dependence of three fortuitous dosemeters from personal electronic devices, measured by optically stimulated luminescence.

PubMed

Beerten, Koen; Vanhavere, Filip

2010-08-01

New data are presented with regard to the relative OSL sensitivity of three different emergency dosemeters irradiated to various photon energies approximately between 48 and 1250 keV using blue excitation light. Investigated components extracted from commonly worn objects include those from USB flash drives (alumina substrate), mobile phones (Ba-rich silicate) and credit cards (chip card module). Several basic properties have been investigated such as the overall radiation sensitivity, the shape of the decay curve and fading of the OSL signal. An increase of the sensitivity for low energies relative to (60)Co gamma rays can be observed for the three dosemeters, the increase being very pronounced for the Ba-rich component (factor of 10) and less pronounced for the chip card module (factor of 2). It is concluded that proper dose correction factors for photon energy have to be applied in order to accurately determine the absorbed dose to tissue. The OSL sensitivity to neutron irradiation was investigated as well, but this was found to be less than the gamma sensitivity.

The development of cortical sensitivity to visual word forms.

PubMed

Ben-Shachar, Michal; Dougherty, Robert F; Deutsch, Gayle K; Wandell, Brian A

2011-09-01

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7-12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition.

The Development of Cortical Sensitivity to Visual Word Forms

PubMed Central

Ben-Shachar, Michal; Dougherty, Robert F.; Deutsch, Gayle K.; Wandell, Brian A.

2011-01-01

The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7–12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition. PMID:21261451

Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

PubMed

Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

2005-11-15

One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

Evaluation of the Diagnostic Utility of the Traditional and Revised WHO Dengue Case Definitions

PubMed Central

Gutiérrez, Gamaliel; Gresh, Lionel; Pérez, María Ángeles; Elizondo, Douglas; Avilés, William; Kuan, Guillermina; Balmaseda, Ángel; Harris, Eva

2013-01-01

Dengue, a mosquito-borne viral illness, is a major public health problem worldwide, and its incidence continues to increase. In 2009, the World Health Organization published guidelines that included a revision of the dengue case definition. Compared to the traditional definition, the revised case definition relies more on signs than on symptoms, making it more applicable to young children. We evaluated the diagnostic utility of both case definitions in two studies of pediatric dengue in Managua, Nicaragua. In a community-based cohort study, we included data from 3,407 suspected dengue cases, of which 476 were laboratory-confirmed. In the second study, we collected information from 1,160 participants recruited at the national pediatric reference hospital (723 laboratory-confirmed). In the cohort study, the traditional definition had 89.3% sensitivity and 43.1% specificity, while the revised definition yielded similar sensitivity (86.6%) and higher specificity (55.2%, p<0.001). In the hospital study, the traditional case definition yielded 96.7% sensitivity and 22.0% specificity, whereas the revised case definition had higher sensitivity (99.3%, p<0.001) but lower specificity (8.5%, p<0.001). We then evaluated the performance of two diagnostic models based on the signs/symptoms included in each definition by analyzing the effect of increasing numbers of signs/symptoms on the sensitivity and specificity of case capture. Receiver operating characteristic analysis showed a slightly better performance for the revised model in both studies. Interestingly, despite containing less symptoms that cannot be readily expressed by children aged less than 4 years, the revised definition did not perform better in this age group. Overall, our results indicate that both case definitions have similar capacity to diagnose dengue. Owing to their high sensitivity and low specificity, they should be primarily used for screening purposes. However, in a primary care setting, neither of the case definitions performed well as a screening test in younger children. PMID:23991237

[Antibiotic consumption and bacterial sensitivity in a teaching hospital: A 5-year study].

PubMed

Cotteret, C; Vallières, E; Roy, H; Ovetchkine, P; Longtin, J; Bussières, J-F

2016-10-01

To reduce risks of antibiotic resistance, governmental and learned societies decreed the optimal use of antibiotics. The relation between antibiotic consumption and bacterial resistance increase has been clearly demonstrated over the last several years. Antibiotic consumption data and bacterial sensitivity data are regularly published, but very few publications have searched for a correlation between these two variables. This study focused on antibiotic use and consumption as well as bacterial sensitivity to these antibiotics. The main objective was to describe the changes in antibiotic consumption and bacterial sensitivity in a mother-child teaching hospital. The secondary objectives were to explore whether antibiotic use and bacterial sensitivity were correlated and to comment on the usefulness of these data for clinicians. This was a 5-year retrospective, descriptive, cross-sectional study. All samples from usually sterile biologic liquids of hospitalized pediatric patients were included in the study. The samples from outpatient clinics were excluded. All types of bacteria identified in more than 30 isolates were included in the study. The antibiotics usually used to treat these bacteria were included. To assess antibiotic consumption, we calculated the number of days of therapy per 1000 patient-days for hospitalized pediatric patients and we calculated the Pearson correlation coefficient between antibiotic consumption and sensitivity rates to these antibiotics. Two scenarios were explored: one with correlation by year and one with the next year for bacterial sensitivity. During the study period (2010-2011 to 2014-2015), overall antibiotics consumption remained relatively stable. Concerning bacterial sensitivity, we noted important changes (sensitivity rates increased for 12 antibiotic-bacteria pairs, remained stable for five, and decreased for 15). We found three significant correlations for the first scenario: Pseudomonas aeruginos-ceftazidime (P=0.01), P. aeruginosa-ciprofloxacin and fluoroquinolone consumption (P=0.02), Enterococcus sp-ampicillin and penicillin consumption (P=0.04). For the second scenario, we found only two significant correlations: coagulase-negative Staphylococcus-oxacilline and penicillin consumption (P=0.02), P. aeruginosa/piperacillin (P=0.04). This exploratory study allowed us to describe antibiotic consumption and bacterial sensitivity progression. To our knowledge, this is the first study exploring the correlation between antibiotic consumption and the bacterial sensitivity rate in pediatrics in Canada. It remains very difficult to show this correlation between these two variables because of the multiple sources of bacterial resistance. These data are particularly useful for the antimicrobial stewardship programs and for clinicians. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients?

PubMed

Nijs, Jo; Loggia, Marco L; Polli, Andrea; Moens, Maarten; Huysmans, Eva; Goudman, Lisa; Meeus, Mira; Vanderweeën, Luc; Ickmans, Kelly; Clauw, Daniel

2017-08-01

The mechanism of sensitization of the central nervous system partly explains the chronic pain experience in many patients, but the etiological mechanisms of this central nervous system dysfunction are poorly understood. Recently, an increasing number of studies suggest that aberrant glial activation takes part in the establishment and/or maintenance of central sensitization. Areas covered: This review focused on preclinical work and mostly on the neurobiochemistry studied in animals, with limited human studies available. Glial overactivation results in a low-grade neuroinflammatory state, characterized by high levels of BDNF, IL-1β, TNF-α, which in turn increases the excitability of the central nervous system neurons through mechanisms like long-term potentiation and increased synaptic efficiency. Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development. Expert opinion: Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, β -adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed.

Additive diagnostic role of imaging in glaucoma: optical coherence tomography and retinal nerve fiber layer photography.

PubMed

Kim, Ko Eun; Kim, Seok Hwan; Oh, Sohee; Jeoung, Jin Wook; Suh, Min Hee; Seo, Je Hyun; Kim, Martha; Park, Ki Ho; Kim, Dong Myung

2014-11-20

To investigate the additive diagnostic role of spectral-domain optical coherence tomography (SD-OCT) and red-free retinal nerve fiber layer photography (RNFLP) in making clinical glaucoma diagnosis. Four diagnostic combination sets, including the most recent image from each measurement of 196 glaucoma eyes (including the 44 preperimetric glaucoma eyes) and 101 healthy eyes, were prepared: (1) stereo disc photography and Humphrey visual field (SH), (2) SH and SD-OCT (SHO), (3) SH and RNFLP (SHR), and (4) SHR and SD-OCT (SHRO). Each randomly sorted set was serially presented at 1-month intervals to five glaucoma specialists who were asked to evaluate them in a subjective and independent manner. The specialists' glaucoma-diagnostic performances based on the sets were then compared. For each specialist, adding SD-OCT to SH or SHR increased the glaucoma-diagnostic sensitivity but not to a level of statistical significance. For one specialist, adding RNFLP to SH significantly increased the sensitivity. Each specialist showed a high level of specificity regardless of the diagnostic set. The overall sensitivity of all specialists' assessments was significantly increased by adding RNFLP or the combination of SD-OCT and RNFLP to SH (P < 0.001); however, adding SD-OCT to SH or SHR did not significantly increase the sensitivity. A similar relationship was noted also for the preperimetric glaucoma subgroup. In contrast to RNFLP, SD-OCT did not significantly enhance the diagnostic accuracy of detecting glaucoma or even of preperimetric glaucoma. Our results suggest that, at least for glaucoma specialists, the additive diagnostic role of OCT is limited. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Epithelial-mesenchymal transition leads to crizotinib resistance in H2228 lung cancer cells with EML4-ALK translocation.

PubMed

Kim, Hyeong Ryul; Kim, Woo Sung; Choi, Yun Jung; Choi, Chang Min; Rho, Jin Kyung; Lee, Jae Cheol

2013-12-01

Epithelial-mesenchymal transition (EMT) is associated with reduced sensitivity to many chemotherapeutic drugs, including EGFR tyrosine kinase inhibitors. Here, we investigated if this reduced sensitivity also contributes to resistance to crizotinib, an ALK inhibitor of lung cancer that exhibits the EML4-ALK translocation. We established a crizotinib-resistant subline (H2228/CR), which was derived from the parental H2228 cell line by long-term exposure to increasing concentrations of crizotinib. Characteristics associated with EMT, including morphology, EMT marker proteins, and cellular mobility, were analyzed. Compared with H2228 cells, the growth of H2228/CR cells was independent of EML4-ALK, and H2228/CR cells showed cross-resistance to TAE-684 (a second-generation ALK inhibitor). Phenotypic changes to the spindle-cell shape were noted in H2228/CR cells, which were accompanied by a decrease in E-cadherin and increase in vimentin and AXL. In addition, H2228/CR cells showed increased secretion and expression of TGF-β1. Invasion and migration capabilities were dramatically increased in H2228/CR cells. Applying TGF-β1 treatment to parental H2228 cells for 72 h induced reversible EMT, leading to crizotinib resistance, but this was reversed by the removal of TGF-β1. Suppression of vimentin in H2228/CR cells by siRNA treatment restored sensitivity to crizotinib. Furthermore, these resistant cells remained highly sensitive to the Hsp90 inhibitors, similar to the parental H2228 cells. In conclusion, we suggest EMT is possibly involved in acquired resistance to crizotinib, and that HSP90 inhibitors could be a promising option for the treatment of EMT. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Digital Inverter Amine Sensing via Synergistic Responses by n and p Organic Semiconductors.

PubMed

Tremblay, Noah J; Jung, Byung Jun; Breysse, Patrick; Katz, Howard E

2011-11-22

Chemiresistors and sensitive OFETs have been substantially developed as cheap, scalable, and versatile sensing platforms. While new materials are expanding OFET sensing capabilities, the device architectures have changed little. Here we report higher order logic circuits utilizing OFETs sensitive to amine vapors. The circuits depend on the synergistic responses of paired p- and n-channel organic semiconductors, including an unprecedented analyte-induced current increase by the n-channel semiconductor. This represents the first step towards 'intelligent sensors' that utilize analog signal changes in sensitive OFETs to produce direct digital readouts suitable for further logic operations.

Digital Inverter Amine Sensing via Synergistic Responses by n and p Organic Semiconductors

PubMed Central

Tremblay, Noah J.; Jung, Byung Jun; Breysse, Patrick; Katz, Howard E.

2013-01-01

Chemiresistors and sensitive OFETs have been substantially developed as cheap, scalable, and versatile sensing platforms. While new materials are expanding OFET sensing capabilities, the device architectures have changed little. Here we report higher order logic circuits utilizing OFETs sensitive to amine vapors. The circuits depend on the synergistic responses of paired p- and n-channel organic semiconductors, including an unprecedented analyte-induced current increase by the n-channel semiconductor. This represents the first step towards ‘intelligent sensors’ that utilize analog signal changes in sensitive OFETs to produce direct digital readouts suitable for further logic operations. PMID:23754969

The development of simple and sensitive small-molecule fluorescent probes for the detection of serum proteins after native polyacrylamide gel electrophoresis.

PubMed

Wang, Fangfang; Huang, Lingyun; Na, Na; He, Dacheng; Sun, Dezhi; Ouyang, Jin

2012-05-21

In this paper, a simple and sensitive small-molecule fluorescent probe, 2,5-dihydroxy-4'-dimethylaminochalcone (DHDMAC), was designed and synthesized for the detection of human serum proteins via hydrophobic interactions after polyacrylamide gel electrophoresis (PAGE). This probe produced lower fluorescence emission in the absence of proteins, and the emission intensity was significantly increased after the interaction with serum proteins. To demonstrate the imaging performance of this probe as a fluorescent dye, a series of experiments was conducted that included sensitivity comparison and 2D-PAGE. The results indicated that the sensitivity of DHDMAC staining is comparable to that of the most widely used fluorescent dye, SYPRO Ruby, and more protein spots (including thyroxine-binding globulin, angiotensinogen, afamin, zinc-α-2-glycoprotein and α-1-antichymotrypsin) were detected after 2D-PAGE. Therefore, DHDMAC is a good protein reporter due to its fast staining procedure, low detection limits and high resolution.

Evaluation of the Effects of Conjunctivochalasis Excision on Tear Stability and Contrast Sensitivity

PubMed Central

Qiu, Weiqiang; Zhang, Mingzhou; Xu, Ting; Liu, Ziyuan; Lv, Huibin; Wang, Wei; Li, Xuemin

2016-01-01

Conjunctivochalasis (CCh) disrupts tear flow and damages tear film stability. This study sought to evaluate the tear stability and contrast sensitivity of patients with CCh on whom CCh excision was performed. The study included 39 eyes from 39 patients; all patients had eyes with grade 2 or 3 CCh, underwent CCh excision, and were evaluated before and three months after the surgery. The evaluated variables included the ocular surface disease index (OSDI), the tear break-up time (TBUT), corneal fluorescein staining, corneal surface irregularity, Schirmer’s I test, the tear meniscus area (TMA), and contrast sensitivity. A follow-up of three months was achieved in 36 eyes for 36 patients. All parameters improved significantly after surgery (p < 0.05), except Schirmer’s I test, thus suggesting that CCh excision is an effective method for reconstructing the lower tear meniscus and improving both tear film stability and corneal surface irregularity. The results further demonstrated a simultaneous increase in contrast sensitivity after surgery. PMID:27892479

Reynolds Number Effects on the Stability and Control Characteristics of a Supersonic Transport

NASA Technical Reports Server (NTRS)

Owens, L. R.; Wahls, R. A.; Elzey, M. B.; Hamner, M. P.

2002-01-01

A High Speed Civil Transport (HSCT) configuration was tested in the National Transonic Facility at the NASA Langley Research Center as part of NASA's High Speed Research Program. A series of tests included longitudinal and lateral/directional studies at transonic and low speed, high-lift conditions across a range of Reynolds numbers from that available in conventional wind tunnels to near flight conditions. Results presented focus on Reynolds number sensitivities of the stability and control characteristics at Mach 0.30 and 0.95 for a complete HSCT aircraft configuration including empennage. The angle of attack where the pitching-moment departure occurred increased with higher Reynolds numbers for both the landing and transonic configurations. The stabilizer effectiveness increased with Reynolds number for both configurations. The directional stability also increased with Reynolds number for both configurations. The landing configuration without forebody chines exhibited a large yawing-moment departure at high angles of attack and zero sideslip that varied with increasing Reynolds numbers. This departure characteristic nearly disappeared when forebody chines were added. The landing configuration's rudder effectiveness also exhibited sensitivities to changes in Reynolds number.

Direct questioning is more effective than patient-initiated report for the detection of sexually transmitted infections in a primary care HIV clinic in Western Kenya.

PubMed

Woo, Victoria Gah Hay; Cohen, Craig R; Bukusi, Elizabeth A; Huchko, Megan J

2013-02-01

In resource-limited settings, detection of sexually transmitted infections (STIs) often relies on self-reported symptoms to initiate management. We found self-report demonstrated poor sensitivity for STI detection. Adding clinician-initiated questions about symptoms improved detection rates. Vaginal examination further increased sensitivity. Including clinician-initiated screening in resource-limited settings would improve management of treatable STIs.

Methods to Increase the Sensitivity of High Resolution Melting Single Nucleotide Polymorphism Genotyping in Malaria.

PubMed

Daniels, Rachel; Hamilton, Elizabeth J; Durfee, Katelyn; Ndiaye, Daouda; Wirth, Dyann F; Hartl, Daniel L; Volkman, Sarah K

2015-11-10

Despite decades of eradication efforts, malaria remains a global burden. Recent renewed interest in regional elimination and global eradication has been accompanied by increased genomic information about Plasmodium parasite species responsible for malaria, including characteristics of geographical populations as well as variations associated with reduced susceptibility to anti-malarial drugs. One common genetic variation, single-nucleotide polymorphisms (SNPs), offers attractive targets for parasite genotyping. These markers are useful not only for tracking drug resistance markers but also for tracking parasite populations using markers not under drug or other selective pressures. SNP genotyping methods offer the ability to track drug resistance as well as to fingerprint individual parasites for population surveillance, particularly in response to malaria control efforts in regions nearing elimination status. While informative SNPs have been identified that are agnostic to specific genotyping technologies, high-resolution melting (HRM) analysis is particularly suited to field-based studies. Compared to standard fluorescent-probe based methods that require individual SNPs in a single labeled probe and offer at best 10% sensitivity to detect SNPs in samples that contain multiple genomes (polygenomic), HRM offers 2-5% sensitivity. Modifications to HRM, such as blocked probes and asymmetric primer concentrations as well as optimization of amplification annealing temperatures to bias PCR towards amplification of the minor allele, further increase the sensitivity of HRM. While the sensitivity improvement depends on the specific assay, we have increased detection sensitivities to less than 1% of the minor allele. In regions approaching malaria eradication, early detection of emerging or imported drug resistance is essential for prompt response. Similarly, the ability to detect polygenomic infections and differentiate imported parasite types from cryptic local reservoirs can inform control programs. This manuscript describes modifications to high resolution melting technology that further increase its sensitivity to identify polygenomic infections in patient samples.

Dye-sensitized solar cells using a chlorophyll a derivative as the sensitizer and carotenoids having different conjugation lengths as redox spacers

NASA Astrophysics Data System (ADS)

Wang, Xiao-Feng; Xiang, Junfeng; Wang, Peng; Koyama, Yasushi; Yanagida, Shozo; Wada, Yuji; Hamada, Kazunori; Sasaki, Shin-ichi; Tamiaki, Hitoshi

2005-06-01

Titania-based Grätzel-type solar cells were fabricated by the use of a chlorophyll a derivative (methyl 3-carboxy-3-devinyl-pyropheophorobide a) as the dye sensitizer. A 10% each of carotenoids, including neurosporene, spheroidene, lycopene, anhydrorhodovibrin and spirilloxanthin with numbers of conjugated double bonds, n = 9-13, was added as a conjugated spacer in order to neutralize the dye radical cation and to block the reverse electron transfer. The short-circuit current density ( Jsc) and the solar energy-to-electricity conversion efficiency ( η) systematically increased, with increasing n, from the values of 10.1 mA cm -2 and 3.1% (with no carotenoid) up to 11.5 mA cm -2 and 4.0% (with spirilloxanthin, n = 13), i.e., an enhancement of ≈30%.

Rock-dwelling lizards exhibit less sensitivity of sprint speed to increases in substrate rugosity.

PubMed

Collins, Clint E; Self, Jessica D; Anderson, Roger A; McBrayer, Lance D

2013-06-01

Effectively moving across variable substrates is important to all terrestrial animals. The effects of substrates on lizard performance have ecological ramifications including the partitioning of habitat according to sprinting ability on different surfaces. This phenomenon is known as sprint sensitivity, or the decrease in sprint speed due to change in substrate. However, sprint sensitivity has been characterized only in arboreal Anolis lizards. Our study measured sensitivity to substrate rugosity among six lizard species that occupy rocky, sandy, and/or arboreal habitats. Lizards that use rocky habitats are less sensitive to changes in substrate rugosity, followed by arboreal lizards, and then by lizards that use sandy habitats. We infer from comparative phylogenetic analysis that forelimb, chest, and tail dimensions are important external morphological features related to sensitivity to changes in substrate rugosity. Copyright © 2013 Elsevier GmbH. All rights reserved.

Method of making biocompatible electrodes

DOEpatents

Wollam, John S.

1992-01-01

A process of improving the sensing function of biocompatible electrodes and the product so made are disclosed. The process is designed to alter the surfaces of the electrodes at their tips to provide increased surface area and therefore decreased contact resistance at the electrode-tissue interface for increased sensitivity and essentially includes rendering the tips atomically clean by exposing them to bombardment by ions of an inert gas, depositing an adhesion layer on the cleaned tips, forming a hillocked layer on the adhesion layer by increasing the temperature of the tips, and applying a biocompatible coating on the hillocked layer. The resultant biocompatible electrode is characterized by improved sensitivity, minimum voltage requirement for organ stimulation and a longer battery life for the device in which it is employed.

Application of a Noise Adaptive Contrast Sensitivity Function to Image Data Compression

NASA Astrophysics Data System (ADS)

Daly, Scott J.

1989-08-01

The visual contrast sensitivity function (CSF) has found increasing use in image compression as new algorithms optimize the display-observer interface in order to reduce the bit rate and increase the perceived image quality. In most compression algorithms, increasing the quantization intervals reduces the bit rate at the expense of introducing more quantization error, a potential image quality degradation. The CSF can be used to distribute this error as a function of spatial frequency such that it is undetectable by the human observer. Thus, instead of being mathematically lossless, the compression algorithm can be designed to be visually lossless, with the advantage of a significantly reduced bit rate. However, the CSF is strongly affected by image noise, changing in both shape and peak sensitivity. This work describes a model of the CSF that includes these changes as a function of image noise level by using the concepts of internal visual noise, and tests this model in the context of image compression with an observer study.

Terahertz absorber based on Fano-like resonance of inverted quadrangular frustum pyramid metal grooves and sensor application

NASA Astrophysics Data System (ADS)

Yu, Yingying; Sun, Bo

2018-07-01

We investigate the multi-resonance coupling of inverted quadrangular frustum pyramid (IQFP) groove metal arrays at terahertz frequencies. The surface plasmon resonance (SPR) and groove resonance are induced, resulting in resonance coupling. The dipole of the groove resonance drives the quadrupole of the SPR and creates a sharp Fano-like resonance. The effects of geometry parameters including the width (at the bottom) and height are analyzed in detail. The results show that with the decrease in the sidewall slope of the groove, the confinement of the groove region on the electromagnetic field decreases, thereby increasing the resonance coupling. The Fano-like resonance is enhanced. The sensitivity and quality factor are discussed. The results show that the Fano-like resonance has high sensitivity and quality factor. With the increase in the sidewall slope of the groove, the sensitivity increases, and the quality factor decreases. The results show that the Fano-like resonance of IQFP groove metal arrays has a significant potential for biological monitoring and sensing.

The IL-6 Paradox: Context Dependent Interplay of SOCS3 and AMPK

PubMed Central

Sarvas, Jessica L; Khaper, Neelam; Lees, Simon J

2013-01-01

Insulin resistance is the principle step towards the progression of type 2 diabetes, and has been linked to increased circulating levels of cytokines, leading to chronic low-grade inflammation. Specifically, in chronic disease states increased IL-6 is thought to play a critical role in the regulation of insulin resistance in the peripheral tissues, and has been used as a marker of insulin resistance. There is also an endogenous up-regulation of IL-6 in response to exercise, which has been linked to improved insulin sensitivity. This leads to the question “how can elevated IL-6 lead to the development of insulin resistance, and yet also lead to increased insulin sensitivity?” Resolving the dual role of IL-6 in regulating insulin resistance/sensitivity is critical to the development of potential therapeutic interventions. This review summarizes the literature on the seemingly paradoxical role of elevated IL-6 on insulin signalling, including the activation of AMPK and the involvement of leptin and SOCS3. PMID:24244888

Expanding the HAWC Observatory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Johanna

The High Altitude Water Cherenkov Gamma-Ray Observatory is expanding its current array of 300 water tanks to include 350 outrigger tanks to increase sensitivity to gamma rays above 10 TeV. This involves creating and testing hardware with which to build the new tanks, including photomultiplier tubes, high voltage supply units, and flash analog to digital converters. My responsibilities this summer included preparing, testing and calibrating that equipment.

Modeling the Sensitivity of Field Surveys for Detection of Environmental DNA (eDNA)

PubMed Central

Schultz, Martin T.; Lance, Richard F.

2015-01-01

The environmental DNA (eDNA) method is the practice of collecting environmental samples and analyzing them for the presence of a genetic marker specific to a target species. Little is known about the sensitivity of the eDNA method. Sensitivity is the probability that the target marker will be detected if it is present in the water body. Methods and tools are needed to assess the sensitivity of sampling protocols, design eDNA surveys, and interpret survey results. In this study, the sensitivity of the eDNA method is modeled as a function of ambient target marker concentration. The model accounts for five steps of sample collection and analysis, including: 1) collection of a filtered water sample from the source; 2) extraction of DNA from the filter and isolation in a purified elution; 3) removal of aliquots from the elution for use in the polymerase chain reaction (PCR) assay; 4) PCR; and 5) genetic sequencing. The model is applicable to any target species. For demonstration purposes, the model is parameterized for bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) assuming sampling protocols used in the Chicago Area Waterway System (CAWS). Simulation results show that eDNA surveys have a high false negative rate at low concentrations of the genetic marker. This is attributed to processing of water samples and division of the extraction elution in preparation for the PCR assay. Increases in field survey sensitivity can be achieved by increasing sample volume, sample number, and PCR replicates. Increasing sample volume yields the greatest increase in sensitivity. It is recommended that investigators estimate and communicate the sensitivity of eDNA surveys to help facilitate interpretation of eDNA survey results. In the absence of such information, it is difficult to evaluate the results of surveys in which no water samples test positive for the target marker. It is also recommended that invasive species managers articulate concentration-based sensitivity objectives for eDNA surveys. In the absence of such information, it is difficult to design appropriate sampling protocols. The model provides insights into how sampling protocols can be designed or modified to achieve these sensitivity objectives. PMID:26509674

Modeling the Sensitivity of Field Surveys for Detection of Environmental DNA (eDNA).

PubMed

Schultz, Martin T; Lance, Richard F

2015-01-01

The environmental DNA (eDNA) method is the practice of collecting environmental samples and analyzing them for the presence of a genetic marker specific to a target species. Little is known about the sensitivity of the eDNA method. Sensitivity is the probability that the target marker will be detected if it is present in the water body. Methods and tools are needed to assess the sensitivity of sampling protocols, design eDNA surveys, and interpret survey results. In this study, the sensitivity of the eDNA method is modeled as a function of ambient target marker concentration. The model accounts for five steps of sample collection and analysis, including: 1) collection of a filtered water sample from the source; 2) extraction of DNA from the filter and isolation in a purified elution; 3) removal of aliquots from the elution for use in the polymerase chain reaction (PCR) assay; 4) PCR; and 5) genetic sequencing. The model is applicable to any target species. For demonstration purposes, the model is parameterized for bighead carp (Hypophthalmichthys nobilis) and silver carp (H. molitrix) assuming sampling protocols used in the Chicago Area Waterway System (CAWS). Simulation results show that eDNA surveys have a high false negative rate at low concentrations of the genetic marker. This is attributed to processing of water samples and division of the extraction elution in preparation for the PCR assay. Increases in field survey sensitivity can be achieved by increasing sample volume, sample number, and PCR replicates. Increasing sample volume yields the greatest increase in sensitivity. It is recommended that investigators estimate and communicate the sensitivity of eDNA surveys to help facilitate interpretation of eDNA survey results. In the absence of such information, it is difficult to evaluate the results of surveys in which no water samples test positive for the target marker. It is also recommended that invasive species managers articulate concentration-based sensitivity objectives for eDNA surveys. In the absence of such information, it is difficult to design appropriate sampling protocols. The model provides insights into how sampling protocols can be designed or modified to achieve these sensitivity objectives.

Complex interactions between climate change and toxicants: evidence that temperature variability increases sensitivity to cadmium.

PubMed

Kimberly, David A; Salice, Christopher J

2014-07-01

The Intergovernmental Panel on Climate Change projects that global climate change will have significant impacts on environmental conditions including potential effects on sensitivity of organisms to environmental contaminants. The objective of this study was to test the climate-induced toxicant sensitivity (CITS) hypothesis in which acclimation to altered climate parameters increases toxicant sensitivity. Adult Physa pomilia snails were acclimated to a near optimal 22 °C or a high-normal 28 °C for 28 days. After 28 days, snails from each temperature group were challenged with either low (150 μg/L) or high (300 μg/L) cadmium at each temperature (28 or 22 °C). In contrast to the CITS hypothesis, we found that acclimation temperature did not have a strong influence on cadmium sensitivity except at the high cadmium test concentration where snails acclimated to 28 °C were more cadmium tolerant. However, snails that experienced a switch in temperature for the cadmium challenge, regardless of the switch direction, were the most sensitive to cadmium. Within the snails that were switched between temperatures, snails acclimated at 28 °C and then exposed to high cadmium at 22 °C exhibited significantly greater mortality than those snails acclimated to 22 °C and then exposed to cadmium at 28 °C. Our results point to the importance of temperature variability in increasing toxicant sensitivity but also suggest a potentially complex cost of temperature acclimation. Broadly, the type of temporal stressor exposures we simulated may reduce overall plasticity in responses to stress ultimately rendering populations more vulnerable to adverse effects.

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

PubMed Central

Merrill, Liana; Malley, Susan

2013-01-01

Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1–4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. PMID:23657640

Assessment of cognitive safety in clinical drug development

PubMed Central

Roiser, Jonathan P.; Nathan, Pradeep J.; Mander, Adrian P.; Adusei, Gabriel; Zavitz, Kenton H.; Blackwell, Andrew D.

2016-01-01

Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. However, many drug development programmes do not incorporate sensitive cognitive measurements. Here, we review the rationale for cognitive safety assessment, and explain several basic methodological principles for measuring cognition during clinical drug development, including study design and statistical analysis, from Phase I through to postmarketing. The crucial issue of how cognition should be assessed is emphasized, especially the sensitivity of measurement. We also consider how best to interpret the magnitude of any identified effects, including comparison with benchmarks. We conclude by discussing strategies for the effective communication of cognitive risks. PMID:26610416

Anticipatory stress restores decision-making deficits in heavy drinkers by increasing sensitivity to losses.

PubMed

Gullo, Matthew J; Stieger, Adam A

2011-09-01

Substance abusers are characterized by hypersensitivity to reward. This leads to maladaptive decisions generally, as well as those on laboratory-based decision-making tasks, such as the Iowa Gambling Task (IGT). Negative affect has also been shown to disrupt the decision-making of healthy individuals, particularly decisions made under uncertainty. Neuropsychological theories of learning, including the Somatic Marker Hypothesis (SMH), argue this occurs by amplifying affective responses to punishment. In substance abusers, this might serve to rebalance their sensitivity to reward with punishment, and improve decision-making. Before completing the IGT, 45 heavy and 47 light drinkers were randomly assigned to a control condition, or led to believe they had to give a stressful public speech. IGT performance was analyzed with the Expectancy-Valence (EV) learning model. Working memory and IQ were also assessed. Heavy drinkers made more disadvantageous decisions than light drinkers, due to higher attention to gains (versus losses) on the IGT. Anticipatory stress increased participants' attention to losses, significantly improving heavy drinkers' decision-making. Anticipatory stress increased attention to losses, effectively restoring decision-making deficits in heavy drinkers by rebalancing their reward sensitivity with punishment sensitivity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Current molecular and emerging nanobiotechnology approaches for the detection of microbial pathogens.

PubMed

Theron, Jacques; Eugene Cloete, Thomas; de Kwaadsteniet, Michele

2010-11-01

Waterborne microbial diseases are escalating worldwide increasing the need for powerful and sensitive diagnostics tools. Molecular methodologies, including immunological and nucleic acid-based methods, have only recently been applied in the water sector. Advances in nanotechnology and nanomaterials have opened the door for the development of new diagnostic tools with increased sensitivity and speed, and reduced cost and labor. Quantum dots, flo dots, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, nanowires, and nanocantilevers, with their unique optical and physical properties, have already been applied in nanodiagnostics. Nanobiotechnology, once remaining technical and practical problems has been addressed, will play an important role in the detection of microbial pathogens.

Metabolic Effects of Antipsychotics on Adiposity and Insulin Sensitivity in Youths: A Randomized Clinical Trial.

PubMed

Nicol, Ginger E; Yingling, Michael D; Flavin, Karen S; Schweiger, Julia A; Patterson, Bruce W; Schechtman, Kenneth B; Newcomer, John W

2018-06-13

Antipsychotic medications are commonly used to treat nonpsychotic disruptive behavioral disorders in youths. To characterize the metabolic effects of first exposure to antipsychotics in youths using criterion standard assessments of body composition and insulin sensitivity. This randomized clinical trial recruited antipsychotic-naive youths aged 6 to 18 years in the St Louis, Missouri, metropolitan area who were diagnosed with 1 or more psychiatric disorders and clinically significant aggression and in whom antipsychotic treatment was considered. Participants were enrolled from June 12, 2006, through November 10, 2010. Enrolled participants were randomized (1:1:1) to 1 of 3 antipsychotics commonly used in children with disruptive behavioral disorders and evaluated for 12 weeks. Data were analyzed from January 17, 2011, through August 9, 2017. Twelve weeks of treatment with oral aripiprazole (n = 49), olanzapine (n = 46), or risperidone (n = 49). Primary outcomes included percentage total body fat measured by dual-energy x-ray absorptiometry (DXA) and insulin sensitivity in muscle measured via hyperinsulinemic clamps with stable isotopically labeled tracers. Secondary outcomes included abdominal adiposity measured by magnetic resonance imaging (MRI) and adipose and hepatic tissue insulin sensitivity measured via clamps with tracers. The intention-to-treat sample included 144 participants (98 males [68.1%]; mean [SD] age, 11.3 [2.8] years); 74 (51.4%) were African American, and 43 (29.9%) were overweight or obese at baseline. For the primary outcomes, from baseline to week 12, DXA percentage total body fat increased by 1.18% for risperidone, 4.12% for olanzapine, and 1.66% for aripiprazole and was significantly greater for olanzapine than risperidone or aripiprazole (time by treatment interaction P < .001). From baseline to week 12, insulin-stimulated change in glucose rate of disappearance increased by 2.30% for risperidone and decreased by 29.34% for olanzapine and 30.26% for aripiprazole, with no significant difference across medications (time by treatment interaction, P < .07). This primary measure of insulin sensitivity decreased significantly during 12 weeks in the pooled study sample (effect of time, F = 17.38; P < .001). For the secondary outcomes from baseline to week 12, MRI measured abdominal fat increased, with subcutaneous fat increase significantly greater for olanzapine than risperdone or aripiprazole (time by treatment, P = .003). Behavioral improvements occurred with all treatments. Adverse changes in adiposity and insulin sensitivity were observed during 12 weeks of antipsychotic treatment in youths, with the greatest fat increases on olanzapine. Such changes, likely attributable to treatment, may be associated with risk for premature cardiometabolic morbidity and mortality. The results inform risk-benefit considerations for antipsychotic use in youths. ClinicalTrials.gov identifier: NCT00205699.

Developmental Trajectories of Anxiety Symptoms in Early Adolescence: The Influence of Anxiety Sensitivity

PubMed Central

Allan, Nicholas P.; Capron, Daniel W.; Lejuez, Carl W.; Reynolds, Elizabeth K.; MacPherson, Laura; Schmidt, Norman B.

2014-01-01

Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (Mage=11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder. PMID:24062146

Developmental trajectories of anxiety symptoms in early adolescence: the influence of anxiety sensitivity.

PubMed

Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B

2014-05-01

Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.

Terminal drought-tolerant pearl millet [Pennisetum glaucum (L.) R. Br.] have high leaf ABA and limit transpiration at high vapour pressure deficit

PubMed Central

Kholová, Jana; Hash, C. T.; Kumar, P. Lava; Yadav, Rattan S.; Kočová, Marie; Vadez, Vincent

2010-01-01

It was previously shown that pearl millet genotypes carrying a terminal drought tolerance quantitative trait locus (QTL) had a lower transpiration rate (Tr; g cm−2 d−1) under well-watered conditions than sensitive lines. Here experiments were carried out to test whether this relates to leaf abscisic acid (ABA) and Tr concentration at high vapour pressure deficit (VPD), and whether that leads to transpiration efficiency (TE) differences. These traits were measured in tolerant/sensitive pearl millet genotypes, including near-isogenic lines introgressed with a terminal drought tolerance QTL (NIL-QTLs). Most genotypic differences were found under well-watered conditions. ABA levels under well-watered conditions were higher in tolerant genotypes, including NIL-QTLs, than in sensitive genotypes, and ABA did not increase under water stress. Well-watered Tr was lower in tolerant than in sensitive genotypes at all VPD levels. Except for one line, Tr slowed down in tolerant lines above a breakpoint at 1.40–1.90 kPa, with the slope decreasing >50%, whereas sensitive lines showed no change in that Tr response across the whole VPD range. It is concluded that two water-saving (avoidance) mechanisms may operate under well-watered conditions in tolerant pearl millet: (i) a low Tr even at low VPD conditions, which may relate to leaf ABA; and (ii) a sensitivity to higher VPD that further restricts Tr, which suggests the involvement of hydraulic signals. Both traits, which did not lead to TE differences, could contribute to absolute water saving seen in part due to dry weight increase differences. This water saved would become critical for grain filling and deserves consideration in the breeding of terminal drought-tolerant lines. PMID:20142425

Terminal drought-tolerant pearl millet [Pennisetum glaucum (L.) R. Br.] have high leaf ABA and limit transpiration at high vapour pressure deficit.

PubMed

Kholová, Jana; Hash, C T; Kumar, P Lava; Yadav, Rattan S; Kocová, Marie; Vadez, Vincent

2010-03-01

It was previously shown that pearl millet genotypes carrying a terminal drought tolerance quantitative trait locus (QTL) had a lower transpiration rate (Tr; g cm(-2) d(-1)) under well-watered conditions than sensitive lines. Here experiments were carried out to test whether this relates to leaf abscisic acid (ABA) and Tr concentration at high vapour pressure deficit (VPD), and whether that leads to transpiration efficiency (TE) differences. These traits were measured in tolerant/sensitive pearl millet genotypes, including near-isogenic lines introgressed with a terminal drought tolerance QTL (NIL-QTLs). Most genotypic differences were found under well-watered conditions. ABA levels under well-watered conditions were higher in tolerant genotypes, including NIL-QTLs, than in sensitive genotypes, and ABA did not increase under water stress. Well-watered Tr was lower in tolerant than in sensitive genotypes at all VPD levels. Except for one line, Tr slowed down in tolerant lines above a breakpoint at 1.40-1.90 kPa, with the slope decreasing >50%, whereas sensitive lines showed no change in that Tr response across the whole VPD range. It is concluded that two water-saving (avoidance) mechanisms may operate under well-watered conditions in tolerant pearl millet: (i) a low Tr even at low VPD conditions, which may relate to leaf ABA; and (ii) a sensitivity to higher VPD that further restricts Tr, which suggests the involvement of hydraulic signals. Both traits, which did not lead to TE differences, could contribute to absolute water saving seen in part due to dry weight increase differences. This water saved would become critical for grain filling and deserves consideration in the breeding of terminal drought-tolerant lines.

Inclusion of Linearized Moist Physics in Nasa's Goddard Earth Observing System Data Assimilation Tools

NASA Technical Reports Server (NTRS)

Holdaway, Daniel; Errico, Ronald; Gelaro, Ronaldo; Kim, Jong G.

2013-01-01

Inclusion of moist physics in the linearized version of a weather forecast model is beneficial in terms of variational data assimilation. Further, it improves the capability of important tools, such as adjoint-based observation impacts and sensitivity studies. A linearized version of the relaxed Arakawa-Schubert (RAS) convection scheme has been developed and tested in NASA's Goddard Earth Observing System data assimilation tools. A previous study of the RAS scheme showed it to exhibit reasonable linearity and stability. This motivates the development of a linearization of a near-exact version of the RAS scheme. Linearized large-scale condensation is included through simple conversion of supersaturation into precipitation. The linearization of moist physics is validated against the full nonlinear model for 6- and 24-h intervals, relevant to variational data assimilation and observation impacts, respectively. For a small number of profiles, sudden large growth in the perturbation trajectory is encountered. Efficient filtering of these profiles is achieved by diagnosis of steep gradients in a reduced version of the operator of the tangent linear model. With filtering turned on, the inclusion of linearized moist physics increases the correlation between the nonlinear perturbation trajectory and the linear approximation of the perturbation trajectory. A month-long observation impact experiment is performed and the effect of including moist physics on the impacts is discussed. Impacts from moist-sensitive instruments and channels are increased. The effect of including moist physics is examined for adjoint sensitivity studies. A case study examining an intensifying Northern Hemisphere Atlantic storm is presented. The results show a significant sensitivity with respect to moisture.

p53-regulated autophagy is controlled by glycolysis and determines cell fate

PubMed Central

Duan, Lei; Perez, Ricardo E.; Davaadelger, Batzaya; Dedkova, Elena N.; Blatter, Lothar A.; Maki, Carl G.

2015-01-01

The tumor suppressor p53 regulates downstream targets that determine cell fate. Canonical p53 functions include inducing apoptosis, growth arrest, and senescence. Non-canonical p53 functions include its ability to promote or inhibit autophagy and its ability to regulate metabolism. The extent to which autophagy and/or metabolic regulation determines cell fate by p53 is unclear. To address this, we compared cells resistant or sensitive to apoptosis by the p53 activator Nutlin-3a. In resistant cells, glycolysis was maintained upon Nutlin-3a treatment, and activated p53 promoted prosurvival autophagy. In contrast, in apoptosis sensitive cells activated p53 increased superoxide levels and inhibited glycolysis through repression of glycolytic pathway genes. Glycolysis inhibition and increased superoxide inhibited autophagy by repressing ATG genes essential for autophagic vesicle maturation. Inhibiting glycolysis increased superoxide and blocked autophagy in apoptosis-resistant cells, causing p62-dependent caspase-8 activation. Finally, treatment with 2-DG or the autophagy inhibitors chloroquine or bafilomycin A1 sensitized resistant cells to Nutlin-3a-induced apoptosis. Together, these findings reveal novel links between glycolysis and autophagy that determine apoptosis-sensitivity in response to p53. Specifically, the findings indicate 1) that glycolysis plays an essential role in autophagy by limiting superoxide levels and maintaining expression of ATG genes required for autophagic vesicle maturation, 2) that p53 can promote or inhibit autophagy depending on the status of glycolysis, and 3) that inhibiting protective autophagy can expand the breadth of cells susceptible to Nutlin-3a induced apoptosis. PMID:26337205

JNK pathway activation is controlled by Tao/TAOK3 to modulate ethanol sensitivity.

PubMed

Kapfhamer, David; King, Ian; Zou, Mimi E; Lim, Jana P; Heberlein, Ulrike; Wolf, Fred W

2012-01-01

Neuronal signal transduction by the JNK MAP kinase pathway is altered by a broad array of stimuli including exposure to the widely abused drug ethanol, but the behavioral relevance and the regulation of JNK signaling is unclear. Here we demonstrate that JNK signaling functions downstream of the Sterile20 kinase family gene tao/Taok3 to regulate the behavioral effects of acute ethanol exposure in both the fruit fly Drosophila and mice. In flies tao is required in neurons to promote sensitivity to the locomotor stimulant effects of acute ethanol exposure and to establish specific brain structures. Reduced expression of key JNK pathway genes substantially rescued the structural and behavioral phenotypes of tao mutants. Decreasing and increasing JNK pathway activity resulted in increased and decreased sensitivity to the locomotor stimulant properties of acute ethanol exposure, respectively. Further, JNK expression in a limited pattern of neurons that included brain regions implicated in ethanol responses was sufficient to restore normal behavior. Mice heterozygous for a disrupted allele of the homologous Taok3 gene (Taok3Gt) were resistant to the acute sedative effects of ethanol. JNK activity was constitutively increased in brains of Taok3Gt/+ mice, and acute induction of phospho-JNK in brain tissue by ethanol was occluded in Taok3Gt/+ mice. Finally, acute administration of a JNK inhibitor conferred resistance to the sedative effects of ethanol in wild-type but not Taok3Gt/+ mice. Taken together, these data support a role of a TAO/TAOK3-JNK neuronal signaling pathway in regulating sensitivity to acute ethanol exposure in flies and in mice.

The efficacy of using computer-aided detection (CAD) for detection of breast cancer in mammography screening: a systematic review.

PubMed

Henriksen, Emilie L; Carlsen, Jonathan F; Vejborg, Ilse Mm; Nielsen, Michael B; Lauridsen, Carsten A

2018-01-01

Background Early detection of breast cancer (BC) is crucial in lowering the mortality. Purpose To present an overview of studies concerning computer-aided detection (CAD) in screening mammography for early detection of BC and compare diagnostic accuracy and recall rates (RR) of single reading (SR) with SR + CAD and double reading (DR) with SR + CAD. Material and Methods PRISMA guidelines were used as a review protocol. Articles on clinical trials concerning CAD for detection of BC in a screening population were included. The literature search resulted in 1522 records. A total of 1491 records were excluded by abstract and 18 were excluded by full text reading. A total of 13 articles were included. Results All but two studies from the SR vs. SR + CAD group showed an increased sensitivity and/or cancer detection rate (CDR) when adding CAD. The DR vs. SR + CAD group showed no significant differences in sensitivity and CDR. Adding CAD to SR increased the RR and decreased the specificity in all but one study. For the DR vs. SR + CAD group only one study reported a significant difference in RR. Conclusion All but two studies showed an increase in RR, sensitivity and CDR when adding CAD to SR. Compared to DR no statistically significant differences in sensitivity or CDR were reported. Additional studies based on organized population-based screening programs, with longer follow-up time, high-volume readers, and digital mammography are needed to evaluate the efficacy of CAD.

The changing face of food hypersensitivity in an Asian community.

PubMed

Chiang, W C; Kidon, M I; Liew, W K; Goh, A; Tang, J P L; Chay, O M

2007-07-01

Food allergy seems to be increasing in Asia as well as world-wide. Our aim was to characterize food protein sensitization patterns in a population of Asian children with possible food allergy. Children presenting to our allergy clinic over 3 years with symptomatic allergic disease and at least one specific food allergen sensitization documented on skin prick testing were included in the analysis. Two hundred and twenty-seven patients fulfilled inclusion criteria. Ninety (40%) of the positive skin tests were positive to egg, 87 (39%) to shellfish, 62 (27.3%) to peanut, 30 (13.2%) to fish, 27 (11.8%) to cow's milk, 21 (9.3%) to sesame, 13 (3.7%) to wheat and eight (3.2%) to soy. Peanut sensitization was the third most common sensitizing allergen, and seen mostly in young atopic children with multiple food hypersensitivities and a family history of atopic dermatitis. The median reported age of first exposure to fish and shellfish was 6 and 12 months, respectively. The mean age at presentation of children with shellfish hypersensitivity was at 6.7 years of age. The likelihood of shellfish sensitization was increased in children with concomitant sensitization to cockroaches. In contrast to previously reported low peanut allergy rates in Asia, in our review, peanut sensitization is present in 27% (62/227) of food-allergic children, mostly in patients with multiple food protein sensitizations. Temporal patterns of first exposure of infants to fish and shellfish are unique to the Asian diet. Shellfish are a major sensitizing food source in Asian children, especially in allergic rhinitis patients sensitized to cockroaches.

Online immunoaffinity LC/MS/MS. A general method to increase sensitivity and specificity: How do you do it and what do you need?

PubMed

Dufield, Dawn R; Radabaugh, Melissa R

2012-02-01

There is an increased emphasis on hyphenated techniques such as immunoaffinity LC/MS/MS (IA-LC/MS/MS) or IA-LC/MRM. These techniques offer competitive advantages with respect to sensitivity and selectivity over traditional LC/MS and are complementary to ligand binding assays (LBA) or ELISA's. However, these techniques are not entirely straightforward and there are several tips and tricks to routine sample analysis. We describe here our methods and procedures for how to perform online IA-LC/MS/MS including a detailed protocol for the preparation of antibody (Ab) enrichment columns. We have included sample trapping and Ab methods. Furthermore, we highlight tips, tricks, minimal and optimal approaches. This technology has been shown to be viable for several applications, species and fluids from small molecules to proteins and biomarkers to PK assays. Copyright © 2011 Elsevier Inc. All rights reserved.

Implications of climate change (global warming) for the healthcare system.

PubMed

Raffa, R B; Eltoukhy, N S; Raffa, K F

2012-10-01

Temperature-sensitive pathogenic species and their vectors and hosts are emerging in previously colder regions as a consequence of several factors, including global warming. As a result, an increasing number of people will be exposed to pathogens against which they have not previously needed defences. We illustrate this with a specific example of recent emergence of Cryptococcus gattii infections in more temperate climates. The outbreaks in more temperate climates of the highly virulent--but usually tropically restricted--C. gattii is illustrative of an anticipated growing challenge for the healthcare system. There is a need for preparedness by healthcare professionals in anticipation and for management of such outbreaks, including other infections whose recent increased prevalence in temperate climates can be at least partly associated with global warming. (Re)emergence of temperature-sensitive pathogenic species in more temperate climates will present new challenges for healthcare systems. Preparation for outbreaks should precede their occurrence. © 2012 Blackwell Publishing Ltd.

Highly sensitive troponin and coronary computed tomography angiography in the evaluation of suspected acute coronary syndrome in the emergency department.

PubMed

Ferencik, Maros; Hoffmann, Udo; Bamberg, Fabian; Januzzi, James L

2016-08-07

The evaluation of patients presenting to the emergency department with suspected acute coronary syndrome (ACS) remains a clinical challenge. The traditional assessment includes clinical risk assessment based on cardiovascular risk factors with serial electrocardiograms and cardiac troponin measurements, often followed by advanced cardiac testing as inpatient or outpatient (i.e. stress testing, imaging). Despite this costly and lengthy work-up, there is a non-negligible rate of missed ACS with an increased risk of death. There is a clinical need for diagnostic strategies that will lead to rapid and reliable triage of patients with suspected ACS. We provide an overview of the evidence for the role of highly sensitive troponin (hsTn) in the rapid and efficient evaluation of suspected ACS. Results of recent research studies have led to the introduction of hsTn with rapid rule-in and rule-out protocols into the guidelines. Highly sensitive troponin increases the sensitivity for the detection of myocardial infarction and decreases time to diagnosis; however, it may decrease the specificity, especially when used as a dichotomous variable, rather than continuous variable as recommended by guidelines; this may increase clinician uncertainty. We summarize the evidence for the use of coronary computed tomography angiography (CTA) as the rapid diagnostic tool in this population when used with conventional troponin assays. Coronary CTA significantly decreases time to diagnosis and discharge in patients with suspected ACS, while being safe. However, it may lead to increase in invasive procedures and includes radiation exposure. Finally, we outline the opportunities for the combined use of hsTn and coronary CTA that may result in increased efficiency, decreased need for imaging, lower cost, and decreased radiation dose. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

A Review of Safety Practices and Safety Training for the Explosives Field

DTIC Science & Technology

1985-02-01

reworking. This was discovered when an impact test was run on the received material and a "GO" occurred. If the received material bad been handled as...exist, small quantities of the explosive or explosive mixture should -be subjected to- sensitivity tests (including at least spark sensitivity, impact ...increases more energy is put into the nix which must be considered with respect to blending speeds and tolerances in equip- ment and temperatures. Also

77 FR 26009 - CoStar Group, Inc., Lonestar Acquisition Sub, Inc., and LoopNet, Inc.; Analysis of Agreement...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

... responsible for making sure that your comment does not include any sensitive health information, like medical records or other individually identifiable health information. In addition, do not include any ``[t]rade... between CoStar and Xceligent, Inc. (``Xceligent''), and increasing the likelihood that CoStar will...

Introduction of a hydrolysis probe PCR assay for high-throughput screening of methicillin-resistant Staphylococcus aureus with the ability to include or exclude detection of Staphylococcus argenteus.

PubMed

Bogestam, Katja; Vondracek, Martin; Karlsson, Mattias; Fang, Hong; Giske, Christian G

2018-01-01

Many countries using sensitive screening methods for detection of carriage of methicillin-resistant Staphylococcus aureus (MRSA) have a sustained low incidence of MRSA infections. For diagnostic laboratories with high sample volumes, MRSA screening requires stability, low maintenance and high performance at a low cost. Herein we designed oligonucleotides for a new nuc targeted hydrolysis probe PCR to replace the standard in-house nuc SybrGreen PCR assay. This new, more time-efficient, PCR assay resulted in a 40% increase in daily sample capacity, with maintained high specificity and sensitivity. The assay was also able to detect Staphylococcus aureus clonal cluster 75 (CC75) lineage strains, recently re-classified as Staphylococcus argenteus, with a sensitivity considerably increased compared to our previous assay. While awaiting consensus if the CC75 lineage of S. aureus should be considered as S. argenteus, and whether methicillin-resistant S. argenteus should be included in the MRSA definition, many diagnostic laboratories need to update their MRSA assay sensitivity/specificity towards this lineage/species. The MRSA screening assay presented in this manuscript is comprised of nuc oligonucleotides separately targeting S. aureus and CC75 lineage strains/S. argenteus, thus providing high user flexibility for the detection of CC75 lineage strains/S. argenteus.

Permanent-magnet flowmeter having improved output-terminal means

DOEpatents

August, C.; Myers, H.J.

1981-10-26

Disclosed is an improved permanent magnet flowmeter capable of withstanding bending stresses in the direction of induced emf signals. The flowmeter includes a unique terminal arrangement integrally formed with the flowmeter by trepanning opposing wall sections of the flowmeter body. The terminal arrangement provides increased flowmeter sensitivity by increasing the strength of the induced emf signals.

Permanent magnet flowmeter having improved output terminal means

DOEpatents

August, Charles; Myers, Harry J.

1984-01-01

Disclosed is an improved permanent magnet flowmeter capable of withstanding bending stresses in the direction of induced emf signals. The flowmeter includes a unique terminal arrangement integrally formed with the flowmeter by trepanning opposing wall sections of the flowmeter body. The terminal arrangement provides increased flowmeter sensitivity by increasing the strength of the induced emf signals.

Sensitivity and specificity of detecting reticular pseudodrusen in multimodal imaging in Japanese patients.

PubMed

Ueda-Arakawa, Naoko; Ooto, Sotaro; Tsujikawa, Akitaka; Yamashiro, Kenji; Oishi, Akio; Yoshimura, Nagahisa

2013-03-01

To identify reticular pseudodrusen (RPD) in age-related macular degeneration using multiple imaging modalities, including the blue channel image of fundus photography, infrared reflectance (IR), fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT), and to compare the sensitivities and specificities of these modalities for detecting RPD. This study included 220 eyes from 114 patients with newly diagnosed age-related macular degeneration. Patients underwent fundus photography, IR, fundus autofluorescence, near-infrared fundus autofluorescence, confocal blue reflectance, indocyanine green angiography, and SD-OCT in both eyes. Eyes were diagnosed with RPD if they showed reticular patterns on at least two of the seven imaging modalities. Thirty-seven eyes were diagnosed with RPD. However, SD-OCT and IR had the highest sensitivity (94.6%), and at the same time, SD-OCT had a high specificity (98.4%). The blue channel of color fundus photography, confocal blue reflectance, and indocyanine green angiography had a specificity of 100% but had lower sensitivity than that of SD-OCT and IR. For detecting RPD, IR and SD-OCT had the highest sensitivity. Although SD-OCT had the highest sensitivity and specificity, RPD detection should be confirmed using more than one modality for increased accuracy.

The Diagnostic Performance of Stool DNA Testing for Colorectal Cancer: A Systematic Review and Meta-Analysis.

PubMed

Zhai, Rong-Lin; Xu, Fei; Zhang, Pei; Zhang, Wan-Li; Wang, Hui; Wang, Ji-Liang; Cai, Kai-Lin; Long, Yue-Ping; Lu, Xiao-Ming; Tao, Kai-Xiong; Wang, Guo-Bin

2016-02-01

This meta-analysis was designed to evaluate the diagnostic performance of stool DNA testing for colorectal cancer (CRC) and compare the performance between single-gene and multiple-gene tests.MEDLINE, Cochrane, EMBASE databases were searched using keywords colorectal cancers, stool/fecal, sensitivity, specificity, DNA, and screening. Sensitivity analysis, quality assessments, and performance bias were performed for the included studies.Fifty-three studies were included in the analysis with a total sample size of 7524 patients. The studies were heterogeneous with regard to the genes being analyzed for fecal genetic biomarkers of CRC, as well as the laboratory methods being used for each assay. The sensitivity of the different assays ranged from 2% to 100% and the specificity ranged from 81% to 100%. The meta-analysis found that the pooled sensitivities for single- and multigene assays were 48.0% and 77.8%, respectively, while the pooled specificities were 97.0% and 92.7%. Receiver operator curves and diagnostic odds ratios showed no significant difference between both tests with regard to sensitivity or specificity.This meta-analysis revealed that using assays that evaluated multiple genes compared with single-gene assays did not increase the sensitivity or specificity of stool DNA testing in detecting CRC.

Linear regression metamodeling as a tool to summarize and present simulation model results.

PubMed

Jalal, Hawre; Dowd, Bryan; Sainfort, François; Kuntz, Karen M

2013-10-01

Modelers lack a tool to systematically and clearly present complex model results, including those from sensitivity analyses. The objective was to propose linear regression metamodeling as a tool to increase transparency of decision analytic models and better communicate their results. We used a simplified cancer cure model to demonstrate our approach. The model computed the lifetime cost and benefit of 3 treatment options for cancer patients. We simulated 10,000 cohorts in a probabilistic sensitivity analysis (PSA) and regressed the model outcomes on the standardized input parameter values in a set of regression analyses. We used the regression coefficients to describe measures of sensitivity analyses, including threshold and parameter sensitivity analyses. We also compared the results of the PSA to deterministic full-factorial and one-factor-at-a-time designs. The regression intercept represented the estimated base-case outcome, and the other coefficients described the relative parameter uncertainty in the model. We defined simple relationships that compute the average and incremental net benefit of each intervention. Metamodeling produced outputs similar to traditional deterministic 1-way or 2-way sensitivity analyses but was more reliable since it used all parameter values. Linear regression metamodeling is a simple, yet powerful, tool that can assist modelers in communicating model characteristics and sensitivity analyses.

[Computed tomography with computer-assisted detection of pulmonary nodules in dogs and cats].

PubMed

Niesterok, C; Piesnack, S; Köhler, C; Ludewig, E; Alef, M; Kiefer, I

2015-01-01

The aim of this study was to assess the potential benefit of computer-assisted detection (CAD) of pulmonary nodules in veterinary medicine. Therefore, the CAD rate was compared to the detection rates of two individual examiners in terms of its sensitivity and false-positive findings. We included 51 dogs and 16 cats with pulmonary nodules previously diagnosed by computed tomography. First, the number of nodules ≥ 3 mm was recorded for each patient by two independent examiners. Subsequently, each examiner used the CAD software for automated nodule detection. With the knowledge of the CAD results, a final consensus decision on the number of nodules was achieved. The software used was a commercially available CAD program. The sensitivity of examiner 1 was 89.2%, while that of examiner 2 reached 87.4%. CAD had a sensitivity of 69.4%. With CAD, the sensitivity of examiner 1 increased to 94.7% and that of examiner 2 to 90.8%. The CAD-system, which we used in our study, had a moderate sensitivity of 69.4%. Despite its severe limitations, with a high level of false-positive and false-negative results, CAD increased the examiners' sensitivity. Therefore, its supportive role in diagnostics appears to be evident.

Methionine Deprivation Induces a Targetable Vulnerability in Triple-negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression

PubMed Central

Strekalova, Elena; Malin, Dmitry; Good, David M.; Cryns, Vincent L.

2015-01-01

Purpose Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Experimental Design Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab or the combination. Results Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Conclusion Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. PMID:25724522

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes

PubMed Central

Hurst, David

2017-01-01

Objective. To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods. A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results. Posthurricane patients had 34.6 times more positive results (p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes (p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes (p < 0.0001). The posthurricane population was younger (p < 0.001) and included more patients with asthma or lower respiratory symptoms (p < 0.05). Conclusion. Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas. PMID:28491100

Increased Sensitization to Mold Allergens Measured by Intradermal Skin Testing following Hurricanes.

PubMed

Saporta, Diego; Hurst, David

2017-01-01

Objective . To report on changes in sensitivity to mold allergens determined by changes in intradermal skin testing reactivity, after exposure to two severe hurricanes. Methods . A random, retrospective allergy charts review divided into 2 groups of 100 patients each: Group A, patients tested between 2003 and 2010 prior to hurricanes, and Group B, patients tested in 2014 and 2015 following hurricanes. Reactivity to eighteen molds was determined by intradermal skin testing. Test results, age, and respiratory symptoms were recorded. Chi-square test determined reactivity/sensitivity differences between groups. Results . Posthurricane patients had 34.6 times more positive results ( p < 0.0001) at weaker dilutions, all tested molds were found to be more reactive, and 95% had at least one positive test versus only 62% before the hurricanes ( p < 0.0001); average mold reactivity was 55% versus 16% while 17% of patients reacted to the entire panel versus none before the hurricanes ( p < 0.0001). The posthurricane population was younger ( p < 0.001) and included more patients with asthma or lower respiratory symptoms ( p < 0.05). Conclusion . Reactivity and sensitization to mold allergens increased compared to patients before the hurricanes. This supports climatologists' hypothesis that environmental changes resulting from hurricanes can be a health risk as reflected in increased allergic sensitivities and symptoms and has significant implications for physicians treating patients from affected areas.

Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer

PubMed Central

Gravina, Giovanni Luca; Mancini, Andrea; Colapietro, Alessandro; Marampon, Francesco; Sferra, Roberta; Pompili, Simona; Biordi, Leda Assunta; Iorio, Roberto; Flati, Vincenzo; Argueta, Christian; Landesman, Yosef; Kauffman, Michael; Shacham, Sharon; Festuccia, Claudio

2017-01-01

Background and aims Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX resistant derivatives. Results and conclusions We show that DTX resistance may involve overexpression of β-III tubulin (TUBB3) and P-glycoprotein as well as increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also observed in DTX resistant cells suggesting that SINE compounds may modulate DTX effectiveness in sensitive cells as well as restore the sensitivity to DTX in resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX through increased tumor shrinkage and apoptosis by preventing DTX-induced cell cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear accumulation increasing the expression of FOXO-responsive genes including p21, p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin supporting apoptosis. βdown-regulated Cyclin D1, c-myc, Nuclear sequestration of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged γ expression. Selinexor treatment increased DTX-mediated double strand breaks (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and Topo2A. Our results provide supportive evidence for the therapeutic use of SINE compounds in combination with DTX suggesting their clinical use in mCRPC patients. PMID:29340049

ATM regulates 3-methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents.

PubMed

Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A; Clarke, Ian D; Barszczyk, Mark S; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W; Taylor, Michael D; Rutka, James T; Jones, Chris; Dirks, Peter B; Zadeh, Gelareh; Hawkins, Cynthia

2014-10-01

Alkylating agents are a first-line therapy for the treatment of several aggressive cancers, including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed, increasing therapeutic response while minimizing toxicity. Using an siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular, the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM), were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. Inhibition of ATM and MPG-mediated BER cooperate to sensitize tumor cells to alkylating agents, impairing tumor growth in vitro and in vivo with no toxicity to normal cells, providing an ideal therapeutic window. ©2014 American Association for Cancer Research.

Identification of conserved pathways of DNA-damage response and radiation protection by genome-wide RNAi.

PubMed

van Haaften, Gijs; Romeijn, Ron; Pothof, Joris; Koole, Wouter; Mullenders, Leon H F; Pastink, Albert; Plasterk, Ronald H A; Tijsterman, Marcel

2006-07-11

Ionizing radiation is extremely harmful for human cells, and DNA double-strand breaks (DSBs) are considered to be the main cytotoxic lesions induced. Improper processing of DSBs contributes to tumorigenesis, and mutations in DSB response genes underlie several inherited disorders characterized by cancer predisposition. Here, we performed a comprehensive screen for genes that protect animal cells against ionizing radiation. A total of 45 C. elegans genes were identified in a genome-wide RNA interference screen for increased sensitivity to ionizing radiation in germ cells. These genes include orthologs of well-known human cancer predisposition genes as well as novel genes, including human disease genes not previously linked to defective DNA-damage responses. Knockdown of eleven genes also impaired radiation-induced cell-cycle arrest, and seven genes were essential for apoptosis upon exposure to irradiation. The gene set was further clustered on the basis of increased sensitivity to DNA-damaging cancer drugs cisplatin and camptothecin. Almost all genes are conserved across animal phylogeny, and their relevance for humans was directly demonstrated by showing that their knockdown in human cells results in radiation sensitivity, indicating that this set of genes is important for future cancer profiling and drug development.

Magnesium Oxide (MgO) pH-sensitive Sensing Membrane in Electrolyte-Insulator-Semiconductor Structures with CF4 Plasma Treatment.

PubMed

Kao, Chyuan-Haur; Chang, Chia Lung; Su, Wei Ming; Chen, Yu Tzu; Lu, Chien Cheng; Lee, Yu Shan; Hong, Chen Hao; Lin, Chan-Yu; Chen, Hsiang

2017-08-03

Magnesium oxide (MgO) sensing membranes in pH-sensitive electrolyte-insulator-semiconductor structures were fabricated on silicon substrate. To optimize the sensing capability of the membrane, CF 4 plasma was incorporated to improve the material quality of MgO films. Multiple material analyses including FESEM, XRD, AFM, and SIMS indicate that plasma treatment might enhance the crystallization and increase the grain size. Therefore, the sensing behaviors in terms of sensitivity, linearity, hysteresis effects, and drift rates might be improved. MgO-based EIS membranes with CF 4 plasma treatment show promise for future industrial biosensing applications.

Protein detection system

DOEpatents

Fruetel, Julie A [Livermore, CA; Fiechtner, Gregory J [Bethesda, MD; Kliner, Dahv A. V. [San Ramon, CA; McIlroy, Andrew [Livermore, CA

2009-05-05

The present embodiment describes a miniature, microfluidic, absorption-based sensor to detect proteins at sensitivities comparable to LIF but without the need for tagging. This instrument utilizes fiber-based evanescent-field cavity-ringdown spectroscopy, in combination with faceted prism microchannels. The combination of these techniques will increase the effective absorption path length by a factor of 10.sup.3 to 10.sup.4 (to .about.1-m), thereby providing unprecedented sensitivity using direct absorption. The coupling of high-sensitivity absorption with high-performance microfluidic separation will enable real-time sensing of biological agents in aqueous samples (including aerosol collector fluids) and will provide a general method with spectral fingerprint capability for detecting specific bio-agents.

Evaluation of the bioNexia Legionella Test, Including Impact of Incubation Time Extension, for Detection of Legionella pneumophila Serogroup 1 Antigen in Urine.

PubMed

Badoux, Paul; Euser, Sjoerd M; Bruin, Jacob P; Mulder, Patrick P G; Yzerman, Ed P F

2017-06-01

In this study, we compared the bioNexia test (bioMérieux, Marcy-l'Étoile, France), a new immunochromatographic assay for the detection of Legionella pneumophila serogroup 1 in urine, with the BinaxNOW urinary antigen test (Alere, Waltham, Massachusetts, USA). After 15 min of incubation (in accordance with the manufacturers' instructions), the sensitivities and specificities were, respectively, 76.5% and 97.2% for the bioNexia test and 87.1% and 100% for the BinaxNOW test. After a prolonged incubation time of 60 min, the sensitivities and specificities increased to, respectively, 89.4% and 97.2% for the bioNexia test and 91.8% and 100% for the BinaxNOW test. When the tests were read after 15 min, the concentration of discrepant urine samples increased the sensitivities to 94.1% for both tests. In conclusion, we found that although the bioNexia test showed lower sensitivity for the detection of L. pneumophila antigen in nonconcentrated urine compared to the BinaxNOW test, a prolonged incubation time as well as the use of concentrated samples showed comparable sensitivities for both tests. Copyright © 2017 American Society for Microbiology.

Estimating the Triple-Point Isotope Effect and the Corresponding Uncertainties for Cryogenic Fixed Points

NASA Astrophysics Data System (ADS)

Tew, W. L.

2008-02-01

The sensitivities of melting temperatures to isotopic variations in monatomic and diatomic atmospheric gases using both theoretical and semi-empirical methods are estimated. The current state of knowledge of the vapor-pressure isotope effects (VPIE) and triple-point isotope effects (TPIE) is briefly summarized for the noble gases (except He), and for selected diatomic molecules including oxygen. An approximate expression is derived to estimate the relative shift in the melting temperature with isotopic substitution. In general, the magnitude of the effects diminishes with increasing molecular mass and increasing temperature. Knowledge of the VPIE, molar volumes, and heat of fusion are sufficient to estimate the temperature shift or isotopic sensitivity coefficient via the derived expression. The usefulness of this approach is demonstrated in the estimation of isotopic sensitivities and uncertainties for triple points of xenon and molecular oxygen for which few documented estimates were previously available. The calculated sensitivities from this study are considerably higher than previous estimates for Xe, and lower than other estimates in the case of oxygen. In both these cases, the predicted sensitivities are small and the resulting variations in triple point temperatures due to mass fractionation effects are less than 20 μK.

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid.

PubMed

Drewes, Asbjørn-Mohr; Reddy, Hariprasad; Staahl, Camilla; Pedersen, Jan; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans

2005-07-28

Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization. Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine. The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change. Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs.

Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid

PubMed Central

Drewes, Asbjorn Mohr; Reddy, Hariprasad; Staahl, Camilla; Pedersen, Jan; Funch-Jensen, Peter; Arendt-Nielsen, Lars; Gregersen, Hans

2005-01-01

AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization. METHODS: Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine. RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change. CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs. PMID:16038036

Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.

PubMed

Knowles, Joshua W; Xie, Weijia; Zhang, Zhongyang; Chennamsetty, Indumathi; Chennemsetty, Indumathi; Assimes, Themistocles L; Paananen, Jussi; Hansson, Ola; Pankow, James; Goodarzi, Mark O; Carcamo-Orive, Ivan; Morris, Andrew P; Chen, Yii-Der I; Mäkinen, Ville-Petteri; Ganna, Andrea; Mahajan, Anubha; Guo, Xiuqing; Abbasi, Fahim; Greenawalt, Danielle M; Lum, Pek; Molony, Cliona; Lind, Lars; Lindgren, Cecilia; Raffel, Leslie J; Tsao, Philip S; Schadt, Eric E; Rotter, Jerome I; Sinaiko, Alan; Reaven, Gerald; Yang, Xia; Hsiung, Chao A; Groop, Leif; Cordell, Heather J; Laakso, Markku; Hao, Ke; Ingelsson, Erik; Frayling, Timothy M; Weedon, Michael N; Walker, Mark; Quertermous, Thomas

2015-04-01

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

Culturally Sensitive Education Can Decrease Hispanic Workers' Risk of Metabolic Syndrome.

PubMed

Marks, Steven

2016-04-08

Metabolic syndrome is a continuing problem in the United States, and the Hispanic population is at increased risk of developing complications from this disease process. Many of the workers at a South Jersey yacht-building company are Hispanic, and a culturally sensitive education program was implemented to improve their overall health. Program assessments included the Latino Dietary Behavior Questionnaire (LDBQ), anthropomorphic measurements, and laboratory studies both pre and post intervention. The intervention included a Spanish-language lecture on metabolic syndrome and healthy nutrition, followed by an interactive culturally appropriate cooking demonstration for the participants and their significant others. Program participants showed reductions in body mass index, blood pressure, lipid levels, and hemoglobin A1c, and more knowledge of healthy nutrition as measured by the LDBQ. This finding supports culturally sensitive education programs to improve the health of Hispanic populations. © 2016 The Author(s).

Pilot evaluation of short-term changes in macular pigment and retinal sensitivity in different phenotypes of early age-related macular degeneration after carotenoid supplementation.

PubMed

Corvi, Federico; Souied, Eric H; Falfoul, Yousra; Georges, Anouk; Jung, Camille; Querques, Lea; Querques, Giuseppe

2017-06-01

To investigate the response of carotenoid supplementation in different phenotypes of early age-related macular degeneration (AMD) by measuring macular pigment optical density (MPOD) and retinal sensitivity. Consecutive patients with only medium/large drusen and only reticular pseudodrusen (RPD) and age-matched and sex-matched controls were enrolled. At baseline, participants underwent a complete ophthalmological examination including measurement of best-corrected visual acuity (BCVA), MPOD and retinal sensitivity. Patients were put on vitamin supplementation (lutein 10 mg/day, zeaxanthin 2 mg/day) and 3 months later underwent a repeated ophthalmological examination. Twenty patients with medium/large drusen, 19 with RPD and 15 control subjects were included. At baseline, in controls, mean MPOD and BCVA were significantly higher compared with RPD (p=0.001 and p=0.01) but similar to medium/large drusen (p=0.9 and p=0.4). Mean retinal sensitivity was significantly higher in controls compared with RPD and medium/large drusen (for all p<0.0001). After 3 months of carotenoid supplementation the mean MPOD significantly increased in RPD (p=0.002), thus showing no more difference compared with controls (p=0.3); no significant changes were found in mean retinal sensitivity and BCVA (p=0.3 and p=0.7). Medium/large drusen did not show significant changes on MPOD, retinal sensitivity and BCVA (p=0.5, p=0.7 and p=0.7, respectively). Patients with early AMD, especially RPD phenotype, show lower macular sensitivity and MPOD than controls. After supplementation, MPOD significantly increased in RPD. These results suggest different pathophysiology for RPD as compared with medium/large drusen and may open new ways to identifying further therapeutic targets in this phenotype of early AMD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effects of Detector Thickness on Geometric Sensitivity and Event Positioning Errors in the Rectangular PET/X Scanner

NASA Astrophysics Data System (ADS)

MacDonald, Lawrence R.; Hunter, William C. J.; Kinahan, Paul E.; Miyaoka, Robert S.

2013-10-01

We used simulations to investigate the relationship between sensitivity and spatial resolution as a function of crystal thickness in a rectangular PET scanner intended for quantitative assessment of breast cancers. The system had two 20 × 15-cm2 and two 10 × 15-cm2 flat detectors forming a box, with the larger detectors separated by 4 or 8 cm. Depth-of-interaction (DOI) resolution was modeled as a function of crystal thickness based on prior measurements. Spatial resolution was evaluated independent of image reconstruction by deriving and validating a surrogate metric from list-mode data ( dFWHM). When increasing crystal thickness from 5 to 40 mm, and without using DOI information, the dFWHM for a centered point source increased from 0.72 to 1.6 mm. Including DOI information improved dFWHM by 12% and 27% for 5- and 40-mm-thick crystals, respectively. For a point source in the corner of the FOV, use of DOI information improved dFWHM by 20% (5-mm crystal) and 44% (40-mm crystal). Sensitivity was 7.7% for 10-mm-thick crystals (8-cm object). Increasing crystal thickness on the smaller side detectors from 10 to 20 mm (keeping 10-mm crystals on the larger detectors) boosted sensitivity by 24% (relative) and degraded dFWHM by only 3%/8% with/without DOI information. The benefits of measuring DOI must be evaluated in terms of the intended clinical task of assessing tracer uptake in small lesions. Increasing crystal thickness on the smaller side detectors provides substantial sensitivity increase with minimal accompanying loss in resolution.

Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production

PubMed Central

Martin, Sophie; Andriambeloson, Emile; Takeda, Ken; Andriantsitohaina, Ramaroson

2002-01-01

The present study investigates the mechanisms by which polyphenolic compounds from red wine elicit Ca2+ mobilization in bovine aortic endothelial cells (BAECs). Two polyphenol-containing red wine extracts, red wine polyphenolic compounds (RWPC) and Provinols™, and delphinidin, an anthocyanin were used. RWPC stimulated a Ca2+-dependent release of nitric oxide (NO) from BAECs accounting for the relaxation of endothelium-denuded rat aortic rings as shown by cascade bioassay. RWPC, Provinols™ and delphinidin increased cytosolic free calcium ([Ca2+]i), by releasing Ca2+ from intracellular stores and by increasing Ca2+ entry. The RWPC-induced increase in [Ca2+]i was decreased by exposure to ryanodine (30 μM), whereas Provinols™ and delphinidin-induced increases in [Ca2+]i were decreased by bradykinin (0.1 μM) and thapsigargin (1 μM) pre-treatment. RWPC, Provinols™ and delphinidin-induced increases in [Ca2+]i were sensitive to inhibitors of phospholipase C (neomycin, 3 mM; U73122, 3 μM) and tyrosine kinase (herbimycin A, 1 μM). RWPC, Provinols™ and delphinidin induced herbimycin A (1 μM)-sensitive tyrosine phosphorylation of several intracellular proteins. Provinols™ released Ca2+ via both a cholera (CTX) and pertussis toxins (PTX)-sensitive pathway, whereas delphinidin released Ca2+ only via a PTX-sensitive mechanism. Our data contribute in defining the mechanisms of endothelial NO production caused by wine polyphenols including the increase in [Ca2+]i and the activation of tyrosine kinases. Furthermore, RWPC, Provinols™ and delphinidin display differences in the process leading to [Ca2+]i increases in endothelial cells illustrating multiple cellular targets of natural dietary polyphenolic compounds. PMID:11906973

Study of the pH-sensitive mechanism of tumor-targeting liposomes.

PubMed

Fan, Yang; Chen, Cong; Huang, Yiheng; Zhang, Fang; Lin, Guimei

2017-03-01

Currently, the phosphatidylethanolamine-based, pH-sensitive, liposome drug-delivery system has been widely developed for efficient, targeted cancer therapy. However, the mechanism of pH sensitivity was unclear; it is a main obstacle in controlling the preparation of pH-sensitive liposomes (PSLs).Therefore, our research is aimed at clarifying the pH-response mechanism of the various molecules that compose liposomes. We chose the small pH-sensitive molecules oleic acid (OA), linoleic acid (LA) and cholesteryl hemisuccinate (CHEMS) and the fundamental lipids cholesterol and phosphatidylethanolamine (PE) as test molecules. The PSLs were prepared using the thin-film hydration method and characterized in detail at various pH values (pH 5.0, 6.0 and 7.4), including particle size, ζ-potential, drug encapsulation efficiency and drug loading. The surface structure was observed by transmission electron microscopy (TEM), and the electrical conductivity of the liposome dispersion was also tested. The calorimetric analysis was conducted by Nano-differential scanning calorimetry (Nano-DSC). The in vitro drug release profile showed that PSLs exhibit good pH sensitivity. At neutral pH, the particle size was approximately 150nm, and it dramatically increased at pH 5.0. The ζ-potential increased as the pH decreased. The Nano-DSC results showed that cholesterol and CHEMS can both increase the stability and phase transfer temperature of PSLs. Conductivity increased to a maximum at pH 5.0 and was rather low at pH 7.4. In conclusion, results show that the three kinds of liposomes have pH responsive release characteristics in acidic pH. The OA-PSLs have a pH sensitive point of 5. Since CHEMS has a cholesterol-like structure, it can stabilizes the phospholipid bilayer under neutral conditions as shown in the Nano-DSC data, and because it has a special steroidal rigid structure, it exhibits better pH response characteristics under acidic conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced Area of Secondary Hyperalgesia in Women with Multiple Stressful Life Events: A Pilot Study.

PubMed

You, Dokyoung S; Creech, Suzannah K; Meagher, Mary W

2016-10-01

Stressful life events are associated with increased pain severity and chronicity. However, the mechanism underlying this association remains disputed. Recent animal studies suggest that chronic stress increases pain sensitivity and persistence by enhancing peripheral and central sensitization mechanisms. To test this hypothesis in humans, the authors examined whether sensitization is enhanced in healthy women reporting more stressful life events using the topical capsaicin test. Thirty-two healthy young women reporting varying levels of stressful life events were invited for laboratory pain testing. Capsaicin was applied topically to the volar forearm. Measurements included capsaicin-induced spontaneous pain and area of secondary hyperalgesia in the region surrounding capsaicin application. Physiological (heart rate and skin conductance) and self-reported affective (emotional valence and arousal) states were also measured. The results indicate that more stressful life events predicted a linear increase in the area of secondary hyperalgesia (β = 0.40, p = 0.023, R 2 = 0.16), but not the intensity of secondary hyperalgesia nor capsaicin-induced spontaneous pain. These findings suggest that life stressors may be associated with heightened central sensitization manifested by an increased area of secondary hyperalgesia. Additionally, life stressors were related to greater sympathetic cardiac, but not to affective responses to capsaicin-induced pain. This study shows that women reporting more stressful life events show a larger area of secondary mechanical hyperalgesia. These preliminary findings suggest that life stressors may facilitate pain processing by enhancing central sensitization. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Lactose intolerance in irritable bowel syndrome patients with diarrhoea: the roles of anxiety, activation of the innate mucosal immune system and visceral sensitivity.

PubMed

Yang, J; Fox, M; Cong, Y; Chu, H; Zheng, X; Long, Y; Fried, M; Dai, N

2014-02-01

Irritable bowel syndrome patients with diarrhoea (IBS-D) often report intolerance to milk; however, the mechanism underlying these symptoms is unknown. To assess the role of psychological factors, immune activation and visceral sensitivity on the development of lactose intolerance (LI) in IBS-D patients. Fifty-five IBS-D patients and 18 healthy controls (HCs) with lactase deficiency underwent a 20-g lactose hydrogen breath test (LHBT). Patients were categorised as lactose malabsorption (LM; malabsorption only) or LI [malabsorption plus increase in total symptom score (TSS). Measurements included (i) psychological status; (ii) enteric biopsies with quantification of mast cells (MCs), T-lymphocytes and enterochromaffin cells; (iii) serum cytokines; (iv) rectal sensitivity before and after lactose ingestion. LI was more prevalent in IBS-D patients than HCs [25/55 (46%) vs. 3/18 (17%), P = 0.029]. IBS-D patients with LI had (i) higher levels of anxiety than those with LM (P = 0.017) or HCs (P = 0.006); (ii) increased mucosal MCs compared with LM (P = 0.006) and HCs (P < 0.001); (iii) raised serum TNF-α compared with LM (P = 0.034) and HCs (P < 0.001) and (iv) increased rectal sensitivity after lactose ingestion compared with LM (P < 0.001) or HCs (P < 0.001). Severity of abdominal symptoms after lactose ingestion was associated with the increase in visceral sensitivity after lactose intake (r = 0.629, P < 0.001), MCs (r = 0.650, P < 0.001) and anxiety (r = 0.519, P < 0.001). IBS-D patients with lactose intolerence are characterised by anxiety, mucosal immune activation and increased visceral sensitivity after lactose ingestion. The presence of these biomarkers may indicate an IBS phenotype that responds to dietary therapy and/or mast cell stabilisers. © 2013 John Wiley & Sons Ltd.

ACOEM practice guidelines: opioids and safety-sensitive work.

PubMed

Hegmann, Kurt T; Weiss, Michael S; Bowden, Kirk; Branco, Fernando; DuBrueler, Kimberly; Els, Charl; Mandel, Steven; McKinney, David W; Miguel, Rafael; Mueller, Kathryn L; Nadig, Robert J; Schaffer, Michael I; Studt, Larry; Talmage, James B; Travis, Russell L; Winters, Thomas; Thiese, Matthew S; Harris, Jeffrey S

2014-07-01

ACOEM has updated the treatment guidelines concerning opioids. This report highlights the safety-sensitive work recommendation that has been developed. Comprehensive literature reviews were accomplished with article abstraction, critiquing, grading, evidence table compilation, and guideline finalization by a multidisciplinary expert panel to develop evidence-based guidance. A total of 12 moderate-quality studies were identified to address motor vehicle crash risk, and none regarding other work among opioid-using patients. Acute or chronic opioid use is not recommended for patients who perform safety-sensitive jobs. These jobs include operating motor vehicles, other modes of transportation, forklift driving, overhead crane operation, heavy equipment operation and tasks involving high levels of cognitive function and judgment. Quality evidence consistently demonstrates increased risk of vehicle crashes and is recommended as the surrogate for other safety-sensitive work tasks.

Desensitization: Overcoming the Immunologic Barriers to Transplantation

PubMed Central

Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

2017-01-01

HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

Evaluating the Spatial Distribution of Toxic Air Contaminants in Multiple Ecosystem Indicators in the Sierra Nevada-Southern Cascades

NASA Astrophysics Data System (ADS)

Nanus, L.; Simonich, S. L.; Rocchio, J.; Flanagan, C.

2013-12-01

Toxic air contaminants originating from agricultural areas of the Central Valley in California threaten vulnerable sensitive receptors including surface water, vegetation, snow, sediments, fish, and amphibians in the Sierra Nevada-Southern Cascades region. The spatial distribution of toxic air contaminants in different ecosystem indicators depends on variation in atmospheric concentrations and deposition, and variation in air toxics accumulation in ecosystems. The spatial distribution of organic air toxics and mercury at over 330 unique sampling locations and sample types over two decades (1990-2009) in the Sierra Nevada-Southern Cascades region were compiled and maps were developed to further understand spatial patterns and linkages between air toxics deposition and ecological effects. Potential ecosystem impacts in the Sierra Nevada-Southern Cascades region include bioaccumulation of air toxics in both aquatic and terrestrial ecosystems, reproductive disruption, and immune suppression. The most sensitive ecological end points in the region that are affected by bioaccumulation of toxic air contaminants are fish. Mercury was detected in all fish and approximately 6% exceeded human consumption thresholds. Organic air toxics were also detected in fish yielding variable spatial patterns. For amphibians, which are sensitive to pesticide exposure and potential immune suppression, increasing trends in current and historic use pesticides are observed from north to south across the region. In other indicators, such as vegetation, pesticide concentrations in lichen increase with increasing elevation. Current and historic use pesticides and mercury were also observed in snowpack at high elevations in the study area. This study shows spatial patterns in toxic air contaminants, evaluates associated risks to sensitive receptors, and identifies data gaps. Future research on atmospheric modeling and information on sources is needed in order to predict which ecosystems are the most sensitive to toxic air contaminants in the Sierra Nevada-Southern Cascades region.

Assessment of the reliability of standard automated perimetry in regions of glaucomatous damage.

PubMed

Gardiner, Stuart K; Swanson, William H; Goren, Deborah; Mansberger, Steven L; Demirel, Shaban

2014-07-01

Visual field testing uses high-contrast stimuli in areas of severe visual field loss. However, retinal ganglion cells saturate with high-contrast stimuli, suggesting that the probability of detecting perimetric stimuli may not increase indefinitely as contrast increases. Driven by this concept, this study examines the lower limit of perimetric sensitivity for reliable testing by standard automated perimetry. Evaluation of a diagnostic test. A total of 34 participants with moderate to severe glaucoma; mean deviation at their last clinic visit averaged -10.90 dB (range, -20.94 to -3.38 dB). A total of 75 of the 136 locations tested had a perimetric sensitivity of ≤ 19 dB. Frequency-of-seeing curves were constructed at 4 nonadjacent visual field locations by the Method of Constant Stimuli (MOCS), using 35 stimulus presentations at each of 7 contrasts. Locations were chosen a priori and included at least 2 with glaucomatous damage but a sensitivity of ≥ 6 dB. Cumulative Gaussian curves were fit to the data, first assuming a 5% false-negative rate and subsequently allowing the asymptotic maximum response probability to be a free parameter. The strength of the relation (R(2)) between perimetric sensitivity (mean of last 2 clinic visits) and MOCS sensitivity (from the experiment) for all locations with perimetric sensitivity within ± 4 dB of each selected value, at 0.5 dB intervals. Bins centered at sensitivities ≥ 19 dB always had R(2) >0.1. All bins centered at sensitivities ≤ 15 dB had R(2) <0.1, an indication that sensitivities are unreliable. No consistent conclusions could be drawn between 15 and 19 dB. At 57 of the 81 locations with perimetric sensitivity <19 dB, including 49 of the 63 locations ≤ 15 dB, the fitted asymptotic maximum response probability was <80%, consistent with the hypothesis of response saturation. At 29 of these locations the asymptotic maximum was <50%, and so contrast sensitivity (50% response rate) is undefined. Clinical visual field testing may be unreliable when visual field locations have sensitivity below approximately 15 to 19 dB because of a reduction in the asymptotic maximum response probability. Researchers and clinicians may have difficulty detecting worsening sensitivity in these visual field locations, and this difficulty may occur commonly in patients with glaucoma with moderate to severe glaucomatous visual field loss. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

IMMUNOTOXICOLOGY: THIRTY YEARS AND COUNTING

EPA Science Inventory

The science of immunotoxicology arguably began in the early 1970s, following the recognition of increased sensitivity to infection following exposure of test species, including guinea pigs, [1] mice, [2, 3] rats, [4] ducks, [5] hamsters and monkeys [6] to various xenobiotics. Re...

Restoring E-cadherin expression increases sensitivity to epidermal growth factor receptor inhibitors in lung cancer cell lines.

PubMed

Witta, Samir E; Gemmill, Robert M; Hirsch, Fred R; Coldren, Christopher D; Hedman, Karla; Ravdel, Larisa; Helfrich, Barbara; Dziadziuszko, Rafal; Chan, Daniel C; Sugita, Michio; Chan, Zeng; Baron, Anna; Franklin, Wilbur; Drabkin, Harry A; Girard, Luc; Gazdar, Adi F; Minna, John D; Bunn, Paul A

2006-01-15

The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC). EGFR tyrosine kinase inhibitors, such as gefitinib and erlotinib, produce 9% to 27% response rates in NSCLC patients. E-Cadherin, a calcium-dependent adhesion molecule, plays an important role in NSCLC prognosis and progression, and interacts with EGFR. The zinc finger transcriptional repressor, ZEB1, inhibits E-cadherin expression by recruiting histone deacetylases (HDAC). We identified a significant correlation between sensitivity to gefitinib and expression of E-cadherin, and ZEB1, suggesting their predictive value for responsiveness to EGFR-tyrosine kinase inhibitors. E-Cadherin transfection into a gefitinib-resistant line increased its sensitivity to gefitinib. Pretreating resistant cell lines with the HDAC inhibitor, MS-275, induced E-cadherin along with EGFR and led to a growth-inhibitory and apoptotic effect of gefitinib similar to that in gefitinib-sensitive NSCLC cell lines including those harboring EGFR mutations. Thus, combined HDAC inhibitor and gefitinib treatment represents a novel pharmacologic strategy for overcoming resistance to EGFR inhibitors in patients with lung cancer.

Increasing Electrochemiluminescence Intensity of a Wireless Electrode Array Chip by Thousands of Times Using a Diode for Sensitive Visual Detection by a Digital Camera.

PubMed

Qi, Liming; Xia, Yong; Qi, Wenjing; Gao, Wenyue; Wu, Fengxia; Xu, Guobao

2016-01-19

Both a wireless electrochemiluminescence (ECL) electrode microarray chip and the dramatic increase in ECL by embedding a diode in an electromagnetic receiver coil have been first reported. The newly designed device consists of a chip and a transmitter. The chip has an electromagnetic receiver coil, a mini-diode, and a gold electrode array. The mini-diode can rectify alternating current into direct current and thus enhance ECL intensities by 18 thousand times, enabling a sensitive visual detection using common cameras or smart phones as low cost detectors. The detection limit of hydrogen peroxide using a digital camera is comparable to that using photomultiplier tube (PMT)-based detectors. Coupled with a PMT-based detector, the device can detect luminol with higher sensitivity with linear ranges from 10 nM to 1 mM. Because of the advantages including high sensitivity, high throughput, low cost, high portability, and simplicity, it is promising in point of care testing, drug screening, and high throughput analysis.

Improving the Sensitivity of Mass Spectrometry by Using a New Sheath Flow Electrospray Emitter Array at Subambient Pressures

DOE PAGES

Cox, Jonathan T.; Marginean, Ioan; Kelly, Ryan T.; ...

2014-03-28

Arrays of chemically etched emitters with individualized sheath gas capillaries have been developed to enhance electrospray ionization (ESI) at subambient pressures. By including an emitter array in a subambient pressure ionization with nanoelectrospray (SPIN) source, ionization and transmission efficiency can be maximized allowing for increased sensitivity in mass spectrometric analyses. The SPIN source eliminates the major ion losses at conventional ESI-mass spectrometry (MS) interface by placing the emitter in the first vacuum region of the instrument. To facilitate stable electrospray currents in such conditions we have developed an improved emitter array with individualized sheath gas around each emitter. The utilitymore » of the new emitter arrays for generating stable multi-electrosprays at subambient pressures was probed by coupling the emitter array/SPIN source with a time of flight (TOF) mass spectrometer. The instrument sensitivity was compared between single emitter/SPIN-MS and multi-emitter/SPIN-MS configurations using an equimolar solution of 9 peptides. An increase in sensitivity correlative to the number of emitters in the array was observed.« less

Improving the Sensitivity of Mass Spectrometry by Using a New Sheath Flow Electrospray Emitter Array at Subambient Pressures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cox, Jonathan T.; Marginean, Ioan; Kelly, Ryan T.

Arrays of chemically etched emitters with individualized sheath gas capillaries have been developed to enhance electrospray ionization (ESI) at subambient pressures. By including an emitter array in a subambient pressure ionization with nanoelectrospray (SPIN) source, ionization and transmission efficiency can be maximized allowing for increased sensitivity in mass spectrometric analyses. The SPIN source eliminates the major ion losses at conventional ESI-mass spectrometry (MS) interface by placing the emitter in the first vacuum region of the instrument. To facilitate stable electrospray currents in such conditions we have developed an improved emitter array with individualized sheath gas around each emitter. The utilitymore » of the new emitter arrays for generating stable multi-electrosprays at subambient pressures was probed by coupling the emitter array/SPIN source with a time of flight (TOF) mass spectrometer. The instrument sensitivity was compared between single emitter/SPIN-MS and multi-emitter/SPIN-MS configurations using an equimolar solution of 9 peptides. An increase in sensitivity correlative to the number of emitters in the array was observed.« less

Development of a time sensitivity score for frequently occurring motor vehicle crash injuries.

PubMed

Schoell, Samantha L; Doud, Andrea N; Weaver, Ashley A; Talton, Jennifer W; Barnard, Ryan T; Martin, R Shayn; Meredith, J Wayne; Stitzel, Joel D

2015-03-01

Injury severity alone is a poor indicator of the time sensitivity of injuries. The purpose of the study was to quantify the urgency with which the most frequent motor vehicle crash injuries require treatment, according to expert physicians. The time sensitivity was quantified for the top 95% most frequently occurring Abbreviated Injury Scale (AIS) 2+ injuries in the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) 2000-2011. A Time Sensitivity Score was developed using expert physician survey data in which physicians were asked to determine whether a particular injury should go to a Level I/II trauma center and the urgency with which that injury required treatment. When stratifying by AIS severity, the mean Time Sensitivity Score increased with increasing AIS severity. The mean Time Sensitivity Scores by AIS severity were as follows: 0.50 (AIS 2); 0.78 (AIS 3); 0.92 (AIS 4); 0.97 (AIS 5); and 0.97 (AIS 6). When stratifying by anatomical region, the head, thorax, and abdomen were the most time sensitive. Appropriate triage depends on multiple factors, including the severity of an injury, the urgency with which it requires treatment, and the propensity of a significant injury to be missed. The Time Sensitivity Score did not correlate highly with the widely used AIS severity scores, which highlights the inability of AIS scores to capture all aspects of injury severity. The Time Sensitivity Score can be useful in Advanced Automatic Crash Notification systems for identifying highly time sensitive injuries in motor vehicle crashes requiring prompt treatment at a trauma center. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Use of long term dermal sensitization followed by intratracheal challenge method to identify low-dose chemical-induced respiratory allergic responses in mice.

PubMed

Fukuyama, Tomoki; Ueda, Hideo; Hayashi, Koichi; Tajima, Yukari; Shuto, Yasufumi; Saito, Toru R; Harada, Takanori; Kosaka, Tadashi

2008-10-01

The inhalation of many types of chemicals, including pesticides, perfumes, and other low-molecular weight chemicals, is a leading cause of allergic respiratory diseases. We attempted to develop a new test protocol to detect environmental chemical-related respiratory hypersensitivity at low and weakly immunogenic doses. We used long-term dermal sensitization followed by a low-dose intratracheal challenge to evaluate sensitization by the well-known respiratory sensitizers trimellitic anhydride (TMA) and toluene diisocyanate (TDI) and the contact sensitizer 2,4-dinitrochlorobenzene (DNCB). After topically sensitizing BALB/c mice (9 times in 3 weeks) and challenging them intratracheally with TMA, TDI, or DNCB, we assayed differential cell counts and chemokine levels in bronchoalveolar lavage fluid (BALF); lymphocyte counts, surface antigen expression of B cells, and local cytokine production in lung-associated lymph nodes (LNs); and antigen-specific IgE levels in serum and BALF. TMA induced marked increases in antigen-specific IgE levels in both serum and BALF, proliferation of eosinophils and chemokines (MCP-1, eotaxin, and MIP-1beta) in BALF, and proliferation of Th2 cytokines (interleukin (IL)-4, IL-10, and IL-13) in restimulated LN cells. TDI induced marked increases in levels of cytokines (IL-4, IL-10, IL-13, and IFN-gamma) produced by restimulated LN cells. In contrast, DNCB treatment yielded, at most, small, nonsignificant increases in all parameters. Our protocol thus detected respiratory allergic responses to low-molecular weight chemicals and may be useful for detecting environmental chemical-related respiratory allergy.

Endurance training attenuates the increase in peripheral chemoreflex sensitivity with intermittent hypoxia

PubMed Central

Miller, Amanda J.; Sauder, Charity L.; Cauffman, Aimee E.; Blaha, Cheryl A.

2017-01-01

Patients with heart failure and sleep apnea have greater chemoreflex sensitivity, presumably due to intermittent hypoxia (IH), and this is predictive of mortality. We hypothesized that endurance training would attenuate the effect of IH on peripheral chemoreflex sensitivity in healthy humans. Fifteen young healthy subjects (9 female, 26 ± 1 yr) participated. Between visits, 11 subjects underwent 8 wk of endurance training that included running four times/wk at 80% predicted maximum heart rate and interval training, and four control subjects did not change activity. Chemoreflex sensitivity (the slope of ventilation responses to serial oxygen desaturations), blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were assessed before and after 30 min of IH. Endurance training decreased resting systolic blood pressure (119 ± 3 to 113 ± 3 mmHg; P = 0.027) and heart rate (67 ± 3 to 61 ± 2 beats/min; P = 0.004) but did not alter respiratory parameters at rest (P > 0.2). Endurance training attenuated the IH-induced increase in chemoreflex sensitivity (pretraining: Δ 0.045 ± 0.026 vs. posttraining: Δ −0.028 ± 0.040 l·min−1·% O2 desaturation−1; P = 0.045). Furthermore, IH increased mean blood pressure and MSNA burst rate before training (P < 0.05), but IH did not alter these measures after training (P > 0.2). All measurements were similar in the control subjects at both visits (P > 0.05). Endurance training attenuates chemoreflex sensitization to IH, which may partially explain the beneficial effects of exercise training in patients with cardiovascular disease. PMID:28039190

Fat-cell mass, serum leptin and adiponectin changes during weight gain and loss in yellow-bellied marmots (Marmota flaviventris).

PubMed

Florant, Gregory L; Porst, Heather; Peiffer, Aubrey; Hudachek, Susan F; Pittman, Chris; Summers, Scott A; Rajala, Michael W; Scherer, Philipp E

2004-11-01

Leptin and adiponectin are proteins produced and secreted from white adipose tissue and are important regulators of energy balance and insulin sensitivity. Seasonal changes in leptin and adiponectin have not been investigated in mammalian hibernators in relationship to changes in fat cell and fat mass. We sought to determine the relationship between serum leptin and adiponectin levels with seasonal changes in lipid mass. We collected serum and tissue samples from marmots (Marmota flaviventris) in different seasons while measuring changes in fat mass, including fat-cell size. We found that leptin is positively associated with increasing fat mass and fat-cell size, while adiponectin is negatively associated with increasing lipid mass. These findings are consistent with the putative roles of these adipokines: leptin increases with fat mass and is involved in enhancing lipid oxidation while adiponectin appears to be higher in summer when hepatic insulin sensitivity should be maintained since the animals are eating. Our data suggest that during autumn/winter animals have switched from a lipogenic condition to a lipolytic state, which may include leptin resistance.

Ignoring correlation in uncertainty and sensitivity analysis in life cycle assessment: what is the risk?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Groen, E.A., E-mail: Evelyne.Groen@gmail.com; Heijungs, R.; Leiden University, Einsteinweg 2, Leiden 2333 CC

Life cycle assessment (LCA) is an established tool to quantify the environmental impact of a product. A good assessment of uncertainty is important for making well-informed decisions in comparative LCA, as well as for correctly prioritising data collection efforts. Under- or overestimation of output uncertainty (e.g. output variance) will lead to incorrect decisions in such matters. The presence of correlations between input parameters during uncertainty propagation, can increase or decrease the the output variance. However, most LCA studies that include uncertainty analysis, ignore correlations between input parameters during uncertainty propagation, which may lead to incorrect conclusions. Two approaches to include correlationsmore » between input parameters during uncertainty propagation and global sensitivity analysis were studied: an analytical approach and a sampling approach. The use of both approaches is illustrated for an artificial case study of electricity production. Results demonstrate that both approaches yield approximately the same output variance and sensitivity indices for this specific case study. Furthermore, we demonstrate that the analytical approach can be used to quantify the risk of ignoring correlations between input parameters during uncertainty propagation in LCA. We demonstrate that: (1) we can predict if including correlations among input parameters in uncertainty propagation will increase or decrease output variance; (2) we can quantify the risk of ignoring correlations on the output variance and the global sensitivity indices. Moreover, this procedure requires only little data. - Highlights: • Ignoring correlation leads to under- or overestimation of the output variance. • We demonstrated that the risk of ignoring correlation can be quantified. • The procedure proposed is generally applicable in life cycle assessment. • In some cases, ignoring correlation has a minimal effect on decision-making tools.« less

Potential sensitivity of photosynthesis and isoprene emission to direct radiative effects of atmospheric aerosol pollution

NASA Astrophysics Data System (ADS)

Strada, Susanna; Unger, Nadine

2016-04-01

A global Earth system model is applied to quantify the impacts of direct anthropogenic aerosol effective radiative forcing on gross primary productivity (GPP) and isoprene emission. The impacts of different pollution aerosol sources (anthropogenic, biomass burning, and non-biomass burning) are investigated by performing sensitivity experiments. The model framework includes all known light and meteorological responses of photosynthesis, but uses fixed canopy structures and phenology. On a global scale, our results show that global land carbon fluxes (GPP and isoprene emission) are not sensitive to pollution aerosols, even under a global decline in surface solar radiation (direct + diffuse) by ˜ 9 %. At a regional scale, GPP and isoprene emission show a robust but opposite sensitivity to pollution aerosols in regions where forested canopies dominate. In eastern North America and Eurasia, anthropogenic pollution aerosols (mainly from non-biomass burning sources) enhance GPP by +5-8 % on an annual average. In the northwestern Amazon Basin and central Africa, biomass burning aerosols increase GPP by +2-5 % on an annual average, with a peak in the northwestern Amazon Basin during the dry-fire season (+5-8 %). The prevailing mechanism varies across regions: light scattering dominates in eastern North America, while a reduction in direct radiation dominates in Europe and China. Aerosol-induced GPP productivity increases in the Amazon and central Africa include an additional positive feedback from reduced canopy temperatures in response to increases in canopy conductance. In Eurasia and northeastern China, anthropogenic pollution aerosols drive a decrease in isoprene emission of -2 to -12 % on an annual average. Future research needs to incorporate the indirect effects of aerosols and possible feedbacks from dynamic carbon allocation and phenology.

THE REELIN RECEPTORS VLDLR AND ApoER2 REGULATE SENSORIMOTOR GATING IN MICE

PubMed Central

Barr, Alasdair M.; Fish, Kenneth N.; Markou, Athina

2007-01-01

Summary Postmortem brain loss of reelin is noted in schizophrenia patients. Accordingly, heterozygous reeler mutant mice have been proposed as a putative model of this disorder. Little is known, however, about the involvement of the two receptors for reelin, Very-Low-Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2), on pre-cognitive processes of relevance to deficits seen in schizophrenia. Thus, we evaluated sensorimotor gating in mutant mice heterozygous or homozygous for the two reelin receptors. Mutant mice lacking one of these reelin receptors were tested for prepulse inhibition (PPI) of the acoustic startle reflex prior to and following puberty, and on a crossmodal PPI task, involving the presentation of acoustic and tactile stimuli. Furthermore, because schizophrenia patients show increased sensitivity to N-methyl-D-aspartate (NMDA) receptor blockade, we assessed the sensitivity of these mice to the PPI-disruptive effects of the NMDA receptor antagonist phencyclidine. The results demonstrated that acoustic PPI did not differ between mutant and wildtype mice. However, VLDLR homozygous mice displayed significant deficits in crossmodal PPI, while ApoER2 heterozygous and homozygous mice displayed significantly increased crossmodal PPI. Both ApoER2 and VLDLR heterozygous and homozygous mice exhibited greater sensitivity to the PPI-disruptive effects of phencyclidine than wildtype mice. These results indicate that partial or complete loss of either one of the reelin receptors results in a complex pattern of alterations in PPI function that include alterations in crossmodal, but not acoustic, PPI and increased sensitivity to NMDA receptor blockade. Thus, reelin receptor function appears to be critically involved in crossmodal PPI and the modulation of the PPI response by NMDA receptors. These findings have relevance to a range of neuropsychiatric disorders that involve sensorimotor gating deficits, including schizophrenia.. PMID:17261317

Cardiothoracic ratio for prediction of left ventricular dilation: a systematic review and pooled analysis.

PubMed

Loomba, Rohit S; Shah, Parinda H; Nijhawan, Karan; Aggarwal, Saurabh; Arora, Rohit

2015-03-01

Increased cardiothoracic ratio noted on chest radiographs often prompts concern and further evaluation with additional imaging. This study pools available data assessing the utility of cardiothoracic ratio in predicting left ventricular dilation. A systematic review of the literature was conducted to identify studies comparing cardiothoracic ratio by chest x-ray to left ventricular dilation by echocardiography. Electronic databases were used to identify studies which were then assessed for quality and bias, with those with adequate quality and minimal bias ultimately being included in the pooled analysis. The pooled data were used to determine the sensitivity, specificity, positive predictive value and negative predictive value of cardiomegaly in predicting left ventricular dilation. A total of six studies consisting of 466 patients were included in this analysis. Cardiothoracic ratio had 83.3% sensitivity, 45.4% specificity, 43.5% positive predictive value and 82.7% negative predictive value. When a secondary analysis was conducted with a pediatric study excluded, a total of five studies consisting of 371 patients were included. Cardiothoracic ratio had 86.2% sensitivity, 25.2% specificity, 42.5% positive predictive value and 74.0% negative predictive value. Cardiothoracic ratio as determined by chest radiograph is sensitive but not specific for identifying left ventricular dilation. Cardiothoracic ratio also has a strong negative predictive value for identifying left ventricular dilation.

Expanding health insurance to increase health care utilization: will it have different effects in rural vs. urban areas?

PubMed

Erlyana, Erlyana; Damrongplasit, Kannika Kampanya; Melnick, Glenn

2011-05-01

This study investigates the importance of medical fee and distance to health care provider on individual's decision to seek care in developing countries. The estimation method used a mixed logit model applied to data from the third wave of the Indonesian family life survey (2000). The key variables of interest include medical fee and distance to different types of health care provider and individual characteristic variables. Urban dweller's decision to choose health care providers are sensitive to the monetary cost of medical care as measured by medical fee but they are not sensitive to distance. For those who reside in rural area, they are sensitive to the non-medical component cost of care as measured by travel distance but they are not sensitive to medical fee. As a result of those findings, policy makers should consider different sets of policy instruments when attempting to expand health service's usage in urban and rural areas of Indonesia. To increase access in urban areas, we recommend expansion of health insurance coverage in order to lower out-of-pocket medical expenditures. As for rural areas, expansion of medical infrastructures to reduce commuting distance and costs will be needed to increase utilization. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Methylation-sensitive amplified polymorphism analysis of Verticillium wilt-stressed cotton (Gossypium).

PubMed

Wang, W; Zhang, M; Chen, H D; Cai, X X; Xu, M L; Lei, K Y; Niu, J H; Deng, L; Liu, J; Ge, Z J; Yu, S X; Wang, B H

2016-10-06

In this study, a methylation-sensitive amplification polymorphism analysis system was used to analyze DNA methylation level in three cotton accessions. Two disease-sensitive near-isogenic lines, PD94042 and IL41, and one disease-resistant Gossypium mustelinum accession were exposed to Verticillium wilt, to investigate molecular disease resistance mechanisms in cotton. We observed multiple different DNA methylation types across the three accessions following Verticillium wilt exposure. These included hypomethylation, hypermethylation, and other patterns. In general, the global DNA methylation level was significantly increased in the disease-resistant accession G. mustelinum following disease exposure. In contrast, there was no significant difference in the disease-sensitive accession PD94042, and a significant decrease was observed in IL41. Our results suggest that disease-resistant cotton might employ a mechanism to increase methylation level in response to disease stress. The differing methylation patterns, together with the increase in global DNA methylation level, might play important roles in tolerance to Verticillium wilt in cotton. Through cloning and analysis of differently methylated DNA sequences, we were also able to identify several genes that may contribute to disease resistance in cotton. Our results revealed the effect of DNA methylation on cotton disease resistance, and also identified genes that played important roles, which may shed light on the future cotton disease-resistant molecular breeding.

Implication of microRNAs in drug resistance for designing novel cancer therapy

PubMed Central

Sarkar, Fazlul H; Li, Yiwei; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan

2010-01-01

Recently, microRNAs (miRNAs) have received increasing attention in the field of cancer research. miRNAs play important roles in many normal biological processes; however, the aberrant miRNA expression and its correlation with the development and progression of cancers is an emerging field. Therefore, miRNAs could be used as biomarkers for diagnosis of cancer and prediction of prognosis. Importantly, some miRNAs could regulate the formation of cancer stem cells and the acquisition of epithelial-mesenchymal transition, which are critically associated with drug resistance. Moreover, some miRNAs could target genes related to drug-sensitivity, resulting in the altered sensitivity of cancer cells to anti-cancer drugs. Emerging evidences have also shown that knock-down or re-expression of specific miRNAs by synthetic antisense oligonucleotides or pre-miRNAs could induce drug sensitivity, leading to increased inhibition of cancer cell growth, invasion, and metastasis. More importantly, recent studies have shown that natural agents including isoflavone, 3,3′-diindolylmethane, and (−)-epigallocatechin-3-gallate altered miRNA expression profiles, leading to an increased sensitivity of cancer cells to conventional therapeutics. These emerging results suggest that specific targeting of miRNAs by different approaches could open new avenues for cancer treatment through overcoming drug resistance and thereby improve the outcome of cancer therapy. PMID:20236855

Climate, Tree Growth, Forest Drought Stress, and Tree Mortality in Forests of Western North America: Long-Term Patterns and Recent Trends

NASA Astrophysics Data System (ADS)

Allen, C. D.; Williams, P.

2012-12-01

Ongoing climate changes are increasingly affecting the world's forests, particularly including high latitude and high elevation coniferous forests. Although forest growth has improved in some regions due to greater growing season length and warmth (perhaps along with increased atmospheric CO2 or N), large growth declines or increased mortality from droughts or hotter temperatures also are being observed. We present and interpret information on regional variation in climate-tree growth relationships and trends, and on patterns and trends of climate-related forest disturbances, from western North America. From 235 tree-ring chronologies in the Southwest US we show that tree-ring growth records from warmer southwestern sites are more sensitive to temperature than tree-ring growth records from cooler southwestern sites. Assessment of 59 tree-ring records from 11 species in the Cascade Mountains of the Pacific Northwest shows that trees growing in cool places respond positively to increased temperature and trees in warm places respond negatively, implying that trees historically not sensitive to temperature may become sensitive as mean temperatures warm. An analysis of 59 white spruce populations in Alaska supports the hypothesis that warming has caused tree growth to lose sensitivity to cold temperatures. Comparing ring widths to temperature during just the coldest 50% of years during the 20th century, tree growth was sensitive to cold temperatures, and this effect was strongest at the coldest sites; whereas during the warmest 50% of years, trees were not at all sensitive to cold temperatures, even at the cold sites. Drought and vapor pressure deficit are among the variables that emerge as being increasingly important to these Alaska boreal forests as mean temperatures rise. Most recently, from 346 tree-ring chronologies in the Southwest US we establish a tree-ring-based Forest Drought Stress Index (FDSI) for the three most widespread conifer species (Pinus edulis, Pinus ponderosa, and Pseudotsuga menziesii) in this region. FDSI responds sensitively and nonlinearly to growing season daily maximum temperatures which increase vapor pressure deficit, resulting in greater tree physiological stress and reduced tree growth. Drought conditions and warming temperatures in the Southwest since ca. 1996 have caused FDSI values in particular years since 2000 to start to exceed the most extreme values reconstructed from tree-rings for the past 1000 years for this region. FDSI demonstrates strong correlations with the spatial extent of major forest disturbances in the Southwest, including high-severity wildfire and bark beetle infestations, which over the past 20 years also have affected historically unprecedented levels. Similar trends of increasing extent and severity of forest disturbances are apparent across large portions of western North America. For the Southwest US, given relatively robust projections of substantial further increases in warmer temperatures and drought stress in coming decades, by ~2050 projected levels of FDSI and associated disturbances would reach extreme values, suggesting that current forest ecosystems likely would be forced to reorganize through wholesale tree mortality and the establishment of new dominant species.

Recommendations on Model Fidelity for Wind Turbine Gearbox Simulations; NREL (National Renewable Energy Laboratory)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keller, J.; Lacava, W.; Austin, J.

2015-02-01

This work investigates the minimum level of fidelity required to accurately simulate wind turbine gearboxes using state-of-the-art design tools. Excessive model fidelity including drivetrain complexity, gearbox complexity, excitation sources, and imperfections, significantly increases computational time, but may not provide a commensurate increase in the value of the results. Essential designparameters are evaluated, including the planetary load-sharing factor, gear tooth load distribution, and sun orbit motion. Based on the sensitivity study results, recommendations for the minimum model fidelities are provided.

Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems With Switching [Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems

DOE PAGES

Zhang, Hong; Abhyankar, Shrirang; Constantinescu, Emil; ...

2017-01-24

Sensitivity analysis is an important tool for describing power system dynamic behavior in response to parameter variations. It is a central component in preventive and corrective control applications. The existing approaches for sensitivity calculations, namely, finite-difference and forward sensitivity analysis, require a computational effort that increases linearly with the number of sensitivity parameters. In this paper, we investigate, implement, and test a discrete adjoint sensitivity approach whose computational effort is effectively independent of the number of sensitivity parameters. The proposed approach is highly efficient for calculating sensitivities of larger systems and is consistent, within machine precision, with the function whosemore » sensitivity we are seeking. This is an essential feature for use in optimization applications. Moreover, our approach includes a consistent treatment of systems with switching, such as dc exciters, by deriving and implementing the adjoint jump conditions that arise from state-dependent and time-dependent switchings. The accuracy and the computational efficiency of the proposed approach are demonstrated in comparison with the forward sensitivity analysis approach. In conclusion, this paper focuses primarily on the power system dynamics, but the approach is general and can be applied to hybrid dynamical systems in a broader range of fields.« less

Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems With Switching [Discrete Adjoint Sensitivity Analysis of Hybrid Dynamical Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Hong; Abhyankar, Shrirang; Constantinescu, Emil

Sensitivity analysis is an important tool for describing power system dynamic behavior in response to parameter variations. It is a central component in preventive and corrective control applications. The existing approaches for sensitivity calculations, namely, finite-difference and forward sensitivity analysis, require a computational effort that increases linearly with the number of sensitivity parameters. In this paper, we investigate, implement, and test a discrete adjoint sensitivity approach whose computational effort is effectively independent of the number of sensitivity parameters. The proposed approach is highly efficient for calculating sensitivities of larger systems and is consistent, within machine precision, with the function whosemore » sensitivity we are seeking. This is an essential feature for use in optimization applications. Moreover, our approach includes a consistent treatment of systems with switching, such as dc exciters, by deriving and implementing the adjoint jump conditions that arise from state-dependent and time-dependent switchings. The accuracy and the computational efficiency of the proposed approach are demonstrated in comparison with the forward sensitivity analysis approach. In conclusion, this paper focuses primarily on the power system dynamics, but the approach is general and can be applied to hybrid dynamical systems in a broader range of fields.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmon, S; Jeraj, R; Galavis, P

Purpose: Sensitivity of PET-derived texture features to reconstruction methods has been reported for features extracted from axial planes; however, studies often utilize three dimensional techniques. This work aims to quantify the impact of multi-plane (3D) vs. single-plane (2D) feature extraction on radiomics-based analysis, including sensitivity to reconstruction parameters and potential loss of spatial information. Methods: Twenty-three patients with solid tumors underwent [{sup 18}F]FDG PET/CT scans under identical protocols. PET data were reconstructed using five sets of reconstruction parameters. Tumors were segmented using an automatic, in-house algorithm robust to reconstruction variations. 50 texture features were extracted using two Methods: 2D patchesmore » along axial planes and 3D patches. For each method, sensitivity of features to reconstruction parameters was calculated as percent difference relative to the average value across reconstructions. Correlations between feature values were compared when using 2D and 3D extraction. Results: 21/50 features showed significantly different sensitivity to reconstruction parameters when extracted in 2D vs 3D (wilcoxon α<0.05), assessed by overall range of variation, Rangevar(%). Eleven showed greater sensitivity to reconstruction in 2D extraction, primarily first-order and co-occurrence features (average Rangevar increase 83%). The remaining ten showed higher variation in 3D extraction (average Range{sub var}increase 27%), mainly co-occurence and greylevel run-length features. Correlation of feature value extracted in 2D and feature value extracted in 3D was poor (R<0.5) in 12/50 features, including eight co-occurrence features. Feature-to-feature correlations in 2D were marginally higher than 3D, ∣R∣>0.8 in 16% and 13% of all feature combinations, respectively. Larger sensitivity to reconstruction parameters were seen for inter-feature correlation in 2D(σ=6%) than 3D (σ<1%) extraction. Conclusion: Sensitivity and correlation of various texture features were shown to significantly differ between 2D and 3D extraction. Additionally, inter-feature correlations were more sensitive to reconstruction variation using single-plane extraction. This work highlights a need for standardized feature extraction/selection techniques in radiomics.« less

Outcomes sensitive to nursing service quality in ambulatory cancer chemotherapy: Systematic scoping review.

PubMed

Griffiths, Peter; Richardson, Alison; Blackwell, Rebecca

2012-07-01

There is long standing interest in identifying patient outcomes that are sensitive to nursing care and an increasing number of systems that include outcomes in order to demonstrate or monitor the quality of nursing care. We undertook scoping reviews of the literature in order to identify patient outcomes sensitive to the quality of nursing services in ambulatory cancer chemotherapy settings to guide the development of an outcomes-based quality measurement system. A 2-stage scoping review to identify potential outcome areas which were subsequently assessed for their sensitivity to nursing was carried out. Data sources included the Cochrane Library, Medline, Embase, the British Nursing Index, Google and Google scholar. We identified a broad range of outcomes potentially sensitive to nursing. Individual trials support many nursing interventions but we found relatively little clear evidence of effect on outcomes derived from systematic reviews and no evidence associating characteristics of nursing services with outcomes. The purpose of identifying a set of outcomes as specifically nurse-sensitive for quality measurement is to give clear responsibility and create an expectation of strong clinical leadership by nurses in terms of monitoring and acting on results. It is important to select those outcomes that nurses have most impact upon. Patient experience, nausea, vomiting, mucositis and safe medication administration were outcome areas most likely to yield sensitive measures of nursing service quality in ambulatory cancer chemotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ten Basic Suggestions to Social Studies Students for Improving Your Writing

ERIC Educational Resources Information Center

Roselle, Daniel

1977-01-01

Ten guidelines to help students improve their writing include clear expression, specificity, originality, avoiding stereotyping, linking paragraphs, setting time by parallel events, linking past and present, use of primary sources, giving evidence for generalizations, and reading to increase sensitivity. (AV)

El Paso's Organizational Development Model

ERIC Educational Resources Information Center

de los Santos, Gilberto

1975-01-01

The success of El Paso Community College (Texas) is attributed to its early definition of instructional thrusts including: systematizing and individualizing instruction; increasing awareness, sensitivity, and appreciation of the culture of the students; development of staff bilingual capabilities; development of staff teams versed in management by…

Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder

PubMed Central

van Zuiden, Mirjam; Koch, Saskia B.J.; Frijling, Jessie L.; Veltman, Dick J.; Olff, Miranda

2017-01-01

Abstract Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. PMID:27614769

Dimethylsulfide model calibration and parametric sensitivity analysis for the Greenland Sea

NASA Astrophysics Data System (ADS)

Qu, Bo; Gabric, Albert J.; Zeng, Meifang; Xi, Jiaojiao; Jiang, Limei; Zhao, Li

2017-09-01

Sea-to-air fluxes of marine biogenic aerosols have the potential to modify cloud microphysics and regional radiative budgets, and thus moderate Earth's warming. Polar regions play a critical role in the evolution of global climate. In this work, we use a well-established biogeochemical model to simulate the DMS flux from the Greenland Sea (20°W-10°E and 70°N-80°N) for the period 2003-2004. Parameter sensitivity analysis is employed to identify the most sensitive parameters in the model. A genetic algorithm (GA) technique is used for DMS model parameter calibration. Data from phase 5 of the Coupled Model Intercomparison Project (CMIP5) are used to drive the DMS model under 4 × CO2 conditions. DMS flux under quadrupled CO2 levels increases more than 300% compared with late 20th century levels (1 × CO2). Reasons for the increase in DMS flux include changes in the ocean state-namely an increase in sea surface temperature (SST) and loss of sea ice-and an increase in DMS transfer velocity, especially in spring and summer. Such a large increase in DMS flux could slow the rate of warming in the Arctic via radiative budget changes associated with DMS-derived aerosols.

Characterization of Cannabis sativa allergens.

PubMed

Nayak, Ajay P; Green, Brett J; Sussman, Gordon; Berlin, Noam; Lata, Hemant; Chandra, Suman; ElSohly, Mahmoud A; Hettick, Justin M; Beezhold, Donald H

2013-07-01

Allergic sensitization to Cannabis sativa is rarely reported, but the increasing consumption of marijuana has resulted in an increase in the number of individuals who become sensitized. To date, little is known about the causal allergens associated with C sativa. To characterize marijuana allergens in different components of the C sativa plant using serum IgE from marijuana sensitized patients. Serum samples from 23 patients with a positive skin prick test result to a crude C sativa extract were evaluated. IgE reactivity was variable between patients and C sativa extracts. IgE reactivity to C sativa proteins in Western blots was heterogeneous and ranged from 10 to 70 kDa. Putative allergens derived from 2-dimensional gels were identified. Prominent IgE reactive bands included a 23-kDa oxygen-evolving enhancer protein 2 and a 50-kDa protein identified to be the photosynthetic enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase. Additional proteins were identified in the proteomic analysis, including those from adenosine triphosphate synthase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and luminal binding protein (heat shock protein 70), suggesting these proteins are potential allergens. Deglycosylation studies helped refine protein allergen identification and demonstrated significant IgE antibodies against plant oligosaccharides that could help explain cross-reactivity. Identification and characterization of allergens from C sativa may be helpful in further understanding allergic sensitization to this plant species. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Small-volume cavity cell using hollow optical fiber for Raman scattering-based gas detection

NASA Astrophysics Data System (ADS)

Okita, Y.; Katagiri, T.; Matsuura, Y.

2011-03-01

The highly sensitive Raman cell based on the hollow optical fiber that is suitable for the real-time breath analysis is reported. Hollow optical fiber with inner coating of silver is used as a gas cell and a Stokes light collector. A very small cell whose volume is only 0.4 ml or less enables fast response and real-time measurement of trace gases. To increase the sensitivity the cell is arranged in a cavity which includes of a long-pass filter and a high reflective mirror. The sensitivity of the cavity cell is more than two times higher than that of the cell without cavity.

Perspectives on MEMS in bioengineering: a novel capacitive position microsensor.

PubMed

Pedrocchi, A; Hoen, S; Ferrigno, G; Pedotti, A

2000-01-01

We describe a novel capacitive position sensor using micromachining to achieve high sensitivity and large range of motion. These sensors require a new theoretical framework to describe and optimize their performance. Employing a complete description of the electrical fields, the sensor should deviate from the standard geometries used for capacitive sensors. By this optimization, the sensor gains a twofold increase in sensitivity. Results on a PC board 10x model imply that the micromachined sensor should achieve a sensitivity of less than 10 nm over 500-micron range of travel. Some bioengineering applications are addressed, including positioning of micromirrors for laser surgery and dose control for implantable drug delivery systems.

Impact of test sensitivity and specificity on pig producer incentives to control Mycobacterium avium infections in finishing pigs.

PubMed

van Wagenberg, Coen P A; Backus, Gé B C; Wisselink, Henk J; van der Vorst, Jack G A J; Urlings, Bert A P

2013-09-01

In this paper we analyze the impact of the sensitivity and specificity of a Mycobacterium avium (Ma) test on pig producer incentives to control Ma in finishing pigs. A possible Ma control system which includes a serodiagnostic test and a penalty on finishing pigs in herds detected with Ma infection was modelled. Using a dynamic optimization model and a grid search of deliveries of herds from pig producers to slaughterhouse, optimal control measures for pig producers and optimal penalty values for deliveries with increased Ma risk were identified for different sensitivity and specificity values. Results showed that higher sensitivity and lower specificity induced use of more intense control measures and resulted in higher pig producer costs and lower Ma seroprevalence. The minimal penalty value needed to comply with a threshold for Ma seroprevalence in finishing pigs at slaughter was lower at higher sensitivity and lower specificity. With imperfect specificity a larger sample size decreased pig producer incentives to control Ma seroprevalence, because the higher number of false positives resulted in an increased probability of rejecting a batch of finishing pigs irrespective of whether the pig producer applied control measures. We conclude that test sensitivity and specificity must be considered in incentive system design to induce pig producers to control Ma in finishing pigs with minimum negative effects. Copyright © 2013 Elsevier B.V. All rights reserved.

Possible mechanisms for the relative efficacies of ortho-phthalaldehyde and glutaraldehyde against glutaraldehyde-resistant Mycobacterium chelonae.

PubMed

Walsh, S E; Maillard, J Y; Russell, A D; Hann, A C

2001-07-01

This investigation compared glutaraldehyde (GTA)-sensitive and -resistant strains of Mycobacterium chelonae and examined the effects of pretreatment of GTA-sensitive and -resistant strains of Myco. chelonae with chemical agents that interfere with cell wall synthesis. When exposed to 2% (v/v) GTA at 25 degrees C, GTA-resistant strains of Myco. chelonae dried on to glass carriers were not inactivated to any significant extent. By contrast, GTA-sensitive strains of Myco. chelonae and a strain of Myco. terrae suffered a > 6 log reduction in viability in 5 min. However, ortho-phthalaldehyde (OPA; 0.5% w/v) achieved a corresponding inactivation against two GTA-resistant strains within 5-10 and 10-20 min, respectively. Electron microscopy, using a non-aldehyde fixation process and also negative staining, failed to detect any extensive changes in GTA-sensitive and -resistant cultures exposed to GTA or OPA. Thin-layer chromatography was unsuccessful in detecting differences between GTA-resistant and -sensitive strains of Myco. chelonae. However, pretreatment of GTA-resistant cells with mycobacterial cell wall synthesis inhibitors increased their subsequent susceptibility further to OPA but not to GTA. Ortho-phthalaldehyde is an effective new biocidal agent that, at its in-use concentration, is rapidly bactericidal to non-sporulating bacteria, including GTA-sensitive and -resistant mycobacteria. Pretreatment of GTA-resistant cells with mycobacterial cell wall synthesis inhibitors increased their subsequent susceptibility to OPA but not to GTA.

Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness

PubMed Central

Volta, Umberto; Caio, Giacomo; Tovoli, Francesco; De Giorgio, Roberto

2013-01-01

Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues. PMID:23934026

Pim kinase inhibition sensitizes FLT3-ITD acute myeloid leukemia cells to topoisomerase 2 inhibitors through increased DNA damage and oxidative stress

PubMed Central

Doshi, Kshama A.; Trotta, Rossana; Natarajan, Karthika; Rassool, Feyruz V.; Tron, Adriana E.; Huszar, Dennis; Perrotti, Danilo; Baer, Maria R.

2016-01-01

Internal tandem duplication of fms-like tyrosine kinase-3 (FLT3-ITD) is frequent (30 percent) in acute myeloid leukemia (AML), and is associated with short disease-free survival following chemotherapy. The serine threonine kinase Pim-1 is a pro-survival oncogene transcriptionally upregulated by FLT3-ITD that also promotes its signaling in a positive feedback loop. Thus inhibiting Pim-1 represents an attractive approach in targeting FLT3-ITD cells. Indeed, co-treatment with the pan-Pim kinase inhibitor AZD1208 or expression of a kinase-dead Pim-1 mutant sensitized FLT3-ITD cell lines to apoptosis triggered by chemotherapy drugs including the topoisomerase 2 inhibitors daunorubicin, etoposide and mitoxantrone, but not the nucleoside analog cytarabine. AZD1208 sensitized primary AML cells with FLT3-ITD to topoisomerase 2 inhibitors, but did not sensitize AML cells with wild-type FLT3 or remission bone marrow cells, supporting a favorable therapeutic index. Mechanistically, the enhanced apoptosis observed with AZD1208 and topoisomerase 2 inhibitor combination treatment was associated with increased DNA double-strand breaks and increased levels of reactive oxygen species (ROS), and co-treatment with the ROS scavenger N-acetyl cysteine rescued FLT3-ITD cells from AZD1208 sensitization to topoisomerase 2 inhibitors. Our data support testing of Pim kinase inhibitors with topoisomerase 2 inhibitors, but not with cytarabine, to improve treatment outcomes in AML with FLT3-ITD. PMID:27374090

Quantification of tumor fluorescence during intraoperative optical cancer imaging.

PubMed

Judy, Ryan P; Keating, Jane J; DeJesus, Elizabeth M; Jiang, Jack X; Okusanya, Olugbenga T; Nie, Shuming; Holt, David E; Arlauckas, Sean P; Low, Phillip S; Delikatny, E James; Singhal, Sunil

2015-11-13

Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation to measure tumor fluorescence. Three imaging systems (Spectropen, Glomax, Flocam) measured and quantified fluorescent signal-to-background ratios (SBR) in vitro, murine xenografts, tissue phantoms and clinically. Evaluation criteria included the detection of small changes in fluorescence, sensitivity of signal detection at increasing depths and practicality of use. In vitro, spectroscopy was superior in detecting incremental differences in fluorescence than luminescence and digital imaging (Ln[SBR] = 6.8 ± 0.6, 2.4 ± 0.3, 2.6 ± 0.1, p = 0.0001). In fluorescent tumor cells, digital imaging measured higher SBRs than luminescence (6.1 ± 0.2 vs. 4.3 ± 0.4, p = 0.001). Spectroscopy was more sensitive than luminometry and digital imaging in identifying murine tumor fluorescence (SBR = 41.7 ± 11.5, 5.1 ± 1.8, 4.1 ± 0.9, p = 0.0001), and more sensitive than digital imaging at detecting fluorescence at increasing depths (SBR = 7.0 ± 3.4 vs. 2.4 ± 0.5, p = 0.03). Lastly, digital imaging was the most practical and least time-consuming. All methods detected incremental differences in fluorescence. Spectroscopy was the most sensitive for small changes in fluorescence. Digital imaging was the most practical considering its wide field of view, background noise filtering capability, and sensitivity to increasing depth.

Diagnostic performance of matrix-assisted laser desorption ionisation time-of-flight mass spectrometry in blood bacterial infections: a systematic review and meta-analysis.

PubMed

Scott, Jamie S; Sterling, Sarah A; To, Harrison; Seals, Samantha R; Jones, Alan E

2016-07-01

Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) has shown promise in decreasing time to identification of causative organisms compared to traditional methods; however, the utility of MALDI-TOF MS in a heterogeneous clinical setting is uncertain. To perform a systematic review on the operational performance of the Bruker MALDI-TOF MS system and evaluate published cut-off values compared to traditional blood cultures. A comprehensive literature search was performed. Studies were included if they performed direct MALDI-TOF MS analysis of blood culture specimens in human patients with suspected bacterial infections using the Bruker Biotyper software. Sensitivities and specificities of the combined studies were estimated using a hierarchical random effects linear model (REML) incorporating cut-off scores of ≥1.7 and ≥2.0. Fifty publications were identified, with 11 studies included after final review. The estimated sensitivity utilising a cut-off of ≥2.0 from the combined studies was 74.6% (95% CI = 67.9-89.3%), with an estimated specificity of 88.0% (95% CI = 74.8-94.7%). When assessing a cut-off of ≥1.7, the combined sensitivity increases to 92.8% (95% CI = 87.4-96.0%), but the estimated specificity decreased to 81.2% (95% CI = 61.9-96.6%). In this analysis, MALDI-TOF MS showed acceptable sensitivity and specificity in bacterial speciation with the current recommended cut-off point compared to blood cultures; however, lowering the cut-off point from ≥2.0 to ≥1.7 would increase the sensitivity of the test without significant detrimental effect on the specificity, which could improve clinician confidence in their results.

Distinctive postprandial modulation of beta cell function and insulin sensitivity by dietary fats: monounsaturated compared with saturated fatty acids.

PubMed

López, Sergio; Bermúdez, Beatriz; Pacheco, Yolanda M; Villar, José; Abia, Rocío; Muriana, Francisco J G

2008-09-01

Exaggerated and prolonged postprandial triglyceride concentrations are associated with numerous conditions related to insulin resistance, including obesity, type 2 diabetes, and the metabolic syndrome. Although dietary fats profoundly affect postprandial hypertriglyceridemia, limited data exist regarding their effects on postprandial glucose homeostasis. We sought to determine whether postprandial glucose homeostasis is modulated distinctly by high-fat meals enriched in saturated fatty acids (SFAs) or monounsaturated fatty acids (MUFAs). Normotriglyceridemic subjects with normal fasting glucose and normal glucose tolerance were studied. Blood samples were collected over the 8 h after ingestion of a glucose and triglyceride tolerance test meal (GTTTM) in which a panel of dietary fats with a gradual change in the ratio of MUFAs to SFAs was included. On 5 separate occasions, basal and postprandial concentrations of glucose, insulin, triglyceride, and free fatty acids (FFAs) were measured. High-fat meals increased the postprandial concentrations of insulin, triglycerides, and FFAs, and they enhanced postprandial beta cell function while decreasing insulin sensitivity (as assessed with different model-based and empirical indexes: insulinogenic index, insulinogenic index/homeostasis model assessment of insulin resistance, area under the curve for insulin/area under the curve for glucose, homeostasis model assessment for beta cell function, and GTTTM-determined insulin sensitivity, oral glucose insulin sensitivity, and the postprandial Belfiore indexes for glycemia and blood FFAs. These effects were significantly ameliorated, in a direct linear relation, when MUFAs were substituted for SFAs. The data presented here suggest that beta cell function and insulin sensitivity progressively improve in the postprandial state as the proportion of MUFAs with respect to SFAs in dietary fats increases.

Human T-Cell Leukemia Virus I Tax Protein Sensitizes p53-Mutant Cells to DNA Damage

PubMed Central

Mihaylova, Valia T.; Green, Allison M.; Khurgel, Moshe; Semmes, Oliver J.; Kupfer, Gary M.

2018-01-01

Mutations in p53 are a common cause of resistance of cancers to standard chemotherapy and, thus, treatment failure. Reports have shown that Tax, a human T-cell leukemia virus type I encoded protein that has been associated with genomic instability and perturbation of transcription and cell cycle, sensitizes HeLa cells to UV treatment. The extent to which Tax can sensitize cells and the mechanism by which it exerts its effect are unknown. In this study, we show that Tax sensitizes p53-mutant cells to a broad range of DNA-damaging agents, including mitomycin C, a bifunctional alkylator, etoposide, a topoisomerase II drug, and UV light, but not ionizing radiation, a double-strand break agent, or vinblastine, a tubulin poison. Tax caused hypersensitivity in all p53-deleted cell lines and several, but not all, mutant-expressed p53–containing cell lines, while unexpectedly being protective in p53 wild-type (wt) cells. The effect observed in p53-deleted lines could be reversed for this by transfection of wt p53. We also show that Tax activates a p53-independent proapoptotic program through decreased expression of the retinoblastoma protein and subsequent increased E2F1 expression. The expression of several proapoptotic proteins was also induced by Tax, including Puma and Noxa, culminating in a substantial increase in Bax dimerization. Our results show that Tax can sensitize p53-mutant cells to DNA damage while protecting p53 wt cells, a side benefit that might result in reduced toxicity in normal cells. Such studies hold the promise of a novel adjunctive therapy that could make cancer chemotherapy more effective. PMID:18559532

Sensitivity analysis of a multilayer, finite-difference model of the Southeastern Coastal Plain regional aquifer system; Mississippi, Alabama, Georgia, and South Carolina

USGS Publications Warehouse

Pernik, Meribeth

1987-01-01

The sensitivity of a multilayer finite-difference regional flow model was tested by changing the calibrated values for five parameters in the steady-state model and one in the transient-state model. The parameters that changed under the steady-state condition were those that had been routinely adjusted during the calibration process as part of the effort to match pre-development potentiometric surfaces, and elements of the water budget. The tested steady-state parameters include: recharge, riverbed conductance, transmissivity, confining unit leakance, and boundary location. In the transient-state model, the storage coefficient was adjusted. The sensitivity of the model to changes in the calibrated values of these parameters was evaluated with respect to the simulated response of net base flow to the rivers, and the mean value of the absolute head residual. To provide a standard measurement of sensitivity from one parameter to another, the standard deviation of the absolute head residual was calculated. The steady-state model was shown to be most sensitive to changes in rates of recharge. When the recharge rate was held constant, the model was more sensitive to variations in transmissivity. Near the rivers, the riverbed conductance becomes the dominant parameter in controlling the heads. Changes in confining unit leakance had little effect on simulated base flow, but greatly affected head residuals. The model was relatively insensitive to changes in the location of no-flow boundaries and to moderate changes in the altitude of constant head boundaries. The storage coefficient was adjusted under transient conditions to illustrate the model 's sensitivity to changes in storativity. The model is less sensitive to an increase in storage coefficient than it is to a decrease in storage coefficient. As the storage coefficient decreased, the aquifer drawdown increases, the base flow decreased. The opposite response occurred when the storage coefficient was increased. (Author 's abstract)

Spectral shifts of mammalian ultraviolet-sensitive pigments (short wavelength-sensitive opsin 1) are associated with eye length and photic niche evolution.

PubMed

Emerling, Christopher A; Huynh, Hieu T; Nguyen, Minh A; Meredith, Robert W; Springer, Mark S

2015-11-22

Retinal opsin photopigments initiate mammalian vision when stimulated by light. Most mammals possess a short wavelength-sensitive opsin 1 (SWS1) pigment that is primarily sensitive to either ultraviolet or violet light, leading to variation in colour perception across species. Despite knowledge of both ultraviolet- and violet-sensitive SWS1 classes in mammals for 25 years, the adaptive significance of this variation has not been subjected to hypothesis testing, resulting in minimal understanding of the basis for mammalian SWS1 spectral tuning evolution. Here, we gathered data on SWS1 for 403 mammal species, including novel SWS1 sequences for 97 species. Ancestral sequence reconstructions suggest that the most recent common ancestor of Theria possessed an ultraviolet SWS1 pigment, and that violet-sensitive pigments evolved at least 12 times in mammalian history. We also observed that ultraviolet pigments, previously considered to be a rarity, are common in mammals. We then used phylogenetic comparative methods to test the hypotheses that the evolution of violet-sensitive SWS1 is associated with increased light exposure, extended longevity and longer eye length. We discovered that diurnal mammals and species with longer eyes are more likely to have violet-sensitive pigments and less likely to possess UV-sensitive pigments. We hypothesize that (i) as mammals evolved larger body sizes, they evolved longer eyes, which limited transmittance of ultraviolet light to the retina due to an increase in Rayleigh scattering, and (ii) as mammals began to invade diurnal temporal niches, they evolved lenses with low UV transmittance to reduce chromatic aberration and/or photo-oxidative damage. © 2015 The Author(s).

Spectral shifts of mammalian ultraviolet-sensitive pigments (short wavelength-sensitive opsin 1) are associated with eye length and photic niche evolution

PubMed Central

Emerling, Christopher A.; Huynh, Hieu T.; Nguyen, Minh A.; Meredith, Robert W.; Springer, Mark S.

2015-01-01

Retinal opsin photopigments initiate mammalian vision when stimulated by light. Most mammals possess a short wavelength-sensitive opsin 1 (SWS1) pigment that is primarily sensitive to either ultraviolet or violet light, leading to variation in colour perception across species. Despite knowledge of both ultraviolet- and violet-sensitive SWS1 classes in mammals for 25 years, the adaptive significance of this variation has not been subjected to hypothesis testing, resulting in minimal understanding of the basis for mammalian SWS1 spectral tuning evolution. Here, we gathered data on SWS1 for 403 mammal species, including novel SWS1 sequences for 97 species. Ancestral sequence reconstructions suggest that the most recent common ancestor of Theria possessed an ultraviolet SWS1 pigment, and that violet-sensitive pigments evolved at least 12 times in mammalian history. We also observed that ultraviolet pigments, previously considered to be a rarity, are common in mammals. We then used phylogenetic comparative methods to test the hypotheses that the evolution of violet-sensitive SWS1 is associated with increased light exposure, extended longevity and longer eye length. We discovered that diurnal mammals and species with longer eyes are more likely to have violet-sensitive pigments and less likely to possess UV-sensitive pigments. We hypothesize that (i) as mammals evolved larger body sizes, they evolved longer eyes, which limited transmittance of ultraviolet light to the retina due to an increase in Rayleigh scattering, and (ii) as mammals began to invade diurnal temporal niches, they evolved lenses with low UV transmittance to reduce chromatic aberration and/or photo-oxidative damage. PMID:26582021

The Relationship Between Cultural Sensitivity and Assertiveness in Nursing Students from Turkey.

PubMed

Kılıç, Serap Parlar; Sevinç, Sibel

2018-07-01

As foreigners live in and visit Turkey for various reasons, it is essential to provide culturally appropriate health care. This study was conducted to determine the relationship between cultural sensitivity and assertiveness in university nursing students. This descriptive, cross-sectional study was conducted at two universities in the cities of Kilis and Elazığ, Turkey. The study sample consisted of 444 nursing students. Data collection tools included a questionnaire about participant sociodemographic characteristics, Chen and Starosta's Intercultural Sensitivity Scale, and the Rathus Assertiveness Scale. The mean age of participants was 21.09 years. Most students (71.6%) were female and 34.7% of the students stayed at the hostel. Of the students, 44.4%, 27.5%, and 28.2% attended were the second-, third-, and fourth-year students, respectively. Participants were asked about problems related to caring for patients who speak different languages. The mean score for the Intercultural Sensitivity Scale was 89.42 ± 13.55 and the total score for all students for the Assertiveness Scale was 112.64 ± 15.61. We identified a positive relationship between total scores for the Intercultural Sensitivity Scale and the Assertiveness Scale ( p < .001). There was relationship between cultural sensitivity and gender and want to work overseas; assertiveness and year of nursing education and want to work overseas. Nursing students at both schools had a moderate level of cultural sensitivity and assertiveness. It has been determined that as assertiveness level of the students increased, intercultural sensitivity of them also increased. Consequently, it is concluded that training as assertive and self-confident individuals during the nursing education of students has a contribution to making patient-specific and culture-sensitive care.

[The global climate: a sick patient].

PubMed

Lidegaard, Øjvind; Lidegaard, Martin

2008-08-25

Over the last 100 years the human use of fossil fuel has increased the atmospheric CO2 content from 280 parts per million (ppm) to 380 ppm. This increase is expected to increase the global average temperature by a few degrees. The global climate is very sensitive to an increase in temperature, and major climatic disasters, including health threats to millions of people, are probable if the CO2 emission increases further. Therefore, serious global initiatives should be taken now in order to prevent global over heating. Denmark should be at the forefront of these initiatives.

Radiation sensitive devices and systems for detection of radioactive materials and related methods

DOEpatents

Kotter, Dale K

2014-12-02

Radiation sensitive devices include a substrate comprising a radiation sensitive material and a plurality of resonance elements coupled to the substrate. Each resonance element is configured to resonate responsive to non-ionizing incident radiation. Systems for detecting radiation from a special nuclear material include a radiation sensitive device and a sensor located remotely from the radiation sensitive device and configured to measure an output signal from the radiation sensitive device. In such systems, the radiation sensitive device includes a radiation sensitive material and a plurality of resonance elements positioned on the radiation sensitive material. Methods for detecting a presence of a special nuclear material include positioning a radiation sensitive device in a location where special nuclear materials are to be detected and remotely interrogating the radiation sensitive device with a sensor.

Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

PubMed

Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2017-01-01

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

Psychological Stress Induces Temporary Masticatory Muscle Mechanical Sensitivity in Rats

PubMed Central

Huang, Fei; Zhang, Min; Chen, Yong-Jin; Li, Qiang; Wu, An-Zhen

2011-01-01

To explore the relationship between psychological stress and masticatory muscle pain, we created a communication stress animal model to determine whether psychological stress could induce increased mechanical sensitivity in masticatory muscles and to study the changes of mechanical nociceptive thresholds after stress removal. Forty-eight male Sprague-Dawley rats were divided into a control group (CON), a foot-shocked group (FS, including 3 subgroups recorded as FS-1, FS-2, and FS-3), a psychological stress group (PS), and a drug treatment group (DT). PS and DT rats were confined in a communication box for one hour a day to observe the psychological responses of neighboring FS rats.Measurements of the mechanical nociceptive thresholds of the bilateral temporal and masseter muscles showed a stimulus-response relationship between psychological stress and muscle mechanical sensitivity. The DT rats, who received a diazepam injection, showed almost the same mechanical sensitivity of the masticatory muscles to that of the control in response to psychological stress. Fourteen days after the psychological stressor was removed, the mechanical nociceptive thresholds returned to normal. These findings suggest that psychological stress is directly related to masticatory muscle pain. Removal of the stressor could be a useful method for relieving mechanical sensitivity increase induced by psychological stress. PMID:21331360

Decision-making, sensitivity to reward, and attrition in weight-management

PubMed Central

Koritzky, Gilly; Dieterle, Camille; Rice, Chantelle; Jordan, Katie; Bechara, Antoine

2014-01-01

Objective Attrition is a common problem in weight-management. Understanding the risk factors for attrition should enhance professionals’ ability to increase completion rates and improve health outcomes for more individuals. We propose a model that draws upon neuropsychological knowledge on reward-sensitivity in obesity and overeating to predict attrition. Design & Methods 52 participants in a weight-management program completed a complex decision-making task.Decision-making characteristics – including sensitivity to reward – were further estimated using a quantitative model. Impulsivity and risk-taking measures were also administered. Results Consistent with the hypothesis that sensitivity to reward predicted attrition, program dropouts had higher sensitivity to reward than completers (p < 0.03). No differences were observed between completers and dropouts in initial BMI, age, employment status, or the number of prior weight-loss attempts (p ≥ 0.07). Completers had a slightly higher education level than dropouts, but its inclusion in the model did not increase predictive power. Impulsivity, delay of gratification, and risk-taking did not predict attrition, either. Conclusions Findings link attrition in weight-management to the neural mechanisms associated with reward-seeking and related influences on decision-making. Individual differences in the magnitude of response elicited by rewards may account for the relative difficulty experienced by dieters in adhering to treatment. PMID:24771588

Development of a HIV-1 Virus Detection System Based on Nanotechnology.

PubMed

Lee, Jin-Ho; Oh, Byung-Keun; Choi, Jeong-Woo

2015-04-27

Development of a sensitive and selective detection system for pathogenic viral agents is essential for medical healthcare from diagnostics to therapeutics. However, conventional detection systems are time consuming, resource-intensive and tedious to perform. Hence, the demand for sensitive and selective detection system for virus are highly increasing. To attain this aim, different aspects and techniques have been applied to develop virus sensor with improved sensitivity and selectivity. Here, among those aspects and techniques, this article reviews HIV virus particle detection systems incorporated with nanotechnology to enhance the sensitivity. This review mainly focused on four different detection system including vertically configured electrical detection based on scanning tunneling microscopy (STM), electrochemical detection based on direct electron transfer in virus, optical detection system based on localized surface plasmon resonance (LSPR) and surface enhanced Raman spectroscopy (SERS) using plasmonic nanoparticle.

Spatial and spectral characterization of acid rain stress in Canadian Shield lakes

NASA Technical Reports Server (NTRS)

Marshall, Elizabeth J.; Tanis, Frederick J.

1989-01-01

Results from this study demonstrate that a remote sensor can discriminate lake clarity based upon reflection. The basic hypothesis was that seasonal and multiyear changes in lake optical transparency are indicative of sensitivity to acidic deposition. In many acid-sensitive lakes optical transparency is controlled by the amount of dissolved organic carbon (DOC) present. DOC is a strong absorbing, nonscattering material which has the greatest impact at short visible wavelengths, including Thematic Mapper band 1. Acid-sensitive lakes have high concentrations of aluminum which have been mobilized by acidic components contained in the runoff. Aluminum complexing with DOC is considered to be the primary mechanism to account for observed increases in lake transparency in acid-sensitive lakes. Thus seasonal changes in the optical transparency of lakes should provide an indication of the stress due to acid deposition and loading.

A Safe Zone for Veterans: Developing the VET NET Ally Program to Increase Faculty and Staff Awareness and Sensitivity to the Needs of Military Veterans in Higher Education

ERIC Educational Resources Information Center

Thomas, Marshall W.

2010-01-01

Given the increased educational benefits of the Post 9/11 G. I. Bill for veterans, and as the current conflicts in Iraq and Afghanistan wind down and the troops come home, the number of military veterans entering colleges and universities is expected to increase. As non-traditional students with significant life experience, often including combat,…

ATM regulates 3-Methylpurine-DNA glycosylase and promotes therapeutic resistance to alkylating agents

PubMed Central

Agnihotri, Sameer; Burrell, Kelly; Buczkowicz, Pawel; Remke, Marc; Golbourn, Brian; Chornenkyy, Yevgen; Gajadhar, Aaron; Fernandez, Nestor A.; Clarke, Ian D.; Barszczyk, Mark S.; Pajovic, Sanja; Ternamian, Christian; Head, Renee; Sabha, Nesrin; Sobol, Robert W.; Taylor, Michael D; Rutka, James T.; Jones, Chris; Dirks, Peter B.; Zadeh, Gelareh; Hawkins, Cynthia

2014-01-01

Alkylating agents are a frontline therapy for the treatment of several aggressive cancers including pediatric glioblastoma, a lethal tumor in children. Unfortunately, many tumors are resistant to this therapy. We sought to identify ways of sensitizing tumor cells to alkylating agents while leaving normal cells unharmed; increasing therapeutic response while minimizing toxicity. Using a siRNA screen targeting over 240 DNA damage response genes, we identified novel sensitizers to alkylating agents. In particular the base excision repair (BER) pathway, including 3-methylpurine-DNA glycosylase (MPG), as well as ataxia telangiectasia mutated (ATM) were identified in our screen. Interestingly, we identified MPG as a direct novel substrate of ATM. ATM-mediated phosphorylation of MPG was required for enhanced MPG function. Importantly, combined inhibition or loss of MPG and ATM resulted in increased alkylating agent-induced cytotoxicity in vitro and prolonged survival in vivo. The discovery of the ATM-MPG axis will lead to improved treatment of alkylating agent-resistant tumors. PMID:25100205

Critical loads of atmospheric deposition to Adirondack lake watersheds: A guide for policymakers

USGS Publications Warehouse

Burns, Douglas A.; Sullivan, Timothy J.

2015-01-01

Acid deposition is sometimes referred to as “acid rain,” although part of the acid load reaches the surface by means other than rainfall. In the eastern U.S., acid deposition consists of several forms of sulfur and nitrogen that largely originate as emissions to the atmosphere from sources such as electricity-generating facilities (coal, oil, and natural gas), diesel- and gasoline-burning vehicles, some agricultural activities, and smokestack industries. Acid deposition is known to cause deleterious effects to sensitive ecosystems of which the Adirondack region of New York State provides several well-known and well-studied examples. This largely forested region includes abundant lakes, streams, and wetlands and possesses several landscape features that result in high ecosystem sensitivity to acid deposition. These features include bedrock that weathers slowly, steep slopes, and thin, naturally acidic soils. An ecosystem is described as sensitive to, or affected by, acid deposition if prolonged exposure to acid deposition has resulted in detrimental ecosystem effects. Soils, streams, and lakes that are less sensitive are better able to buffer acid deposition. A principal reason that acidification is a concern for resource managers is because of the changes induced in native biota and their habitat on land and in water. As the chemistry of soils and surface waters in sensitive landscapes changes in response to prolonged exposure to acid deposition, organisms that cannot tolerate high acidity, such as sugar maple trees and many species of fish and aquatic insects, may be gradually eliminated from the ecosystem. Other biota such as red spruce may experience increased stress and reduced growth rates as a result of acidification, exposing these species to increased susceptibility to disease and other natural stressors and perhaps increased mortality. The ecological effects of acid deposition have been documented by extensive research that began in the U.S. in the 1970s and continues today. This report does not provide a detailed discussion of these ecological effects, but interested readers can refer to four publications that provide good summaries of current scientific knowledge of these effects, including extensive reference to previous research in the Adirondacks (Driscoll et al. 2001, Jenkins et al. 2007, Burns et al. 2011, Sullivan 2015).

Chronic physical illness and mental health in children. Results from a large-scale population study.

PubMed

Hysing, Mari; Elgen, Irene; Gillberg, Christopher; Lie, Stein Atle; Lundervold, Astri J

2007-08-01

The aim of the present study was to evaluate the sensitivity and specificity of the Strengths and Difficulties Questionnaire (SDQ) in detecting emotional and behavioural problems among children with chronic illness (CI). Parents and teachers of a population of primary school children in Norway (n = 9430) completed a questionnaire including the SDQ, and a question about chronic illness. A total of 74% (n = 7007) of the parents participated. A sub-sample (n = 1040) was given a psychiatric diagnostic evaluation according to the Development and Well-Being Assessment (DAWBA). According to parent reports, 537 (8%) children had a CI. The SDQ revealed an increased risk of emotional and behavioural problems in children with CI as compared with non-CI peers, both among boys (OR = 2.10 CI 95% 1.56-2.83) and girls (OR = 2.11 CI 95% 1.49-2.99). Children with CI also showed an increased risk of psychiatric disorder as assessed by the DAWBA (OR = 1.70 CI 95% 1.04-2.85). Both the sensitivity and specificity of the SDQ in predicting a psychiatric diagnosis were high, even when only information from parents was included. Children with CI in the general population are at increased risk of behavioural and emotional problems and psychiatric disorders. Given its high sensitivity and specificity the SDQ might work well as a screening instrument for behaviour/emotional problems and psychiatric disorder in children with CI.

Nicotine behavioral pharmacology: clues from planarians

PubMed Central

Rawls, Scott M.; Patil, Tanvi; Tallarida, Christopher S.; Baron, Steven; Kim, Myongji; Song, Kevin; Ward, Sara; Raffa, Robert B.

2011-01-01

Background Nicotine is one of the world’s most addictive substances and the primary reason that humans inhale tobacco smoke. The pharmacological effects of nicotine can be investigated in planarians, aquatic flatworms that possess an integrated neural network including cephalic ganglia that some consider the earliest “brain” and spinal cord. Here, we tested the hypothesis that nicotine exposure elicits mammalian-like behaviors in planarians. Methods Planarian motility and stereotypy (C-shape hyperkinesias) were quantified following acute nicotine exposure. During repeated nicotine exposure, we investigated the presence of withdrawal, tolerance, behavioral sensitization, and environmental place conditioning. Results Acute nicotine exposure increased stereotypical activity and elicited biphasic effects on motility. A low concentration (0.01 mM) increased motility whereas higher concentrations (0.3 – 10 mM) elicited the opposite effect. Planarians exposed to nicotine (0.03 mM) for 60 min and then tested in water displayed reduced motility that was not observed during exposure to water, acute nicotine, or continuous nicotine. Nicotine-treated planarians withdrawn from the drug for 3 days before being challenged with nicotine displayed behavioral sensitization at low concentrations (0.1, 0.3 mM) but tolerance at higher concentrations (1, 3 mM). Planarians conditioned with nicotine in the ambient light (non-preferred environment) displayed a reduction in their natural preference for a dark environment. Conclusions The present results suggest nicotine elicits mammalian-like effects in planarians, including decreased motility and increased stereotypy following acute administration and abstinence-induced withdrawal, behavioral sensitization, tolerance, and place conditioning during repeated exposure. PMID:21530106

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bae, Soo Ya; Jeong, Jaein I.; Park, R.

We examine the effect of anthropogenic aerosols on the weekly variability of precipitation in Korea in summer 2004 by using Weather Research and Forecasting (WRF) and Community Multiscale Air Quality (CMAQ) models. We con-duct two WRF simulations including a baseline simulation with empirically based cloud condensation nuclei (CCN) number concentrations and a sensitivity simulation with our implementation to account for the effect of aerosols on CCN number concentrations. The first simulation underestimates observed precipitation amounts, particularly in northeastern coastal areas of Korea, whereas the latter shows higher precipitation amounts that are in better agree-ment with the observations. In addition, themore » sensitivity model with the aerosol effects reproduces the observed weekly variability, particularly for precipitation frequency with a high R at 0.85, showing 20% increase of precipita-tion events during the weekend than those during weekdays. We find that the aerosol effect results in higher CCN number concentrations during the weekdays and a three-fold increase of the cloud water mixing ratio through en-hanced condensation. As a result, the amount of warm rain is generally suppressed because of the low auto-conversion process from cloud water to rain water under high aerosol conditions. The inefficient conversion, how-ever, leads to higher vertical development of clouds in the mid-atmosphere with stronger updrafts in the sensitivity model, which increases by 21% cold-phase hydrometeors including ice, snow, and graupel relative to the baseline model and ultimately results in higher precipitation amounts in summer.« less

Light adaptation alters inner retinal inhibition to shape OFF retinal pathway signaling

PubMed Central

Mazade, Reece E.

2016-01-01

The retina adjusts its signaling gain over a wide range of light levels. A functional result of this is increased visual acuity at brighter luminance levels (light adaptation) due to shifts in the excitatory center-inhibitory surround receptive field parameters of ganglion cells that increases their sensitivity to smaller light stimuli. Recent work supports the idea that changes in ganglion cell spatial sensitivity with background luminance are due in part to inner retinal mechanisms, possibly including modulation of inhibition onto bipolar cells. To determine how the receptive fields of OFF cone bipolar cells may contribute to changes in ganglion cell resolution, the spatial extent and magnitude of inhibitory and excitatory inputs were measured from OFF bipolar cells under dark- and light-adapted conditions. There was no change in the OFF bipolar cell excitatory input with light adaptation; however, the spatial distributions of inhibitory inputs, including both glycinergic and GABAergic sources, became significantly narrower, smaller, and more transient. The magnitude and size of the OFF bipolar cell center-surround receptive fields as well as light-adapted changes in resting membrane potential were incorporated into a spatial model of OFF bipolar cell output to the downstream ganglion cells, which predicted an increase in signal output strength with light adaptation. We show a prominent role for inner retinal spatial signals in modulating the modeled strength of bipolar cell output to potentially play a role in ganglion cell visual sensitivity and acuity. PMID:26912599

Association Between Genetic Polymorphisms and Pain Sensitivity in Patients with Hip Osteoarthritis.

PubMed

Olesen, Anne E; Nielsen, Lecia M; Feddersen, Søren; Erlenwein, Joachim; Petzke, Frank; Przemeck, Michael; Christrup, Lona L; Drewes, Asbjørn M

2018-06-01

Factors such as age, gender, and genetic polymorphisms may explain individual differences in pain phenotype. Genetic associations with pain sensitivity have previously been investigated in osteoarthritis patients, with a focus on the P2X7, TRPV1, and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease, and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system. The aim of this study was to investigate if genetic variants of mu, kappa, and delta opioid receptor genes (OPRM1, OPRK1, and OPRD1) and the catechol-O-methyltransferase gene (COMT) influenced the pain phenotype in patients with osteoarthritis. The frequencies of 17 polymorphisms were examined. Pain sensitivity was assessed preoperatively by (1) hip rotation, (2) contact heat stimulation, (3) conditioned pain modulation effect, and (4) pressure stimulation at the tibia in both the affected and the unaffected leg. Ninety-two patients (mean age 66 years) with unilateral hip osteoarthritis were included in the study. Carriage of the OPRM1 rs589046T allele was found to be associated with increased pain ratings during hip rotation (P = 0.04) and increased conditioned pain modulation (P = 0.049). Carriage of the OPRD1 rs2234918C allele was found to be associated with an increased pain detection threshold to contact heat stimulation (P = 0.001). No other associations were found (all P > 0.05). Results from the present study suggest that, in patients with hip osteoarthritis, genetic variants in OPRM1 and OPRD1 may contribute to the pain phenotype. © 2017 World Institute of Pain.

Higher-eigenmode piezoresponse force microscopy: a path towards increased sensitivity and the elimination of electrostatic artifacts

NASA Astrophysics Data System (ADS)

MacDonald, Gordon A.; DelRio, Frank W.; Killgore, Jason P.

2018-03-01

Piezoresponse force microscopy (PFM) and related bias-induced strain sensing atomic force microscopy techniques provide unique characterization of material-functionality at the nanoscale. However, these techniques are prone to unwanted artifact signals that influence the vibration amplitude of the detecting cantilever. Here, we show that higher-order contact resonance eigenmodes can be readily excited in PFM. The benefits of using the higher-order eigenmodes include absolute sensitivity enhancement, electrostatic artifact reduction, and lateral versus normal strain decoupling. This approach can significantly increase the proportion of total signal arising from desired strain (as opposed to non-strain artifacts) in measurements with cantilevers exhibiting typical, few N m‑1 spring constants to cantilevers up to 1000× softer than typically used.

Digital breast tomosynthesis for breast cancer screening and diagnosis in women with dense breasts - a systematic review and meta-analysis.

PubMed

Phi, Xuan-Anh; Tagliafico, Alberto; Houssami, Nehmat; Greuter, Marcel J W; de Bock, Geertruida H

2018-04-03

This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis. Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity. Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%-90%) versus DM alone (69%-86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02-1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20-1.47 for retrospective studies; RR: 1.52, 95% CI 1.08-2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64-0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76-1.63). In women with mammographically dense breasts, DBT+/-DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/-DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.

Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus.

PubMed

Whitehead, N; White, H

2013-04-01

Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes. Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors. Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200-500 mg) significantly increased blood glucose concentrations by 16-28% of the area under the curve (AUC) and insulin concentrations by 19-48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14-37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400-500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC. Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger-scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

Lepidoglyphus destructor acarus in the urban house environment.

PubMed

Juliá, J C; Martorell, A; Ventas, P; Cerdá, J C; Torró, I; Carreira, J; Guinot, E; Sanz, J; Alvarez, V

1995-01-01

To assess the presence of Lepidoglyphus destructor in the household environment of sensitized children living in an urban environment, samples of house dust were collected at the homes where two groups of patients were living, as well as in two bakeries in the city of Valencia, which were taken as a reference. Patients were divided into two groups. Group A included atopic children suffering from rhinitis and/or asthma, who were sensitized to L. destructor, as proven by prick test and specific IgE (CAP). Group B included children with the same features as those included in Group A, who were sensitized to Dermatophagoides pteronyssinus, with prick and CAP tests showing no significant sensitization to L. destructor. The samples of dust were analyzed, and the amounts of Der p I, Der f I, Der II and Lep d I per gram of dust were assessed through a solid-phase ELISA with monoclonal antibodies. In Group A, all patients but two showed a sensitization to D. pteronyssinus by prick test and serum IgE. At the homes of the patients from both groups, significant levels of Dermatophagoides were found. In Group A, only three houses showed levels of L. destructor which were comparable to those found in bakeries. Lep d I was not found in the houses of Group B patients. This means that a sensitization to L. destructor, as assessed with full extracts, is not always an indicator of its presence at the patient's house environment; it may rather refer to cross-reactivity to Dermatophagoides. Thus, availability of the main antigen Lep d I seems necessary to increase the specificity of the allergologic study.

Verification bias: an under-recognized source of error in assessing the efficacy of MRI of the meniscii.

PubMed

Richardson, Michael L; Petscavage, Jonelle M

2011-11-01

The sensitivity and specificity of magnetic resonance imaging (MRI) for diagnosis of meniscal tears has been studied extensively, with tears usually verified by surgery. However, surgically unverified cases are often not considered in these studies, leading to verification bias, which can falsely increase the sensitivity and decrease the specificity estimates. Our study suggests that such bias may be very common in the meniscal MRI literature, and illustrates techniques to detect and correct for such bias. PubMed was searched for articles estimating sensitivity and specificity of MRI for meniscal tears. These were assessed for verification bias, deemed potentially present if a study included any patients whose MRI findings were not surgically verified. Retrospective global sensitivity analysis (GSA) was performed when possible. Thirty-nine of the 314 studies retrieved from PubMed specifically dealt with meniscal tears. All 39 included unverified patients, and hence, potential verification bias. Only seven articles included sufficient information to perform GSA. Of these, one showed definite verification bias, two showed no bias, and four others showed bias within certain ranges of disease prevalence. Only 9 of 39 acknowledged the possibility of verification bias. Verification bias is underrecognized and potentially common in published estimates of the sensitivity and specificity of MRI for the diagnosis of meniscal tears. When possible, it should be avoided by proper study design. If unavoidable, it should be acknowledged. Investigators should tabulate unverified as well as verified data. Finally, verification bias should be estimated; if present, corrected estimates of sensitivity and specificity should be used. Our online web-based calculator makes this process relatively easy. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

Modulating influences of memory strength and sensitivity of the retrieval test on the detectability of the sleep consolidation effect.

PubMed

Schoch, Sarah F; Cordi, Maren J; Rasch, Björn

2017-11-01

Emotionality can increase recall probability of memories as emotional information is highly relevant for future adaptive behavior. It has been proposed that memory processes acting during sleep selectively promote the consolidation of emotional memories, so that neutral memories no longer profit from sleep consolidation after learning. This appears as a selective effect of sleep for emotional memories. However, other factors contribute to the appearance of a consolidation benefit and influence this interpretation. Here we show that the strength of the memory trace before sleep and the sensitivity of the retrieval test after sleep are critical factors contributing to the detection of the benefit of sleep on memory for emotional and neutral stimuli. 228 subjects learned emotional and neutral pictures and completed a free recall after a 12-h retention interval of either sleep or wakefulness. We manipulated memory strength by including an immediate retrieval test before the retention interval in half of the participants. In addition, we varied the sensitivity of the retrieval test by including an interference learning task before retrieval testing in half of the participants. We show that a "selective" benefit of sleep for emotional memories only occurs in the condition with high memory strength. Furthermore, this "selective" benefit disappeared when we controlled for the memory strength before the retention interval and used a highly sensitive retrieval test. Our results indicate that although sleep benefits are more robust for emotional memories, neutral memories similarly profit from sleep after learning when more sensitive indicators are used. We conclude that whether sleep benefits on memory appear depends on several factors, including emotion, memory strength and sensitivity of the retrieval test. Copyright © 2017 Elsevier Inc. All rights reserved.

Utilization of the ex vivo LLNA: BrdU-ELISA to distinguish the sensitizers from irritants in respect of 3 end points-lymphocyte proliferation, ear swelling, and cytokine profiles.

PubMed

Arancioglu, Seren; Ulker, Ozge Cemiloglu; Karakaya, Asuman

2015-01-01

Dermal exposure to chemicals may result in allergic or irritant contact dermatitis. In this study, we performed ex vivo local lymph node assay: bromodeoxyuridine-enzyme-linked immunosorbent assay (LLNA: BrdU-ELISA) to compare the differences between irritation and sensitization potency of some chemicals in terms of the 3 end points: lymphocyte proliferation, cytokine profiles (interleukin 2 [IL-2], interferon-γ (IFN-γ), IL-4, IL-5, IL-1, and tumor necrosis factor α [TNF-α]), and ear swelling. Different concentrations of the following well-known sensitizers and irritant chemicals were applied to mice: dinitrochlorobenzene, eugenol, isoeugenol, sodium lauryl sulfate (SLS), and croton oil. According to the lymph node results; the auricular lymph node weights and lymph node cell counts increased after application of both sensitizers and irritants in high concentrations. On the other hand, according to lymph node cell proliferation results, there was a 3-fold increase in proliferation of lymph node cells (stimulation index) for sensitizer chemicals and SLS in the applied concentrations; however, there was not a 3-fold increase for croton oil and negative control. The SLS gave a false-positive response. Cytokine analysis demonstrated that 4 cytokines including IL-2, IFN-γ, IL-4, and IL-5 were released in lymph node cell cultures, with a clear dose trend for sensitizers whereas only TNF-α was released in response to irritants. Taken together, our results suggest that the ex vivo LLNA: BrdU-ELISA method can be useful for discriminating irritants and allergens. © The Author(s) 2015.

S-Ketamine Rapidly Reverses Synaptic and Vascular Deficits of Hippocampus in Genetic Animal Model of Depression.

PubMed

Ardalan, Maryam; Wegener, Gregers; Rafati, Ali H; Nyengaard, Jens R

2017-03-01

The neurovascular plasticity of hippocampus is an important theory underlying major depression. Ketamine as a novel glutamatergic antidepressant drug can induce a rapid antidepressant effect within hours. In a mechanistic proof of this concept, we examined whether ketamine leads to an increase in synaptogenesis and vascularization within 24 hours after a single injection in a genetic rat model of depression. Flinders Sensitive Line and Flinders Resistant Line rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline. One day later, their behavior was evaluated by a modified forced swim test. Microvessel length was evaluated with global spatial sampling and optical microscopy, whereas the number of asymmetric synapses was quantified through serial section electron microscopy by using physical disector method in the CA1.stratum radiatum area of hippocampus. The immobility time in the forced swim test among Flinders Sensitive Line rats with ketamine treatment was significantly lower compared with Flinders Sensitive Line rats without treatment. The number of nonperforated and perforated synapses was significantly higher in the Flinders Sensitive Line-ketamine vs the Flinders Sensitive Line-vehicle group; however, ketamine did not induce a significant increase in the number of shaft synapses. Additionally, total length of microvessels was significantly increased 1 day after ketamine treatment in Flinders Sensitive Line rats in the hippocampal subregions, including the CA1.stratum radiatum. Our findings indicate that hippocampal vascularization and synaptogenesis is co-regulated rapidly after ketamine, and microvascular elongation may be a supportive factor for synaptic plasticity and neuronal activity. These findings go hand-in-hand with the behavioral observations, where ketamine acts as a potent antidepressant. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Cold hypersensitivity increases with age in mice with sickle cell disease.

PubMed

Zappia, Katherine J; Garrison, Sheldon R; Hillery, Cheryl A; Stucky, Cheryl L

2014-12-01

Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. In addition, both humans and mice with SCD experience heightened cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization or its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Furthermore, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the transient receptor potential melastatin 8 (Trpm8) and transient receptor potential ankyrin 1 (Trpa1) channels, as well as the 2-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk10), and TRAAK (Kcnk4). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes, and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Dimethyl sulfoxide in a 10% concentration has no effect on oxidation stress induced by ovalbumin-sensitization in a guinea-pig model of allergic asthma.

PubMed

Mikolka, P; Mokra, D; Drgova, A; Petras, M; Mokry, J

2012-04-01

In allergic asthma, activated cells produce various substances including reactive oxygen species (ROS). As heterogenic pathophysiology of asthma results to different response to the therapy, testing novel interventions continues. Because of water-insolubility of some potentially beneficial drugs, dimethyl sulfoxide (DMSO) is often used as a solvent. Based on its antioxidant properties, this study evaluated effects of DMSO on mobilization of leukocytes into the lungs, and oxidation processes induced by ovalbumin (OVA)-sensitization in a guinea-pig model of allergic asthma. Guinea-pigs were divided into OVA-sensitized and naive animals. One group of OVA-sensitized animals and one group of naive animals were pretreated with 10% DMSO, the other two groups were given saline. After sacrificing animals, blood samples were taken and total antioxidant status (TAS) in the plasma was determined. Left lungs were saline-lavaged and differential leukocyte count in bronchoalveolar lavage fluid (BAL) was made. Right lung tissue was homogenized, TAS and products of lipid and protein oxidation were determined in the lung homogenate and in isolated mitochondria. OVA-sensitization increased total number of cells and percentages of eosinophils and neutrophils in BAL fluid; increased lipid and protein oxidation in the lung homogenate and mitochondria, and decreased TAS in the lungs and plasma compared with naive animals. However, no differences were observed in DMSO-instilled animals compared to controls. In conclusion, OVA-sensitization increased mobilization of leukocytes into the lungs and elevated production of ROS, accompanied by decrease in TAS. 10% DMSO had no effect on lipid and protein oxidation in a guinea-pig model of allergic asthma.

The resolution sensitivity of the South Asian monsoon and Indo-Pacific in a global 0.35° AGCM

NASA Astrophysics Data System (ADS)

Johnson, Stephanie J.; Levine, Richard C.; Turner, Andrew G.; Martin, Gill M.; Woolnough, Steven J.; Schiemann, Reinhard; Mizielinski, Matthew S.; Roberts, Malcolm J.; Vidale, Pier Luigi; Demory, Marie-Estelle; Strachan, Jane

2016-02-01

The South Asian monsoon is one of the most significant manifestations of the seasonal cycle. It directly impacts nearly one third of the world's population and also has substantial global influence. Using 27-year integrations of a high-resolution atmospheric general circulation model (Met Office Unified Model), we study changes in South Asian monsoon precipitation and circulation when horizontal resolution is increased from approximately 200-40 km at the equator (N96-N512, 1.9°-0.35°). The high resolution, integration length and ensemble size of the dataset make this the most extensive dataset used to evaluate the resolution sensitivity of the South Asian monsoon to date. We find a consistent pattern of JJAS precipitation and circulation changes as resolution increases, which include a slight increase in precipitation over peninsular India, changes in Indian and Indochinese orographic rain bands, increasing wind speeds in the Somali Jet, increasing precipitation over the Maritime Continent islands and decreasing precipitation over the northern Maritime Continent seas. To diagnose which resolution-related processes cause these changes, we compare them to published sensitivity experiments that change regional orography and coastlines. Our analysis indicates that improved resolution of the East African Highlands results in the improved representation of the Somali Jet and further suggests that improved resolution of orography over Indochina and the Maritime Continent results in more precipitation over the Maritime Continent islands at the expense of reduced precipitation further north. We also evaluate the resolution sensitivity of monsoon depressions and lows, which contribute more precipitation over northeast India at higher resolution. We conclude that while increasing resolution at these scales does not solve the many monsoon biases that exist in GCMs, it has a number of small, beneficial impacts.

Sensitivity of Crustaceans to Substrate-Borne Vibration.

PubMed

Roberts, Louise; Breithaupt, Thomas

2016-01-01

There is increasing interest in the responsiveness of crustaceans to vibrations, especially in the context of marine developments where techniques such as pile driving create strong vibrations that are readily transmitted through the seabed. Experiments were undertaken under controlled conditions to investigate the sensitivity of unconditioned crustaceans to substrate-borne vibration. The subjects were exposed to a range of frequencies and amplitudes using the staircase method of presentation to determine the thresholds of response. Behavior varied according to the strength of the stimuli and included bursts of movement and rapid bouts of movement.

Modelling the sensitivity of soil mercury storage to climate-induced changes in soil carbon pools

NASA Astrophysics Data System (ADS)

Hararuk, O.; Obrist, D.; Luo, Y.

2013-04-01

Substantial amounts of mercury (Hg) in the terrestrial environment reside in soils and are associated with soil organic carbon (C) pools, where they accumulated due to increased atmospheric deposition resulting from anthropogenic activities. The purpose of this study was to examine potential sensitivity of surface soil Hg pools to global change variables, particularly affected by predicted changes in soil C pools, in the contiguous US. To investigate, we included a soil Hg component in the Community Land Model based on empirical statistical relationships between soil Hg / C ratios and precipitation, latitude, and clay; and subsequently explored the sensitivity of soil C and soil Hg densities (i.e., areal-mass) to climate scenarios in which we altered annual precipitation, carbon dioxide (CO2) concentrations and temperature. Our model simulations showed that current sequestration of Hg in the contiguous US accounted for 15 230 metric tons of Hg in the top 0-40 cm of soils, or for over 300 000 metric tons when extrapolated globally. In the simulations, US soil Hg pools were most sensitive to changes in precipitation because of strong effects on soil C pools, plus a direct effect of precipitation on soil Hg / C ratios. Soil Hg pools were predicted to increase beyond present-day values following an increase in precipitation amounts and decrease following a reduction in precipitation. We found pronounced regional differences in sensitivity of soil Hg to precipitation, which were particularly high along high-precipitation areas along the West and East Coasts. Modelled increases in CO2 concentrations to 700 ppm stimulated soil C and Hg accrual, while increased air temperatures had small negative effects on soil C and Hg densities. The combined effects of increased CO2, increased temperature and increased or decreased precipitation were strongly governed by precipitation and CO2 showing pronounced regional patterns. Based on these results, we conclude that the combination of precipitation and CO2 should be emphasised when assessing how climate-induced changes in soil C may affect sequestration of Hg in soils.

Association between pet ownership and the sensitization to pet allergens in adults with various allergic diseases.

PubMed

Park, Yong-Bum; Mo, Eun-Kyung; Lee, Jae-Young; Kim, Joo-Hee; Kim, Cheol-Hong; Hyun, In-Gyu; Choi, Jeong-Hee

2013-09-01

As pet ownership increases, sensitization to animal allergens due to domestic exposure is a concern. Sensitization to animal allergens may occur from indirect exposure, as well as direct ownership of animals. However, there have been conflicting results regarding the association between pet ownership and sensitization to animal allergens in adults. In total, 401 patients with various allergic diseases were enrolled in this study. We performed skin prick tests with 55 common inhalant and food allergens, including dog, cat, and rabbit allergens. A mean wheal diameter of 3 mm or greater was considered a positive reaction. The exposure modality to each animal allergen was investigated using a questionnaire and included present ownership, past ownership, occupational exposure, occasional exposure, contact with pet owner, and no contact. Present ownership, past ownership, occupational, and occasional exposure were regarded as direct exposure. The sensitization rate for animal allergens was 20.4% for dog, 15.0% for cat, and 9.0% for rabbit. Direct exposure to dogs (72.0%) was significantly higher than that of other animals (18.4% for cats and 16.7% for rabbits), whereas 'no contact' with cats (78.3%) and rabbits (83.3%) was significantly higher than with dogs (26.8%; P<0.0001). Independent risk factors for sensitization to animal allergens were sensitization to Dermatophagoides pteronyssinus (OR=2.4, P=0.052), Dermatophagoides farinae (OR=5.1, P<0.001), cat (OR=4.4, P<0.0001), and direct exposure to dogs (OR=1.5, P=0.029) for dog, and sensitization to dog (OR=4.4, P<0.0001) and rabbit (OR=2.6, P=0.036) for cats. Finally, for rabbits, the independent risk factor was sensitization to Alternaria (OR=6.0, P<0.002). These results suggest that direct exposure to dogs contributes to the sensitization to dog allergens in patients with allergic diseases, whereas indirect exposure to cats and rabbits may induce sensitization to each animal's allergen.

Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome

PubMed Central

Theodorou, Vassilia; Belgnaoui, Afifa Ait; Agostini, Simona; Eutamene, Helene

2014-01-01

The last ten years’ wide progress in the gut microbiota phylogenetic and functional characterization has been made evidencing dysbiosis in several gastrointestinal diseases including inflammatory bowel diseases and irritable bowel syndrome (IBS). IBS is a functional gut disease with high prevalence and negative impact on patient’s quality of life characterized mainly by visceral pain and/or discomfort, representing a good paradigm of chronic gut hypersensitivity. The IBS features are strongly regulated by bidirectional gut-brain interactions and there is increasing evidence for the involvement of gut bacteria and/or their metabolites in these features, including visceral pain. Further, gut microbiota modulation by antibiotics or probiotics has been promising in IBS. Mechanistic data provided mainly by animal studies highlight that commensals or probiotics may exert a direct action through bacterial metabolites on sensitive nerve endings in the gut mucosa, or indirect pathways targeting the intestinal epithelial barrier, the mucosal and/or systemic immune activation, and subsequent neuronal sensitization and/or activation. PMID:25184834

Hyperspectral data analysis procedures with reduced sensitivity to noise

NASA Technical Reports Server (NTRS)

Landgrebe, David A.

1993-01-01

Multispectral sensor systems have become steadily improved over the years in their ability to deliver increased spectral detail. With the advent of hyperspectral sensors, including imaging spectrometers, this technology is in the process of taking a large leap forward, thus providing the possibility of enabling delivery of much more detailed information. However, this direction of development has drawn even more attention to the matter of noise and other deleterious effects in the data, because reducing the fundamental limitations of spectral detail on information collection raises the limitations presented by noise to even greater importance. Much current effort in remote sensing research is thus being devoted to adjusting the data to mitigate the effects of noise and other deleterious effects. A parallel approach to the problem is to look for analysis approaches and procedures which have reduced sensitivity to such effects. We discuss some of the fundamental principles which define analysis algorithm characteristics providing such reduced sensitivity. One such analysis procedure including an example analysis of a data set is described, illustrating this effect.

Acute airway effects of airborne formaldehyde in sensitized and non-sensitized mice housed in a dry or humid environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larsen, Søren Thor, E-mail: stl@nrcwe.dk; Wolkoff, Peder, E-mail: pwo@nrcwe.dk; Hammer, Maria, E-mail: mha@nrcwe.dk

We investigated the role of air humidity and allergic sensitization on the acute airway response to inhaled formaldehyde (FA) vapor. Mice were sensitized to the immunogen ovalbumin (OVA) by three intraperitoneal injections followed by two aerosol challenges, giving rise to allergic airway inflammation. Control mice were sham sensitized by saline injections and challenged by saline aerosols. Once sensitized, the mice were housed at high (85–89%) or low (< 10%) relative humidity, respectively for 48 h prior to a 60-min exposure to either 0.4, 1.8 or about 5 ppm FA. Before, during and after exposure, breathing parameters were monitored. These includedmore » the specific markers of nose and lung irritations as well as the expiratory flow rate, the latter being a marker of airflow limitation. The sensory irritation response in the upper airways was not affected by allergic inflammation or changes in humidity. At high relative humidity, the OVA-sensitized mice had a decreased expiratory airflow rate compared to the saline control mice after exposure to approximately 5 ppm FA. This is in accordance with the observations that asthmatics are more sensitive than non-asthmatics to higher concentrations of airway irritants including FA. In the dry environment, the opposite trend was seen; here, the saline control mice had a significantly decreased expiratory airflow rate compared to OVA-sensitized mice when exposed to 1.8 and 4 ppm FA. We speculate that increased mucus production in the OVA-sensitized mice has increased the “scrubber effect” in the nose, consequently protecting the conducting and lower airways. - Highlights: ► Role of air humidity and allergy on sensitivity to an airway irritant was studied. ► In the humid environment, allergy amplified the effects of formaldehyde. ► In the dry environment, allergy reduced the effect of formaldehyde. ► Neither allergy nor humidity changed the formaldehyde-induced nasal irritation.« less

Refractive index sensors based on the fused tapered special multi-mode fiber

NASA Astrophysics Data System (ADS)

Fu, Xing-hu; Xiu, Yan-li; Liu, Qin; Xie, Hai-yang; Yang, Chuan-qing; Zhang, Shun-yang; Fu, Guang-wei; Bi, Wei-hong

2016-01-01

In this paper, a novel refractive index (RI) sensor is proposed based on the fused tapered special multi-mode fiber (SMMF). Firstly, a section of SMMF is spliced between two single-mode fibers (SMFs). Then, the SMMF is processed by a fused tapering machine, and a tapered fiber structure is fabricated. Finally, a fused tapered SMMF sensor is obtained for measuring external RI. The RI sensing mechanism of tapered SMMF sensor is analyzed in detail. For different fused tapering lengths, the experimental results show that the RI sensitivity can be up to 444.517 81 nm/RIU in the RI range of 1.334 9—1.347 0. The RI sensitivity is increased with the increase of fused tapering length. Moreover, it has many advantages, including high sensitivity, compact structure, fast response and wide application range. So it can be used to measure the solution concentration in the fields of biochemistry, health care and food processing.

Upregulation of circulating IL-15 by treadmill running in healthy individuals: is IL-15 an endocrine mediator of the beneficial effects of endurance exercise?

PubMed

Tamura, Yoshiaki; Watanabe, Keiichi; Kantani, Tomomi; Hayashi, Junichi; Ishida, Nobuhiko; Kaneki, Masao

2011-01-01

The beneficial effects of endurance exercise include insulin-sensitization and reduction of fat mass. Limited knowledge is available about the mechanisms by which endurance exercise exerts the salutary effects. Myokines, cytokines secreted by skeletal muscle, have been recognized as a potential mediator. Recently, a role of skeletal muscle-derived interleukin-15 (IL-15) in improvement of fat-lean body mass composition and insulin sensitivity has been proposed. Yet, previous studies have reported that endurance training does not increase production or secretion of IL-15 in skeletal muscle. Here, we show that in opposition to previous findings, 30-min treadmill running at 70% of age-predicted maximum heart rate resulted in a significant increase in circulating IL-15 level in untrained healthy young men. These findings suggest that IL-15 might play a role in the systemic anti-obesogenic and insulin-sensitizing effects of endurance exercise, not only as a paracrine and autocrine but also as an endocrine factor.

The driver vigilance telemetric control system (DVTCS): investigating sensitivity to experimentally induced sleep loss and fatigue.

PubMed

Dorrian, Jillian; Lamond, Nicole; Kozuchowski, Karolina; Dawson, Drew

2008-11-01

Vigilance technologies are used in the Australian rail industry to address the risks associated with driver sleepiness and fatigue. The aim of this study was to investigate whether a new device, designed to detect lowered states of arousal using electrodermal activity (EDA), would be sensitive to experimentally induced sleepiness and fatigue. Fifteen individuals (7 of them female, 9 male; 18-32 years of age) spent 3 consecutive days in the laboratory, which included 1 night of sustained wakefulness (28 h). The participants completed a 10-min psychomotor vigilance task (PVT) and fatigue and sleepiness ratings every 2 h, and a 30-min driving simulator every 4 h. As was expected, simulated driving, PVT, and subjective ratings indicated increasing levels of sleepiness and fatigue during sustained wakefulness. The EDA device output did not coincide with these findings. The results indicated that the EDA indicator was not sensitive to increased sleepiness and fatigue at the levels produced in the present study.

Contrasting effects of elevated CO2 and warming on temperature sensitivity of soil organic matter decomposition in a Chinese paddy field.

PubMed

Chen, Zhaozhi; Wang, Bingyu; Wang, Jinyang; Pan, Genxing; Xiong, Zhengqin

2015-10-01

Climate changes including elevated CO2 and temperature have been known to affect soil carbon (C) storage, while the effects of climate changes on the temperature sensitivity of soil organic matter (SOM) are unclear. A 365-day laboratory incubation was used to investigate the temperature sensitivity for decomposition of labile (Q 10-L) and recalcitrant (Q 10-R) SOMs by comparing the time required to decompose a given amount of C at 25 and 35 °C. Soils were collected from a paddy field that was subjected to four treatments: ambient CO2 and temperature, elevated CO2 (500 μmol/mol), enhanced temperature (+2 °C), and their combination. The results showed that the temperature sensitivity of SOM decomposition increased with increasing SOM recalcitrance in this paddy soil (Q 10-L = 2.21 ± 0.16 vs. Q 10-R = 2.78 ± 0.42; mean ± SD). Elevated CO2 and enhanced temperature showed contrasting effects on the temperature sensitivity of SOM decomposition. Elevated CO2 stimulated Q 10-R but had no effect on Q 10-L; in contrast, enhanced temperature increased Q 10-L but had no effect on Q 10-R. Furthermore, the elevated CO2 combined with enhanced temperature treatment significantly increased Q 10-L and Q 10-R by 18.9 and 10.2 %, respectively, compared to the ambient conditions. Results suggested that the responses of SOM to temperature, especially for the recalcitrant SOM pool, were altered by climate changes. The greatly enhanced temperature sensitivity of SOM decomposition by elevated CO2 and temperature indicates that more CO2 will be released to the atmosphere and losses of soil C may be even greater than that previously expected in paddy field.

Methionine Deprivation Induces a Targetable Vulnerability in Triple-Negative Breast Cancer Cells by Enhancing TRAIL Receptor-2 Expression.

PubMed

Strekalova, Elena; Malin, Dmitry; Good, David M; Cryns, Vincent L

2015-06-15

Many neoplasms are vulnerable to methionine deficiency by mechanisms that are poorly understood. Because gene profiling studies have revealed that methionine depletion increases TNF-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) mRNA, we postulated that methionine stress sensitizes breast cancer cells to proapoptotic TRAIL-R2 agonists. Human triple (ER/PR/HER2)-negative breast carcinoma cell lines were cultured in control or methionine-free media. The effects of methionine depletion on TRAIL receptor expression and sensitivity to chemotherapy or a humanized agonistic TRAIL-R2 monoclonal antibody (lexatumumab) were determined. The melanoma-associated antigen MAGED2 was silenced to delineate its functional role in sensitizing TNBC cells to methionine stress. An orthotopic TNBC model was utilized to evaluate the effects of dietary methionine deficiency, lexatumumab, or the combination. Methionine depletion sensitized TNBC cells to lexatumumab-induced caspase activation and apoptosis by increasing TRAIL-R2 mRNA and cell surface expression. MCF-10A cells transformed by oncogenic H-Ras, but not untransformed cells, and matrix-detached TNBC cells were highly sensitive to the combination of lexatumumab and methionine depletion. Proteomics analyses revealed that MAGED2, which has been reported to reduce TRAIL-R2 expression, was suppressed by methionine stress. Silencing MAGED2 recapitulated features of methionine deprivation, including enhanced mRNA and cell surface expression of TRAIL receptors and increased sensitivity to TRAIL receptor agonists. Dietary methionine deprivation enhanced the antitumor effects of lexatumumab in an orthotopic metastatic TNBC model. Methionine depletion exposes a targetable defect in TNBC cells by increasing TRAIL-R2 expression. Our findings provide the foundation for a clinical trial combining dietary methionine restriction and TRAIL-R2 agonists. Clin Cancer Res; 21(12); 2780-91. ©2015 AACR. ©2015 American Association for Cancer Research.

Aerial spray adjuvants for herbicidal drift control.

Treesearch

Gratkowski H.; Stewart R.

1973-01-01

Increased public concern about pesticides requires that foresters reduce drift and insure precise application of herbicides to the areas requiring treatment. Drift control is necessary near waterways and other ecologically sensitive areas. This publication discusses available drift control adjuvants for herbicidal sprays. These include invert emulsions, thickening...

Multicultural Issues in Child Care.

ERIC Educational Resources Information Center

Gonzalez-Mena, Janet

This volume focuses on cultural differences relevant to all child-care-giving settings, including day care, nursery, and preschool programs. Based on respect for cultural pluralism, this concise supplementary text is designed to increase caregiver sensitivity to different cultural child-care practices and values and to improve communication and…

[Epidemiology of contact dermatitis: prevalence of sensitization to different allergens and associated factors].

PubMed

Bordel-Gómez, Ma T; Miranda-Romero, A; Castrodeza-Sanz, J

2010-01-01

In clinical practice, contact dermatitis is a relatively common skin complaint, whose prevalence has increased in recent years. Study by patch testing is essential for diagnosis of contact sensitization. To study the prevalence of sensitization to different allergens in a standard battery and observe the influence of different epidemiological and clinical variables on contact sensitization. A large number of allergens were included in our battery in order to detect new sensitizations whose prevalence might justify further study. This was a retrospective, observational, epidemiological study of 1092 patients, conducted in our skin allergy unit between January 1, 2000, and December 31, 2005. All patients were studied with a battery of 51 allergens. We assessed the following variables: sex, age, type of referral, occupation, site and course of skin lesions, personal and family history of atopy, positive patch tests, clinical significance, diagnosis, source of sensitization, and occupational relationship. At least 1 positive result was found in 55% of the patients, and 55.7% presented atopic dermatitis in one of its clinical variants: allergic contact dermatitis (28.2%), irritant contact dermatitis (20.1%), photoallergic contact dermatitis (2.2%), and phototoxic contact dermatitis (1.2%). The most prevalent allergens were nickel sulfate (29.3%), palladium chloride (11.7%), cobalt chloride (10.8%), potassium dichromate (7.5%), fragrance blends (6.3%), and p-phenylenediamine (6.1%). A positive occupational relationship was found in 41.1%, and 21.3% of the patients studied were diagnosed with occupational contact dermatitis. Metal workers, construction workers, and professional hairdressers were the most strongly represented groups. The most common source of sensitization was contact with metallic objects, followed by drugs, cosmetics, and rubber items. Female sex was the only independent variable that had a significant influence on the risk of contact sensitization in general. Women became sensitized at a younger age than men, and the frequency of positive results in the patch tests increased with age, reaching a maximum at between 60 and 69 years of age, when the greatest rate of sensitization occurred. Comparison of our results with other Spanish data showed a progressive and constant increase in sensitization to nickel sulfate, fragrance blends, balsam of Peru, and rosin, and a decrease in sensitization to potassium dichromate. The inclusion of new allergens such as palladium chloride, diallyl disulfide, and p-toluene sulfonamide formaldehyde improved the sensitivity of the standard battery in the detection of contact sensitization. We therefore recommend further studies of these allergens.

The sensitivity of laboratory tests assessing driving related skills to dose-related impairment of alcohol: A literature review.

PubMed

Jongen, S; Vuurman, E F P M; Ramaekers, J G; Vermeeren, A

2016-04-01

Laboratory tests assessing driving related skills can be useful as initial screening tools to assess potential drug induced impairment as part of a standardized behavioural assessment. Unfortunately, consensus about which laboratory tests should be included to reliably assess drug induced impairment has not yet been reached. The aim of the present review was to evaluate the sensitivity of laboratory tests to the dose dependent effects of alcohol, as a benchmark, on performance parameters. In total, 179 experimental studies were included. Results show that a cued go/no-go task and a divided attention test with primary tracking and secondary visual search were consistently sensitive to the impairing effects at medium and high blood alcohol concentrations. Driving performance assessed in a simulator was less sensitive to the effects of alcohol as compared to naturalistic, on-the-road driving. In conclusion, replicating results of several potentially useful tests and their predictive validity of actual driving impairment should deserve further research. In addition, driving simulators should be validated and compared head to head to naturalistic driving in order to increase construct validity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Deoxycytidine Deaminase-Deficient Escherichia coli Strains Display Acute Sensitivity to Cytidine, Adenosine, and Guanosine and Increased Sensitivity to a Range of Antibiotics, Including Vancomycin

PubMed Central

Kang, Tina Manzhu; Yuan, Jessica; Zhou, Alice; Beppler, Casey

2014-01-01

We show here that deoxycytidine deaminase (DCD)-deficient mutants of Escherichia coli are hypersensitive to killing by exogenous cytidine, adenosine, or guanosine, whereas wild-type cells are not. This hypersensitivity is reversed by exogenous thymidine. The mechanism likely involves the allosteric regulation of ribonucleotide reductase and severe limitations of the dTTP pools, resulting in thymineless death, the phenomenon of cell death due to thymidine starvation. We also report here that DCD-deficient mutants of E. coli are more sensitive to a series of different antibiotics, including vancomycin, and we show synergistic killing with the combination of vancomycin and cytidine. One possibility is that a very low, subinhibitory concentration of vancomycin enters Gram-negative cells and that this concentration is potentiated by chromosomal lesions resulting from the thymineless state. A second possibility is that the metabolic imbalance resulting from DCD deficiency affects the assembly of the outer membrane, which normally presents a barrier to drugs such as vancomycin. We consider these findings with regard to ideas of rendering Gram-negative bacteria sensitive to drugs such as vancomycin. PMID:24633874

System and process for pulsed multiple reaction monitoring

DOEpatents

Belov, Mikhail E

2013-05-17

A new pulsed multiple reaction monitoring process and system are disclosed that uses a pulsed ion injection mode for use in conjunction with triple-quadrupole instruments. The pulsed injection mode approach reduces background ion noise at the detector, increases amplitude of the ion signal, and includes a unity duty cycle that provides a significant sensitivity increase for reliable quantitation of proteins/peptides present at attomole levels in highly complex biological mixtures.

Complement C5a-C5aR interaction enhances MAPK signaling pathway activities to mediate renal injury in trichloroethylene sensitized BALB/c mice.

PubMed

Zhang, Jia-xiang; Zha, Wan-sheng; Ye, Liang-ping; Wang, Feng; Wang, Hui; Shen, Tong; Wu, Chang-hao; Zhu, Qi-xing

2016-02-01

We have previously shown complement activation as a possible mechanism for trichloroethylene (TCE) sensitization, leading to multi-organ damage including the kidneys. In particular, excessive deposition of C5 and C5b-9-the membrane attack complex, which can generate significant tissue damage, was observed in the kidney tissue after TCE sensitization. The present study tested the hypothesis that anaphylatoxin C5a binding to its receptor C5aR mediates renal injury in TCE-sensitized BALB/c mice. BALB/c mice were sensitized through skin challenge with TCE, with or without pretreatment by the C5aR antagonist W54011. Kidney histopathology and the renal functional test were performed to assess renal injury, and immunohistochemistry and fluorescent labeling were carried out to assess C5a and C5aR expressions. TCE sensitization up-regulated C5a and C5aR expressions in kidney tissue, generated inflammatory infiltration, renal tubule damage, glomerular hypercellularity and impaired renal function. Antagonist pretreatment blocked C5a binding to C5aR and attenuated TCE-induced tissue damage and renal dysfunction. TCE sensitization also caused the deposition of major pro-inflammatory cytokines IL-2, TNF-α and IFN-γ in the kidney tissue (P < 0.05); this was accompanied by increased expression of P-p38, P-ERK and P-JNK proteins (P < 0.05). Pretreatment with the C5aR antagonist attenuated the increase of expression of P-p38, P-ERK and P-JNK proteins (P < 0.05) and also consistently reduced the TCE sensitization-induced increase of IL-2, TNF-α and IFN-γ (P < 0.05). These data identify C5a binding to C5aR, MAP kinase activation, and inflammatory cytokine release as a novel mechanism for complement-mediated renal injury by sensitization with TCE or other environmental chemicals. Copyright © 2015 John Wiley & Sons, Ltd.

UTI diagnosis and antibiogram using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Kastanos, Evdokia; Kyriakides, Alexandros; Hadjigeorgiou, Katerina; Pitris, Constantinos

2009-07-01

Urinary tract infection diagnosis and antibiogram require a 48 hour waiting period using conventional methods. This results in ineffective treatments, increased costs and most importantly in increased resistance to antibiotics. In this work, a novel method for classifying bacteria and determining their sensitivity to an antibiotic using Raman spectroscopy is described. Raman spectra of three species of gram negative Enterobacteria, most commonly responsible for urinary tract infections, were collected. The study included 25 samples each of E.coli, Klebsiella p. and Proteus spp. A novel algorithm based on spectral ratios followed by discriminant analysis resulted in classification with over 94% accuracy. Sensitivity and specificity for the three types of bacteria ranged from 88-100%. For the development of an antibiogram, bacterial samples were treated with the antibiotic ciprofloxacin to which they were all sensitive. Sensitivity to the antibiotic was evident after analysis of the Raman signatures of bacteria treated or not treated with this antibiotic as early as two hours after exposure. This technique can lead to the development of new technology for urinary tract infection diagnosis and antibiogram with same day results, bypassing urine cultures and avoiding all undesirable consequences of current practice.

Urinary tract infection diagnosis and response to antibiotics using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Kastanos, Evdokia; Kyriakides, Alexandros; Hadjigeorgiou, Katerina; Pitris, Constantinos

2009-02-01

Urinary tract infection diagnosis and antibiogram require a 48 hour waiting period using conventional methods. This results in ineffective treatments, increased costs and most importantly in increased resistance to antibiotics. In this work, a novel method for classifying bacteria and determining their sensitivity to an antibiotic using Raman spectroscopy is described. Raman spectra of three species of gram negative Enterobacteria, most commonly responsible for urinary tract infections, were collected. The study included 25 samples each of E.coli, Klebsiella p. and Proteus spp. A novel algorithm based on spectral ratios followed by discriminant analysis resulted in classification with over 94% accuracy. Sensitivity and specificity for the three types of bacteria ranged from 88-100%. For the development of an antibiogram, bacterial samples were treated with the antibiotic ciprofloxacin to which they were all sensitive. Sensitivity to the antibiotic was evident after analysis of the Raman signatures of bacteria treated or not treated with this antibiotic as early as two hours after exposure. This technique can lead to the development of new technology for urinary tract infection diagnosis and antibiogram with same day results, bypassing urine cultures and avoiding all undesirable consequences of current practice.

Radiosensitization: enhancing the radiation inactivation of foodborne bacteria

NASA Astrophysics Data System (ADS)

Borsa, J.; Lacroix, M.; Ouattara, B.; Chiasson, F.

2004-09-01

Irradiation of meat products to kill pathogens can be limited by radiation-induced detriment of sensory quality. Since such detriment is directly related to dose, one approach to reduce it is by devising means to lower the dose of radiation required for processing. Increasing the radiation sensitivity of the target microorganisms would lower the dose required for a given level of microbial kill. In this work, the radiation sensitivities of inoculated Escherichia coli and Salmonella typhi in ground beef were examined under a variety of conditions. Results showed that specific manipulations of treatment conditions significantly increased the radiation sensitivity of the test organisms, ranging from a few percent to several-fold reduction in D10. In particular, radiation sensitization could be effected by certain additives, including carvacrol, thymol and trans-cinnamaldehyde, and also by certain compositions of modified atmosphere in the package headspace. A combination of additives and modified atmosphere effected a greater radiosensitization effect than could be achieved by either factor applied alone. Radiosensitization could be demonstrated with irradiation of either fresh or frozen ground meat. The radiosensitization phenomenon may be of practical utility in enhancing the technical effectiveness and feasibility of irradiation of a variety of meat and other food products.

Exploring the Relationship between Reward and Punishment Sensitivity and Gambling Disorder in a Clinical Sample: A Path Modeling Analysis.

PubMed

Jiménez-Murcia, Susana; Fernández-Aranda, Fernando; Mestre-Bach, Gemma; Granero, Roser; Tárrega, Salomé; Torrubia, Rafael; Aymamí, Neus; Gómez-Peña, Mónica; Soriano-Mas, Carles; Steward, Trevor; Moragas, Laura; Baño, Marta; Del Pino-Gutiérrez, Amparo; Menchón, José M

2017-06-01

Most individuals will gamble during their lifetime, yet only a select few will develop gambling disorder. Gray's Reinforcement Sensitivity Theory holds promise for providing insight into gambling disorder etiology and symptomatology as it ascertains that neurobiological differences in reward and punishment sensitivity play a crucial role in determining an individual's affect and motives. The aim of the study was to assess a mediational pathway, which included patients' sex, personality traits, reward and punishment sensitivity, and gambling-severity variables. The Sensitivity to Punishment and Sensitivity to Reward Questionnaire, the South Oaks Gambling Screen, the Symptom Checklist-Revised, and the Temperament and Character Inventory-Revised were administered to a sample of gambling disorder outpatients (N = 831), diagnosed according to DSM-5 criteria, attending a specialized outpatient unit. Sociodemographic variables were also recorded. A structural equation model found that both reward and punishment sensitivity were positively and directly associated with increased gambling severity, sociodemographic variables, and certain personality traits while also revealing a complex mediational role for these dimensions. To this end, our findings suggest that the Sensitivity to Punishment and Sensitivity to Reward Questionnaire could be a useful tool for gaining a better understanding of different gambling disorder phenotypes and developing tailored interventions.

Sensitivity of the Dengue Surveillance System in Brazil for Detecting Hospitalized Cases

PubMed Central

2016-01-01

We evaluated the sensitivity of the dengue surveillance system in detecting hospitalized cases in ten capital cities in Brazil from 2008 to 2013 using a probabilistic record linkage of two independent information systems hospitalization (SIH-SUS) adopted as the gold standard and surveillance (SINAN). Sensitivity was defined as the proportion of cases reported to the surveillance system amid the suspected hospitalized cases registered in SIH-SUS. Of the 48,174 hospitalizations registered in SIH-SUS, 24,469 (50.7%) were reported and registered in SINAN, indicating an overall sensitivity of 50.8% (95%CI 50.3–51.2). The observed sensitivity for each of the municipalities included in the study ranged from 22.0% to 99.1%. The combination of the two data sources identified 71,161 hospitalizations, an increase of 97.0% over SINAN itself. Our results allowed establishing the proportion of underreported dengue hospitalizations in the public health system in Brazil, highlighting the use of probabilistic record linkage as a valuable tool for evaluating surveillance systems. PMID:27192405

Recent approaches in sensitive enantioseparations by CE.

PubMed

Sánchez-Hernández, Laura; Castro-Puyana, María; Marina, María Luisa; Crego, Antonio L

2012-01-01

The latest strategies and instrumental improvements for enhancing the detection sensitivity in chiral analysis by CE are reviewed in this work. Following the previous reviews by García-Ruiz et al. (Electrophoresis 2006, 27, 195-212) and Sánchez-Hernández et al. (Electrophoresis 2008, 29, 237-251; Electrophoresis 2010, 31, 28-43), this review includes those papers that were published during the period from June 2009 to May 2011. These works describe the use of offline and online sample treatment techniques, online sample preconcentration techniques based on electrophoretic principles, and alternative detection systems to UV-Vis to increase the detection sensitivity. The application of the above-mentioned strategies, either alone or combined, to improve the sensitivity in the enantiomeric analysis of a broad range of samples, such as pharmaceutical, biological, food and environmental samples, enables to decrease the limits of detection up to 10⁻¹² M. The use of microchips to achieve sensitive chiral separations is also discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Making your skin crawl: The role of tactile sensitivity in disease avoidance.

PubMed

Hunt, David Francis; Cannell, Grace; Davenhill, Nicholas A; Horsford, Stephanie A; Fleischman, Diana S; Park, Justin H

2017-07-01

Mounting evidence indicates that animals, including humans, have evolved a behavioral disease-avoidance system designed to facilitate the detection and avoidance of sources of pathogens, and that this system interacts with physiological defenses. The skin acts as an important anatomical barrier, yet little research has investigated the role of tactile sensitivity in disease avoidance. Increased tactile sensitivity in the presence of potential sources of pathogens may facilitate prophylactic behaviors such as self-grooming. Across multiple studies, we tested the hypothesis that the induction of disgust-the key emotion underlying disease avoidance-may lead to greater tactile sensitivity compared to control conditions. A nonsignificant trend was found in a pilot study, which was replicated (and found to be significant) in Studies 1 and 2. To our knowledge, these results are the first to demonstrate disgust-induced changes in tactile sensitivity, and they contribute to the growing literature on the integrated evolved defenses against infectious disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Method and apparatus for ultra-high-sensitivity, incremental and absolute optical encoding

NASA Technical Reports Server (NTRS)

Leviton, Douglas B. (Inventor)

1999-01-01

An absolute optical linear or rotary encoder which encodes the motion of an object (3) with increased resolution and encoding range and decreased sensitivity to damage to the scale includes a scale (5), which moves with the object and is illuminated by a light source (11). The scale carries a pattern (9) which is imaged by a microscope optical system (13) on a CCD array (17) in a camera head (15). The pattern includes both fiducial markings (31) which are identical for each period of the pattern and code areas (33) which include binary codings of numbers identifying the individual periods of the pattern. The image of the pattern formed on the CCD array is analyzed by an image processor (23) to locate the fiducial marking, decode the information encoded in the code area, and thereby determine the position of the object.

Screening for modulators of cisplatin sensitivity: unbiased screens reveal common themes.

PubMed

Nijwening, Jeroen H; Kuiken, Hendrik J; Beijersbergen, Roderick L

2011-02-01

Cisplatin is a widely used chemotherapeutic agent to treat a variety of solid tumors. The cytotoxic mode of action of cisplatin is mediated by inducing conformational changes in DNA including intra- and inter-strand crosslink adducts. Recognition of these adducts results in the activation of the DNA damage response resulting in cell cycle arrest, repair, and potentially, apoptosis. Despite the clinical efficacy of cisplatin, many tumors are either intrinsically resistant or acquire resistance during treatment. The identification of cisplatin drug response modulators can help us understand these resistance mechanisms, provide biomarkers for treatment strategies, or provide drug targets for combination therapy. Here we discuss functional genetic screens, including one performed by us, set up to identify genes whose inhibition results in increased sensitivity to cisplatin. In summary, the validated genes identified in these screens mainly operate in DNA damage response including nucleotide excision repair, translesion synthesis, and homologous recombination.

Examining longitudinal train dynamics in ore car tipplers

NASA Astrophysics Data System (ADS)

Cole, Colin; Spiryagin, Maksym; Bosomworth, Chris

2017-04-01

Train simulation has been adapted in this paper to model the behaviour of indexing operations in ore car tippler operations. An important consideration in simulations at these low speeds (less than 4 km/h) is the increased rolling resistance transitioning from stationary conditions to motion. Most formulations of rolling resistance equations do not include this range although there are empirical values in some railway standards. The indexer control utilised here has a target trapezoidal velocity profile. The indexer to train connection was modelled as a stiff linear spring, a damper and a gap element. A sensitivity analysis was completed considering variations in wagon connections including wedge static friction, preload, coupling slack and tippler slack. Track topography including downhill grades of 0.1% and 0.2% and a valley profile were also investigated. Results showed high sensitivity to draft gear parameters of static friction and preload, but minimal benefit from downhill grades and changes in coupling slack.

The Role of Allergen Exposure and Avoidance in Asthma

PubMed Central

Baxi, Sachin N.; Phipatanakul, Wanda

2010-01-01

Allergy testing and avoidance of allergens plays an important role in asthma control. Increased allergen exposure, in genetically susceptible individuals, can lead to allergic sensitization. Continued allergen exposure can increase the risk of asthma and other allergic diseases. In a patient with persistent asthma, identification of indoor and outdoor allergens and subsequent avoidance can improve symptoms. Often times, a patient will have multiple allergies and the avoidance plan should target all positive allergens. Several studies have shown that successful allergen remediation includes a comprehensive approach including education, cleaning, physical barriers and maintaining these practices. PMID:20568555

Necrotizing Soft Tissue Infection: Diagnostic Accuracy of Physical Examination, Imaging, and LRINEC Score: A Systematic Review and Meta-Analysis.

PubMed

Fernando, Shannon M; Tran, Alexandre; Cheng, Wei; Rochwerg, Bram; Kyeremanteng, Kwadwo; Seely, Andrew J E; Inaba, Kenji; Perry, Jeffrey J

2018-04-18

We sought to summarize accuracy of physical examination, imaging, and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score in diagnosis of necrotizing soft tissue infection (NSTI) in adults with a soft tissue infection clinically concerning for NSTI. NSTI is a life-threatening diagnosis. Delay to diagnosis and surgical management is associated with increased mortality. We searched 6 databases from inception through November 2017. We included English-language studies reporting diagnostic accuracy of testing or LRINEC Score. Outcome was NSTI confirmed by surgery or histopathology. Two reviewers screened all citations and extracted data independently. Summary measures were obtained from the Hierarchical Summary Receiver Operating Characteristic model. From 2,290 citations, we included 23 studies (n = 5982). Of physical examination signs, pooled sensitivity and specificity for fever was 46.0% and 77.0% respectively, for hemorrhagic bullae 25.2% and 95.8%, and for hypotension 21.0% and 97.7%. Computed tomography (CT) had sensitivity of 88.5% and specificity of 93.3%, while plain radiography had sensitivity of 48.9% and specificity of 94.0%. Finally, LRINEC ≥ 6 had sensitivity of 68.2% and specificity of 84.8%, while LRINEC ≥ 8 had sensitivity of 40.8% and specificity of 94.9%. Absence of any 1 physical examination feature (eg, fever or hypotension) is not sufficient to rule-out NSTI. CT is superior to plain radiography. LRINEC had poor sensitivity, and should not be used to rule-out NSTI. Given the poor sensitivity of these tests, a high clinical suspicion warrants early surgical consultation for definitive diagnosis and management.

Laser-initiated decomposition products of indocyanine green (ICG) and carbon black sensitized biological tissues

NASA Astrophysics Data System (ADS)

Kokosa, John M.; Przyjazny, Andrzej; Bartels, Kenneth E.; Motamedi, Massoud; Hayes, Donald J.; Wallace, David B.; Frederickson, Christopher J.

1997-05-01

Organic dyes have found increasing use a s sensitizers in laser surgical procedures, due to their high optical absorbances. Little is known, however, about the nature of the degradation products formed when these dyes are irradiated with a laser. Previous work in our laboratories has shown that irradiation of polymeric and biological tissues with CO2 and Nd:YAG lasers produces a host of volatile and semivolatile by-products, some of which are known to be potential carcinogens. This work focuses on the identification of the chemical by-products formed by diode laser and Nd:YAG laser irradiation of indocyanine green (ICG) and carbon black based ink sensitized tissues, including bone, tendon and sheep's teeth. Samples were mounted in a 0.5-L Pyrex sample chamber equipped with quartz optical windows, charcoal filtered air inlet and an outlet attached to an appropriate sample trap and a constant flow pump. By-products were analyzed by GC/MS and HPLC. Volatiles identified included benzene and formaldehyde. Semi-volatiles included traces of polycyclic aromatics, arising from the biological matrix and inks, as well as fragments of ICG and the carbon ink components. The significance of these results will be discussed, including the necessity of using appropriate evacuation devices when utilizing lasers for surgical procedures.

Influence of changing water sources and mineral chemistry on the everglades ecosystem

USGS Publications Warehouse

McCormick, P.V.; Harvey, J.W.; Crawford, E.S.

2011-01-01

Human influences during the previous century increased mineral inputs to the Florida Everglades by changing the sources and chemistry of surface inflows. Biogeochemical responses to this enrichment include changes in the availability of key limiting nutrients such as P, the potential for increased turnover of nutrient pools due to accelerated plant decomposition, and increased rates of mercury methylation associated with sulfate enrichment. Mineral enrichment has also been linked to the loss of sensitive macrophyte species, although dominant Everglades species appear tolerant of a broad range of mineral chemistry. Shifts in periphyton community composition and function provide an especially sensitive indicator of mineral enrichment. Understanding the influence of mineral chemistry on Everglades processes and biota may improve predictions of ecosystem responses to ongoing hydrologic restoration efforts and provide guidelines for protecting remaining mineral-poor areas of this peatland. Copyright ?? 2011 Taylor & Francis Group, LLC.

Substance P enhances the activation of AMPK and cellular lipid accumulation in 3T3‑L1 cells in response to high levels of glucose.

PubMed

Dubon, Maria Jose; Byeon, Yeji; Park, Ki-Sook

2015-12-01

The rescue of glucose tolerance and insulin‑sensitivity in peripheral tissues, including adipose tissue, is essential in therapeutic strategies for diabetes. The present study demonstrated that substance P (SP) increases the accumulation of lipids in 3T3‑L1 cells during their differentiation into adipocytes in response to a high concentration of glucose. SP reciprocally regulated the activities of AMP‑activated protein kinase (AMPK) and Akt: SP enhanced the activation of AMPK, although the activity of Akt was downregulated. Notably, SP induced an increase in the expression level of glucose transporter 4 in the 3T3‑L1 adipocytes. Therefore, it is possible that SP leads to an increase in glucose uptake and the accumulation of lipids in adipocytes, and may contribute towards the rescue of insulin‑sensitivity in diabetes.

Experimentally induced central sensitization in the cervical spine evokes postural stiffening strategies in healthy young adults.

PubMed

Huntley, Andrew H; Srbely, John Z; Zettel, John L

2015-02-01

Dysequilibrium of cervicogenic origin can result from pain and injury to cervical paraspinal tissues post-whiplash; however, the specific physiological mechanisms still remain unclear. Central sensitization is a neuradaptive process which has been clinically associated with conditions of chronic pain and hypersensitivity. Strong links have been demonstrated between pain hypersensitivity and postural deficits post-whiplash; however, the precise mechanisms are still poorly understood. The purpose of this study was to explore the mechanisms of cervicogenic disequilibrium by investigating the effect of experimentally induced central sensitization in the cervical spine on postural stability in young healthy adults. Sixteen healthy young adults (7 males (22.6±1.13 years) and 9 females (22±2.69 years)) performed 30-s full-tandem stance trials on an AMTI force plate under normal and centrally sensitized conditions. The primary outcome variables included the standard deviation of the center of pressure (COP) position in medio-lateral (M-L) and antero-posterior (A-P) directions; sway range of the COP in M-L and A-P directions and the mean power frequency (MPF) of the COP and horizontal ground shear forces. Variability and sway range of the COP decreased with experimental induction of central sensitization, accompanied by an increase in MPF of COP displacement in both M-L and A-P directions, suggesting an increase in postural stiffening post-sensitization versus non-sensitized controls. Future studies need to further explore this relationship in clinical (whiplash, chronic pain) populations. Copyright © 2015 Elsevier B.V. All rights reserved.

Developmental programming: insulin sensitizer treatment improves reproductive function in prenatal testosterone-treated female sheep.

PubMed

Veiga-Lopez, Almudena; Lee, James S; Padmanabhan, Vasantha

2010-08-01

Prenatal testosterone (T) excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested the hypothesis that insulin resistance contributes toward severity of reproductive disruptions in prenatally T-treated females. Pregnant sheep were injected im with 100 mg of T-propionate semiweekly from d 30-90 of gestation. Immediately after the first breeding season, a subset of controls and prenatal T-treated (TR) sheep were administered an insulin sensitizer (rosiglitazone; 8 mg/d) orally for 8 months. Untreated control and prenatal T-treated females (T group) were studied in parallel. Biochemical analyses revealed rosiglitazone to be safe for use in sheep. Glucose tolerance tests performed before and after the insulin sensitizer treatment found that insulin sensitizer decreased cumulative insulin, cumulative insulin/glucose ratio, and insulin area under the curve by about 50% and increased the insulin sensitivity index by about 70% in the TR compared with the T group. Twenty percent of TR females showed a reduced number of cycles in the second relative to first breeding season as opposed to 80% of T group females showing such deterioration. Insulin sensitizer treatment also decreased the number of aberrant cycles (>/=18 d) during the second breeding season in the TR group relative to the first as opposed to the T group females showing an increase in the second breeding season relative to the first. These findings provide evidence that insulin sensitizer treatment prevents further deterioration of the reproductive axis in prenatal T-treated sheep, a finding of translational relevance to women with polycystic ovary syndrome.

A systematic computational study of electronic effects on hydrogen sensitivity of olefin polymerization catalysts (abstract only).

PubMed

Coussens, Betty B; Budzelaar, Peter H M; Friederichs, Nic

2008-02-13

One of the important product parameters of polyolefins is their molecular weight (distribution). A common way to control this parameter is to add molecular hydrogen during the polymerization, which then acts as a chain transfer agent. The factors governing the hydrogen sensitivity of olefin polymerization catalysts are poorly understood and have attracted little attention from computational chemists. To explore the electronic factors determining hydrogen sensitivity we performed density functional calculations on a wide range of simple model systems including some metallocenes and a few basic models of heterogeneous catalysts. As a quantitative measure for hydrogen sensitivity we used the ratio of (i) the rate constant for chain transfer to hydrogen to (ii) the rate constant for ethene insertion, k(h)/k(p) (see the scheme below), and as a measure of electrophilicity we used the energy of complexation to the probe molecule ammonia. [Formula: see text] For isolated species in the gas phase, complexation energies appear to dominate the chemistry. Ethene complexes more strongly than hydrogen and with increasing electrophilicity of the metal centre this difference grows; the hydrogen sensitivity decreases accordingly. Although many factors (like catalyst dormancy and deactivation issues) complicate the comparison with experiment, this result seems to agree both in broad terms with the experimental lower hydrogen sensitivity of heterogeneous catalysts, and more specifically with the increased hydrogen sensitivity of highly alkylated or fused metallocenes. The opposite conclusion reached by Blom (see Blom et al 2002 Macromol. Chem. Phys. 203 381-7) is due to the use of a very different measure of electrophilicity, rather than to different experimental data.

Comparison of the Efficacy of Atopalm(®) Multi-Lamellar Emulsion Cream and Physiogel(®) Intensive Cream in Improving Epidermal Permeability Barrier in Sensitive Skin.

PubMed

Jeong, Sekyoo; Lee, Sin Hee; Park, Byeong Deog; Wu, Yan; Man, George; Man, Mao-Qiang

2016-03-01

The management of sensitive skin, which affects over 60% of the general population, has been a long-standing challenge for both patients and clinicians. Because defective epidermal permeability barrier is one of the clinical features of sensitive skin, barrier-enhancing products could be an optimal regimen for sensitive skin. In the present study, we evaluated the efficacy and safety of two barrier-enhancing products, i.e., Atopalm (®) Multi-Lamellar Emulsion (MLE) Cream and Physiogel (®) Intensive Cream for sensitive skin. 60 patients with sensitive skin, aged 22-40 years old, were randomly assigned to one group treated with Atopalm MLE Cream, and another group treated with Physiogel Intensive Cream twice daily for 4 weeks. Lactic acid stinging test scores (LASTS), stratum hydration (SC) and transepidermal water loss (TEWL) were assessed before, 2 and 4 weeks after the treatment. Atopalm MLE Cream significantly lowered TEWL after 2 and 4 weeks of treatment (p < 0.01). In contrast, Physiogel Intensive Cream significantly increased TEWL after 2 weeks of treatment (p < 0.05) while TEWL significantly decreased after 4-week treatments. Moreover, both Atopalm MLE Cream and Physiogel Intensive Cream significantly increased SC hydration, and improved LASTS after 4 weeks of treatment. Both barrier-enhancing products are effective and safe for improving epidermal functions, including permeability barrier, SC hydration and LASTS, in sensitive skin. These products could be a valuable alternative for management of sensitive skin. Veterans Affairs Medical Center, San Francisco, California, USA, and NeoPharm Co., Ltd., Daejeon, Korea.

Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.

PubMed

Giannoni, Alberto; Aimo, Alberto; Mancuso, Michelangelo; Piepoli, Massimo Francesco; Orsucci, Daniele; Aquaro, Giovanni Donato; Barison, Andrea; De Marchi, Daniele; Taddei, Claudia; Cameli, Matteo; Raglianti, Valentina; Siciliano, Gabriele; Passino, Claudio; Emdin, Michele

2017-12-01

Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement. Twenty-five MD patients (aged 46 ± 3 years, 32% male) with skeletal myopathy but without known cardiac disease, underwent a thorough evaluation including BNPs, galectin-3, soluble suppression of tumorigenesis 2 (sST2), high sensitivity troponin T/I, catecholamines, ECG, 24-h ECG recording, cardiopulmonary exercise testing, echocardiography, cardiac/muscle magnetic resonance (C/MMR), and ergoreflex assessment. Thirteen age- and sex-matched healthy controls were chosen. Among these myopathic patients, subclinical cardiac damage was detected in up to 80%, with 44% showing fibrosis at CMR. Ergoreflex sensitivity was markedly higher in patients than in controls (64% vs. 37%, P < 0.001), and correlated with muscle fat to water ratio and extracellular volume at MMR (both P < 0.05). Among patients, ergoreflex sensitivity was higher in those with cardiac involvement (P = 0.034). Patients showed a lower peak oxygen consumption (VO 2 /kg) than controls (P < 0.001), as well as ventilatory inefficiency (P = 0.024). Ergoreflex sensitivity correlated with reduced workload and peak VO 2 /kg (both P < 0.001), and several indicators of autonomic imbalance (P < 0.05). Plasma norepinephrine was the unique predictor of myocardial fibrosis at univariate analysis (P < 0.05). Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Ground water flow modeling with sensitivity analyses to guide field data collection in a mountain watershed

USGS Publications Warehouse

Johnson, Raymond H.

2007-01-01

In mountain watersheds, the increased demand for clean water resources has led to an increased need for an understanding of ground water flow in alpine settings. In Prospect Gulch, located in southwestern Colorado, understanding the ground water flow system is an important first step in addressing metal loads from acid-mine drainage and acid-rock drainage in an area with historical mining. Ground water flow modeling with sensitivity analyses are presented as a general tool to guide future field data collection, which is applicable to any ground water study, including mountain watersheds. For a series of conceptual models, the observation and sensitivity capabilities of MODFLOW-2000 are used to determine composite scaled sensitivities, dimensionless scaled sensitivities, and 1% scaled sensitivity maps of hydraulic head. These sensitivities determine the most important input parameter(s) along with the location of observation data that are most useful for future model calibration. The results are generally independent of the conceptual model and indicate recharge in a high-elevation recharge zone as the most important parameter, followed by the hydraulic conductivities in all layers and recharge in the next lower-elevation zone. The most important observation data in determining these parameters are hydraulic heads at high elevations, with a depth of less than 100 m being adequate. Evaluation of a possible geologic structure with a different hydraulic conductivity than the surrounding bedrock indicates that ground water discharge to individual stream reaches has the potential to identify some of these structures. Results of these sensitivity analyses can be used to prioritize data collection in an effort to reduce time and money spend by collecting the most relevant model calibration data.

[Isothiazolinones as causal factors of contact allergy epidemics in the 20th and 21st centuries].

PubMed

Chomiczewska-Skóra, Dorota; Kręcisz, Beata; Kieć-Świerczyńska, Marta

2014-01-01

Chloromethylisothiazolinone (MCI) and methylisothiazolinone (MI) have been widely used as preservatives in cosmetics, household products and industrial products since the late 1970s. First cases of contact allergy to the MCI/MI combination were noted in 1980-1982 in Sweden. Then, a significant increase in the frequency of sensitization to these compounds was observed in many European centers. The increase has been stopped by the introduction of legislation on their maximum concentrations in consumer and industrial products in Europe and in some non-European countries. But approval of the use of MI alone without limits in industrial products (from 2000) and at a maximum concentration of 100 ppm in cosmetics (from 2005) resulted in an unprecedented increase in the number of individuals sensitized to this compound. Allergic contact dermatitis due to MI occurs in both adults and children. It is often manifested by severe symptoms, which may be also induced by airborne exposure. The most important sources of sensitization include cosmetic products and paints. To counteract the increasing problem of contact allergy epidemic to MI, the recommendations have been developed, suggesting the ban on the use of MI in "leave-on" cosmetics and maximum concentration of 15 ppm in "rinse-off" products. The recommendations are likely to be implemented in 2014.

Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

PubMed Central

Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

2015-01-01

Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

Behavioral Control and Reward Sensitivity in Adolescents' Risk Taking Behavior: A Longitudinal TRAILS Study.

PubMed

Peeters, Margot; Oldehinkel, Tineke; Vollebergh, Wilma

2017-01-01

Neurodevelopmental theories of risk behavior hypothesize that low behavioral control in combination with high reward sensitivity explains adolescents' risk behavior. However, empirical studies examining this hypothesis while including actual risk taking behavior in adolescence are lacking. In this study we tested whether the imbalance between behavioral control and reward sensitivity underlies risk taking behavior in adolescence, using a nationally representative longitudinal sample of 715 adolescents, of which 66% revealed an increased risk for mental health problems. To assess behavioral control at age 11 we used both self-report (effortful control) as well as behavioral measures of cognitive control (i.e., working memory and response inhibition). Reward sensitivity was assessed with the Bangor Gambling Task. The main finding of this study was that effortful control at age 11 was the best predictor of risk taking behavior (alcohol and cannabis use) at age 16, particularly among adolescents who were more reward sensitive. Risk taking behavior in adolescents might be explained by relatively weak behavioral control functioning combined with high sensitivity for reward.

Differentiating food allergies from food intolerances.

PubMed

Guandalini, Stefano; Newland, Catherine

2011-10-01

Adverse reactions to foods are extremely common, and generally they are attributed to allergy. However, clinical manifestations of various degrees of severity related to ingestion of foods can arise as a result of a number of disorders, only some of which can be defined as allergic, implying an immune mechanism. Recent epidemiological data in North America showed that the prevalence of food allergy in children has increased. The most common food allergens in the United States include egg, milk, peanut, tree nuts, wheat, crustacean shellfish, and soy. This review examines the various forms of food intolerances (immunoglobulin E [IgE] and non-IgE mediated), including celiac disease and gluten sensitivity. Immune mediated reactions can be either IgE mediated or non-IgE mediated. Among the first group, Immediate GI hypersensitivity and oral allergy syndrome are the best described. Often, but not always, IgE-mediated food allergies are entities such as eosinophilic esophagitis and eosinophilic gastroenteropathy. Non IgE-mediated immune mediated food reactions include celiac disease and gluten sensitivity, two increasingly recognized disorders. Finally, non-immune mediated reactions encompass different categories such as disorders of digestion and absorption, inborn errors of metabolism, as well as pharmacological and toxic reactions.

[The fasting calcium/creatinine ratio in patients with calcium stones and the relation with hypercalciuria and phosphocalcium metabolism].

PubMed

Arrabal-Polo, Miguel Ángel; del Carmen Cano-García, María; Arrabal-Martín, Miguel

2016-04-01

To determine the importance of fasting calcium/creatinine ratio in patients with calcium stones and its relation with hypercalciuria and phospho-calcium metabolism. Cross-sectional study including 143 patients divided into two groups according to fasting calcium/creatinine. Group 1: 66 patients (calcium/ creatinine<0.11); Group 2: 77 patients (calcium/ creatinine>0.11). A comparative study is performed between groups including phospho-calcium metabolism parameters and excretion of urinary lithogenic markers. Linear correlation studying calciuria and fasting calcium/ creatinine was performed. SPSS 17.0 statistical analysis software was used, considering p≤0.05. It is noteworthy that group 2 had increased 24 h urine calcium excretion in comparison to group 1 (229.3 vs 158.1; p=0.0001) and calcium/citrate (0.47 vs 0.34; p=0.001). There is a positive and significant correlation between calcium levels in 24 h urine and fasting calcium/creatinine (R=0.455; p=0.0001) and a cutoff is set at 0.127 (sensitivity 72%, specificity 66%) to determine hypercalciuria (>260 mg in 24 h). Increased fasting calcium/creatinine determines increased 24 hours calcium excretion, although the sensitivity and specificity to determine hypercalciuria is not high.

Omega-3 Eicosapentaenoic Acid Decreases CD133 Colon Cancer Stem-Like Cell Marker Expression While Increasing Sensitivity to Chemotherapy

PubMed Central

De Carlo, Flavia; Witte, Theodore R.; Hardman, W. Elaine; Claudio, Pier Paolo

2013-01-01

Colorectal cancer is the third leading cause of cancer-related death in the western world. In vitro and in vivo experiments showed that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer cells, including colon cancer, and increase the efficacy of various anticancer drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs) that are responsible for tumor formation and maintenance. CSLCs have also been linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon CSLCs have been immunophenotyped using several antibodies against cellular markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to isolate a population of colon cancer cells that retains stem cells properties (CSLCs) from both established cell lines and primary cell cultures. We demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased the cell number of the overall population of cancer cells, but not of the CD133 (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20 (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the sensitivity of COLO 320 DM cells (total population) to both standard-of-care chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil. PMID:23874993

[Frequency of contact sensitization to modern dressings used to treat chronic leg ulcer].

PubMed

Garval, E; Plee, J; Lesage, C; Grange-Prunier, A; Bernard, P; Perceau, G

2018-05-01

Allergic contact dermatitis around chronic leg ulcers (CLU) is a common complication in patients presenting CLU and prolongs healing times. The aim of this study was to describe the rate of sensitization to modern dressings (MD) used in these patients and to assess whether there is a relation between the number of sensitizations and ulcer type, the time from onset of the ulcer, and patient age and gender. We conducted a retrospective study at Reims University Hospital between 2010 and 2014 that included all patients with CLU of vascular etiology surrounded by eczematous lesions, and who had one of the patch-tests in the following 3 series: European baseline±leg ulcers±corticosteroids. Among the 73 patients included, 43 % were polysensitized. Thirty-three patients (45 %) were sensitized to MD (38 % to hydrocolloids, 18 % to hydrogels, 7 % to hydrocellular dressings, 7 % to hydrofiber dressings, 5 % to contact layers and 3 % to alginates). Median age and sex did not differ between "polysensitized" patients and "non-polysensitized" patients (P=0.84 and P=0.25, respectively). Polysensitization was more frequent among patients presenting ulcers for more than 5 years (P=0.032). Practically half of all patients presenting CLU with surrounding contact dermatitis had sensitization to modern dressings (mostly hydrocolloids and hydrogels). The rate of sensitization increased with the length of presence of CLU. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Diagnosis of X-Linked Hypohidrotic Ectodermal Dysplasia by Meibography and Infrared Thermography of the Eye.

PubMed

Kaercher, Thomas; Dietz, Jasna; Jacobi, Christina; Berz, Reinhold; Schneider, Holm

2015-09-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical characteristics include meibomian gland disorder and the resulting hyperevaporative dry eye. In this study, we evaluated meibography and ocular infrared thermography as novel methods to diagnose XLHED. Eight infants, 12 boys and 14 male adults with XLHED and 12 healthy control subjects were subjected to a panel of tests including the ocular surface disease index (OSDI), meibography and infrared thermography, non-invasive measurement of tear film break-up time (NIBUT) and osmolarity, Schirmer's test, lissamine green staining and fluorescein staining. Sensitivity and specificity were determined for single tests and selected test combinations. Meibography had 100% sensitivity and specificity for identifying XLHED. Infrared thermography, a completely non-invasive procedure, revealed a typical pattern for male subjects with XLHED. It was, however, less sensitive (86% for adults and 67% for children) than meibography or a combination of established routine tests. In adults, OSDI and NIBUT were the best single routine tests (sensitivity of 86% and 71%, respectively), whereas increased tear osmolarity appeared as a rather unspecific ophthalmic symptom. In children, NIBUT was the most convincing routine test (sensitivity of 91%). Meibography is the most reliable ophthalmic examination to establish a clinical diagnosis in individuals with suspected hypohidrotic ectodermal dysplasia, even before genetic test results are available. Tear film tests and ocular surface staining are less sensitive in children, but very helpful for estimating the severity of ocular surface disease in individuals with known XLHED.

Roadmap to Clinical Use of Gold Nanoparticles for Radiation Sensitization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuemann, Jan, E-mail: jschuemann@mgh.harvard.edu; Berbeco, Ross; Chithrani, Devika B.

2016-01-01

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translationmore » of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage.« less

Comparison of presumptive blood test kits including hexagon OBTI.

PubMed

Johnston, Emma; Ames, Carole E; Dagnall, Kathryn E; Foster, John; Daniel, Barbara E

2008-05-01

Four presumptive blood tests, Hexagon OBTI, Hemastix(R), Leucomalachite green (LMG), and Kastle-Meyer (KM) were compared for their sensitivity in the identification of dried bloodstains. Stains of varying blood dilutions were subjected to each presumptive test and the results compared. The Hexagon OBTI buffer volume was also reduced to ascertain whether this increased the sensitivity of the kit. The study found that Hemastix(R) was the most sensitive test for trace blood detection. Only with the reduced buffer volume was the Hexagon OBTI kit as sensitive as the LMG and KM tests. However, the Hexagon OBTI kit has the advantage of being a primate specific blood detection kit. This study also investigated whether the OBTI buffer within the kit could be utilized for DNA profiling after presumptive testing. The results show that DNA profiles can be obtained from the Hexagon OBTI kit buffer directly.

Increased sensitivity to climate change in disturbed ecosystems.

PubMed

Kröel-Dulay, György; Ransijn, Johannes; Schmidt, Inger Kappel; Beier, Claus; De Angelis, Paolo; de Dato, Giovanbattista; Dukes, Jeffrey S; Emmett, Bridget; Estiarte, Marc; Garadnai, János; Kongstad, Jane; Kovács-Láng, Edit; Larsen, Klaus Steenberg; Liberati, Dario; Ogaya, Romà; Riis-Nielsen, Torben; Smith, Andrew R; Sowerby, Alwyn; Tietema, Albert; Penuelas, Josep

2015-03-24

Human domination of the biosphere includes changes to disturbance regimes, which push many ecosystems towards early-successional states. Ecological theory predicts that early-successional ecosystems are more sensitive to perturbations than mature systems, but little evidence supports this relationship for the perturbation of climate change. Here we show that vegetation (abundance, species richness and species composition) across seven European shrublands is quite resistant to moderate experimental warming and drought, and responsiveness is associated with the dynamic state of the ecosystem, with recently disturbed sites responding to treatments. Furthermore, most of these responses are not rapid (2-5 years) but emerge over a longer term (7-14 years). These results suggest that successional state influences the sensitivity of ecosystems to climate change, and that ecosystems recovering from disturbances may be sensitive to even modest climatic changes. A research bias towards undisturbed ecosystems might thus lead to an underestimation of the impacts of climate change.

Inversion of magnetotelluric data using integral equation approach with variable sensitivity domain: Application to EarthScope MT data

NASA Astrophysics Data System (ADS)

Čuma, Martin; Gribenko, Alexander; Zhdanov, Michael S.

2017-09-01

We have developed a multi-level parallel magnetotelluric (MT) integral equation based inversion program which uses variable sensitivity domain. The limited sensitivity of the data, which decreases with increasing frequency, is exploited by a receiver sensitivity domain, which also varies with frequency. We assess the effect of inverting principal impedances, full impedance tensor, and full tensor jointly with magnetovariational data (tipper). We first apply this method to several models and then invert the EarthScope MT data. We recover well the prominent features in the area including resistive structure associated with the Juan de Fuca slab subducting beneath the northwestern United States, the conductive zone of partially melted material above the subducting slab at the Cascade volcanic arc, conductive features in the Great Basin and in the area of Yellowstone associated with the hot spot, and resistive areas to the east corresponding to the older and more stable cratons.

Laser ablation surface-enhanced Raman microspectroscopy.

PubMed

Londero, Pablo S; Lombardi, John R; Leona, Marco

2013-06-04

Improved identification of trace organic compounds in complex matrixes is critical for a variety of fields such as material science, heritage science, and forensics. Surface-enhanced Raman scattering (SERS) is a vibrational spectroscopy technique that can attain single-molecule sensitivity and has been shown to complement mass spectrometry, but lacks widespread application without a robust method that utilizes the effect. We demonstrate a new, highly sensitive, and widely applicable approach to SERS analysis based on laser ablation in the presence of a tailored plasmonic substrate. We analyze several challenging compounds, including non-water-soluble pigments and dyed leather from an ancient Egyptian chariot, achieving sensitivity as high as 120 amol for a 1:1 signal-to-noise ratio and 5 μm spatial resolution. This represents orders of magnitude improvement in spatial resolution and sensitivity compared to those of other SERS approaches intended for widespread application, greatly increasing the applicability of SERS.

Thermal effects on nonlinear vibration of a carbon nanotube-based mass sensor using finite element analysis

NASA Astrophysics Data System (ADS)

Kang, Dong-Keun; Kim, Chang-Wan; Yang, Hyun-Ik

2017-01-01

In the present study we carried out a dynamic analysis of a CNT-based mass sensor by using a finite element method (FEM)-based nonlinear analysis model of the CNT resonator to elucidate the combined effects of thermal effects and nonlinear oscillation behavior upon the overall mass detection sensitivity. Mass sensors using carbon nanotube (CNT) resonators provide very high sensing performance. Because CNT-based resonators can have high aspect ratios, they can easily exhibit nonlinear oscillation behavior due to large displacements. Also, CNT-based devices may experience high temperatures during their manufacture and operation. These geometrical nonlinearities and temperature changes affect the sensing performance of CNT-based mass sensors. However, it is very hard to find previous literature addressing the detection sensitivity of CNT-based mass sensors including considerations of both these nonlinear behaviors and thermal effects. We modeled the nonlinear equation of motion by using the von Karman nonlinear strain-displacement relation, taking into account the additional axial force associated with the thermal effect. The FEM was employed to solve the nonlinear equation of motion because it can effortlessly handle the more complex geometries and boundary conditions. A doubly clamped CNT resonator actuated by distributed electrostatic force was the configuration subjected to the numerical experiments. Thermal effects upon the fundamental resonance behavior and the shift of resonance frequency due to attached mass, i.e., the mass detection sensitivity, were examined in environments of both high and low (or room) temperature. The fundamental resonance frequency increased with decreasing temperature in the high temperature environment, and increased with increasing temperature in the low temperature environment. The magnitude of the shift in resonance frequency caused by an attached mass represents the sensing performance of a mass sensor, i.e., its mass detection sensitivity, and it can be seen that this shift is affected by the temperature change and the amount of electrostatic force. The thermal effects on the mass detection sensitivity are intensified in the linear oscillation regime and increase with increasing CNT length; this intensification can either improve or worsen the detection sensitivity.

Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS

PubMed Central

Manno, Carlo; Figueroa, Lourdes; Fitts, Robert

2013-01-01

Imaging, optical mapping, and optical multisite recording of transmembrane potential (Vm) are essential for studying excitable cells and systems. The naphthylstyryl voltage-sensitive dyes, including di-8-ANEPPS, shift both their fluorescence excitation and emission spectra upon changes in Vm. Accordingly, they have been used for monitoring Vm in nonratioing and both emission and excitation ratioing modes. Their changes in fluorescence are usually much less than 10% per 100 mV. Conventional ratioing increases sensitivity to between 3 and 15% per 100 mV. Low sensitivity limits the value of these dyes, especially when imaged with low light systems like confocal scanners. Here we demonstrate the improvement afforded by shifted excitation and emission ratioing (SEER) as applied to imaging membrane potential in flexor digitorum brevis muscle fibers of adult mice. SEER—the ratioing of two images of fluorescence, obtained with different excitation wavelengths in different emission bands—was implemented in two commercial confocal systems. A conventional pinhole scanner, affording optimal setting of emission bands but less than ideal excitation wavelengths, achieved a sensitivity of up to 27% per 100 mV, nearly doubling the value found by conventional ratioing of the same data. A better pair of excitation lights should increase the sensitivity further, to 35% per 100 mV. The maximum acquisition rate with this system was 1 kHz. A fast “slit scanner” increased the effective rate to 8 kHz, but sensitivity was lower. In its high-sensitivity implementation, the technique demonstrated progressive deterioration of action potentials upon fatiguing tetani induced by stimulation patterns at >40 Hz, thereby identifying action potential decay as a contributor to fatigue onset. Using the fast implementation, we could image for the first time an action potential simultaneously at multiple locations along the t-tubule system. These images resolved the radially varying lag associated with propagation at a finite velocity. PMID:23440278

Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS.

PubMed

Manno, Carlo; Figueroa, Lourdes; Fitts, Robert; Ríos, Eduardo

2013-03-01

Imaging, optical mapping, and optical multisite recording of transmembrane potential (V(m)) are essential for studying excitable cells and systems. The naphthylstyryl voltage-sensitive dyes, including di-8-ANEPPS, shift both their fluorescence excitation and emission spectra upon changes in V(m). Accordingly, they have been used for monitoring V(m) in nonratioing and both emission and excitation ratioing modes. Their changes in fluorescence are usually much less than 10% per 100 mV. Conventional ratioing increases sensitivity to between 3 and 15% per 100 mV. Low sensitivity limits the value of these dyes, especially when imaged with low light systems like confocal scanners. Here we demonstrate the improvement afforded by shifted excitation and emission ratioing (SEER) as applied to imaging membrane potential in flexor digitorum brevis muscle fibers of adult mice. SEER--the ratioing of two images of fluorescence, obtained with different excitation wavelengths in different emission bands-was implemented in two commercial confocal systems. A conventional pinhole scanner, affording optimal setting of emission bands but less than ideal excitation wavelengths, achieved a sensitivity of up to 27% per 100 mV, nearly doubling the value found by conventional ratioing of the same data. A better pair of excitation lights should increase the sensitivity further, to 35% per 100 mV. The maximum acquisition rate with this system was 1 kHz. A fast "slit scanner" increased the effective rate to 8 kHz, but sensitivity was lower. In its high-sensitivity implementation, the technique demonstrated progressive deterioration of action potentials upon fatiguing tetani induced by stimulation patterns at >40 Hz, thereby identifying action potential decay as a contributor to fatigue onset. Using the fast implementation, we could image for the first time an action potential simultaneously at multiple locations along the t-tubule system. These images resolved the radially varying lag associated with propagation at a finite velocity.

CHD7 Expression Predicts Survival Outcomes in Patients with Resected Pancreatic Cancer

PubMed Central

Colbert, Lauren E.; Petrova, Aleksandra V.; Fisher, Sarah B.; Pantazides, Brooke G.; Madden, Matthew Z.; Hardy, Claire W.; Warren, Matthew D.; Pan, Yunfeng; Nagaraju, Ganji P.; Liu, Elaine A.; Saka, Burcu; Hall, William A.; Shelton, Joseph W.; Gandhi, Khanjan; Pauly, Rini; Kowalski, Jeanne; Kooby, David A.; El-Rayes, Bassel F.; Staley, Charles A.; Adsay, N. Volkan; Curran, Walter J.; Landry, Jerome C.; Maithel, Shishir K.; Yu, David S.

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor outcomes with current therapies. Gemcitabine is the primary adjuvant drug used clinically, but its effectiveness is limited. In this study, our objective was to utilize a rationale-driven approach to identify novel biomarkers for outcome in patients with early-stage resected PDAC treated with adjuvant gemcitabine. Using a synthetic lethal screen in human PDAC cells, we identified 93 genes including 55 genes linked to DNA damage responses (DDR) that demonstrated gemcitabine sensitization when silenced, including CHD7 which functions in chromatin remodeling. CHD7 depletion sensitized PDAC cells to gemcitabine and delayed their growth in tumor xenografts. Moreover, CHD7 silencing impaired ATR-dependent phosphorylation of CHK1 and increased DNA damage induced by gemcitabine. CHD7 was dysregulated, ranking above the 90th percentile in differential expression in a panel of PDAC clinical specimens, highlighting its potential as a biomarker. Immunohistochemical analysis of specimens from 59 resected PDAC patients receiving adjuvant gemcitabine revealed that low CHD7 expression was associated with increased recurrence-free survival (RFS) and overall survival (OS), in univariate and multivariate analyses. Notably, CHD7 expression was not associated with RFS or OS for patients not receiving gemcitabine. Thus, low CHD7 expression was correlated selectively with gemcitabine sensitivity in this patient population. These results supported our rationale-driven strategy to exploit dysregulated DDR pathways in PDAC to identify genetic determinants of gemcitabine sensitivity, identifying CHD7 as a novel biomarker candidate to evaluate further for individualizing PDAC treatment. PMID:24626090

Economics in "Global Health 2035": a sensitivity analysis of the value of a life year estimates.

PubMed

Chang, Angela Y; Robinson, Lisa A; Hammitt, James K; Resch, Stephen C

2017-06-01

In "Global health 2035: a world converging within a generation," The Lancet Commission on Investing in Health (CIH) adds the value of increased life expectancy to the value of growth in gross domestic product (GDP) when assessing national well-being. To value changes in life expectancy, the CIH relies on several strong assumptions to bridge gaps in the empirical research. It finds that the value of a life year (VLY) averages 2.3 times GDP per capita for low- and middle-income countries (LMICs) assuming the changes in life expectancy they experienced from 2000 to 2011 are permanent. The CIH VLY estimate is based on a specific shift in population life expectancy and includes a 50 percent reduction for children ages 0 through 4. We investigate the sensitivity of this estimate to the underlying assumptions, including the effects of income, age, and life expectancy, and the sequencing of the calculations. We find that reasonable alternative assumptions regarding the effects of income, age, and life expectancy may reduce the VLY estimates to 0.2 to 2.1 times GDP per capita for LMICs. Removing the reduction for young children increases the VLY, while reversing the sequencing of the calculations reduces the VLY. Because the VLY is sensitive to the underlying assumptions, analysts interested in applying this approach elsewhere must tailor the estimates to the impacts of the intervention and the characteristics of the affected population. Analysts should test the sensitivity of their conclusions to reasonable alternative assumptions. More work is needed to investigate options for improving the approach.

The Library and the Pluralistic Campus in the Year 2000: Implications for Administrators.

ERIC Educational Resources Information Center

Welch, Janet E.; Lam, R. Errol

1991-01-01

Discussion of changing demographics and implications for academic libraries focuses on the expected increases in the numbers of Blacks and international students. Educational trends are discussed; and program ideas for academic libraries preparing for a multicultural environment are suggested, including sensitivity training for staff, minority…

Development of a qPCR direct detection method for Listeria monocytogenes in milk

USDA-ARS?s Scientific Manuscript database

There is a growing movement among consumers in the US and Europe towards minimally processed foods, including raw milk and dairy products. This trend significantly increases exposure to dairy-borne pathogens and indicates a need for rapid, sensitive screening tests for raw dairy products to reduce ...

Differential Susceptibility to the Environment: Are Developmental Models Compatible with the Evidence from Twin Studies?

ERIC Educational Resources Information Center

Del Giudice, Marco

2016-01-01

According to models of differential susceptibility, the same neurobiological and temperamental traits that determine increased sensitivity to stress and adversity also confer enhanced responsivity to the positive aspects of the environment. Differential susceptibility models have expanded to include complex developmental processes in which genetic…

EFFECTS OF SIZE FRACTIONATED AMBIENT PM SAMPLES ON INDUCTION OF PULMONARY ALLERGY IN MICE

EPA Science Inventory

There is increasing evidence that exposure to certain air pollutants including ozone and diesel exhaust can enhance allergic sensitization to allergens. Previous work from our laboratory has shown that exposure to residual oil fly ash or its associated transition metals can ...

COMPARISON OF THE NON-ADDITIVE INTERACTIONS OF AN ORGANOPHOSPHORUS PESTICIDE MIXTURE IN ADULT AND PREWEANLING RATS.

EPA Science Inventory

Critical features of risk assessment include the evaluation of risk following exposure to pesticide mixtures as well as the potential for increased sensitivity of the young. This research tested for interaction(s) using a mixture of five organophosphorus (OP) pesticides (chlorp...

NON-ADDITIVE INTERACTIONS OF AN ORGANOPHOSPHORUS PESTICIDE MIXTURE IN ADULT AND PREWEANLING RATS.

EPA Science Inventory

Critical features of risk assessment include the evaluation of risk following exposure to pesticide mixtures as well as the potential for increased sensitivity of the young. The US EPA is required to regulate pesticides acting via a common mechanism of action as a group, e.g.,...

Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

PubMed

Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

2017-02-01

Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

Severe Adverse Reactions Following Ketoconazole, Fluconazole, and Environmental Exposures: A Case Report.

PubMed

Lieberman, Allan; Curtis, Luke

2018-04-18

In this case report, we describe a 66-year-old man who developed multiple adverse reactions beginning at age 56 after exposure to several azole antifungal drugs including ketoconazole and fluconazole. He also had a history of more than 40 years exposure to chemicals including pesticides, wood preservatives, fertilizers, and welding chemicals. His reactions involved dehydration (requiring several liters of intravenous fluids in less than an hour to alleviate this condition), angioedema, nausea, tinnitus, hypotension, and difficulty breathing. His acute adverse reactions were triggered by a wide range of chemicals including gasoline, diesel fuel, pesticides, chlorine, topical isopropyl alcohol, and paper mill emissions. His acute reactions were also triggered by a wide range of foods such as bananas, apples, milk, white potatoes, and processed sweets. A number of mechanisms could be responsible for his increased sensitivity to chemicals following exposure to fluconazole/ketoconazole, including inhibition of P450 and other detoxification enzymes, acetaldehyde buildup, and neurogenic sensitization.

The Relationship of Mean Platelet Volume/Platelet Distribution Width and Duodenal Ulcer Perforation.

PubMed

Fan, Zhe; Zhuang, Chengjun

2017-03-01

Duodenal ulcer perforation (DUP) is a severe acute abdominal disease. Mean platelet volume (MPV) and platelet distribution width (PDW) are two platelet parameters, participating in many inflammatory processes. This study aims to investigate the relation of MPV/PDW and DUP. A total of 165 patients were studied retrospectively, including 21 females and 144 males. The study included two groups: 87 normal patients (control group) and 78 duodenal ulcer perforation patients (DUP group). Routine blood parameters were collected for analysis including white blood cell count (WBC), neutrophil ratio (NR), platelet count (PLT), MPV and PDW. Receiver operating curve (ROC) analysis was applied to evaluate the parameters' sensitivity. No significant differences were observed between the control group and DUP group in age and gender. WBC, NR and PDW were significantly increased in the DUP group ( P <0.001, respectively); PLT and MPV were significantly decreased in the DUP group ( P <0.001, respectively) compared to controls. MPV had the high sensitivity. Our results suggested a potential association between MPV/PDW and disease activity in DUP patients, and high sensitivity of MPV. © 2017 by the Association of Clinical Scientists, Inc.

Potential impacts of climate change on infectious diseases in the Arctic.

PubMed

Parkinson, Alan J; Butler, Jay C

2005-12-01

Climate change could cause changes in the incidence of infectious diseases in Arctic regions. Higher ambient temperatures in the Arctic may result in an increase in some temperature sensitive foodborne diseases such as gastroenteritis, paralytic shellfish poisoning and botulism. An increase in mean temperature may also influence the incidence of infectious diseases of animals that are spread to humans (zoonoses) by changing the population and range of animal hosts and insect vectors. An increase in flooding events may result in outbreaks of waterborne infection, such as Giardia lamblia or Cryptospordium parvum. A change in rodent and fox populations may result in an increase in rabies or echinococcosis. Temperature and humidity influence the distribution and density of many arthropod vectors which in turn may influence the incidence and northern range of vectorborne diseases such as West Nile virus. Recommendations include: the strenghtening of public health systems, disease surveillance coordinated with climate monitoring, and research into the detection, prevention, control and treatment of temperature-sensitive infectious diseases.

Sensitivity of agricultural runoff loads to rising levels of CO2 and climate change in the San Joaquin Valley watershed of California.

PubMed

Ficklin, Darren L; Luo, Yuzhou; Luedeling, Eike; Gatzke, Sarah E; Zhang, Minghua

2010-01-01

The Soil and Water Assessment Tool (SWAT) was used to assess the impact of climate change on sediment, nitrate, phosphorus and pesticide (diazinon and chlorpyrifos) runoff in the San Joaquin watershed in California. This study used modeling techniques that include variations of CO(2), temperature, and precipitation to quantify these responses. Precipitation had a greater impact on agricultural runoff compared to changes in either CO(2) concentration or temperature. Increase of precipitation by +/-10% and +/-20% generally changed agricultural runoff proportionally. Solely increasing CO(2) concentration resulted in an increase in nitrate, phosphorus, and chlorpyrifos yield by 4.2, 7.8, and 6.4%, respectively, and a decrease in sediment and diazinon yield by 6.3 and 5.3%, respectively, in comparison to the present-day reference scenario. Only increasing temperature reduced yields of all agricultural runoff components. The results suggest that agricultural runoff in the San Joaquin watershed is sensitive to precipitation, temperature, and CO(2) concentration changes.

Permalloy-Based Thin Film Structures: Magnetic Properties and the Giant Magnetoimpedance Effect in the Temperature Range Important for Biomedical Applications

PubMed Central

Chlenova, Anna A.; Moiseev, Alexey A.; Derevyanko, Mikhail S.; Semirov, Aleksandr V.; Lepalovsky, Vladimir N.

2017-01-01

Permalloy-based thin film structures are excellent materials for sensor applications. Temperature dependencies of the magnetic properties and giant magneto-impedance (GMI) were studied for Fe19Ni81-based multilayered structures obtained by the ion-plasma sputtering technique. Selected temperature interval of 25 °C to 50 °C corresponds to the temperature range of functionality of many devices, including magnetic biosensors. A (Cu/FeNi)5/Cu/(Cu/FeNi)5 multilayered structure with well-defined traverse magnetic anisotropy showed an increase in the GMI ratio for the total impedance and its real part with temperature increased. The maximum of the GMI of the total impedance ratio ΔZ/Z = 56% was observed at a frequency of 80 MHz, with a sensitivity of 18%/Oe, and the maximum GMI of the real part ΔR/R = 170% at a frequency of 10 MHz, with a sensitivity of 46%/Oe. As the magnetization and direct current electrical resistance vary very little with the temperature, the most probable mechanism of the unexpected increase of the GMI sensitivity is the stress relaxation mechanism associated with magnetoelastic anisotropy. PMID:28817084

Social Stress Increases Cortisol and Hampers Attention in Adolescents with Excess Weight

PubMed Central

Verdejo-Garcia, Antonio; Moreno-Padilla, Maria; Garcia-Rios, M. Carmen; Lopez-Torrecillas, Francisca; Delgado-Rico, Elena; Schmidt-Rio-Valle, Jacqueline; Fernandez-Serrano, Maria J.

2015-01-01

Objective To experimentally examine if adolescents with excess weight are more sensitive to social stress and hence more sensitive to harmful effects of stress in cognition. Design and Methods We conducted an experimental study in 84 adolescents aged 12 to 18 years old classified in two groups based on age adjusted Body Mass Index percentile: Normal weight (n=42) and Excess weight (n=42). Both groups were exposed to social stress as induced by the virtual reality version of the Trier Social Stress Task --participants were requested to give a public speech about positive and negative aspects of their personalities in front of a virtual audience. The outcome measures were salivary cortisol levels and performance in cognitive tests before and after the social stressor. Cognitive tests included the CANTAB Rapid Visual Processing Test (measuring attention response latency and discriminability) and the Iowa Gambling Task (measuring decision-making). Results Adolescents with excess weight compared to healthy weight controls displayed increased cortisol response and less improvement of attentional performance after the social stressor. Decision-making performance decreased after the social stressor in both groups. Conclusion Adolescents who are overweight or obese have increased sensitivity to social stress, which detrimentally impacts attentional skills. PMID:25898204

Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization.

PubMed

Sutton, Blair C; Opp, Mark R

2014-03-01

Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization. Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved.

Does Assessing Eye Alignment along with Refractive Error or Visual Acuity Increase Sensitivity for Detection of Strabismus in Preschool Vision Screening?

PubMed Central

2007-01-01

Purpose Preschool vision screenings often include refractive error or visual acuity (VA) testing to detect amblyopia, as well as alignment testing to detect strabismus. The purpose of this study was to determine the effect of combining screening for eye alignment with screening for refractive error or reduced VA on sensitivity for detection of strabismus, with specificity set at 90% and 94%. Methods Over 3 years, 4040 preschool children were screened in the Vision in Preschoolers (VIP) Study, with different screening tests administered each year. Examinations were performed to identify children with strabismus. The best screening tests for detecting children with any targeted condition were noncycloplegic retinoscopy (NCR), Retinomax autorefractor (Right Manufacturing, Virginia Beach, VA), SureSight Vision Screener (Welch-Allyn, Inc., Skaneateles, NY), and Lea Symbols (Precision Vision, LaSalle, IL and Good-Lite Co., Elgin, IL) and HOTV optotypes VA tests. Analyses were conducted with these tests of refractive error or VA paired with the best tests for detecting strabismus (unilateral cover testing, Random Dot “E” [RDE] and Stereo Smile Test II [Stereo Optical, Inc., Chicago, IL]; and MTI PhotoScreener [PhotoScreener, Inc., Palm Beach, FL]). The change in sensitivity that resulted from combining a test of eye alignment with a test of refractive error or VA was determined with specificity set at 90% and 94%. Results Among the 4040 children, 157 were identified as having strabismus. For screening tests conducted by eye care professionals, the addition of a unilateral cover test to a test of refraction generally resulted in a statistically significant increase (range, 15%–25%) in detection of strabismus. For screening tests administered by trained lay screeners, the addition of Stereo Smile II to SureSight resulted in a statistically significant increase (21%) in sensitivity for detection of strabismus. Conclusions The most efficient and low-cost ways to achieve a statistically significant increase in sensitivity for detection of strabismus were by combining the unilateral cover test with the autorefractor (Retinomax) administered by eye care professionals and by combining Stereo Smile II with SureSight administered by trained lay screeners. The decision of whether to include a test of alignment should be based on the screening program’s goals (e.g., targeted visual conditions) and resources. PMID:17591881

Analysis of Publically Available Skin Sensitization Data from REACH Registrations 2008–2014

PubMed Central

Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P.; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

2017-01-01

Summary The public data on skin sensitization from REACH registrations already included 19,111 studies on skin sensitization in December 2014, making it the largest repository of such data so far (1,470 substances with mouse LLNA, 2,787 with GPMT, 762 with both in vivo and in vitro and 139 with only in vitro data). 21% were classified as sensitizers. The extracted skin sensitization data was analyzed to identify relationships in skin sensitization guidelines, visualize structural relationships of sensitizers, and build models to predict sensitization. A chemical with molecular weight > 500 Da is generally considered non-sensitizing owing to low bioavailability, but 49 sensitizing chemicals with a molecular weight > 500 Da were found. A chemical similarity map was produced using PubChem’s 2D Tanimoto similarity metric and Gephi force layout visualization. Nine clusters of chemicals were identified by Blondel’s module recognition algorithm revealing wide module-dependent variation. Approximately 31% of mapped chemicals are Michael’s acceptors but alone this does not imply skin sensitization. A simple sensitization model using molecular weight and five ToxTree structural alerts showed a balanced accuracy of 65.8% (specificity 80.4%, sensitivity 51.4%), demonstrating that structural alerts have information value. A simple variant of k-nearest neighbors outperformed the ToxTree approach even at 75% similarity threshold (82% balanced accuracy at 0.95 threshold). At higher thresholds, the balanced accuracy increased. Lower similarity thresholds decrease sensitivity faster than specificity. This analysis scopes the landscape of chemical skin sensitization, demonstrating the value of large public datasets for health hazard prediction. PMID:26863411

The Effect of Ocular Surface Regularity on Contrast Sensitivity and Straylight in Dry Eye.

PubMed

Koh, Shizuka; Maeda, Naoyuki; Ikeda, Chikako; Asonuma, Sanae; Ogawa, Mai; Hiraoka, Takahiro; Oshika, Tetsuro; Nishida, Kohji

2017-05-01

To investigate the association between visual function and ocular surface regularity in dry eye. We enrolled 52 eyes of 52 dry eye patients (34 dry eyes with superficial punctate keratopathy [SPK] in the central corneal region [central SPK] and 18 dry eyes without central SPK) and 20 eyes of 20 normal control subjects. All eyes had a best-corrected distance visual acuity better than 20/20. We measured two indices of contrast sensitivity function under photopic conditions: contrast sensitivity and letter contrast sensitivity. The area under the log contrast sensitivity function (AULCSF) was calculated from the obtained contrast sensitivity data. Straylight was quantified using a straylight meter. Dry eyes with central SPK had significantly decreased contrast sensitivity function, including AULCSF and letter contrast sensitivity than those without central SPK and normal eyes (P < 0.05 for each). While the straylight values in both dry eye groups did not differ, straylight values were greater than those in normal eyes (P < 0.05 for both). In dry eye, the AULCSF and letter contrast sensitivity negatively correlated with the central SPK score (R = -0.485, P < 0.001, and R = -0.541, P < 0.001, respectively). In dry eye, reduced contrast sensitivity in part results from central SPK overlying the optical zone and the increased straylight results from tear film instability rather than central SPK.

Using imaginative literature to foster cultural sensitivity.

PubMed

Newcomb, Patricia; Cagle, Carolyn; Walker, Charles

2006-01-01

Readings from two novels, Sandra Cisneros' The House on Mango Street and Toni Morrison's The Bluest Eye, were included in maternal-child clinical courses as part of a pilot project to identify potentially effective strategies for increasing student cultural sensitivity and reflective thinking skills. The authors analyzed student journals to determine student values and beliefs during maternal-child clinical experiences. The study sample consisted of 40 young women enrolled in a baccalaureate nursing program in a private, liberal arts university. These young women consistently interpreted ;the other' in their own image. They responded most strongly to themes of belonging, including the struggles of immigrants to ;fit in,' the ways of being acceptable and valued in U.S. society, and the process through which students as nurses learn to accept and care for others who are different.

The cost of a case of subclinical ketosis in Canadian dairy herds

PubMed Central

Gohary, Khaled; Overton, Michael W.; Von Massow, Michael; LeBlanc, Stephen J.; Lissemore, Kerry D.; Duffield, Todd F.

2016-01-01

The objective of this study was to develop a model to estimate the cost of a case of subclinical ketosis (SCK) in Canadian dairy herds. Costs were derived from the default inputs, and included increased clinical disease incidence attributable to SCK, $76; longer time to pregnancy, $57; culling and death in early lactation attributable to SCK, $26; milk production loss, $44. Given these figures, the cost of 1 case of SCK was estimated to be $203. Sensitivity analysis showed that the estimated cost of a case of SCK was most sensitive to the herd-level incidence of SCK and the cost of 1 day open. In conclusion, SCK negatively impacts dairy herds and losses are dependent on the herd-level incidence and factors included in the calculation. PMID:27429460

The cost of a case of subclinical ketosis in Canadian dairy herds.

PubMed

Gohary, Khaled; Overton, Michael W; Von Massow, Michael; LeBlanc, Stephen J; Lissemore, Kerry D; Duffield, Todd F

2016-07-01

The objective of this study was to develop a model to estimate the cost of a case of subclinical ketosis (SCK) in Canadian dairy herds. Costs were derived from the default inputs, and included increased clinical disease incidence attributable to SCK, $76; longer time to pregnancy, $57; culling and death in early lactation attributable to SCK, $26; milk production loss, $44. Given these figures, the cost of 1 case of SCK was estimated to be $203. Sensitivity analysis showed that the estimated cost of a case of SCK was most sensitive to the herd-level incidence of SCK and the cost of 1 day open. In conclusion, SCK negatively impacts dairy herds and losses are dependent on the herd-level incidence and factors included in the calculation.

Abnormal norepinephrine clearance and adrenergic receptor sensitivity in idiopathic orthostatic intolerance

NASA Technical Reports Server (NTRS)

Jacob, G.; Shannon, J. R.; Costa, F.; Furlan, R.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.

1999-01-01

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of inadequate cerebral perfusion with standing, in the absence of significant orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible underlying pathophysiologies include hypovolemia, partial dysautonomia, or a primary hyperadrenergic state. We tested the hypothesis that patients with OI have functional abnormalities in autonomic neurons regulating cardiovascular responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE) kinetics were determined with the patients supine and standing before and after tyramine administration. In addition, baroreflex sensitivity, hemodynamic responses to bolus injections of adrenergic agonists, and intrinsic heart rate were determined. Resting supine NE spillover and clearance were similar in both groups. With standing, patients had a greater decrease in NE clearance than control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover did not change significantly in patients but increased 50+/-10% in control subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25 bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1 microg, P<0.005), and the dose of phenylephrine required to increase systolic blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11 versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients (12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic agonists demonstrate dramatically disordered sympathetic cardiovascular regulation in patients with chronic OI.

Allergic contact dermatitis caused by isobornyl acrylate in OmniPod, an innovative tubeless insulin pump.

PubMed

Raison-Peyron, Nadia; Mowitz, Martin; Bonardel, Nathalie; Aerts, Olivier; Bruze, Magnus

2018-04-10

The frequency of allergic contact dermatitis caused by (meth)acrylates is increasing worldwide, and isobornyl acrylate (IBOA) has been identified as a culprit sensitizer in FreeStyle Libre, a medical device used by diabetic patients. To report on 4 patients sensitized to IBOA contained in OmniPod, a new, tubeless insulin pump, and to describe the clinical and chemical analytical work-up. Four patients with eczematous skin eruptions after using OmniPod, including 2 with previous adverse skin reactions to FreeStyle Libre, were patch tested with a baseline series and additional (meth)acrylates, including IBOA in several concentrations and/or vehicles. Gas chromatography-mass spectrometry (GC-MS) was used to identify the presence of IBOA in OmniPod. All patients were shown to be sensitized to IBOA. GC-MS identified IBOA in OmniPod, with the highest concentrations being found in the unit itself and not in the adhesive patch. The OmniPod tubeless insulin pump is another source of IBOA, and its use may lead to primary sensitization to this acrylate, or may provoke elicitation of allergic contact dermatitis in previously sensitized patients. Our cases highlight the need to obtain satisfactory cooperation from pharmaceutical companies involved in the manufacture of these widely used medical devices. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Stress Sensitivity Is Associated with Differential Accumulation of Reactive Oxygen and Nitrogen Species in Maize Genotypes with Contrasting Levels of Drought Tolerance

PubMed Central

Yang, Liming; Fountain, Jake C.; Wang, Hui; Ni, Xinzhi; Ji, Pingsheng; Lee, Robert D.; Kemerait, Robert C.; Scully, Brian T.; Guo, Baozhu

2015-01-01

Drought stress decreases crop growth, yield, and can further exacerbate pre-harvest aflatoxin contamination. Tolerance and adaptation to drought stress is an important trait of agricultural crops like maize. However, maize genotypes with contrasting drought tolerances have been shown to possess both common and genotype-specific adaptations to cope with drought stress. In this research, the physiological and metabolic response patterns in the leaves of maize seedlings subjected to drought stress were investigated using six maize genotypes including: A638, B73, Grace-E5, Lo964, Lo1016, and Va35. During drought treatments, drought-sensitive maize seedlings displayed more severe symptoms such as chlorosis and wilting, exhibited significant decreases in photosynthetic parameters, and accumulated significantly more reactive oxygen species (ROS) and reactive nitrogen species (RNS) than tolerant genotypes. Sensitive genotypes also showed rapid increases in enzyme activities involved in ROS and RNS metabolism. However, the measured antioxidant enzyme activities were higher in the tolerant genotypes than in the sensitive genotypes in which increased rapidly following drought stress. The results suggest that drought stress causes differential responses to oxidative and nitrosative stress in maize genotypes with tolerant genotypes with slower reaction and less ROS and RNS production than sensitive ones. These differential patterns may be utilized as potential biological markers for use in marker assisted breeding. PMID:26492235

A role for tyrosinase-related protein 1 in 4-tert-butylphenol-induced toxicity in melanocytes: Implications for vitiligo.

PubMed

Manga, Prashiela; Sheyn, David; Yang, Fan; Sarangarajan, Rangaprasad; Boissy, Raymond E

2006-11-01

Vitiligo presents with depigmented cutaneous lesions following localized melanocyte death. Multiple factors contribute to cell death, including genetically determined susceptibility to trauma, and environmental factors, such as exposure to 4-tert-butylphenol (4-TBP). We demonstrate that 4-TBP induces oxidative stress that is more readily overcome by melanocytes from normally pigmented individuals than from two individuals with vitiligo. The antioxidant catalase selectively and significantly reduced death of melanocytes derived from two individuals with vitiligo, indicating a role for oxidative stress in vitiligo pathogenesis. In normal melanocytes, oxidative stress results in reduced expression of microphthalmia-associated transcription factor (MITF). Melanocyte-stimulating hormone-induced expression of MITF protein caused increased sensitivity to 4-TBP, whereas sensitivity of melanomas correlated with MITF expression. MITF stimulates melanin synthesis by up-regulating expression of melanogenic enzymes such as tyrosinase-related protein-1 (Tyrp1). Although melanin content per se did not affect sensitivity to 4-TBP, expression of Tyrp1 significantly increased sensitivity. Melanocytes and melanomas that express functional Tyrp1 were significantly more sensitive to 4-TBP than Tyrp1-null cells. Thus, normal melanocytes respond to 4-TBP by reducing expression of MITF and Tyrp1. We hypothesize that melanocytes in vitiligo demonstrate reduced ability to withstand oxidative stress due, partly, to a disruption in MITF regulation of Tyrp1.

The Role of Aldosterone in Obesity-Related Hypertension

PubMed Central

Kawarazaki, Wakako

2016-01-01

Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin–angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension. PMID:26927805

Subjective Visual Performance and Objective Optical Quality With Intraocular Lens Glistening and Surface Light Scattering.

PubMed

Luo, Furong; Bao, Xuan; Qin, Yingyan; Hou, Min; Wu, Mingxing

2018-06-01

To evaluate the long-term effect of glistenings and surface light scattering of intraocular lenses (IOLs) on visual and optical performance after cataract surgery. Pseudophakic eyes that underwent standard phacoemulsification and two types of hydrophobic acrylic spherical IOL implantation without complications for at least 5 years were included in this retrospective study. Participants were divided into the glistenings, surface light scattering, and control groups according to the current condition of the IOLs. Then participants received a follow-up examination including uncorrected and corrected distance visual acuity (UDVA and CDVA), contrast sensitivity, straylight, and intraocular higher order aberrations, as well as point spread function (PSF) and modulation transfer function (MTF). A total of 140 eyes were included in the study. UDVA, CDVA, and glare sensitivity were not significantly different among the three groups (P > .05). However, compared with the control group, the IOLs of the glistenings and surface light scattering groups were associated with significantly lower contrast sensitivity under no glare conditions. Furthermore, eye with glistenings exhibited the highest straylight value (P < .05), whereas no difference was found between the surface light scattering and control groups. In contrast to the control group, the spherical aberration increased and the mean values of PSF and MTF decreased in the glistenings and surface light scattering groups. Both glistenings and surface light scattering tend to impair subjective visual performance, such as contrast sensitivity, and potentially affect objective optical quality, including straylight, spherical aberration, PSF, and MTF. [J Refract Surg. 2018;34(6):372-378.]. Copyright 2018, SLACK Incorporated.

Exercise Training-Induced Adaptations Associated with Increases in Skeletal Muscle Glycogen Content

PubMed Central

Manabe, Yasuko; Gollisch, Katja S.C.; Holton, Laura; Kim, Young–Bum; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.

2012-01-01

Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism for increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4, or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. Compared to sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase 3 (GSK3). Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1, GSK3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks and may function as a negative feedback to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase and PP1activity. PMID:23206309

The Usefulness of Selected Physicochemical Indices, Cell Membrane Integrity and Sperm Chromatin Structure in Assessments of Boar Semen Sensitivity

PubMed Central

Wysokińska, A.; Kondracki, S.; Iwanina, M.

2015-01-01

The present work describes experiments undertaken to evaluate the usefulness of selected physicochemical indices of semen, cell membrane integrity and sperm chromatin structure for the assessment of boar semen sensitivity to processes connected with pre-insemination procedures. The experiments were carried out on 30 boars: including 15 regarded as providers of sensitive semen and 15 regarded as providers of semen that is little sensitive to laboratory processing. The selection of boars for both groups was based on sperm morphology analyses, assuming secondary morphological change incidence in spermatozoa as the criterion. Two ejaculates were manually collected from each boar at an interval of 3 to 4 months. The following analyses were carried out for each ejaculate: sperm motility assessment, sperm pH measurement, sperm morphology assessment, sperm chromatin structure evaluation and cell membrane integrity assessment. The analyses were performed three times. Semen storage did not cause an increase in the incidence of secondary morphological changes in the group of boars considered to provide sperm of low sensitivity. On the other hand, with continued storage there was a marked increase in the incidence of spermatozoa with secondary morphological changes in the group of boars regarded as producing more sensitive semen. Ejaculates of group I boars evaluated directly after collection had an approximately 6% smaller share of spermatozoa with undamaged cell membranes than the ejaculates of boars in group II (p≤0.05). In the process of time the percentage of spermatozoa with undamaged cell membranes decreased. The sperm of group I boars was characterised with a lower sperm motility than the semen of group II boars. After 1 hour of storing diluted semen, the sperm motility of boars producing highly sensitive semen was already 4% lower (p≤0.05), and after 24 hours of storage it was 6.33% lower than that of the boars that produced semen with a low sensitivity. Factors that confirm the accuracy of insemination male selection can include a low rate of sperm motility decrease during the storage of diluted semen, low and contained incidence of secondary morphological changes in spermatozoa during semen storage and a high frequency of spermatozoa with undamaged cell membranes. PMID:26580438

Stimulation of erythrocyte phosphatidylserine exposure by mercury ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eisele, Kerstin; Lang, Philipp A.; Kempe, Daniela S.

2006-01-15

The sequelae of mercury intoxication include induction of apoptosis. In nucleated cells, Hg{sup 2+}-induced apoptosis involves mitochondrial damage. The present study has been performed to elucidate effects of Hg{sup 2+} in erythrocytes which lack mitochondria but are able to undergo apoptosis-like alterations of the cell membrane. Previous studies have documented that activation of a Ca{sup 2+}-sensitive erythrocyte scramblase leads to exposure of phosphatidylserine at the erythrocyte surface, a typical feature of apoptotic cells. The erythrocyte scramblase is activated by osmotic shock, oxidative stress and/or energy depletion which increase cytosolic Ca{sup 2+} activity and/or activate a sphingomyelinase leading to formation ofmore » ceramide. Ceramide sensitizes the scramblase to Ca{sup 2+}. The present experiments explored the effect of Hg{sup 2+} ions on erythrocytes. Phosphatidylserine exposure after mercury treatment was estimated from annexin binding as determined in FACS analysis. Exposure to Hg{sup 2+} (1 {mu}M) indeed significantly increased annexin binding from 2.3 {+-} 0.5% (control condition) to 23 {+-} 6% (n = 6). This effect was paralleled by activation of a clotrimazole-sensitive K{sup +}-selective conductance as measured by patch-clamp recordings and by transient cell shrinkage. Further experiments revealed also an increase of ceramide formation by {approx}66% (n = 7) after challenge with mercury (1 {mu}M). In conclusion, mercury ions activate a clotrimazole-sensitive K{sup +}-selective conductance leading to transient cell shrinkage. Moreover, Hg{sup 2+} increases ceramide formation. The observed mechanisms could similarly participate in the triggering of apoptosis in nucleated cells by Hg{sup 2+}.« less

Sensitivity of nocturnal boundary layer temperature to tropospheric aerosol surface radiative forcing under clear-sky conditions

NASA Astrophysics Data System (ADS)

Nair, Udaysankar S.; McNider, Richard; Patadia, Falguni; Christopher, Sundar A.; Fuller, Kirk

2011-01-01

Since the middle of the last century, global surface air temperature exhibits an increasing trend, with nocturnal temperatures increasing at a much higher rate. Proposed causative mechanisms include the radiative impact of atmospheric aerosols on the nocturnal boundary layer (NBL) where the temperature response is amplified due to shallow depth and its sensitivity to potential destabilization. A 1-D version of the Regional Atmospheric Modeling System is used to examine the sensitivity of the nocturnal boundary layer temperature to the surface longwave radiative forcing (SLWRF) from urban aerosol loading and doubled atmospheric carbon dioxide concentrations. The analysis is conducted for typical midlatitude nocturnal boundary layer case days from the CASES-99 field experiment and is further extended to urban sites in Pune and New Delhi, India. For the cases studied, locally, the nocturnal SLWRF from urban atmospheric aerosols (2.7-47 W m-2) is comparable or exceeds that caused by doubled atmospheric carbon dioxide (3 W m-2), with the surface temperature response ranging from a compensation for daytime cooling to an increase in the nocturnal minimum temperature. The sensitivity of the NBL to radiative forcing is approximately 4 times higher compared to the daytime boundary layer. Nighttime warming or cooling may occur depending on the nature of diurnal variations in aerosol optical depth. Soil moisture also modulates the magnitude of SLWRF, decreasing from 3 to 1 W m-2 when soil saturation increases from 37% to 70%. These results show the importance of aerosols on the radiative balance of the climate system.

A clinical perspective on a pain neuroscience education approach to manual therapy.

PubMed

Louw, Adriaan; Nijs, Jo; Puentedura, Emilio J

2017-07-01

In recent years, there has been an increased interest in pain neuroscience education (PNE) in physical therapy. There is growing evidence for the efficacy of PNE to decrease pain, disability, fear-avoidance, pain catastrophization, limited movement, and health care utilization in people struggling with pain. PNE teaches people in pain more about the biology and physiology of their pain experience including processes such as central sensitization, peripheral sensitization, allodynia, inhibition, facilitation, neuroplasticity and more. PNE's neurobiological model often finds itself at odds with traditional biomedical models used in physical therapy. Traditional biomedical models, focusing on anatomy, pathoanatomy, and biomechanics have been shown to have limited efficacy in helping people understand their pain, especially chronic pain, and may in fact even increase a person's pain experience by increasing fear-avoidance and pain catastrophization. An area of physical therapy where the biomedical model is used a lot is manual therapy. This contrast between PNE and manual therapy has seemingly polarized followers from each approach to see PNE as a 'hands-off' approach even having clinicians categorize patients as either in need of receiving PNE (with no hands-on), or hands-on with no PNE. In this paper, we explore the notion of PNE and manual therapy co-existing. PNE research has shown to have immediate effects of various clinical signs and symptoms associated with central sensitization. Using a model of sensitization (innocuous, noxious, and allodynia), we argue that PNE can be used in a manual therapy model, especially treating someone where the nervous system has become increasingly hypervigilant. Level of Evidence : VII.

Rapid Clinical Score for the Diagnosis of Tuberculous Meningitis: A Retrospective Cohort Study

PubMed Central

Jipa, Raluca; Olaru, Ioana D.; Manea, Eliza; Merisor, Simona; Hristea, Adriana

2017-01-01

Objective: The aim of our study was to retrospectively validate a previously described rapid clinical score (RCS) in distinguishing tuberculous meningitis (TBM) from viral meningitis (VM) in people who are at increased risk of tuberculosis, as well as from cryptococcal meningitis (CM) in HIV-infected patients. Methods: We performed a retrospective study of patients admitted with a diagnosis of aseptic meningitis between January 2012 and December 2015, to a referral hospital for infectious diseases. The variables included in RCS were duration of symptoms before admission, neurological stage, cerebrospinal fluid (CSF) to blood glucose ratio, and CSF protein. We included in this retrospective study 31 patients with definite or probable TBM including 14 HIV-infected patients, 62 HIV-noninfected patients with VM, and 18 HIV-infected patients with CM. Results: The sensitivity of RCS to distinguish TBM from VM was 96.7%, with a specificity of 81.1% and the area under the receiver operating characteristic (ROC) curve was 0.949 (0.90–0.99). When all four criteria from the RCS were present, the specificity increased at 100%. In HIV-infected patients, the sensitivity and specificity of RCS in differentiating TBM from CM were 86.6% and 27.7%, respectively, and the area under the ROC curve was 0.669 (0.48–0.85). Conclusion: This easy-to-use RCS was found to be helpful in differentiating TBM from VM, with a better sensitivity than molecular amplification techniques and a relatively good specificity. However, the RCS was not useful to differentiate between TBM and CM in HIV-infected patients. PMID:29184338

Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

PubMed Central

2011-01-01

Background We and others have demonstrated previously that ghrelin receptor (GhrR) knock out (KO) mice fed a high fat diet (HFD) have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd), and decreased hepatic glucose production (HGP). HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is characterized by robust improvements of glucose disposal in both normal and metabolically challenged states, relative to WT controls. GhrR KO mice have an intact 1st phase insulin response but require significantly less insulin for glucose disposal. Our experiments reveal that the insulin sensitivity of GhrR KO mice is due to both BW independent and dependent factors. We also provide several lines of evidence that a key feature of the GhrR KO mouse is maintenance of hepatic insulin sensitivity during metabolic challenge. PMID:21211044

Behavioral economic analysis of withdrawal- and cue-elicited craving for tobacco: an initial investigation.

PubMed

MacKillop, James; Brown, Courtney L; Stojek, Monika K; Murphy, Cara M; Sweet, Lawrence; Niaura, Ray S

2012-12-01

The role of craving in nicotine dependence remains controversial and may be a function of measurement challenges. The current study used behavioral economic approach to test the hypotheses that subjective craving from acute withdrawal and exposure to tobacco cues dynamically increases the relative value of cigarettes. Using a 2 (1-hr/12-hr deprivation) × 2 (neutral/tobacco cues) within-subjects design, 33 nicotine dependent adults completed 2 laboratory sessions. Assessment included subjective craving and behavioral economic indices of cigarette demand, namely Intensity (i.e., cigarette consumption at zero cost), O(max) (i.e., maximum total expenditure), Breakpoint (i.e., highest acceptable price for cigarettes), P(max) (i.e., price at which consumption becomes sensitive to price), and elasticity (i.e., price sensitivity). Behavioral economic indices were generated using a Cigarette Purchase Task in which participants selected between cigarettes for a subsequent 2-hr self-administration period and money. Main effects of deprivation and tobacco cues were present for subjective craving and multiple behavioral economic indices of cigarette demand. Interestingly, deprivation significantly increased Breakpoint (p ≤ .01) and P(max) (p ≤ .05) and had trend-level effects on Intensity and O(max) (p ≤ .10); whereas cues significantly reduced elasticity (p ≤ .01), reflecting lower sensitivity to increasing prices. Heterogeneous associations were evident among the motivational variables but with aggregations suggesting variably overlapping motivational channels. These findings further support a behavioral economic approach to craving and a multidimensional conception of acute motivation for addictive drugs. Methodological considerations, including potential order effects, and the need for further refinement of these findings are discussed.

Study design for a randomized controlled trial to increase the relative reinforcing value of vegetable consumption using incentive sensitization among obese and overweight people.

PubMed

Jahns, Lisa; Roemmich, James N

2016-09-01

In this manuscript, we present the protocol for a study that applies incentive sensitization theory to improve vegetable intake in overweight and obese adults. This 8-week, randomized, controlled, community-based feeding study with an 8-week follow-up seeks to use repeated exposure to amounts of vegetables recommended by federal guidance to increase the primary outcome of the relative reinforcing value of vegetables compared to a snack food. A community-based design is used to give participants autonomy in choosing their method of exposure. Secondary outcomes include: 1) Determine potential moderators of incentive sensitization of vegetables, including genetic polymorphisms associated with food reinforcement and obesity, 6-n-propylthiouracil tasting status, and delay discounting. 2) Determine whether adding vegetables to the diet results in participants substituting low-energy-dense vegetables for energy-dense foods or whether energy-dense food consumption is independent of vegetable consumption. 3) Determine whether reductions in adiposity are associated with substitution of vegetables in the diet. 4) Determine if markers of bone turnover change. 5) Assess changes in self-reported secondary outcomes measured by questionnaire such as self-efficacy to eat vegetables. The results of this study will provide information about the drivers of individual choice to consume recommended amounts of vegetables. The understanding gained will help increase the effectiveness and sustainability of behavior-based interventions focused on improving vegetable intake. This information may also be used to assist in setting dietary guidance targets for the amounts and types of vegetables Americans can, and should, consume. Published by Elsevier Inc.

Sex-dependent effects of chronic psychosocial stress on myocardial sensitivity to ischemic injury.

PubMed

Rorabaugh, Boyd R; Krivenko, Anna; Eisenmann, Eric D; Bui, Albert D; Seeley, Sarah; Fry, Megan E; Lawson, Joseph D; Stoner, Lauren E; Johnson, Brandon L; Zoladz, Phillip R

2015-01-01

Individuals with post-traumatic stress disorder (PTSD) experience many debilitating symptoms, including intrusive memories, persistent anxiety and avoidance of trauma-related cues. PTSD also results in numerous physiological complications, including increased risk for cardiovascular disease (CVD). However, characterization of PTSD-induced cardiovascular alterations is lacking, especially in preclinical models of the disorder. Thus, we examined the impact of a psychosocial predator-based animal model of PTSD on myocardial sensitivity to ischemic injury. Male and female Sprague-Dawley rats were exposed to psychosocial stress or control conditions for 31 days. Stressed rats were given two cat exposures, separated by a period of 10 days, and were subjected to daily social instability throughout the paradigm. Control rats were handled daily for the duration of the experiment. Rats were tested on the elevated plus maze (EPM) on day 32, and hearts were isolated on day 33 and subjected to 20 min ischemia and 2 h reperfusion on a Langendorff isolated heart system. Stressed male and female rats gained less body weight relative to controls, but only stressed males exhibited increased anxiety on the EPM. Male, but not female, rats exposed to psychosocial stress exhibited significantly larger infarcts and attenuated post-ischemic recovery of contractile function compared to controls. Our data demonstrate that predator stress combined with daily social instability sex-dependently increases myocardial sensitivity to ischemic injury. Thus, this manipulation may be useful for studying potential mechanisms underlying cardiovascular alterations in PTSD, as well as sex differences in the cardiovascular stress response.

Do land surface models need to include differential plant species responses to drought? Examining model predictions across a mesic-xeric gradient in Europe

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Kauwe, M. G.; Zhou, S. -X.; Medlyn, B. E.

Future climate change has the potential to increase drought in many regions of the globe, making it essential that land surface models (LSMs) used in coupled climate models realistically capture the drought responses of vegetation. Recent data syntheses show that drought sensitivity varies considerably among plants from different climate zones, but state-of-the-art LSMs currently assume the same drought sensitivity for all vegetation. We tested whether variable drought sensitivities are needed to explain the observed large-scale patterns of drought impact on the carbon, water and energy fluxes. We implemented data-driven drought sensitivities in the Community Atmosphere Biosphere Land Exchange (CABLE) LSMmore » and evaluated alternative sensitivities across a latitudinal gradient in Europe during the 2003 heatwave. The model predicted an overly abrupt onset of drought unless average soil water potential was calculated with dynamic weighting across soil layers. We found that high drought sensitivity at the most mesic sites, and low drought sensitivity at the most xeric sites, was necessary to accurately model responses during drought. Furthermore, our results indicate that LSMs will over-estimate drought impacts in drier climates unless different sensitivity of vegetation to drought is taken into account.« less

Anhedonia and anxiety sensitivity: prospective relationships to nicotine withdrawal symptoms during smoking cessation.

PubMed

Langdon, Kirsten J; Leventhal, Adam M; Stewart, Sherry; Rosenfield, David; Steeves, Dan; Zvolensky, Michael J

2013-05-01

The aim of the present investigation was to explore the main and interactive effects of anhedonic depressive symptoms and anxiety sensitivity in terms of the individual components of nicotine withdrawal symptoms experienced on quit day as well as throughout the initial 14 days of cessation. Participants included 65 daily cigarette smokers (38 women; Mage = 46.08 years, SD = 9.12) undergoing psychosocial-pharmacological cessation treatment. Results indicated that, after controlling for the effects of participant sex and nicotine dependence, anhedonic depression symptoms, but not anxiety sensitivity, significantly predicted quit day levels of mood-based nicotine withdrawal symptoms. Conversely, anxiety sensitivity, but not anhedonic depression symptoms, was significantly related to the change in most nicotine withdrawal symptoms over time. Finally, our results revealed a significant interaction between anxiety sensitivity and anhedonic depression symptoms related to the slope of certain withdrawal symptoms over time. Specifically, among participants with higher levels of anxiety sensitivity, greater levels of anhedonic depression symptoms were related to greater increases in withdrawal symptoms over time for two of the nine anxiety-relevant components of nicotine withdrawal (restlessness and frustration). Among high anxiety-sensitivity persons, compared with those low in anxiety sensitivity, anhedonic depression symptoms may be more relevant to the experience of some withdrawal symptoms being more intense and persistent during the early phases of quitting.

Sensory focusing versus distraction and pain: moderating effects of anxiety sensitivity in males and females.

PubMed

Thompson, Trevor; Keogh, Edmund; French, Christopher C

2011-08-01

Although previous research has examined whether the relative effects of distraction and sensory focusing on pain are dependent upon anxiety sensitivity, such research has concentrated primarily on females. Given the increasing emergence of sex differences in pain processing, the current study aimed to examine whether any influence of anxiety sensitivity on coping effectiveness differs for males and females. The sample consisted of 76 healthy adults (41 males and 35 females), all of whom received distraction and sensory-focusing instructions and underwent noxious thermal testing (cold and heat). Results showed that anxiety sensitivity was positively associated with the emotional qualities of cold pain, and that males exhibited significantly greater heat pain tolerance than females. In addition, within males, a significant coping × anxiety sensitivity effect was found for cold tolerance, with distraction superior to sensory focusing only when anxiety sensitivity was high. In females, however, distraction was a superior strategy irrespective of anxiety sensitivity. This study highlights the importance of considering anxiety sensitivity and sex when examining the relative effectiveness of attentional pain coping strategies. This finding may be potentially beneficial to clinicians considering pain management interventions that include a cognitive or attentional component. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Do land surface models need to include differential plant species responses to drought? Examining model predictions across a mesic-xeric gradient in Europe

DOE PAGES

De Kauwe, M. G.; Zhou, S. -X.; Medlyn, B. E.; ...

2015-12-21

Future climate change has the potential to increase drought in many regions of the globe, making it essential that land surface models (LSMs) used in coupled climate models realistically capture the drought responses of vegetation. Recent data syntheses show that drought sensitivity varies considerably among plants from different climate zones, but state-of-the-art LSMs currently assume the same drought sensitivity for all vegetation. We tested whether variable drought sensitivities are needed to explain the observed large-scale patterns of drought impact on the carbon, water and energy fluxes. We implemented data-driven drought sensitivities in the Community Atmosphere Biosphere Land Exchange (CABLE) LSMmore » and evaluated alternative sensitivities across a latitudinal gradient in Europe during the 2003 heatwave. The model predicted an overly abrupt onset of drought unless average soil water potential was calculated with dynamic weighting across soil layers. We found that high drought sensitivity at the most mesic sites, and low drought sensitivity at the most xeric sites, was necessary to accurately model responses during drought. Furthermore, our results indicate that LSMs will over-estimate drought impacts in drier climates unless different sensitivity of vegetation to drought is taken into account.« less

Rebelling against the (Insulin) Resistance: A Review of the Proposed Insulin-Sensitizing Actions of Soybeans, Chickpeas, and Their Bioactive Compounds

PubMed Central

Zahradka, Peter

2018-01-01

Insulin resistance is a major risk factor for diseases such as type 2 diabetes and metabolic syndrome. Current methods for management of insulin resistance include pharmacological therapies and lifestyle modifications. Several clinical studies have shown that leguminous plants such as soybeans and pulses (dried beans, dried peas, chickpeas, lentils) are able to reduce insulin resistance and related type 2 diabetes parameters. However, to date, no one has summarized the evidence supporting a mechanism of action for soybeans and pulses that explains their ability to lower insulin resistance. While it is commonly assumed that the biological activities of soybeans and pulses are due to their antioxidant activities, these bioactive compounds may operate independent of their antioxidant properties and, thus, their ability to potentially improve insulin sensitivity via alternative mechanisms needs to be acknowledged. Based on published studies using in vivo and in vitro models representing insulin resistant states, the proposed mechanisms of action for insulin-sensitizing actions of soybeans, chickpeas, and their bioactive compounds include increasing glucose transporter-4 levels, inhibiting adipogenesis by down-regulating peroxisome proliferator-activated receptor-γ, reducing adiposity, positively affecting adipokines, and increasing short-chain fatty acid-producing bacteria in the gut. Therefore, this review will discuss the current evidence surrounding the proposed mechanisms of action for soybeans and certain pulses, and their bioactive compounds, to effectively reduce insulin resistance. PMID:29601521

Sensitivity of climate and atmospheric CO2 to deep-ocean and shallow-ocean carbonate burial

NASA Technical Reports Server (NTRS)

Volk, Tyler

1989-01-01

A model of the carbonate-silicate geochemical cycle is presented that distinguishes carbonate masses produced by shallow-ocean and deep-ocean carbonate burial and shows that reasonable increases in deep-ocean burial could produce substantial warmings over a few hundred million years. The model includes exchanges between crust and mantle; transients from burial shifts are found to be sensitive to the fraction of nondegassed carbonates subducted into the mantle. Without the habitation of the open ocean by plankton such as foraminifera and coccolithophores, today's climate would be substantially colder.

Antibody-free PRISM-SRM for multiplexed protein quantification: Is this the new competition for immunoassays in bioanalysis?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shi, Tujin; Qian, Weijun

2013-02-01

Highly sensitive technologies for multiplexed quantification of a large number of candidate proteins will play an increasingly important role in clinical biomarker discovery, systems biology, and general biomedical research. Herein we introduce the new PRISM-SRM technology, which represents a highly sensitive multiplexed quantification technology capable of simultaneous quantification of many low-abundance proteins without the need of affinity reagents. The versatility of antibody-free PRISM-SRM for quantifying various types of targets including protein isoforms, protein modifications, metabolites, and others, thus offering new competition with immunoassays.

Protective Properties of Radio-Chemoresistant Glioblastoma Stem Cell Clones Are Associated with Metabolic Adaptation to Reduced Glucose Dependence

PubMed Central

Yamada, Kazunari; Tso, Jonathan L.; Menjivar, Jimmy C.; Tian, Jane Y.; Yong, William H.; Schaue, Dörthe; Mischel, Paul S.; Cloughesy, Timothy F.; Nelson, Stanley F.; Liau, Linda M.; McBride, William; Tso, Cho-Lea

2013-01-01

Glioblastoma stem cells (GSC) are a significant cell model for explaining brain tumor recurrence. However, mechanisms underlying their radiochemoresistance remain obscure. Here we show that most clonogenic cells in GSC cultures are sensitive to radiation treatment (RT) with or without temozolomide (TMZ). Only a few single cells survive treatment and regain their self-repopulating capacity. Cells re-populated from treatment-resistant GSC clones contain more clonogenic cells compared to those grown from treatment-sensitive GSC clones, and repeated treatment cycles rapidly enriched clonogenic survival. When compared to sensitive clones, resistant clones exhibited slower tumor development in animals. Upregulated genes identified in resistant clones via comparative expression microarray analysis characterized cells under metabolic stress, including blocked glucose uptake, impaired insulin/Akt signaling, enhanced lipid catabolism and oxidative stress, and suppressed growth and inflammation. Moreover, many upregulated genes highlighted maintenance and repair activities, including detoxifying lipid peroxidation products, activating lysosomal autophagy/ubiquitin-proteasome pathways, and enhancing telomere maintenance and DNA repair, closely resembling the anti-aging effects of caloric/glucose restriction (CR/GR), a nutritional intervention that is known to increase lifespan and stress resistance in model organisms. Although treatment–introduced genetic mutations were detected in resistant clones, all resistant and sensitive clones were subclassified to either proneural (PN) or mesenchymal (MES) glioblastoma subtype based on their expression profiles. Functional assays demonstrated the association of treatment resistance with energy stress, including reduced glucose uptake, fatty acid oxidation (FAO)-dependent ATP maintenance, elevated reactive oxygen species (ROS) production and autophagic activity, and increased AMPK activity and NAD+ levels accompanied by upregulated mRNA levels of SIRT1/PGC-1α axis and DNA repair genes. These data support the view that treatment resistance may arise from quiescent GSC exhibiting a GR-like phenotype, and suggest that targeting stress response pathways of resistant GSC may provide a novel strategy in combination with standard treatment for glioblastoma. PMID:24260384

Feasibility study for rocket ozone measurements in the 50 to 80 km region using a chemiluminescent technique

NASA Technical Reports Server (NTRS)

Goodman, P.

1973-01-01

A study has been conducted to determine the feasibility of increasing sensitivity for ozone detection. The detection technique employed is the chemiluminescent reaction of ozone with a rhodamine-B impregnated disk. Previously achieved sensitivities are required to be increased by a factor of about 20 to permit measurements at altitudes of 80 km. Sensitivity was increased by using a more sensitive photomultiplier tube, by increasing the gas velocity past the disk, by different disk preparation techniques, and by using reflective coatings in the disk chamber and on the uncoated side of the glass disk. Reflective coatings provided the largest sensitivity increase. The sum of all these changes was a sensitivity increased by an estimated factor of 70, more than sufficient to permit measurement of ambient ozone concentrations at altitudes of 80 km.

Male-typical courtship, spawning behavior, and olfactory sensitivity are induced to different extents by androgens in the goldfish suggesting they are controlled by different neuroendocrine mechanisms.

PubMed

Ghosal, Ratna; Sorensen, Peter W

2016-06-01

Male-typical reproductive behaviors vary greatly between different species of fishes with androgens playing a variety of roles that appear especially important in the gonochorist cypriniform fishes. The goldfish is an important model for the cypriniformes and while it is clear that male goldfish are fully feminized by prostaglandin F2α(PGF2α), it is not clear whether females will exhibit normal levels of male-typical reproductive behaviors as well as olfactory function when treated with androgens. To answer this question, we exposed sexually-regressed adult female goldfish to several types of androgen and monitored their tendencies to court (inspect females) and mate (spawn, or attempt to release gametes) while monitoring their olfactory sensitivity until changes in these attributes were maximized. Untreated adult males (intact) were included to determine the extent of masculinization. Treatments included the natural androgens, 11-ketotestosterone and testosterone (KT and T), administered via capsules (KT+T-implanted fish); the artificial androgen, methyltestosterone (MT), administered via capsules (MT-C); and MT administered in the fishes' water (MT-B). Male-typical olfactory sensitivity to a pheromone (15keto-PGF2α) increased in all androgen-treated groups and by week 6 was fully equivalent to that of males. Male-typical courtship behavior increased in all androgen-treated groups although slowly, and only MT-B females came to exhibit levels equivalent to those of males after 18weeks. In contrast, male-typical mating activity increased only slightly, with MT-B females reaching levels one-third that of males after 30weeks. We conclude that while androgens fully masculinize olfactory sensitivity and courtship behavior in goldfish, mating behavior is controlled by a different neuroendocrine mechanism(s) that has yet to be fully elucidated. Copyright © 2016 Elsevier Inc. All rights reserved.

Slow Temporal Summation of Pain for Assessment of Central Pain Sensitivity and Clinical Pain of Fibromyalgia Patients

PubMed Central

Staud, Roland; Weyl, Elizabeth E.; Riley, Joseph L.; Fillingim, Roger B.

2014-01-01

Background In healthy individuals slow temporal summation of pain or wind-up (WU) can be evoked by repetitive heat-pulses at frequencies of ≥.33 Hz. Previous WU studies have used various stimulus frequencies and intensities to characterize central sensitization of human subjects including fibromyalgia (FM) patients. However, many trials demonstrated considerable WU-variability including zero WU or even wind-down (WD) at stimulus intensities sufficient for activating C-nociceptors. Additionally, few WU-protocols have controlled for contributions of individual pain sensitivity to WU-magnitude, which is critical for WU-comparisons. We hypothesized that integration of 3 different WU-trains into a single WU-response function (WU-RF) would not only control for individuals’ pain sensitivity but also better characterize their central pain responding including WU and WD. Methods 33 normal controls (NC) and 38 FM patients participated in a study of heat-WU. We systematically varied stimulus intensities of.4 Hz heat-pulse trains applied to the hands. Pain summation was calculated as difference scores of 1st and 5th heat-pulse ratings. WU-difference (WU-Δ) scores related to 3 heat-pulse trains (44°C, 46°C, 48°C) were integrated into WU-response functions whose slopes were used to assess group differences in central pain sensitivity. WU-aftersensations (WU-AS) at 15 s and 30 s were used to predict clinical FM pain intensity. Results WU-Δ scores linearly accelerated with increasing stimulus intensity (p<.001) in both groups of subjects (FM>NC) from WD to WU. Slope of WU-RF, which is representative of central pain sensitivity, was significantly steeper in FM patients than NC (p<.003). WU-AS predicted clinical FM pain intensity (Pearson’s r = .4; p<.04). Conclusions Compared to single WU series, WU-RFs integrate individuals’ pain sensitivity as well as WU and WD. Slope of WU-RFs was significantly different between FM patients and NC. Therefore WU-RF may be useful for assessing central sensitization of chronic pain patients in research and clinical practice. PMID:24558475

Increasing productivity for the analysis of trace contaminants in food by gas chromatography-mass spectrometry using automated liner exchange, backflushing and heart-cutting.

PubMed

David, Frank; Tienpont, Bart; Devos, Christophe; Lerch, Oliver; Sandra, Pat

2013-10-25

Laboratories focusing on residue analysis in food are continuously seeking to increase sample throughput by minimizing sample preparation. Generic sample extraction methods such as QuEChERS lack selectivity and consequently extracts are not free from non-volatile material that contaminates the analytical system. Co-extracted matrix constituents interfere with target analytes, even if highly sensitive and selective GC-MS/MS is used. A number of GC approaches are described that can be used to increase laboratory productivity. These techniques include automated inlet liner exchange and column backflushing for preservation of the performance of the analytical system and heart-cutting two-dimensional GC for increasing sensitivity and selectivity. The application of these tools is illustrated by the analysis of pesticides in vegetables and fruits, PCBs in milk powder and coplanar PCBs in fish. It is demonstrated that considerable increase in productivity can be achieved by decreasing instrument down-time, while analytical performance is equal or better compared to conventional trace contaminant analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

Thoracoscopic sympathectomy increases efferent cardiac vagal activity and baroreceptor sensitivity.

PubMed

Bygstad, Elisabeth; Terkelsen, Astrid J; Pilegaard, Hans K; Hansen, John; Mølgaard, Henning; Hjortdal, Vibeke E

2013-09-01

Thoracoscopic sympathectomy at levels T2 or T2-T3 is a treatment for focal hyperhidrosis and facial blushing. These levels of the sympathetic trunk innervate the heart, and consequently, the procedure is reported to change the heart rate variability due to changes in efferent cardiac autonomic activity. Our objective was to investigate the effects of thoracoscopic sympathectomy on global autonomic control, including baroreceptor sensitivity. Eight patients (6 F, median age 28 years [range 20-58 years]) were exposed to the tilt-table test and cardiopulmonary exercise test before, and 3 months after, thoracoscopic sympathectomy. Eight healthy age-, gender- and BMI-matched controls were used as controls and underwent the same tests once. During tilt-table testing electrocardiogram, blood pressure, impedance cardiography and respiration were measured continuously, and efferent cardiac autonomic balance was estimated. The heart rate measured during orthostatic stress test was lowered after thoracoscopic sympathectomy (between-group; P = 0.01) due to a change in autonomic tone, with increased vagal (high-frequency power n.u.; P = 0.001), and reduced sympathetic efferent cardiac activity (low-frequency power n.u.; P < 0.001). Baroreceptor sensitivity measured during rest was increased (26 ± 13 vs 44 ± 19 ms/mmHg; P = 0.01), and diastolic blood pressure reduced after surgery (P = 0.01). The increases in systolic blood pressure and the sympathetic marker CCV-LF in response to orthostatic stress were higher before sympathectomy, with almost no increases post-surgically (condition × group interaction; P = 0.01 and P = 0.001, respectively). We found no change in post-procedure exercise capacity, although patients had a lower peak VO2 and maximal cardiac index than controls. Thoracoscopic sympathectomy changes the autonomic tone towards increased vagal activity; this is potentially cardioprotective. To our knowledge, this is the first study to show increased baroreceptor sensitivity after thoracoscopic sympathectomy.

A Preliminary Survey of Short Time-Scale Optical Variables with ROTSE

NASA Astrophysics Data System (ADS)

McKay, T.; Akerlof, C.; Balsano, R.; Bloch, J.; Casperson, D.; Gisler, G.; Kehoe, R.; Lee, B.; Marshall, S.; Rykoff, E.; Smith, D. A.; Szymanski, J.; Wren, J.; ROTSE Collaboration

2000-12-01

We have performed a preliminary optical survey of short timescale variability with the ROTSE-I telephoto array. The data sample is divided into two parts. The first is a survey of 256 square degrees ( 120k sources) imaged every 80 s for a cumulative 20 hrs to a sensitivity of approximately magnitude 15.5. The second is a similarly sensitive survey of 512 square degrees ( 250k sources) imaged every 80 s (with 7 minute gaps) for a total of approximately 60 hrs. A further 0.4 mag. increase in sensitivity is obtained by co-adding these frames in pairs. We have identified a variety of new variable stars in this sample, including many Delta Scuti stars and contact binaries. Preliminary characterization of these sources will be presented.

Gluten sensitivity: fact or fashion statement?

PubMed

Khalid, Ayesha N; McMains, Kevin C

2016-06-01

In recent years, the concern over food sensitivities in general and gluten intolerance in particular has sharply increased. Patients and medical providers are awash in various claims about the potential implications of including or excluding gluten from the diet. Three main conditions are described with respect to gluten: wheat allergy, celiac disease, and nonceliac gluten sensitivity (NCGS). Wheat allergy is a type 1 hypersensitivity reaction to nongluten proteins within wheat. Celiac disease is an autoimmune reaction to the gluten protein resulting in damage to the small intestine with genetic associations. NCGS is a diagnosis of exclusion and, to date, no biomarkers have been identified for this condition. When evaluating and treating patients with potential reactions to gluten, it is important to distinguish among wheat allergy, celiac disease, and NCGS. Each condition has distinct dietary and treatment implications.

Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults

PubMed Central

Kim, Jennifer S; Ouyang, Fengxiu; Pongracic, Jacqueline A; Fang, Yaping; Wang, Binyan; Liu, Xue; Xing, Houxun; Caruso, Deanna; Liu, Xin; Zhang, Shanchun; Xu, Xiping; Wang, Xiaobin

2009-01-01

Background The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization. Objective To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population. Methods The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs. Results Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%. Conclusions Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low. Clinical Implications Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed. Capsule summary Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low. PMID:18805578

Addressing Racial Awareness and Color-Blindness in Higher Education

ERIC Educational Resources Information Center

Diggles, Kimberly

2014-01-01

Racial awareness is a critical foundation to racial sensitivity, and it is a necessity for future professionals who want to be prepared to succeed in an increasingly diverse society. Several factors have been shown to influence racial awareness in professionals including their own race, their personal experience with racism, and the amount/quality…

The Issue of Death and Dying: Employing Problem-Based Learning in Nursing Education.

ERIC Educational Resources Information Center

Mok, Esther; Lee, Wai Man; Wong, Frances Kam-yuet

2002-01-01

Hong Kong nursing students used journals to problem-based learning (PBL) related to dying patients. Increased self-awareness, positive attitude toward death, and culturally sensitive care resulted. PBL methods included information searches, interviews with experts and patients, and tutorials for sharing feelings and information. (Contains 21…

Quantification of protein carbonylation.

PubMed

Wehr, Nancy B; Levine, Rodney L

2013-01-01

Protein carbonylation is the most commonly used measure of oxidative modification of proteins. It is most often measured spectrophotometrically or immunochemically by derivatizing proteins with the classical carbonyl reagent 2,4 dinitrophenylhydrazine (DNPH). We present protocols for the derivatization and quantification of protein carbonylation with these two methods, including a newly described dot blot with greatly increased sensitivity.

[The use of a detector of the extremely weak radiation as a variometer of gravitation field].

PubMed

Gorshkov, E S; Bondarenko, E G; Shapovalov, S N; Sokolovskiĭ, V V; Troshichev, O A

2001-01-01

It was shown that the detector of extremely weak radiation with selectively increased sensitivity to the nonelectromagnetic, including the gravitational component of the spectrum of active physical fields can be used as the basis for constructing a variometer of gravitational field of a new type.

Cognitive-Behavioral Treatment of Late-Life Anxiety Disorders.

ERIC Educational Resources Information Center

Gorenstein, Ethan E.; Papp, Lazlo A.

In the absence of data, pharmacotherapy with benzodiazepines has become the mainstay of anxiety management in the elderly population. However, the use of benzodiazepines in the elderly has many problems. Elderly persons are more sensitive to anti-anxiety medications and are subject to a variety of increased risks, including cognitive impairment,…

Fabrication of a novel transparent SERS substrate comprised of Ag-nanoparticle arrays and its application in rapid detection of ractopamine on meat

USDA-ARS?s Scientific Manuscript database

Surface-enhanced Raman spectroscopy (SERS) is an emerging analytical tool that boasts the feature of high detection sensitivity and molecular fingerprint specificity attracting increased attention and showing promise in applications including detecting residues of veterinary drugs. In practice, spec...

Morning Versus Evening Bright Light Treatment at Home to Improve Function and Pain Sensitivity for Women with Fibromyalgia: A Pilot Study.

PubMed

Burgess, Helen J; Park, Margaret; Ong, Jason C; Shakoor, Najia; Williams, David A; Burns, John

2017-01-01

To test the feasibility, acceptability, and effects of a home-based morning versus evening bright light treatment on function and pain sensitivity in women with fibromyalgia. A single blind randomized study with two treatment arms: 6 days of a 1 hour morning light treatment or 6 days of a 1 hour evening light treatment. Function, pain sensitivity, and circadian timing were assessed before and after treatment. Participants slept at home, except for two nights in Sleep Center. Ten women meeting the American College of Rheumatology's diagnostic criteria for fibromyalgia, including normal blood test results. Self-reported function was assessed with the Fibromyalgia Impact Questionnaire (FIQ). Pain sensitivity was assessed using a heat stimulus that gave measures of threshold and tolerance. Circadian timing was assessed with the dim light melatonin onset. Both morning and evening light treatments led to improvements in function and pain sensitivity. However, only the morning light treatment led to a clinically meaningful improvement in function (>14% reduction from baseline FIQ) and morning light significantly increased pain threshold more than evening light ( P  < 0.05). Phase advances in circadian timing were associated with an increase in pain tolerance (r = 0.67, P  < 0.05). Bright light treatment appears to be a feasible and acceptable adjunctive treatment to women with fibromyalgia. Those who undergo morning light treatment may show improvements in function and pain sensitivity. Advances in circadian timing may be one mechanism by which morning light improves pain sensitivity. Findings can inform the design of a randomized controlled trial. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Different sensitivities of snowpacks to warming in Mediterranean climate mountain areas

NASA Astrophysics Data System (ADS)

López-Moreno, J. I.; Gascoin, S.; Herrero, J.; Sproles, E. A.; Pons, M.; Alonso-González, E.; Hanich, L.; Boudhar, A.; Musselman, K. N.; Molotch, N. P.; Sickman, J.; Pomeroy, J.

2017-07-01

In this study we quantified the sensitivity of snow to climate warming in selected mountain sites having a Mediterranean climate, including the Pyrenees in Spain and Andorra, the Sierra Nevada in Spain and California (USA), the Atlas in Morocco, and the Andes in Chile. Meteorological observations from high elevations were used to simulate the snow energy and mass balance (SEMB) and calculate its sensitivity to climate. Very different climate sensitivities were evident amongst the various sites. For example, reductions of 9%-19% and 6-28 days in the mean snow water equivalent (SWE) and snow duration, respectively, were found per °C increase. Simulated changes in precipitation (±20%) did not affect the sensitivities. The Andes and Atlas Mountains have a shallow and cold snowpack, and net radiation dominates the SEMB; and explains their relatively low sensitivity to climate warming. The Pyrenees and USA Sierra Nevada have a deeper and warmer snowpack, and sensible heat flux is more important in the SEMB; this explains the much greater sensitivities of these regions. Differences in sensitivity help explain why, in regions where climate models project relatively greater temperature increases and drier conditions by 2050 (such as the Spanish Sierra Nevada and the Moroccan Atlas Mountains), the decline in snow accumulation and duration is similar to other sites (such as the Pyrenees and the USA Sierra Nevada), where models project stable precipitation and more attenuated warming. The snowpack in the Andes (Chile) exhibited the lowest sensitivity to warming, and is expected to undergo only moderate change (a decrease of <12% in mean SWE, and a reduction of < 7 days in snow duration under RCP 4.5). Snow accumulation and duration in the other regions are projected to decrease substantially (a minimum of 40% in mean SWE and 15 days in snow duration) by 2050.

Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.

PubMed

Ketel, Iris J G; Stehouwer, Coen D A; Serné, Erik H; Korsen, Ted J M; Hompes, Peter G A; Smulders, Yvo M; de Jongh, Renate T; Homburg, Roy; Lambalk, Cornelis B

2008-09-01

Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). Obese women were more insulin resistant than normal-weight women (P < 0.001), and obese PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent of PCOS. Therefore, obese PCOS women in particular may be at increased risk of metabolic and cardiovascular diseases.

Process Monitoring Evaluation and Implementation for the Wood Abrasive Machining Process

PubMed Central

Saloni, Daniel E.; Lemaster, Richard L.; Jackson, Steven D.

2010-01-01

Wood processing industries have continuously developed and improved technologies and processes to transform wood to obtain better final product quality and thus increase profits. Abrasive machining is one of the most important of these processes and therefore merits special attention and study. The objective of this work was to evaluate and demonstrate a process monitoring system for use in the abrasive machining of wood and wood based products. The system developed increases the life of the belt by detecting (using process monitoring sensors) and removing (by cleaning) the abrasive loading during the machining process. This study focused on abrasive belt machining processes and included substantial background work, which provided a solid base for understanding the behavior of the abrasive, and the different ways that the abrasive machining process can be monitored. In addition, the background research showed that abrasive belts can effectively be cleaned by the appropriate cleaning technique. The process monitoring system developed included acoustic emission sensors which tended to be sensitive to belt wear, as well as platen vibration, but not loading, and optical sensors which were sensitive to abrasive loading. PMID:22163477

The Role of Hypothalamic Estrogen Receptors in Metabolic Regulation

PubMed Central

Frank, Aaron; Brown, Lynda M.; Clegg, Deborah J.

2014-01-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ”classical“ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. PMID:24882636

The role of hypothalamic estrogen receptors in metabolic regulation.

PubMed

Frank, Aaron; Brown, Lynda M; Clegg, Deborah J

2014-10-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two 'classical' estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1(-/-)); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

THz Dynamic Nuclear Polarization NMR

PubMed Central

Nanni, Emilio A.; Barnes, Alexander B.; Griffin, Robert G.; Temkin, Richard J.

2013-01-01

Dynamic nuclear polarization (DNP) increases the sensitivity of nuclear magnetic resonance (NMR) spectroscopy by using high frequency microwaves to transfer the polarization of the electrons to the nuclear spins. The enhancement in NMR sensitivity can amount to a factor of well above 100, enabling faster data acquisition and greatly improved NMR measurements. With the increasing magnetic fields (up to 23 T) used in NMR research, the required frequency for DNP falls into the THz band (140–600 GHz). Gyrotrons have been developed to meet the demanding specifications for DNP NMR, including power levels of tens of watts; frequency stability of a few megahertz; and power stability of 1% over runs that last for several days to weeks. Continuous gyrotron frequency tuning of over 1 GHz has also been demonstrated. The complete DNP NMR system must include a low loss transmission line; an optimized antenna; and a holder for efficient coupling of the THz radiation to the sample. This paper describes the DNP NMR process and illustrates the THz systems needed for this demanding spectroscopic application. THz DNP NMR is a rapidly developing, exciting area of THz science and technology. PMID:24639915

Ovarian Cancer Screening Pilot Trial In High Risk Women — EDRN Public Portal

Cancer.gov

BACKGROUND: No proven ovarian cancer (OC) screening strategy exists for women who are at increased risk for the disease. A risk of ovarian cancer algorithm (ROCA) using serial CA125 values have previously shown greater positive predictive value (PPV) and sensitivity than a single CA125 in screening women at general population risk. We hypothesized that using ROCA would yield a reasonable PPV for ovarian cancer screening in a cohort at increased risk. METHODS: Between 7/2001 and 9/2006, 25 sites (14 CGN, 3 ovarian SPOREs, 1 EDRN, 7 others) prospectively enrolled patients. Inclusion criteria included: among self, 1st degree and 2nd degree relatives in same lineage either (i) BRCA 1/2 mutation, or (ii) two of OC or early onset (age 1% to ultrasound (US) and risk > 10% additionally to a gynecologic oncologist. Objectives included PPV for study indicated surgery, sensitivity, and compliance. Sample size was chosen to observe 8 OC endpoints with a power of 80% to rule out PPV < or = 10% if the true PPV = 20%.

HIF-1 and ventilatory acclimatization to chronic hypoxia

PubMed Central

Powell, Frank L.; Fu, Zhenxing

2008-01-01

Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in ventilation and ventilatory O2-sensitivity that involves plasticity in carotid body chemoreceptors and CNS respiratory centers. Hypoxia inducible factor-1α (HIF-1α) controls the expression of several genes that increase physiological O2 supply. Studies using transgenic mice show HIF-1α expression in the carotid bodies and CNS with chronic sustained and intermittent hypoxia is important for VAH. Other O2-sensitive transcription factors such as HIF-2α may be important for VAH by reducing metabolic O2 demands also. Specific gene targets of HIF-1α shown to be involved in VAH include erythropoietin, endothelin-1, neuronal nitric oxide synthase and tyrosine hydroxylase. Other HIF-1α targets that may be involved in VAH include vascular endothelial growth factor, heme oxygenase 1 and cytoglobin. Interactions between these multiple pathways and feedback control of HIF-1α expression from some of the targets support a complex and powerful role for HIF-1α in neural plasticity of physiological control circuits with chronic hypoxia. PMID:18708172

Sleep Fragmentation Exacerbates Mechanical Hypersensitivity and Alters Subsequent Sleep-Wake Behavior in a Mouse Model of Musculoskeletal Sensitization

PubMed Central

Sutton, Blair C.; Opp, Mark R.

2014-01-01

Study Objectives: Sleep deprivation, or sleep disruption, enhances pain in human subjects. Chronic musculoskeletal pain is prevalent in our society, and constitutes a tremendous public health burden. Although preclinical models of neuropathic and inflammatory pain demonstrate effects on sleep, few studies focus on musculoskeletal pain. We reported elsewhere in this issue of SLEEP that musculoskeletal sensitization alters sleep of mice. In this study we hypothesize that sleep fragmentation during the development of musculoskeletal sensitization will exacerbate subsequent pain responses and alter sleep-wake behavior of mice. Design: This is a preclinical study using C57BL/6J mice to determine the effect on behavioral outcomes of sleep fragmentation combined with musculoskeletal sensitization. Methods: Musculoskeletal sensitization, a model of chronic muscle pain, was induced using two unilateral injections of acidified saline (pH 4.0) into the gastrocnemius muscle, spaced 5 days apart. Musculoskeletal sensitization manifests as mechanical hypersensitivity determined by von Frey filament testing at the hindpaws. Sleep fragmentation took place during the consecutive 12-h light periods of the 5 days between intramuscular injections. Electroencephalogram (EEG) and body temperature were recorded from some mice at baseline and for 3 weeks after musculoskeletal sensitization. Mechanical hypersensitivity was determined at preinjection baseline and on days 1, 3, 7, 14, and 21 after sensitization. Two additional experiments were conducted to determine the independent effects of sleep fragmentation or musculoskeletal sensitization on mechanical hypersensitivity. Results: Five days of sleep fragmentation alone did not induce mechanical hypersensitivity, whereas sleep fragmentation combined with musculoskeletal sensitization resulted in prolonged and exacerbated mechanical hypersensitivity. Sleep fragmentation combined with musculoskeletal sensitization had an effect on subsequent sleep of mice as demonstrated by increased numbers of sleep-wake state transitions during the light and dark periods; changes in nonrapid eye movement (NREM) sleep, rapid eye movement sleep, and wakefulness; and altered delta power during NREM sleep. These effects persisted for at least 3 weeks postsensitization. Conclusions: Our data demonstrate that sleep fragmentation combined with musculoskeletal sensitization exacerbates the physiological and behavioral responses of mice to musculoskeletal sensitization, including mechanical hypersensitivity and sleep-wake behavior. These data contribute to increasing literature demonstrating bidirectional relationships between sleep and pain. The prevalence and incidence of insufficient sleep and pathologies characterized by chronic musculoskeletal pain are increasing in the United States. These demographic data underscore the need for research focused on insufficient sleep and chronic pain so that the quality of life for the millions of individuals with these conditions may be improved. Citation: Sutton BC; Opp MR. Sleep fragmentation exacerbates mechanical hypersensitivity and alters subsequent sleep-wake behavior in a mouse model of musculoskeletal sensitization. SLEEP 2014;37(3):515-524. PMID:24587574

A systematic review of the sensitivity and specificity of the toe-brachial index for detecting peripheral artery disease.

PubMed

Tehan, Peta Ellen; Santos, Derek; Chuter, Vivienne Helaine

2016-08-01

The toe-brachial index (TBI) is used as an adjunct to the ankle-brachial index (ABI) for non-invasive lower limb vascular screening. With increasing evidence suggesting limitations of the ABI for diagnosis of vascular complications, particularly in specific populations including diabetes cohorts, the TBI is being used more widely. The aim of this review was to determine the sensitivity and specificity of the TBI for detecting peripheral artery disease (PAD) in populations at risk of this disease. A database search was conducted to identify current work relating to the sensitivity and specificity of toe-brachial indices up to July 2015. Only studies using valid diagnostic imaging as a reference standard were included. The QUADAS-2 tool was used to critically appraise included articles. Seven studies met the inclusion criteria. Sensitivity of the TBI for PAD was reported in all seven studies and ranged from 45% to 100%; specificity was reported by five studies only and ranged from 16% to 100%. In conclusion, this review suggests that the TBI has variable diagnostic accuracy for the presence of PAD in specific populations at risk of developing the disease. There was a notable lack of large-scale diagnostic accuracy studies determining the diagnostic accuracy of the TBI in detecting PAD in different at-risk cohorts. However, standardised normal values need to be established for the TBI to conclusively determine the diagnostic accuracy of this test. © The Author(s) 2016.

Effects of menopause and high-intensity training on insulin sensitivity and muscle metabolism.

PubMed

Mandrup, Camilla M; Egelund, Jon; Nyberg, Michael; Enevoldsen, Lotte Hahn; Kjær, Andreas; Clemmensen, Andreas E; Christensen, Anders Nymark; Suetta, Charlotte; Frikke-Schmidt, Ruth; Steenberg, Dorte Enggaard; Wojtaszewski, Jørgen F P; Hellsten, Ylva; Stallknecht, Bente M

2018-02-01

To investigate peripheral insulin sensitivity and skeletal muscle glucose metabolism in premenopausal and postmenopausal women, and evaluate whether exercise training benefits are maintained after menopause. Sedentary, healthy, normal-weight, late premenopausal (n = 21), and early postmenopausal (n = 20) women were included in a 3-month high-intensity exercise training intervention. Body composition was assessed by magnetic resonance imaging and dual-energy x-ray absorptiometry, whole body glucose disposal rate (GDR) by hyperinsulinemic euglycemic clamp (40 mU/m/min), and femoral muscle glucose uptake by positron emission tomography/computed tomography, using the glucose analog fluorodeoxyglucose, expressed as estimated metabolic rate (eMR). Insulin signaling was investigated in muscle biopsies. Age difference between groups was 4.5 years, and no difference was observed in body composition. Training increased lean body mass (estimate [95% confidence interval] 0.5 [0.2-0.9] kg, P < 0.01) and thigh muscle mass (0.2 [-0.1 to 0.6] kg, P < 0.01), and decreased fat percentage (1.0 [0.5-1.5]%, P < 0.01) similarly in the two groups. The postmenopausal women had lower eMR in vastus lateralis muscle than the premenopausal women (-14.0 [-26.0 to -2.0] μmol/min/kg, P = 0.02), and tended to have lower eMR in femoral muscles (-11.2 [-22.7 to 0.4] μmol/min/kg, P = 0.06), and also GDR (-59.3 [-124.8 to 6.3] mg/min, P = 0.08), but increased similarly in both groups with training (eMR vastus lateralis muscle: 27.8 [19.6-36.0] μmol/min/kg, P < 0.01; eMR femoral muscle: 20.0 [13.1-26.7] μmol/min/kg, P < 0.01, respectively; GDR: 43.6 [10.4-76.9] mg/min, P = 0.01). Potential mechanisms underlying the training-induced increases in insulin sensitivity included increased expression of hexokinase (19.2 [5.0-24.7] AU, P = 0.02) and glycogen synthase (32.4 [15.0-49.8] AU, P < 0.01), and also increased insulin activation of Akt2 (20.6 [3.4-29.0], P = 0.03) and dephosphorylation of glycogen synthase (-41.8 [-82.9 to -0.7], P = 0.05). Insulin sensitivity was reduced in early postmenopausal women. However, postmenopausal women increased peripheral insulin sensitivity, skeletal muscle insulin-stimulated glucose uptake, and skeletal muscle mass to the same extent as premenopausal women after 3 months of high-intensity exercise training.

Targeting protein-trafficking pathways alters melanoma treatment sensitivity

PubMed Central

Huang, Zhi-ming; Chinen, Milka; Chang, Philip J.; Xie, Tong; Zhong, Lily; Demetriou, Stephanie; Patel, Mira P.; Scherzer, Rebecca; Sviderskaya, Elena V.; Bennett, Dorothy C.; Millhauser, Glenn L.; Oh, Dennis H.; Cleaver, James E.; Wei, Maria L.

2012-01-01

Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide together with velaparib, an inhibitor of poly (ADP ribose) polymerase 1, is increased by up to 10-fold by targeting genes that regulate both protein trafficking and the formation of melanosomes, intracellular organelles unique to melanocytes and melanoma cells. Melanoma cells depleted of either of the protein-trafficking regulators vacuolar protein sorting 33A protein (VPS33A) or cappuccino protein (CNO) have increased nuclear localization of cDDP, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. Depleted cells also exhibit a decreased proportion of intracellular, mature melanosomes compared with undepleted cells. Modulation of protein trafficking via cell-surface signaling by binding the melanocortin 1 receptor with the antagonist agouti-signaling protein decreased the proportion of mature melanosomes formed and increased cDDP sensitivity, whereas receptor binding with the agonist melanocyte-stimulating hormone resulted in an increased proportion of mature melanosomes formed and in decreased sensitivity (i.e., increased resistance) to cDDP. Mutation of the protein-trafficking gene Hps6, known to impair the formation of mature melanosomes, also increased cDDP sensitivity. Together, these results indicate that targeting protein-trafficking molecules markedly increases melanoma treatment sensitivity and influences the degree of melanosomes available for sequestration of therapeutic agents. PMID:22203954

Natural history of allergic sensitization in infants with early-onset atopic dermatitis: results from ORCA Study.

PubMed

Just, Jocelyne; Deslandes-Boutmy, Emmanuelle; Amat, Flore; Desseaux, Kristell; Nemni, Ariane; Bourrat, Emmanuelle; Sahraoui, Fatia; Pansé, Isabelle; Bagot, Martine; Fouéré, Sébastien

2014-11-01

Early-onset atopic dermatitis (AD) is a particular phenotype that may convey a risk of developing multiple sensitizations to allergens but little is known about the pathway of sensitization. The aims of this study were to describe the natural history of sensitization to allergens for this phenotype and to identify the most predictive marker associated with the risk of developing sensitization to inhaled allergens in a well-selected cohort of infants with AD. Infants with active AD were enrolled and prospectively explored for biological markers of atopy every year until the age of 6 yr. Allergic sensitization was defined as the presence of positive specific IgEs to allergens and multiple sensitizations as being sensitized to ≥2 allergens. Elevated blood eosinophilia was defined as an eosinophil blood count ≥470 eosinophils/mm(3) and elevated total IgE as a serum IgE level ≥45 kU/l. Two hundred and twenty-nine infants were included. Elevated blood eosinophilia was observed at baseline in 60 children (26.2%) and elevated total IgE in 85 (37.1%). When elevated at baseline, eosinophilia and IgE levels remained significantly higher during the follow-up period. Sensitization to food allergens decreased from 58% to 34%, whereas sensitization to inhaled allergens increased over time from 17% to 67%. Initial multiple sensitizations to food allergens were the most predictive factor for the risk of developing sensitization to inhaled allergens at 6 yr (OR 3.72 [1.68-8.30] p < 0.001). In the early-onset AD phenotype, multiple sensitization to food allergens conveys a higher risk of sensitization to inhaled allergens than single sensitization. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study.

PubMed

Carroccio, Antonio; Soresi, Maurizio; D'Alcamo, Alberto; Sciumè, Carmelo; Iacono, Giuseppe; Geraci, Girolamo; Brusca, Ignazio; Seidita, Aurelio; Adragna, Floriana; Carta, Miriam; Mansueto, Pasquale

2014-11-28

Non-celiac gluten sensitivity (NCGS) or 'wheat sensitivity' (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics. This prospective observation study included 75 NCWS patients (63 women; median age 36 years) with irritable bowel syndrome (IBS)-like symptoms, 65 IBS and 50 celiac controls. Patients were recruited at two Internal Medicine Departments. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, HLA DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake. DBPC cow's milk proteins challenge showed that 30 of the 75 NCWS patients suffered from multiple food sensitivity. Osteopenia and osteoporosis frequency increased from IBS to NCWS and to celiac disease (CD) (P <0.0001). Thirty-five NCWS patients (46.6%) showed osteopenia or osteoporosis. Low BMD was related to low BMI and multiple food sensitivity. Values of daily dietary calcium intake in NCWS patients were significantly lower than in IBS controls. An elevated frequency of bone mass loss in NCWS patients was found; this was related to low BMI and was more frequent in patients with NCWS associated with other food sensitivity. A low daily intake of dietary calcium was observed in patients with NCWS.

Mitochondrial genome-knockout cells demonstrate a dual mechanism of action for the electron transport complex I inhibitor mycothiazole.

PubMed

Meyer, Kirsten J; Singh, A Jonathan; Cameron, Alanna; Tan, An S; Leahy, Dora C; O'Sullivan, David; Joshi, Praneta; La Flamme, Anne C; Northcote, Peter T; Berridge, Michael V; Miller, John H

2012-04-01

Mycothiazole, a polyketide metabolite isolated from the marine sponge Cacospongia mycofijiensis, is a potent inhibitor of metabolic activity and mitochondrial electron transport chain complex I in sensitive cells, but other cells are relatively insensitive to the drug. Sensitive cell lines (IC(50) 0.36-13.8 nM) include HeLa, P815, RAW 264.7, MDCK, HeLa S3, 143B, 4T1, B16, and CD4/CD8 T cells. Insensitive cell lines (IC(50) 12.2-26.5 μM) include HL-60, LN18, and Jurkat. Thus, there is a 34,000-fold difference in sensitivity between HeLa and HL-60 cells. Some sensitive cell lines show a biphasic response, suggesting more than one mechanism of action. Mitochondrial genome-knockout ρ(0) cell lines are insensitive to mycothiazole, supporting a conditional mitochondrial site of action. Mycothiazole is cytostatic rather than cytotoxic in sensitive cells, has a long lag period of about 12 h, and unlike the complex I inhibitor, rotenone, does not cause G(2)/M cell cycle arrest. Mycothiazole decreases, rather than increases the levels of reactive oxygen species after 24 h. It is concluded that the cytostatic inhibitory effects of mycothiazole on mitochondrial electron transport function in sensitive cell lines may depend on a pre-activation step that is absent in insensitive cell lines with intact mitochondria, and that a second lower-affinity cytotoxic target may also be involved in the metabolic and growth inhibition of cells.

Cocaine-induced behavioral sensitization decreases the expression of endocannabinoid signaling-related proteins in the mouse hippocampus.

PubMed

Blanco, Eduardo; Galeano, Pablo; Palomino, Ana; Pavón, Francisco J; Rivera, Patricia; Serrano, Antonia; Alen, Francisco; Rubio, Leticia; Vargas, Antonio; Castilla-Ortega, Estela; Decara, Juan; Bilbao, Ainhoa; de Fonseca, Fernando Rodríguez; Suárez, Juan

2016-03-01

In the reward mesocorticolimbic circuits, the glutamatergic and endocannabinoid systems are implicated in neurobiological mechanisms underlying cocaine addiction. However, the involvement of both systems in the hippocampus, a critical region to process relational information relevant for encoding drug-associated memories, in cocaine-related behaviors remains unknown. In the present work, we studied whether the hippocampal gene/protein expression of relevant glutamate signaling components, including glutamate-synthesizing enzymes and metabotropic and ionotropic receptors, and the hippocampal gene/protein expression of cannabinoid type 1 (CB1) receptor and endocannabinoid metabolic enzymes were altered following acute and/or repeated cocaine administration resulting in conditioned locomotion and locomotor sensitization. Results showed that acute cocaine administration induced an overall down-regulation of glutamate-related gene expression and, specifically, a low phosphorylation level of GluA1. In contrast, locomotor sensitization to cocaine produced an up-regulation of several glutamate receptor-related genes and, specifically, an increased protein expression of the GluN1 receptor subunit. Regarding the endocannabinoid system, acute and repeated cocaine administration were associated with an increased gene/protein expression of CB1 receptors and a decreased gene/protein expression of the endocannabinoid-synthesis enzymes N-acyl phosphatidylethanolamine D (NAPE-PLD) and diacylglycerol lipase alpha (DAGLα). These changes resulted in an overall decrease in endocannabinoid synthesis/degradation ratios, especially NAPE-PLD/fatty acid amide hydrolase and DAGLα/monoacylglycerol lipase, suggesting a reduced endocannabinoid production associated with a compensatory up-regulation of CB1 receptor. Overall, these findings suggest that repeated cocaine administration resulting in locomotor sensitization induces a down-regulation of the endocannabinoid signaling that could contribute to the specifically increased GluN1 expression observed in the hippocampus of cocaine-sensitized mice. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Quantification of tumor fluorescence during intraoperative optical cancer imaging

PubMed Central

Judy, Ryan P.; Keating, Jane J.; DeJesus, Elizabeth M.; Jiang, Jack X.; Okusanya, Olugbenga T.; Nie, Shuming; Holt, David E.; Arlauckas, Sean P.; Low, Phillip S.; Delikatny, E. James; Singhal, Sunil

2015-01-01

Intraoperative optical cancer imaging is an emerging technology in which surgeons employ fluorophores to visualize tumors, identify tumor-positive margins and lymph nodes containing metastases. This study compares instrumentation to measure tumor fluorescence. Three imaging systems (Spectropen, Glomax, Flocam) measured and quantified fluorescent signal-to-background ratios (SBR) in vitro, murine xenografts, tissue phantoms and clinically. Evaluation criteria included the detection of small changes in fluorescence, sensitivity of signal detection at increasing depths and practicality of use. In vitro, spectroscopy was superior in detecting incremental differences in fluorescence than luminescence and digital imaging (Ln[SBR] = 6.8 ± 0.6, 2.4 ± 0.3, 2.6 ± 0.1, p = 0.0001). In fluorescent tumor cells, digital imaging measured higher SBRs than luminescence (6.1 ± 0.2 vs. 4.3 ± 0.4, p = 0.001). Spectroscopy was more sensitive than luminometry and digital imaging in identifying murine tumor fluorescence (SBR = 41.7 ± 11.5, 5.1 ± 1.8, 4.1 ± 0.9, p = 0.0001), and more sensitive than digital imaging at detecting fluorescence at increasing depths (SBR = 7.0 ± 3.4 vs. 2.4 ± 0.5, p = 0.03). Lastly, digital imaging was the most practical and least time-consuming. All methods detected incremental differences in fluorescence. Spectroscopy was the most sensitive for small changes in fluorescence. Digital imaging was the most practical considering its wide field of view, background noise filtering capability, and sensitivity to increasing depth. PMID:26563091

Evaluating the effect of database inflation in proteogenomic search on sensitive and reliable peptide identification.

PubMed

Li, Honglan; Joh, Yoon Sung; Kim, Hyunwoo; Paek, Eunok; Lee, Sang-Won; Hwang, Kyu-Baek

2016-12-22

Proteogenomics is a promising approach for various tasks ranging from gene annotation to cancer research. Databases for proteogenomic searches are often constructed by adding peptide sequences inferred from genomic or transcriptomic evidence to reference protein sequences. Such inflation of databases has potential of identifying novel peptides. However, it also raises concerns on sensitive and reliable peptide identification. Spurious peptides included in target databases may result in underestimated false discovery rate (FDR). On the other hand, inflation of decoy databases could decrease the sensitivity of peptide identification due to the increased number of high-scoring random hits. Although several studies have addressed these issues, widely applicable guidelines for sensitive and reliable proteogenomic search have hardly been available. To systematically evaluate the effect of database inflation in proteogenomic searches, we constructed a variety of real and simulated proteogenomic databases for yeast and human tandem mass spectrometry (MS/MS) data, respectively. Against these databases, we tested two popular database search tools with various approaches to search result validation: the target-decoy search strategy (with and without a refined scoring-metric) and a mixture model-based method. The effect of separate filtering of known and novel peptides was also examined. The results from real and simulated proteogenomic searches confirmed that separate filtering increases the sensitivity and reliability in proteogenomic search. However, no one method consistently identified the largest (or the smallest) number of novel peptides from real proteogenomic searches. We propose to use a set of search result validation methods with separate filtering, for sensitive and reliable identification of peptides in proteogenomic search.

Single-Tier Testing with the C6 Peptide ELISA Kit Compared with Two-Tier Testing for Lyme Disease

PubMed Central

Wormser, Gary P.; Schriefer, Martin; Aguero-Rosenfeld, Maria E.; Levin, Andrew; Steere, Allen C.; Nadelman, Robert B.; Nowakowski, John; Marques, Adriana; Johnson, Barbara J. B.; Dumler, J. Stephen

2014-01-01

Background The two-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time and labor; and subjectivity in the interpretation of immunoblots. Methods The diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with two-tier testing. Results The C6 ELISA was significantly more sensitive than two-tier testing with sensitivities of 66.5% (95% C.I.:61.7-71.1) and 35.2% (95%C.I.:30.6-40.1), respectively (p<0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to two-tier testing in sera from Lyme disease patients with early neurological manifestations (88.6% vs. 77.3%, p=0.13) or arthritis (98.3% vs. 95.6%, p= 0.38). Te specificities of C6 ELISA and two-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (p<0.05, 95% C.I. surrounding the 0.6 percentage point difference of 0.04 to 1.15). Conclusions Using a reference standard of two-tier testing, the C6 ELISA as a single step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with two-tier testing in routine clinical practice. PMID:23062467

Environmental health indicators of climate change for the United States: findings from the State Environmental Health Indicator Collaborative.

PubMed

English, Paul B; Sinclair, Amber H; Ross, Zev; Anderson, Henry; Boothe, Vicki; Davis, Christine; Ebi, Kristie; Kagey, Betsy; Malecki, Kristen; Shultz, Rebecca; Simms, Erin

2009-11-01

To develop public health adaptation strategies and to project the impacts of climate change on human health, indicators of vulnerability and preparedness along with accurate surveillance data on climate-sensitive health outcomes are needed. We researched and developed environmental health indicators for inputs into human health vulnerability assessments for climate change and to propose public health preventative actions. We conducted a review of the scientific literature to identify outcomes and actions that were related to climate change. Data sources included governmental and nongovernmental agencies and the published literature. Sources were identified and assessed for completeness, usability, and accuracy. Priority was then given to identifying longitudinal data sets that were applicable at the state and community level. We present a list of surveillance indicators for practitioners and policy makers that include climate-sensitive health outcomes and environmental and vulnerability indicators, as well as mitigation, adaptation, and policy indicators of climate change. A review of environmental health indicators for climate change shows that data exist for many of these measures, but more evaluation of their sensitivity and usefulness is needed. Further attention is necessary to increase data quality and availability and to develop new surveillance databases, especially for climate-sensitive morbidity.

Environmental Health Indicators of Climate Change for the United States: Findings from the State Environmental Health Indicator Collaborative

PubMed Central

English, Paul B.; Sinclair, Amber H.; Ross, Zev; Anderson, Henry; Boothe, Vicki; Davis, Christine; Ebi, Kristie; Kagey, Betsy; Malecki, Kristen; Shultz, Rebecca; Simms, Erin

2009-01-01

Objective To develop public health adaptation strategies and to project the impacts of climate change on human health, indicators of vulnerability and preparedness along with accurate surveillance data on climate-sensitive health outcomes are needed. We researched and developed environmental health indicators for inputs into human health vulnerability assessments for climate change and to propose public health preventative actions. Data sources We conducted a review of the scientific literature to identify outcomes and actions that were related to climate change. Data sources included governmental and nongovernmental agencies and the published literature. Data extraction Sources were identified and assessed for completeness, usability, and accuracy. Priority was then given to identifying longitudinal data sets that were applicable at the state and community level. Data synthesis We present a list of surveillance indicators for practitioners and policy makers that include climate-sensitive health outcomes and environmental and vulnerability indicators, as well as mitigation, adaptation, and policy indicators of climate change. Conclusions A review of environmental health indicators for climate change shows that data exist for many of these measures, but more evaluation of their sensitivity and usefulness is needed. Further attention is necessary to increase data quality and availability and to develop new surveillance databases, especially for climate-sensitive morbidity. PMID:20049116

Disturbance of microcirculation due to unhealthy lifestyle: Cause of type 2 diabetes.

PubMed

Matsumoto, Yukihiro; Ohno, Hideki; Noguchi, Izumi; Kikuchi, Yuji; Kurihara, Takeshi

2006-01-01

Recently, type 2 diabetes seems to be increasing annually in all developed countries. The outcome of type 2 diabetes is often tragic due to succession of complications including renal disorders requiring hemodialysis, blindness, and limb amputation. The expenses for the care of diabetic patients are also a large burden on the society. These circumstances strongly indicate the necessity of prevention. For satisfactory prevention, the clarification of the etiology related to lifestyle is important, but it remains insufficient to date. In this paper, we present a hypothesis of the etiology of type 2 diabetes from the viewpoint of microcirculation. As mentioned later, an unhealthy lifestyle first causes disturbance of the microcirculation, and a portion of the blood is considered to bypass the capillaries via arteriovenous shunts. This prevents the delivery of glucose and insulin to cells of peripheral tissues, causing hyperglycemia unrelated to the cell insulin sensitivity or the endocrine state, i.e., apparent reduction of insulin sensitivity. Disturbance of the microcirculation also causes oxidative stress in peripheral tissues by inducing ischemia and hypoxia. This oxidative stress is considered to further exacerbate reduction of insulin sensitivity. This hypothesis is supported by the well-known fact that insulin sensitivity recovers with improvement in lifestyle including moderate exercise.

Sensitivities of projected 1980 photovoltaic system costs to major system cost drivers

NASA Technical Reports Server (NTRS)

Zimmerman, L. W.; Smith, J. L.

1984-01-01

The sensitivity of projected 1990 photovoltaic (PV) system costs to major system cost drivers was examined. It includes: (1) module costs and module efficiencies; (2) area related balance of system (BOS) costs; (3) inverter costs and efficiencies; and (4) module marketing and distribution markups and system integration fees. Recent PV system cost experiences and the high costs of electricity from the systems are reviewed. The 1990 system costs are projected for five classes of PV systems, including four ground mounted 5-MWp systems and one residential 5-kWp system. System cost projections are derived by first projecting costs and efficiencies for all subsystems and components. Sensitivity analyses reveal that reductions in module cost and engineering and system integration fees seem to have the greatest potential for contributing to system cost reduction. Although module cost is clearly the prime candidate for fruitful PV research and development activities, engineering and system integration fees seem to be more amenable to reduction through appropriate choice of system size and market strategy. Increases in inverter and module efficiency yield significant benefits, especially for systems with high area related costs.

The role of rapid antigen testing for influenza in the era of molecular diagnostics.

PubMed

Dale, Suzanne E

2010-08-01

Rapid antigen testing for influenza has been both maligned and revered since its conception. Microbiologists have long lamented the lack of sensitivity of commercial rapid influenza detection tests (RIDTs), whereas many clinicians have eschewed their utility by emphasizing the value of definitely diagnosing influenza at the patient's bedside. RIDTs, although quick and easy to perform, are widely accepted as being less sensitive than traditional culture techniques and newer molecular methods, including reverse-transcription polymerase chain reaction (RT-PCR). Moreover, the performance characteristics of RIDTs vary widely, and their applications as clinical diagnostic tools are not well understood. In contrast, traditional techniques are time consuming and require significant expertise to perform. Often, the delay in diagnosing influenza through these methods has little impact on patient care. The benefits of achieving a diagnosis of influenza at the point of care are numerous and include increased access to appropriate antivirals, appropriate patient cohorting for infection control purposes, and better resource utilization. Therefore, it behooves the microbiology community to communicate these issues to clinicians and to work to improve the sensitivity of RIDTs.

Association between alcohol consumption and skin prick test reactivity to aeroallergens.

PubMed

Assing, Kristian; Bodtger, Uffe; Linneberg, Allan; Malling, Hans Jørgen; Poulsen, Lars K

2007-01-01

A few studies have indicated a positive association between consumption of alcohol and allergic sensitization in age and socioeconomically heterogeneous populations. To investigate the association between consumption of alcohol and allergic sensitization in a young homogenous population of high social class (a group with a suspected high prevalence of sensitization). A total of 1,668 students aged 18 to 35 years recruited from universities in Copenhagen, Denmark, underwent skin prick testing (SPT) in October or November 2002 and completed a questionnaire about respiratory disease and lifestyle habits, including alcohol consumption. SPT positivity was defined as a positive reaction (> or =3 mm) against at least 1 of 10 common inhalant allergens. Before and after adjustment for sex, age, smoking, atopic predisposition, and pet keeping, no significant association was found between alcohol consumption (including type of beverage) and SPT positivity. Increasing alcohol consumption was significantly negatively associated with asthma symptoms and hay fever symptoms. Alcohol consumption does not favor SPT positivity, but cumulated effects were not addressed in the present study. Individuals with asthma or hay fever symptoms seem to reduce alcohol intake (a healthy drinkers' effect).

Effect of guaifenesin on cough reflex sensitivity.

PubMed

Dicpinigaitis, Peter V; Gayle, Yvonne E

2003-12-01

Guaifenesin, a commonly used agent for the treatment of cough, is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity, thereby promoting effective cough. Despite its common usage, relatively few studies, yielding contrasting results, have been performed to investigate the action and efficacy of guaifenesin. To evaluate the effect of guaifenesin on cough reflex sensitivity. Randomized, double-blind, placebo-controlled trial. Academic medical center. Fourteen subjects with acute viral upper respiratory tract infection (URI) and 14 healthy volunteers. On 2 separate days, subjects underwent capsaicin cough challenge 1 to 2 h after receiving a single, 400-mg dose (capsules) of guaifenesin or matched placebo. The concentration of capsaicin inducing five or more coughs (C(5)) was determined. Among subjects with URI, mean (+/- SEM) log C(5) after guaifenesin and placebo were 0.92 +/- 0.17 and 0.66 +/- 0.14, respectively (p = 0.028). No effect on cough sensitivity was observed in healthy volunteers. Our results demonstrate that guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume serving as a barrier shielding cough receptors within the respiratory epithelium from the tussive stimulus.

Novel nanoarchitectures for electrochemical biosensing

NASA Astrophysics Data System (ADS)

Archibald, Michelle M.

Sensitive, real-time detection of biomarkers is of critical importance for rapid and accurate diagnosis of disease for point-of-care (POC) technologies. Current methods, while sensitive, do not adequately allow for POC applications due to several limitations, including complex instrumentation, high reagent consumption, and cost. We have investigated two novel nanoarchitectures, the nanocoax and the nanodendrite, as electrochemical biosensors towards the POC detection of infectious disease biomarkers to overcome these limitations. The nanocoax architecture is composed of vertically-oriented, nanoscale coaxial electrodes, with coax cores and shields serving as integrated working and counter electrodes, respectively. The dendritic structure consists of metallic nanocrystals extending from the working electrode, increasing sensor surface area. Nanocoaxial- and nanodendritic-based electrochemical sensors were fabricated and developed for the detection of bacterial toxins using an electrochemical enzyme-linked immunosorbent assay (ELISA) and differential pulse voltammetry (DPV). Proof-of-concept was demonstrated for the detection of cholera toxin (CT). Both nanoarchitectures exhibited levels of sensitivity that are comparable to the standard optical ELISA used widely in clinical applications. In addition to matching the detection profile of the standard ELISA, these electrochemical nanosensors provide a simple electrochemical readout and a miniaturized platform with multiplexing capabilities toward POC implementation. Further development as suggested in this thesis may lead to increases in sensitivity, enhancing the attractiveness of the architectures for future POC devices.

A fast scintillator Compton telescope for medium-energy gamma-ray astronomy

NASA Astrophysics Data System (ADS)

Bloser, Peter F.; Ryan, James M.; Legere, Jason S.; Julien, Manuel; Bancroft, Christopher M.; McConnell, Mark L.; Wallace, Mark; Kippen, R. Marc; Tornga, Shawn

2010-07-01

The field of medium-energy gamma-ray astronomy urgently needs a new mission to build on the success of the COMPTEL instrument on the Compton Gamma Ray Observatory. This mission must achieve sensitivity significantly greater than that of COMPTEL in order to advance the science of relativistic particle accelerators, nuclear astrophysics, and diffuse backgrounds, and bridge the gap between current and future hard X-ray missions and the high-energy Fermi mission. Such an increase in sensitivity can only come about via a dramatic decrease in the instrumental background. We are currently developing a concept for a low-background Compton telescope that employs modern scintillator technology to achieve this increase in sensitivity. Specifically, by employing LaBr3 scintillators for the calorimeter, one can take advantage of the unique speed and resolving power of this material to improve the instrument sensitivity while simultaneously enhancing its spectroscopic and imaging performance. Also, using deuterated organic scintillator in the scattering detector will reduce internal background from neutron capture. We present calibration results from a laboratory prototype of such an instrument, including time-of-flight, energy, and angular resolution, and compare them to simulation results using a detailed Monte Carlo model. We also describe the balloon payload we have built for a test flight of the instrument in the fall of 2010.

Computer-aided Classification of Mammographic Masses Using Visually Sensitive Image Features

PubMed Central

Wang, Yunzhi; Aghaei, Faranak; Zarafshani, Ali; Qiu, Yuchen; Qian, Wei; Zheng, Bin

2017-01-01

Purpose To develop a new computer-aided diagnosis (CAD) scheme that computes visually sensitive image features routinely used by radiologists to develop a machine learning classifier and distinguish between the malignant and benign breast masses detected from digital mammograms. Methods An image dataset including 301 breast masses was retrospectively selected. From each segmented mass region, we computed image features that mimic five categories of visually sensitive features routinely used by radiologists in reading mammograms. We then selected five optimal features in the five feature categories and applied logistic regression models for classification. A new CAD interface was also designed to show lesion segmentation, computed feature values and classification score. Results Areas under ROC curves (AUC) were 0.786±0.026 and 0.758±0.027 when to classify mass regions depicting on two view images, respectively. By fusing classification scores computed from two regions, AUC increased to 0.806±0.025. Conclusion This study demonstrated a new approach to develop CAD scheme based on 5 visually sensitive image features. Combining with a “visual aid” interface, CAD results may be much more easily explainable to the observers and increase their confidence to consider CAD generated classification results than using other conventional CAD approaches, which involve many complicated and visually insensitive texture features. PMID:27911353

EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.

PubMed

Gorthi, Aparna; Romero, July Carolina; Loranc, Eva; Cao, Lin; Lawrence, Liesl A; Goodale, Elicia; Iniguez, Amanda Balboni; Bernard, Xavier; Masamsetti, V Pragathi; Roston, Sydney; Lawlor, Elizabeth R; Toretsky, Jeffrey A; Stegmaier, Kimberly; Lessnick, Stephen L; Chen, Yidong; Bishop, Alexander J R

2018-03-15

Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.

Longitudinal Changes in Behavioral Approach System Sensitivity and Brain Structures Involved in Reward Processing during Adolescence

ERIC Educational Resources Information Center

Urosevic, Snezana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin; Luciana, Monica

2012-01-01

Adolescence is a period of radical normative changes and increased risk for substance use, mood disorders, and physical injury. Researchers have proposed that increases in reward sensitivity (i.e., sensitivity of the behavioral approach system [BAS]) and/or increases in reactivity to all emotional stimuli (i.e., reward and threat sensitivities)…

Accuracy of diagnosing gastroesophageal reflux disease by GerdQ, esophageal impedance monitoring and histology.

PubMed

Zhou, Li Ya; Wang, Ye; Lu, Jing Jing; Lin, Lin; Cui, Rong Li; Zhang, He Jun; Xue, Yan; Ding, Shi Gang; Lin, San Ren

2014-05-01

To assess the performance of self-assessment gastroesophageal reflux disease questionnaire (GerdQ), 24-h impedance monitoring, proton pump inhibitor (PPI) test and intercellular space of esophageal mucosal epithelial cells in the diagnosis of gastroesophageal reflux disease (GERD). Patients with symptoms suspected of GERD were administered the GerdQ and underwent endoscopy (measurement of intercellular space in the biopsy specimen sampling at 2 cm above the Z-line) and 24-h impedance pH monitoring, together with a 2-week experimental treatment with esomeprazole. A total of 636 patients were included for the final analysis, including 352 with GERD. The sensitivity and specificity of GerdQ and 24-h impedance monitoring for diagnosing GERD were 57.7% and 48.9%, and 66.4% and 43.3%, respectively. The sensitivity of 24-h impedance pH monitoring increased to 93.7%. The sensitivity and specificity of dilated intercellular spaces (DIS) (≥0.9 μm) for diagnosing GERD were 61.2% and 56.1%, respectively, whereas those for PPI test were 70.5% and 44.4%. GerdQ score or PPI test alone cannot accurately diagnose GERD in a Chinese population suspected of GERD. A definitive diagnosis of GERD still depends on endoscopy or 24-h pH monitoring. 24-h impedance pH monitoring may increase the sensitivity for diagnosing GERD by 20%; however, when used alone, it results in poor specificity in patients without acid suppressive therapy. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

A Functional, Genome-wide Evaluation of Liposensitive Yeast Identifies the “ARE2 Required for Viability” (ARV1) Gene Product as a Major Component of Eukaryotic Fatty Acid Resistance*

PubMed Central

Ruggles, Kelly V.; Garbarino, Jeanne; Liu, Ying; Moon, James; Schneider, Kerry; Henneberry, Annette; Billheimer, Jeff; Millar, John S.; Marchadier, Dawn; Valasek, Mark A.; Joblin-Mills, Aidan; Gulati, Sonia; Munkacsi, Andrew B.; Repa, Joyce J.; Rader, Dan; Sturley, Stephen L.

2014-01-01

The toxic subcellular accumulation of lipids predisposes several human metabolic syndromes, including obesity, type 2 diabetes, and some forms of neurodegeneration. To identify pathways that prevent lipid-induced cell death, we performed a genome-wide fatty acid sensitivity screen in Saccharomyces cerevisiae. We identified 167 yeast mutants as sensitive to 0.5 mm palmitoleate, 45% of which define pathways that were conserved in humans. 63 lesions also impacted the status of the lipid droplet; however, this was not correlated to the degree of fatty acid sensitivity. The most liposensitive yeast strain arose due to deletion of the “ARE2 required for viability” (ARV1) gene, encoding an evolutionarily conserved, potential lipid transporter that localizes to the endoplasmic reticulum membrane. Down-regulation of mammalian ARV1 in MIN6 pancreatic β-cells or HEK293 cells resulted in decreased neutral lipid synthesis, increased fatty acid sensitivity, and lipoapoptosis. Conversely, elevated expression of human ARV1 in HEK293 cells or mouse liver significantly increased triglyceride mass and lipid droplet number. The ARV1-induced hepatic triglyceride accumulation was accompanied by up-regulation of DGAT1, a triglyceride synthesis gene, and the fatty acid transporter, CD36. Furthermore, ARV1 was identified as a transcriptional of the protein peroxisome proliferator-activated receptor α (PPARα), a key regulator of lipid homeostasis whose transcriptional targets include DGAT1 and CD36. These results implicate ARV1 as a protective factor in lipotoxic diseases due to modulation of fatty acid metabolism. In conclusion, a lipotoxicity-based genetic screen in a model microorganism has identified 75 human genes that may play key roles in neutral lipid metabolism and disease. PMID:24273168

Economics in “Global Health 2035”: a sensitivity analysis of the value of a life year estimates

PubMed Central

Chang, Angela Y; Robinson, Lisa A; Hammitt, James K; Resch, Stephen C

2017-01-01

Background In “Global health 2035: a world converging within a generation,” The Lancet Commission on Investing in Health (CIH) adds the value of increased life expectancy to the value of growth in gross domestic product (GDP) when assessing national well–being. To value changes in life expectancy, the CIH relies on several strong assumptions to bridge gaps in the empirical research. It finds that the value of a life year (VLY) averages 2.3 times GDP per capita for low– and middle–income countries (LMICs) assuming the changes in life expectancy they experienced from 2000 to 2011 are permanent. Methods The CIH VLY estimate is based on a specific shift in population life expectancy and includes a 50 percent reduction for children ages 0 through 4. We investigate the sensitivity of this estimate to the underlying assumptions, including the effects of income, age, and life expectancy, and the sequencing of the calculations. Findings We find that reasonable alternative assumptions regarding the effects of income, age, and life expectancy may reduce the VLY estimates to 0.2 to 2.1 times GDP per capita for LMICs. Removing the reduction for young children increases the VLY, while reversing the sequencing of the calculations reduces the VLY. Conclusion Because the VLY is sensitive to the underlying assumptions, analysts interested in applying this approach elsewhere must tailor the estimates to the impacts of the intervention and the characteristics of the affected population. Analysts should test the sensitivity of their conclusions to reasonable alternative assumptions. More work is needed to investigate options for improving the approach. PMID:28400950

Evaluation of the Clearview® Malaria pLDH Malaria Rapid Diagnostic Test in a non-endemic setting.

PubMed

Houzé, Sandrine; Hubert, Véronique; Cohen, Dorit Pessler; Rivetz, Baruch; Le Bras, Jacques

2011-09-27

Malaria Rapid Diagnostic Tests (RDTs) are widely used to diagnose malaria. The present study evaluated a new RDT, the Clearview® Malaria pLDH test targeting the pan-Plasmodium antigen lactate dehydrogenase (pLDH). The Clearview® Malaria pLDH test was evaluated on fresh samples obtained in returned international travellers using microscopy corrected by PCR as the reference method. Included samples were Plasmodium falciparum (139), Plasmodium vivax (22), Plasmodium ovale (20), Plasmodium malariae (7), and 102 negative. Overall sensitivity for the detection of Plasmodium spp was 93.2%. For P. falciparum, the sensitivity was 98.6%; for P. vivax, P. ovale and P. malariae, overall sensitivities were 90.9%, 60.0% and 85.7% respectively. For P. falciparum and for P. vivax, the sensitivities increased to 100% at parasite densities above 100/μl. The specificity was 100%. The test was easily to perform and the result was stable for at least 1 hour. The Clearview® Malaria pLDH was efficient for the diagnosis of malaria. The test was very sensitive for P. falciparum and P. vivax detection. The sensitivities for P. ovale and P. malariae were better than other RDTs.

An economic evaluation of second-trimester genetic ultrasonography for prenatal detection of down syndrome.

PubMed

Vintzileos, A M; Ananth, C V; Fisher, A J; Smulian, J C; Day-Salvatore, D; Beazoglou, T; Knuppel, R A

1998-11-01

The objective of this study was to perform an economic evaluation of second-trimester genetic ultrasonography for prenatal detection of Down syndrome. More specifically, we sought to determine the following: (1) the diagnostic accuracy requirements (from the cost-benefit point of view) of genetic ultrasonography versus genetic amniocentesis for women at increased risk for fetal Down syndrome and (2) the possible economic impact of second-trimester genetic ultrasonography for the US population on the basis of the ultrasonographic accuracies reported in previously published studies. A cost-benefit equation was developed from the hypothesis that the cost of universal genetic amniocentesis of patients at increased risk for carrying a fetus with Down syndrome should be at least equal to the cost of universal genetic ultrasonography with amniocentesis used only for those with abnormal ultrasonographic results. The main components of the equation included the diagnostic accuracy of genetic ultrasonography (sensitivity and specificity for detecting Down syndrome), the costs of the amniocentesis package and genetic ultrasonography, and the lifetime cost of Down syndrome cases not detected by the genetic ultrasonography. After appropriate manipulation of the equation a graph was constructed, representing the balance between sensitivity and false-positive rate of genetic ultrasonography; this was used to examine the accuracy of previously published studies from the cost-benefit point of view. Sensitivity analyses included individual risks for Down syndrome ranging from 1:261 (risk of a 35-year-old at 18 weeks' gestation) to 1:44 (risk of a 44-year-old at 18 weeks' gestation). This economic evaluation was conducted from the societal perspective. Genetic ultrasonography was found to be economically beneficial only if the overall sensitivity for detecting Down syndrome was >74%. Even then, the cost-benefit ratio depended on the corresponding false-positive rate. Of the 7 published studies that used multiple ultrasonographic markers for genetic ultrasonography, 6 had accuracies compatible with benefits. The required ultrasonographic accuracy (sensitivity and false-positive rate) varied according to the prevalence of Down syndrome in the population tested. The cost-benefit ratio of second-trimester genetic ultrasonography depends on its diagnostic accuracy, and it is beneficial only when its overall sensitivity for Down syndrome is >74%.

The influence of L-opsin gene polymorphisms and neural ageing on spatio-chromatic contrast sensitivity in 20-71 year olds.

PubMed

Dees, Elise W; Gilson, Stuart J; Neitz, Maureen; Baraas, Rigmor C

2015-11-01

Chromatic contrast sensitivity may be a more sensitive measure of an individual's visual function than achromatic contrast sensitivity. Here, the first aim was to quantify individual- and age-related variations in chromatic contrast sensitivity to a range of spatial frequencies for stimuli along two complementary directions in color space. The second aim was to examine whether polymorphisms at specific amino acid residues of the L- and M-opsin genes (OPN1LW and OPN1MW) known to affect spectral tuning of the photoreceptors could influence spatio-chromatic contrast sensitivity. Chromatic contrast sensitivity functions were measured in 50 healthy individuals (20-71 years) employing a novel pseudo-isochromatic grating stimulus. The spatio-chromatic contrast sensitivity functions were found to be low pass for all subjects, independent of age and color vision. The results revealed a senescent decline in spatio-chromatic contrast sensitivity. There were considerable between-individual differences in sensitivity within each age decade for individuals 49 years old or younger, and age did not predict sensitivity for these age decades alone. Forty-six subjects (including a color deficient male and eight female carriers) were genotyped for L- and M-opsin genes. The Ser180Ala polymorphisms on the L-opsin gene were found to influence the subject's color discrimination and their sensitivity to spatio-chromatic patterns. The results expose the significant role of neural and genetic factors in the deterioration of visual function with increasing age. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential gene expression responses distinguish contact and respiratory sensitizers and nonsensitizing irritants in the local lymph node assay.

PubMed

Adenuga, David; Woolhiser, Michael R; Gollapudi, B Bhaskar; Boverhof, Darrell R

2012-04-01

Genomic approaches have the potential to enhance the specificity and predictive accuracy of existing toxicology endpoints, including those for chemical sensitization. The present study was conducted to determine whether gene expression responses can distinguish contact sensitizers (1-chloro-2,4-dinitrobenzene [DNCB] and hexyl cinnamic aldehyde [HCA]), respiratory sensitizers (ortho-phthalaldehyde and trimellitic anhydride [TMA]), and nonsensitizing irritants (methyl salicylate [MS] and nonanoic acid [NA]) in the local lymph node assay (LLNA). Female Balb/c mice received doses of each chemical as per the standard LLNA dosing regimen on days 1, 2, and 3. Auricular lymph nodes were analyzed for tritiated thymidine ((3)HTdR) incorporation on day 6 and for gene expression responses on days 6 and 10. All chemicals induced dose-dependent increases in stimulation index, which correlated strongly with the number of differentially expressed genes. A majority of genes modulated by the irritants were similarly altered by the sensitizers, consistent with the irritating effects of the sensitizers. However, a select number of responses involved with immune-specific functions, such as dendritic cell activation, were unique to the sensitizers and may offer the ability to distinguish sensitizers from irritants. Genes for the mast cell proteases 1 and 8, Lgals7, Tim2, Aicda, Il4, and Akr1c18 were more strongly regulated by respiratory sensitizers compared with contact sensitizers and may represent potential biomarkers for discriminating between contact and respiratory sensitizers. Collectively, these data suggest that gene expression responses may serve as useful biomarkers to distinguish between respiratory and contact sensitizers and nonsensitizing irritants in the LLNA.

Intranasal oxytocin enhances neural processing of monetary reward and loss in post-traumatic stress disorder and traumatized controls.

PubMed

Nawijn, Laura; van Zuiden, Mirjam; Koch, Saskia B J; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

2016-04-01

Anhedonia is a significant clinical problem in post-traumatic stress disorder (PTSD). PTSD patients show reduced motivational approach behavior, which may underlie anhedonic symptoms. Oxytocin administration is known to increase reward sensitivity and approach behavior. We therefore investigated whether oxytocin administration affected neural responses during motivational processing in PTSD patients and trauma-exposed controls. 35 police officers with PTSD (21 males) and 37 trauma-exposed police officers without PTSD (19 males) were included in a within-subjects, randomized, placebo-controlled fMRI study. Neural responses during anticipation of monetary reward and loss were investigated with a monetary incentive delay task (MID) after placebo and oxytocin (40 IU) administration. Oxytocin increased neural responses during reward and loss anticipation in PTSD patients and controls in the striatum, dorsal anterior cingulate cortex and insula, key regions in the reward pathway. Although PTSD patients did not differ from controls in motivational processing under placebo, anhedonia severity in PTSD patients was negatively related to reward responsiveness in the ventral striatum. Furthermore, oxytocin effects on reward processing in the ventral striatum were positively associated with anhedonia. Oxytocin administration increased reward pathway sensitivity during reward and loss anticipation in PTSD patients and trauma-exposed controls. Thus, oxytocin administration may increase motivation for goal-directed approach behavior in PTSD patients and controls, providing evidence for a neurobiological pathway through which oxytocin could potentially increase motivation and reward sensitivity in PTSD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of prenatal caffeine exposure on glucose homeostasis of adult offspring rats

NASA Astrophysics Data System (ADS)

Kou, Hao; Wang, Gui-hua; Pei, Lin-guo; Zhang, Li; Shi, Chai; Guo, Yu; Wu, Dong-fang; Wang, Hui

2017-12-01

Epidemiological evidences show that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR). The IUGR offspring also present glucose intolerance and type 2 diabetes mellitus after maturity. We have previously demonstrated that PCE induced IUGR and increased susceptibility to adult metabolic syndrome in rats. This study aimed to further investigate the effects of PCE on glucose homeostasis in adult offspring rats. Pregnant rats were administered caffeine (120 mg/kg/day, intragastrically) from gestational days 11 to 20. PCE offspring presented partial catch-up growth pattern after birth, characterizing by the increased body weight gain rates. Meanwhile, PCE had no significant influences on the basal blood glucose and insulin phenotypes of adult offspring but increased the glucose tolerance, glucose-stimulated insulin section and β cell sensitivity to glucose in female progeny. The insulin sensitivity of both male and female PCE offspring were enhanced accompanied with reduced β cell fraction and mass. Western blotting results revealed that significant augmentation in protein expression of hepatic insulin signaling elements of PCE females, including insulin receptor (INSR), insulin receptor substrate 1 (IRS-1) and the phosphorylation of serine-threonine protein kinase (Akt), was also potentiated. In conclusion, we demonstrated that PCE reduced the pancreatic β mass but increased the glucose tolerance in adult offspring rats, especially for females. The adaptive compensatory enhancement of β cell responsiveness to glucose and elevated insulin sensitivity mainly mediated by upregulated hepatic insulin signaling might coordinately contribute to the increased glucose tolerance.

Sensitivity, Specificity, and Public-Health Utility of Clinical Case Definitions Based on the Signs and Symptoms of Cholera in Africa.

PubMed

Nadri, Johara; Sauvageot, Delphine; Njanpop-Lafourcade, Berthe-Marie; Baltazar, Cynthia S; Banla Kere, Abiba; Bwire, Godfrey; Coulibaly, Daouda; Kacou N'Douba, Adele; Kagirita, Atek; Keita, Sakoba; Koivogui, Lamine; Landoh, Dadja E; Langa, Jose P; Miwanda, Berthe N; Mutombo Ndongala, Guy; Mwakapeje, Elibariki R; Mwambeta, Jacob L; Mengel, Martin A; Gessner, Bradford D

2018-04-01

During 2014, Africa reported more than half of the global suspected cholera cases. Based on the data collected from seven countries in the African Cholera Surveillance Network (Africhol), we assessed the sensitivity, specificity, and positive and negative predictive values of clinical cholera case definitions, including that recommended by the World Health Organization (WHO) using culture confirmation as the gold standard. The study was designed to assess results in real-world field situations in settings with recent cholera outbreaks or endemicity. From June 2011 to July 2015, a total of 5,084 persons with suspected cholera were tested for Vibrio cholerae in seven different countries of which 35.7% had culture confirmation. For all countries combined, the WHO case definition had a sensitivity = 92.7%, specificity = 8.1%, positive predictive value = 36.1%, and negative predictive value = 66.6%. Adding dehydration, vomiting, or rice water stools to the case definition could increase the specificity without a substantial decrease in sensitivity. Future studies could further refine our findings primarily by using more sensitive methods for cholera confirmation.

High-sensitivity bend angle measurements using optical fiber gratings.

PubMed

Rauf, Abdul; Zhao, Jianlin; Jiang, Biqiang

2013-07-20

We present a high-sensitivity and more flexible bend measurement method, which is based on the coupling of core mode to the cladding modes at the bending region in concatenation with optical fiber grating serving as band reflector. The characteristics of a bend sensing arm composed of bending region and optical fiber grating is examined for different configurations including single fiber Bragg grating (FBG), chirped FBG (CFBG), and double FBGs. The bend loss curves for coated, stripped, and etched sections of fiber in the bending region with FBG, CFBG, and double FBG are obtained experimentally. The effect of separation between bending region and optical fiber grating on loss is measured. The loss responses for single FBG and CFBG configurations are compared to discover the effectiveness for practical applications. It is demonstrated that the sensitivity of the double FBG scheme is twice that of the single FBG and CFBG configurations, and hence acts as sensitivity multiplier. The bend loss response for different fiber diameters obtained through etching in 40% hydrofluoric acid, is measured in double FBG scheme that resulted in a significant increase in the sensitivity, and reduction of dead-zone.

Zebrafish embryotoxicity test for developmental (neuro)toxicity: Demo case of an integrated screening approach system using anti-epileptic drugs.

PubMed

Beker van Woudenberg, Anna; Snel, Cor; Rijkmans, Eke; de Groot, Didima; Bouma, Marga; Hermsen, Sanne; Piersma, Aldert; Menke, Aswin; Wolterbeek, André

2014-11-01

To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH) and levetiracetam (LEV). For VPA, histopathology was the most sensitive parameter, showing effects already at 60μM. For CBZ, morphology and MA were the most sensitive parameters, showing effects at 180μM. For ETH, all endpoints showed similar sensitivity (6.6mM), whereas MA was the most sensitive parameter for LEV (40mM). Inclusion of kinetics did not alter the absolute ranking of the compounds, but the relative potency was changed considerably. Taking all together, this demo-case study showed that inclusion of multiple-endpoints in ZET may increase the sensitivity of the assay, contribute to the elucidation of the mode of toxic action and to a better definition of the applicability domain of ZET. Copyright © 2014 Elsevier Inc. All rights reserved.

Sensitivity and specificity of obesity diagnosis in pediatric ambulatory care in the United States.

PubMed

Walsh, Carolyn O; Milliren, Carly E; Feldman, Henry A; Taveras, Elsie M

2013-09-01

We examined the sensitivity and specificity of an obesity diagnosis in a nationally representative sample of pediatric outpatient visits. We used the 2005 to 2009 National Ambulatory Medical Care and National Hospital Ambulatory Medical Care surveys. We included visits with children 2 to 18 years, yielding a sample of 48 145 database visits. We determined 3 methods of identifying obesity: documented body mass index (BMI) ≥95th percentile; International Classification of Diseases, Ninth Revision (ICD-9) code; and positive answer to the question, "Does the patient now have obesity?" Using BMI as the gold standard, we calculated the sensitivity and specificity of a clinical obesity diagnosis. Among the 19.5% of children who were obese by BMI, 7.0% had an ICD-9 code and 15.2% had a positive response to questioning. The sensitivity of an obesity diagnosis was 15.4%, and the specificity was 99.2%. The sensitivity of the obesity diagnosis in pediatric ambulatory visits is low. Efforts are needed to increase identification of obese children.

Dietary Sodium and Health: More Than Just Blood Pressure

PubMed Central

Farquhar, William B.; Edwards, David G.; Jurkovitz, Claudine T.; Weintraub, William S.

2016-01-01

Sodium is essential for cellular homeostasis and physiological function. Excess dietary sodium has been linked to elevations in blood pressure (BP). Salt-sensitivity of BP varies widely, but certain subgroups tend to be more salt-sensitive. The mechanisms underlying sodium-induced increases in BP are not completely understood, but may involve alterations in renal function, fluid volume, fluid regulatory hormones, the vasculature, cardiac function, and the autonomic nervous system. Recent pre-clinical and clinical data support that even in the absence of an increase in BP, excess dietary sodium can adversely affect target organs, including the blood vessels, heart, kidneys, and brain. In this review, we address these issues and the epidemiological literature relating dietary sodium to BP and cardiovascular health outcomes, addressing recent controversies. We also provide information and strategies for reducing dietary sodium. PMID:25766952

Hydrological Sensitivity of Land Use Scenarios for Climate Mitigation

NASA Astrophysics Data System (ADS)

Boegh, E.; Friborg, T.; Hansen, K.; Jensen, R.; Seaby, L. P.

2014-12-01

Bringing atmospheric concentration to 550 ppm CO2 or below by 2100 will require large-scale changes to global and national energy systems, and potentially the use of land (IPCC, 2013) The Danish government aims at reducing greenhouse gas emissions (GHG) by 40 % in 1990-2020 and energy consumption to be based on 100 % renewable energy by 2035. By 2050, GHG emissions should be reduced by 80-95 %. Strategies developed to reach these goals require land use change to increase the production of biomass for bioenergy, further use of catch crops, reduced nitrogen inputs in agriculture, reduced soil tillage, afforestation and establishment of permanent grass fields. Currently, solar radiation in the growing season is not fully exploited, and it is expected that biomass production for bioenergy can be supported without reductions in food and fodder production. Impacts of climate change on the hydrological sensitivity of biomass growth and soil carbon storage are however not known. The present study evaluates the hydrological sensitivity of Danish land use options for climate mitigation in terms of crop yields (including straw for bioenergy) and net CO2 exchange for wheat, barley, maize and clover under current and future climate conditions. Hydrological sensitivity was evaluated using the agrohydrological model Daisy. Simulations during current climate conditions were in good agreement with measured dry matter, crop nitrogen content and eddy covariance fluxes of water vapour and CO2. Climate scenarios from the European ENSEMBLES database were downscaled for simulating water, nitrogen and carbon balance for 2071-2100. The biomass potential generally increase, but water stress also increases in strength and extends over a longer period, thereby increasing sensitivity to water availability. The potential of different land use scenarios to maximize vegetation cover and biomass for climate mitigation is further discussed in relation to impacts on the energy- and water balance.

Results of an integrated structure-control law design sensitivity analysis

NASA Technical Reports Server (NTRS)

Gilbert, Michael G.

1988-01-01

Next generation air and space vehicle designs are driven by increased performance requirements, demanding a high level of design integration between traditionally separate design disciplines. Interdisciplinary analysis capabilities have been developed, for aeroservoelastic aircraft and large flexible spacecraft control for instance, but the requisite integrated design methods are only beginning to be developed. One integrated design method which has received attention is based on hierarchal problem decompositions, optimization, and design sensitivity analyses. This paper highlights a design sensitivity analysis method for Linear Quadratic Cost, Gaussian (LQG) optimal control laws, which predicts change in the optimal control law due to changes in fixed problem parameters using analytical sensitivity equations. Numerical results of a design sensitivity analysis for a realistic aeroservoelastic aircraft example are presented. In this example, the sensitivity of the optimally controlled aircraft's response to various problem formulation and physical aircraft parameters is determined. These results are used to predict the aircraft's new optimally controlled response if the parameter was to have some other nominal value during the control law design process. The sensitivity results are validated by recomputing the optimal control law for discrete variations in parameters, computing the new actual aircraft response, and comparing with the predicted response. These results show an improvement in sensitivity accuracy for integrated design purposes over methods which do not include changess in the optimal control law. Use of the analytical LQG sensitivity expressions is also shown to be more efficient that finite difference methods for the computation of the equivalent sensitivity information.

Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests.

PubMed

Arts, Gertie H P; Belgers, J Dick M; Hoekzema, Conny H; Thissen, Jac T N M

2008-05-01

The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root endpoints, reflecting root growth, were most sensitive in the toxicity tests, while endpoints relating to biomass, growth and shoot length were less sensitive. The endpoints with the lowest coefficients of variation were not necessarily the endpoints, which were toxicologically most sensitive. Differences in sensitivity were in the range of 10-1000 for different macrophyte-specific endpoints. No macrophyte species was consistently the most sensitive. Criteria to select endpoints in macrophyte toxicity tests should include toxicological sensitivity, variance and ecological relevance. Hence, macrophyte toxicity tests should comprise an array of endpoints, including very sensitive endpoints like those relating to root growth.

Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

PubMed

Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

2016-01-01

Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these brain functional characteristics.

Effects of early human handling on the pain sensitivity of young lambs.

PubMed

Guesgen, Mirjam J; Beausoleil, Ngaio J; Stewart, Mairi

2013-01-01

Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Evaluation of a multiplex immunoassay for bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk against two indirect ELISAs using latent class analysis.

PubMed

Toftaker, Ingrid; Toft, Nils; Stokstad, Maria; Sølverød, Liv; Harkiss, Gordon; Watt, Neil; O' Brien, Amanda; Nødtvedt, Ane

2018-06-01

Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV) are responsible for respiratory disease and diarrhea in cattle worldwide. The Norwegian control program against these infections is based on herd-level diagnosis using a new multiplex immunoassay. The objective of this study was to estimate sensitivity and specificity across different cut-off values for the MVD-Enferplex BCV/BRSV multiplex, by comparing them to a commercially available ELISA, the SVANOVIR ® BCV-Ab and SVANOVIR ® BRSV-Ab, respectively. We analyzed bulk tank milk samples from 360 herds in a low- and 360 herds in a high-prevalence area. As none of the tests were considered perfect, estimation of test characteristics was performed using Bayesian latent class models. At the manufacturers' recommended cut-off values, the median sensitivity for the BRSV multiplex and the BRSV ELISA was 94.4 [89.8-98.7 95% Posterior Credibility Interval (PCI)] and 99.8 [98.7-100 95% PCI], respectively. The median specificity for the BRSV multiplex was 90.6 [85.5-94.4 95% PCI], but only 57.4 [50.5-64.4 95% PCI] for the BRSV ELISA. However, increasing the cut-off of the BRSV ELISA increased specificity without compromising sensitivity. For the BCV multiplex we found that by using only one of the three antigens included in the test, the specificity increased, without concurrent loss in sensitivity. At the recommended cut-off this resulted in a sensitivity of 99.9 [99.3-100 95% PCI] and specificity of 93.7 [88.8-97.8 95% PCI] for the multiplex and a sensitivity of 99.5 [98.1-100 95% PCI] and a specificity of 99.6 [97.6-100 95% PCI] for the BCV ELISA. Copyright © 2018 Elsevier B.V. All rights reserved.

Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster

PubMed Central

Corbett-Detig, Russell B.

2016-01-01

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. “Sensitive sites” have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions. PMID:27343234

Selection on Inversion Breakpoints Favors Proximity to Pairing Sensitive Sites in Drosophila melanogaster.

PubMed

Corbett-Detig, Russell B

2016-09-01

Chromosomal inversions are widespread among taxa, and have been implicated in a number of biological processes including adaptation, sex chromosome evolution, and segregation distortion. Consistent with selection favoring linkage between loci, it is well established that length is a selected trait of inversions. However, the factors that affect the distribution of inversion breakpoints remain poorly understood. "Sensitive sites" have been mapped on all euchromatic chromosome arms in Drosophila melanogaster, and may be a source of natural selection on inversion breakpoint positions. Briefly, sensitive sites are genomic regions wherein proximal structural rearrangements result in large reductions in local recombination rates in heterozygotes. Here, I show that breakpoints of common inversions are significantly more likely to lie within a cytological band containing a sensitive site than are breakpoints of rare inversions. Furthermore, common inversions for which neither breakpoint intersects a sensitive site are significantly longer than rare inversions, but common inversions whose breakpoints intersect a sensitive site show no evidence for increased length. I interpret these results to mean that selection favors inversions whose breakpoints disrupt synteny near to sensitive sites, possibly because these inversions suppress recombination in large genomic regions. To my knowledge this is the first evidence consistent with positive selection acting on inversion breakpoint positions. Copyright © 2016 by the Genetics Society of America.

Analysis strategies for high-resolution UHF-fMRI data.

PubMed

Polimeni, Jonathan R; Renvall, Ville; Zaretskaya, Natalia; Fischl, Bruce

2018-03-01

Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential. Copyright © 2017 Elsevier Inc. All rights reserved.

Inhibition of Bcl-2 Sensitizes Mitochondrial Permeability Transition Pore (MPTP) Opening in Ischemia-Damaged Mitochondria

PubMed Central

Chen, Qun; Xu, Haishan; Xu, Aijun; Ross, Thomas; Bowler, Elizabeth; Hu, Ying; Lesnefsky, Edward J.

2015-01-01

Background Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes. Methods Calcium retention capacity (CRC) was used to reflect the sensitivity of the MPTP opening in isolated cardiac mitochondria. To study the relationship between bcl-2 inhibition and MPTP opening, mitochondria were incubated with a bcl-2 inhibitor (HA14-1) and CRC measured. The contribution of preserved bcl-2 content to MPTP opening following ischemia-reperfusion was explored using transgenic bcl-2 overexpressed mice. Results CRC was decreased in mitochondria following reperfusion compared to ischemia alone, indicating that reperfusion further sensitizes to MPTP opening. Incubation of ischemia-damaged mitochondria with increasing HA14-1concentrations increased calcium-stimulated MPTP opening, supporting that functional inhibition of bcl-2 during simulated reperfusion favors MPTP opening. Moreover, HA14-1 sensitivity was increased by ischemia compared to non-ischemic controls. Overexpression of bcl-2 attenuated MPTP opening in following ischemia-reperfusion. HA14-1 inhibition also increased the permeability of the outer membrane in the absence of exogenous calcium, indicating that bcl-2 inhibition favors MOMP when calcium is low. Conclusions The depletion and functional inhibition of bcl-2 contributes to cardiac injury by increasing susceptibility to MPTP opening in high calcium environments and MOMP in the absence of calcium overload. Thus, ischemia-damaged mitochondria with decreased bcl-2 content are susceptible to MPTP opening in early reperfusion and MOMP later in reperfusion when cytosolic calcium has normalized. PMID:25756500

Panel reactive antibody positivity and associated HLA antibodies in Turkish renal transplant candidates.

PubMed

Ozdemir, Fatma Nurhan; Sezer, Siren; Akcay, Ali; Arat, Zubeyde; Turan, Munire; Gulmus, Sale; Kulah, Eyup; Haberal, Mehmet

2004-01-01

Pre- and post-renal transplantation panel reactive antibody (PRA) screening is associated with increased incidence of hyperacute or acute graft rejection and graft loss. This study was designed to find any relationship PRA sensitization and associated human leukocyte antigen (HLA)-specific antibodies in Turkish renal transplant candidates. We included 340 patients who were in the renal transplantation waiting list in the study. We determined PRA sensitization ratio and the associated anti-HLA IgG antibody distribution of the patient group. The PRA testing was currently performed and levels above 30% were accepted to be positive. The PRA class I positivity was determined in 24 (7%) and class II in 34 (10%) of the patients. The most frequent HLA antibodies for class I were B56, A2, A34, A1, A23, A24 and B61; and for class II were DR11, DR14, DQ7, DR10, DQ5, DR1 and DR7, respectively. From these, the increase of the numbers of anti-HLA class II antibodies was significantly correlated with the increase of PRA sensitization ratio. In conclusion, the identification of the associated HLA-specific antibodies and correlation with the Turkish population HLA antigen distribution will identify the high-risk patients who are candidates for transplantation.

Genetic control of enhanced mutability of mitochondrial DNA and gamma-ray sensitivity in Saccharomyces cerevisiae.

PubMed Central

Foury, F; Goffeau, A

1979-01-01

Five nuclear mutants enhancing the spontaneous mutation rate of mtDNA have been isolated in Saccharomyces cerevisiae. These mutators fall into five complementation groups and are located at five genetic loci different from rad50 to rad57 loci. Three mutants (gam1, gam2, and gam4), insensitive or weakly sensitive to gamma-rays, exhibit increased frequency of spontaneous production of mutants with large deletions of the mtDNA (p-) and of all tested mitochondrial drug-resistant mutants. Two other mutants (gam3 and gam5), highly sensitive to gamma-rays, increase only the mutation rate of particular alleles of the mtDNA. The mutant gam5 enhances only the production of p- and erythromycin-resistant clones. The mutant gam3 exhibits an enhanced rate of oligomycin-resistant clones as well as a collateral increase of nuclear mutability. The existence of gam3 and gam5 mutants indicates that at least two common steps control both nuclear DNA repair and the mutability of particular alleles of the mtDNA. However, the general spontaneous mutability of the mtDNA includes at least three steps not involved in the repair of nuclear DNA, as revealed by the gam1, gam2, and gam4 mutations. PMID:392521

Method for modeling driving cycles, fuel use, and emissions for over snow vehicles.

PubMed

Hu, Jiangchuan; Frey, H Christopher; Sandhu, Gurdas S; Graver, Brandon M; Bishop, Gary A; Schuchmann, Brent G; Ray, John D

2014-07-15

As input to a winter use plan, activity, fuel use, and tailpipe exhaust emissions of over snow vehicles (OSV), including five snow coaches and one snowmobile, were measured on a designated route in Yellowstone National Park (YNP). Engine load was quantified in terms of vehicle specific power (VSP), which is a function of speed, acceleration, and road grade. Compared to highway vehicles, VSP for OSVs is more sensitive to rolling resistance and less sensitive to aerodynamic drag. Fuel use rates increased linearly (R2>0.96) with VSP. For gasoline-fueled OSVs, fuel-based emission rates of carbon monoxide (CO) and nitrogen oxides (NOx) typically increased with increasing fuel use rate, with some cases of very high CO emissions. For the diesel OSVs, which had selective catalytic reduction and diesel particulate filters, fuel-based NOx and particulate matter (PM) emission rates were not sensitive to fuel flow rate, and the emission controls were effective. Inter vehicle variability in cycle average fuel use and emissions rates for CO and NOx was substantial. However, there was relatively little inter-cycle variation in cycle average fuel use and emission rates when comparing driving cycles. Recommendations are made regarding how real-world OSV activity, fuel use, and emissions data can be improved.

Computer-aided detection of pulmonary embolism at CT pulmonary angiography: can it improve performance of inexperienced readers?

PubMed

Blackmon, Kevin N; Florin, Charles; Bogoni, Luca; McCain, Joshua W; Koonce, James D; Lee, Heon; Bastarrika, Gorka; Thilo, Christian; Costello, Philip; Salganicoff, Marcos; Joseph Schoepf, U

2011-06-01

To evaluate the effect of a computer-aided detection (CAD) algorithm on the performance of novice readers for detection of pulmonary embolism (PE) at CT pulmonary angiography (CTPA). We included CTPA examinations of 79 patients (50 female, 52 ± 18 years). Studies were evaluated by two independent inexperienced readers who marked all vessels containing PE. After 3 months all studies were reevaluated by the same two readers, this time aided by CAD prototype. A consensus read by three expert radiologists served as the reference standard. Statistical analysis used χ(2) and McNemar testing. Expert consensus revealed 119 PEs in 32 studies. For PE detection, the sensitivity of CAD alone was 78%. Inexperienced readers' initial interpretations had an average per-PE sensitivity of 50%, which improved to 71% (p < 0.001) with CAD as a second reader. False positives increased from 0.18 to 0.25 per study (p = 0.03). Per-study, the readers initially detected 27/32 positive studies (84%); with CAD this number increased to 29.5 studies (92%; p = 0.125). Our results suggest that CAD significantly improves the sensitivity of PE detection for inexperienced readers with a small but appreciable increase in the rate of false positives.

Developmental immunotoxicity of chemicals in rodents and its possible regulatory impact.

PubMed

Hessel, Ellen V S; Tonk, Elisa C M; Bos, Peter M J; van Loveren, Henk; Piersma, Aldert H

2015-01-01

Around 25% of the children in developed countries are affected with immune-based diseases. Juvenile onset diseases such as allergic, inflammatory and autoimmune diseases have shown increasing prevalences in the last decades. The role of chemical exposures in these phenomena is unclear. It is thought that the developmental immune system is more susceptible to toxicants than the mature situation. Developmental immunotoxicity (DIT) testing is nowadays not or minimally included in regulatory toxicology requirements. We reviewed whether developmental immune parameters in rodents would provide relatively sensitive endpoints of toxicity, whose inclusion in regulatory toxicity testing might improve hazard identification and risk assessment of chemicals. For each of the nine reviewed toxicants, the developing immune system was found to be at least as sensitive or more sensitive than the general (developmental) toxicity parameters. Functional immune (antigen-challenged) parameters appear more affected than structural (non-challenged) immune parameters. Especially, antibody responses to immune challenges with keyhole limpet hemocyanine or sheep red blood cells and delayed-type hypersensitivity responses appear to provide sensitive parameters of developmental immune toxicity. Comparison with current tolerable daily intakes (TDI) and their underlying overall no observed adverse effect levels showed that for some of the compounds reviewed, the TDI may need reconsideration based on developmental immune parameters. From these data, it can be concluded that the developing immune system is very sensitive to the disruption of toxicants independent of study design. Consideration of including functional DIT parameters in current hazard identification guidelines and wider application of relevant study protocols is warranted.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

PubMed Central

Carroll, C. Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469

Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

PubMed Central

McQuaid, Robyn J.; McInnis, Opal A.; Matheson, Kimberly; Anisman, Hymie

2016-01-01

Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243), conducted among white university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP) within the oxytocin receptor gene (OXTR), rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype) of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the “protective allele” was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation. PMID:27486392

Dynamic mechanical properties and anisotropy of synthetic shales with different clay minerals under confining pressure

NASA Astrophysics Data System (ADS)

Gong, Fei; Di, Bangrang; Wei, Jianxin; Ding, Pinbo; Shuai, Da

2018-03-01

The presence of clay minerals can alter the elastic behaviour of reservoir rocks significantly as the type of clay minerals, their volume and distribution, and their orientation control the shale's intrinsic anisotropic behaviours. Clay minerals are the most abundant materials in shale, and it has been proven extremely difficult to measure the elastic properties of natural shale by means of a single variable (in this case, the type of clay minerals), due to the influences of multiple factors, including water, TOC content and complex mineral compositions. We used quartz, clay (kaolinite, illite and smectite), carbonate and kerogen extract as the primary materials to construct synthetic shale with different clay minerals. Ultrasonic experiments were conducted to investigate the anisotropy of velocity and mechanical properties in dry synthetic and natural shale as a function of confining pressure. Velocities in synthetic shale are sensitive to the type of clay minerals, possibly due to the different structures of the clay minerals. The velocities increase with confining pressure and show higher rate of velocity increase at low pressures, and P-wave velocity is usually more sensitive than S-wave velocity to confining pressure according to our results. Similarly, the dynamic Young's modulus and Poisson's ratio increase with applied pressure, and the results also reveal that E11 is always larger than E33 and ν31 is smaller than ν12. Velocity and mechanical anisotropy decrease with increasing stress, and are sensitive to stress and the type of clay minerals. However, the changes of mechanical anisotropy with applied stress are larger compared with the velocity anisotropy, indicating that mechanical properties are more sensitive to the change of rock properties.

Efficacy of smoking cessation therapy alone or integrated with prolonged exposure therapy for smokers with PTSD: Study protocol for a randomized controlled trial.

PubMed

Powers, Mark B; Kauffman, Brooke Y; Kleinsasser, Anne L; Lee-Furman, Eunjung; Smits, Jasper A J; Zvolensky, Michael J; Rosenfield, David

2016-09-01

Posttraumatic stress disorder (PTSD) is related to an increased risk of smoking cessation failure. In fact, the quit rate in smokers with PTSD (23.2%) is one of the lowest of all mental disorders. Features of PTSD that contribute to smokers' progression to nicotine dependence and cessation relapse include negative affect, fear, increased arousal, irritability, anger, distress intolerance, and anxiety sensitivity. Anxiety sensitivity is higher in people with PTSD than in any other anxiety disorder except for panic disorder. High anxiety sensitivity is uniquely associated with greater odds of lapse and relapse during quit attempts. Distress intolerance, a perceived or behavioral tendency to not tolerate distress, is related to both the maintenance of PTSD and problems in quitting smoking. Prolonged exposure (PE) and interoceptive exposure (IE) reduce PTSD symptoms, distress intolerance, and anxiety sensitivity. Thus, they emerge as promising candidates to augment standard smoking cessation interventions for individuals with PTSD. The present study tests a 12-session specialized treatment for smokers with PTSD. This Integrated PTSD and Smoking Treatment (IPST) combines cognitive-behavioral therapy and nicotine replacement treatment for smoking cessation (standard care; SC) with PE to target PTSD symptoms and IE to reduce anxiety sensitivity and distress intolerance. Adult smokers (N=80) with PTSD will be randomly assigned to either: (1) IPST or (2) SC. Primary outcomes are assessed at weeks 0, 6, 8, 10, 14, 16, 22, and 30. Copyright © 2016. Published by Elsevier Inc.

Mass spectrometric characterization of a high-field asymmetric waveform ion mobility spectrometer

NASA Astrophysics Data System (ADS)

Purves, Randy W.; Guevremont, Roger; Day, Stephen; Pipich, Charles W.; Matyjaszczyk, Matthew S.

1998-12-01

Ion mobility spectrometry (IMS) has become an important method for the detection of many compounds because of its high sensitivity and amenability to miniaturization for field-portable monitoring; applications include detection of narcotics, explosives, and chemical warfare agents. High-field asymmetric waveform ion mobility spectrometry (FAIMS) differs from IMS in that the electric fields are applied using a high-frequency periodic asymmetric waveform, rather than a dc voltage. Furthermore, in FAIMS the compounds are separated by the difference in the mobility of ions at high electric field relative to low field, rather than by compound to compound differences in mobility at low electric field (IMS). We report here the first cylindrical-geometry-FAIMS interface with mass spectrometry (FAIMS-MS) and the MS identification of the peaks observed in a FAIMS compensation voltage (CV) spectrum. Using both an electrometer-based-FAIMS (FAIMS-E) and FAIMS-MS, several variables that affect the sensitivity of ion detection were examined for two (polarity reversed) asymmetric waveforms (modes 1 and 2) each of which yields a unique spectrum. An increase in the dispersion voltage (DV) was found to improve the sensitivity and separation observed in the FAIMS CV spectrum. This increase in sensitivity and the unexpected dissimilarity in modes 1 and 2 suggest that atmospheric pressure ion focusing is occurring in the FAIMS analyzer. The sensitivity and peak locations in the CV spectra were affected by temperature, gas flow rates, operating pressure, and analyte concentration.

Diagnosis of Zollinger–Ellison syndrome in the era of PPIs, faulty gastrin assays, sensitive imaging and limited access to acid secretory testing

PubMed Central

Metz, David C.; Cadiot, Guillaume; Poitras, Pierre; Ito, Tetsuhide; Jensen, Robert T.

2017-01-01

In recent years the diagnosis of Zollinger-Ellison syndrome (ZES) has become increasingly controversial with several new approaches and criteria proposed, differing from the classical biochemical criterion of inappropriate hypergastrinemia (i.e., hypergastrinemia in the presence of hyperchlorhydria) (Table 1). These changes have come about because of the difficulty and potential dangers of stopping proton pump inhibitors (PPIs) for gastric acid analysis; the recognition than many of the current assays used to assess gastrin concentrations are unreliable; the development of sensitive imaging modalities that detect neuroendocrine tumors (NETs) including an increasing number of the primary gastrinomas; the increased use of percutaneous or endoscopic ultrasound (EUS)-directed biopsies/cytology and the general lack of availability of acid secretory testing. In this article we will discuss the basis for these controversies, review the proposed changes in diagnostic approaches and make recommendations for supporting the diagnosis of ZES in the modern era. PMID:29326808

Key Policy Makers' Awareness of Tobacco Taxation Effectiveness through a Sensitization Program.

PubMed

Heydari, Gholamreza; Ebn Ahmady, Arezoo; Lando, Harry A; Chamyani, Fahimeh; Masjedi, Mohammadreza; Shadmehr, Mohammad B; Fadaizadeh, Lida

2015-12-01

The implementation of 5 of the 6 WHO MPOWER program in Iran is satisfactory; the only notable shortcoming is the lack of tobacco taxation increases. This study was designed to increase key policy makers' awareness of tobacco taxation effectiveness through a sensitization program in Iran. This analytical and semi-experimental study in 2014 included 110 tobacco control key policy makers, who were trained and received educational materials on the importance of tobacco taxation. A valid and reliable questionnaire was completed before and three months after intervention. Data were analyzed using mean (SD), t-Test and analysis of variance. The mean (SD) scores at pre- and post-test were 2.7 ± 3 and 8.8 ± 1 out of 10, respectively. Paired t-tests demonstrated a significant difference in the pre- post-test knowledge scores. Increasing knowledge and promoting favorable attitudes of policy makers can lead to greater attention which could in turn change tobacco taxation policies.

Addiction: decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit.

PubMed

Volkow, Nora D; Wang, Gene-Jack; Fowler, Joanna S; Tomasi, Dardo; Telang, Frank; Baler, Ruben

2010-09-01

Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction.

Development and testing of an electrochemical methane sensor

DOE PAGES

Sekhar, Praveen K.; Kysar, Jesse; Brosha, Eric Lanich; ...

2016-01-12

In this article, the development of an electrochemical methane sensor is presented. The mixed potential based sensor is based on tin doped indium oxide (ITO) and platinum electrodes and yttria-stabilized zirconia (YSZ) electrolyte. The sensor was fabricated using the inexpensive tape-cast method. The sensor responded to methane with a response time of 15 s. The staircase response to methane indicated a 44 mV sensor response to 100 ppm of methane. The sensor response indicated a log-linear relationship with the methane concentration. Upon 500 h of sensor testing, a 5% reduction in methane sensitivity was observed. The cross-sensitivity study on themore » sensor indicated minimal interference to NO, NO 2, and CO 2. To improve the sensitivity to methane, a signal conditioning method referred to as the pulsed discharge technique (PDT) was applied. Finally, a fourfold increase in methane sensitivity was observed when the sensor was subjected to PDT. Future studies include the miniaturization of the sensor with integrated heater design.« less

Development and testing of an electrochemical methane sensor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sekhar, Praveen K.; Kysar, Jesse; Brosha, Eric Lanich

In this article, the development of an electrochemical methane sensor is presented. The mixed potential based sensor is based on tin doped indium oxide (ITO) and platinum electrodes and yttria-stabilized zirconia (YSZ) electrolyte. The sensor was fabricated using the inexpensive tape-cast method. The sensor responded to methane with a response time of 15 s. The staircase response to methane indicated a 44 mV sensor response to 100 ppm of methane. The sensor response indicated a log-linear relationship with the methane concentration. Upon 500 h of sensor testing, a 5% reduction in methane sensitivity was observed. The cross-sensitivity study on themore » sensor indicated minimal interference to NO, NO 2, and CO 2. To improve the sensitivity to methane, a signal conditioning method referred to as the pulsed discharge technique (PDT) was applied. Finally, a fourfold increase in methane sensitivity was observed when the sensor was subjected to PDT. Future studies include the miniaturization of the sensor with integrated heater design.« less

Negative Affect as a Mediator of the Relationship between Vigorous-Intensity Exercise and Smoking

PubMed Central

Tart, Candyce D.; Leyro, Teresa M.; Richter, Ashley; Zvolensky, Michael J.; Rosenfield, David; Smits, Jasper A. J.

2010-01-01

The present cross-sectional study evaluated whether people who engage in vigorous-intensity exercise are better able to regulate negative affective states, thereby changing core maintenance factors of smoking. Participants were a community sample of adults (n = 270) who completed self-report measures of physical activity, cigarette smoking, anxiety sensitivity, and negative affect. Consistent with hypothesis, vigorous-intensity exercise was related to lower levels of cigarette smoking, accounting for 10% of the variance in smoking. Additionally, negative affect mediated the relationship between vigorous-intensity physical activity and cigarette smoking, accounting for about 12% of this relation. Furthermore, these relationships were stronger for individuals with high anxiety sensitivity than for those with low anxiety sensitivity; including anxiety sensitivity as a moderator of the mediated relationship increased the amount of variance accounted for by negative affect to 17%. The findings are discussed in relation to developing further scientific insight into the mechanisms and pathways relevant to understanding the association among vigorous-intensity exercise, smoking, and emotional vulnerability. PMID:20171786

Actinic Flux Calculations: A Model Sensitivity Study

NASA Technical Reports Server (NTRS)

Krotkov, Nickolay A.; Flittner, D.; Ahmad, Z.; Herman, J. R.; Einaudi, Franco (Technical Monitor)

2000-01-01

calculate direct and diffuse surface irradiance and actinic flux (downwelling (2p) and total (4p)) for the reference model. Sensitivity analysis has shown that the accuracy of the radiative transfer flux calculations for a unit ETS (i.e. atmospheric transmittance) together with a numerical interpolation technique for the constituents' vertical profiles is better than 1% for SZA less than 70(sub o) and wavelengths longer than 310 nm. The differences increase for shorter wavelengths and larger SZA, due to the differences in pseudo-spherical correction techniques and vertical discretetization among the codes. Our sensitivity study includes variation of ozone cross-sections, ETS spectra and the effects of wavelength shifts between vacuum and air scales. We also investigate the effects of aerosols on the spectral flux components in the UV and visible spectral regions. The "aerosol correction factors" (ACFs) were calculated at discrete wavelengths and different SZAs for each flux component (direct, diffuse, reflected) and prescribed IPMMI aerosol parameters. Finally, the sensitivity study was extended to calculation of selected photolysis rates coefficients.

Prenatal Depressive Symptoms and Toddler Behavior Problems: The Role of Maternal Sensitivity and Child Sex.

PubMed

Edwards, Renee C; Hans, Sydney L

2016-10-01

Increasing evidence suggests that maternal depression during pregnancy is associated with child behavioral outcomes even after accounting for later maternal depression. The purpose of this study was to examine various mechanisms, including maternal sensitivity, neonatal problems, and concurrent maternal depression, that might explain the association between prenatal maternal depressive symptoms and toddler behavior problems. Young, low income, African American mothers (n = 196) were interviewed during pregnancy and at 24-months postpartum, medical records were collected at the birth, and mother-child interactions were video-recorded at 24 months. Path analyses revealed that the association between prenatal depression and toddler behavior problems was mediated by maternal sensitivity and maternal depressive symptoms at 24 months. No evidence was found for a mediating effect of neonatal problems. Path models examining sex differences suggested that different mediating factors may be important for boys and girls, with boys being particularly susceptible to the effects of maternal sensitivity.

Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?

PubMed

Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica

2011-05-01

Central sensitization accounts for chronic 'unexplained' pain in a wide variety of disorders, including chronic whiplash-associated disorders, temporomandibular disorders, chronic low back pain, osteoarthritis, fibromyalgia, chronic fatigue syndrome and chronic tension-type headache among others. Given the increasing evidence supporting the clinical significance of central sensitization in those with unexplained chronic pain, the awareness is growing that central sensitization should be a treatment target in these patients. This article provides an overview of the treatment options available for desensitizing the CNS in patients with chronic pain due to central sensitization. It focuses on those strategies that specifically target pathophysiological mechanisms known to be involved in central sensitization. In addition, pharmacological options, rehabilitation and neurotechnology options are discussed. Acetaminophen, serotonin-reuptake inhibitor drugs, selective and balanced serototin and norepinephrine-reuptake inhibitor drugs, the serotonin precursor tryptophan, opioids, N-methyl-d-aspartate (NMDA)-receptor antagonists, calcium-channel alpha(2)delta (a2δ) ligands, transcranial magnetic stimulation, transcutaneous electric nerve stimulation (TENS), manual therapy and stress management each target central pain processing mechanisms in animals that - theoretically - desensitize the CNS in humans. To provide a comprehensive treatment for 'unexplained' chronic pain disorders characterized by central sensitization, it is advocated to combine the best evidence available with treatment modalities known to target central sensitization. © 2011 Informa UK, Ltd

Nicotine-induced locomotor sensitization: pharmacological analyses with candidate smoking cessation aids.

PubMed

Goutier, Wouter; Kloeze, Margreet; McCreary, Andrew C

2016-03-01

There are a number of approved therapeutics for the management of alcohol dependence, which might also convey the potential as smoking cessation aids. The present study investigated the effect of a few of these therapeutics and potential candidates (non-peptide vasopressin V1b antagonists) on the expression of nicotine-induced behavioral sensitization in Wistar rats. The following compounds were included in this evaluation: rimonabant, bupropion, topiramate, acamprosate, naltrexone, mecamylamine, nelivaptan (SSR-149415, V1b antagonist) and two novel V1b antagonists. Following the development of nicotine-induced locomotor sensitization and a withdrawal period, the expression of sensitization was assessed in the presence of one of the examined agents given 30 minutes prior to the nicotine challenge injection. Acamprosate, naltrexone, rimonabant, mecamylamine, nelivaptan and V1b antagonist 'compound 2' significantly antagonized the expression of nicotine-induced sensitization. Whereas topiramate showed a trend for effects, the V1b antagonist 'compound 1' did not show any significant effects. Bupropion failed to block sensitization but increased activity alone and was therefore tested in development and cross-sensitization studies. Taken together, these findings provide pre-clinical evidence that these molecules attenuated the expression of nicotine-induced sensitization and should be further investigated as putative treatments for nicotine addiction. Moreover, V1b antagonists should be further investigated as a potential novel smoking cessation aid. © 2014 Society for the Study of Addiction.

In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.

PubMed

Aasa-Chapman, Marlén M I; Cheney, Kelly M; Hué, Stéphane; Forsman, Anna; O'Farrell, Stephen; Pellegrino, Pierre; Williams, Ian; McKnight, Áine

2011-01-01

The rapid and continual viral escape from neutralizing antibodies is well documented in HIV-1 infection. Here we report in vivo emergence of viruses with heightened sensitivity to neutralizing antibodies, sometimes paralleling the development of neutralization escape. Sequential viral envs were amplified from seven HIV-1 infected men monitored from seroconversion up to 5 years after infection. Env-recombinant infectious molecular clones were generated and tested for coreceptor use, macrophage tropism and neutralization sensitivity to homologous and heterologous serum, soluble CD4 and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves sensitivity to contemporaneous neutralizing antibodies during infection. Neutralization sensitive viruses grow out even when potent autologous neutralizing antibodies are present in patient serum. Increased sensitivity to neutralization was associated with susceptibility of the CD4 binding site or epitopes induced after CD4 binding, and mediated by complex envelope determinants including V3 and V4 residues. The development of neutralization sensitive viruses occurred without clinical progression, coreceptor switch or change in tropism for primary macrophages. We propose that an interplay of selective forces for greater virus replication efficiency without the need to resist neutralizing antibodies in a compartment protected from immune surveillance may explain the temporal course described here for the in vivo emergence of HIV-1 isolates with high sensitivity to neutralizing antibodies.

Delignification of high kappa number soda-ODiMAQ pulps with a polyoxometalate

Treesearch

Edward L. Springer; Aziz Ahmed

2001-01-01

Increased use of pressure sensitive adhesives for labels and stamps has introduced another contaminant into the office paper stream: silicone- coated release liners. This study examines methods and conditions for removal of contaminants, including these liners, from a typical batch of discarded office papers. Removal of contaminants contained in the furnish were...

Understanding the science of climate change: Talking points - Impacts to Prairie Potholes and Grasslands

Treesearch

Rachel Loehman

2009-01-01

Climate changes in the Prairie Potholes and Grasslands bioregion include increased seasonal, annual, minimum, and maximum temperature and changing precipitation patterns. Because the region is relatively dry with a strong seasonal climate, it is sensitive to climatic changes and vulnerable to changes in climatic regime. For example, model simulations show that regional...

Childhood Markers of Health Behavior Relate to Hippocampal Health, Memory, and Academic Performance

ERIC Educational Resources Information Center

Hassevoort, Kelsey M.; Khan, Naiman A.; Hillman, Charles H.; Cohen, Neal J.

2016-01-01

There has been an increasing body of evidence that a variety of factors, including physical activity, nutrition, and body composition, have a relationship with brain structure and function in school-aged children. Within the brain, the hippocampus is particularly sensitive to modulation by these lifestyle factors. This brain structure is known to…

Students of Color Studying Abroad: A Qualitative Description of the Factors That Influence Participation and the Perceived Impact of Participation

ERIC Educational Resources Information Center

Perkins, Christel

2017-01-01

Research indicates that study abroad participation has many benefits, including increasing students' language proficiency, intercultural sensitivity and cross-cultural communication skills when compared with students who do not study abroad. Additionally, study abroad have been found to shape students' career paths, and academic pursuits. Despite…

Salinomycin sensitizes antimitotic drugs-treated cancer cells by increasing apoptosis via the prevention of G2 arrest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Ju-Hwa; Yoo, Hye-In; Kang, Han Sung

Highlights: Black-Right-Pointing-Pointer Sal sensitizes antimitotic drugs-treated cancer cells. Black-Right-Pointing-Pointer Sal sensitizes them by prevention of G2 arrest and reduced cyclin D1 levels. Black-Right-Pointing-Pointer Sal also sensitizes them by increasing DNA damage and reducing p21 level. Black-Right-Pointing-Pointer A low concentration of Sal effectively sensitized the cancer cells to antimitotic drugs. -- Abstract: Here, we investigated whether Sal could sensitize cancer cells to antimitotic drugs. We demonstrated that Sal sensitized paclitaxcel (PAC)-, docetaxcel (DOC)-, vinblastin (VIN)-, or colchicine (COL)-treated cancer cell lines, suggesting that Sal has the ability to sensitize the cells to any form of microtubule-targeting drugs. Sensitization to the antimitoticmore » drugs could be achieved with very low concentrations of Sal, suggesting that there is a possibility to minimize Sal toxicity associated with human cancer patient treatments. Sensitization by Sal increased apoptosis, which was observed by C-PARP production. Sal sensitized the cancer cells to antimitotic drugs by preventing G2 arrest, suggesting that Sal contributes to the induction of mitotic catastrophe. Sal generally reduced cyclin D1 levels in PAC-, DOC-, and VIN-treated cells. In addition, Sal treatment increased pH2AX levels and reduced p21 levels in antimitotic drugs-treated cells. These observations suggest that the mechanisms underlying Sal sensitization to DNA-damaging compounds, radiation, and microtubule-targeting drugs are similar. Our data demonstrated that Sal sensitizes cancer cells to antimitotic drugs by increasing apoptosis through the prevention of G2 arrest via conserved Sal-sensitization mechanisms. These results may contribute to the development of Sal-based chemotherapy for cancer patients treated with antimitotic drugs.« less

Effects of aquaculture production noise on hearing, growth, and disease resistance of rainbow trout Oncorhynchus mykiss

USGS Publications Warehouse

Wysocki, L.E.; Davidson, J. W.; Smith, M.E.; Frankel, A.S.; Ellison, W.T.; Mazik, P.M.; Popper, A.N.; Bebak, J.

2007-01-01

Intensive aquaculture production often utilizes equipment (e.g., aerators, air and water pumps, harvesters, blowers, filtration systems, and maintenance machinery) that increases noise levels in fish culture tanks. Consequently, chronic exposure to elevated noise levels in tanks could negatively impact cultured species. Possible effects include impairment of the auditory system, increased stress, and reduced growth rates. The objective of this study was to evaluate the long-term effects of sound exposure on the hearing sensitivity, growth, and survival of cultured rainbow trout (Oncorhynchus mykiss). Two cohorts of rainbow trout were cultured for 8??months in replicated tanks consisting of three sound treatments: 115, 130, or 150 decibels referenced at 1 micropascal (dB re 1????Pa root mean square [RMS]) levels. Auditory evoked potential (AEP) recordings revealed no significant differences in hearing thresholds resulting from exposure to increased ambient sound levels. Although there was no evident noise-induced hearing loss, there were significant differences in hearing thresholds between the two fish cohorts examined. No statistical effect of sound treatment was found for growth rate and mortality within each fish cohort. There was no significant difference in mortality between sound treatments when fish were exposed to the pathogen Yersinia ruckeri, but there was significantly different mortality between cohorts. This study indicated that rainbow trout hearing sensitivity, growth, survival, stress, and disease susceptibility were not negatively impacted by noise levels common to recirculating aquaculture systems. These findings should not be generalized to all cultured fish species, however, because many species, including catfish and cyprinids, have much greater hearing sensitivity than rainbow trout and could be affected differently by noise. ?? 2007 Elsevier B.V. All rights reserved.

Future changes in regional precipitation simulated by a half-degree coupled climate model: Sensitivity to horizontal resolution

DOE PAGES

Shields, Christine A.; Kiehl, Jeffrey T.; Meehl, Gerald A.

2016-06-02

The global fully coupled half-degree Community Climate System Model Version 4 (CCSM4) was integrated for a suite of climate change ensemble simulations including five historical runs, five Representative Concentration Pathway 8.5 [RCP8.5) runs, and a long Pre-Industrial control run. This study focuses on precipitation at regional scales and its sensitivity to horizontal resolution. The half-degree historical CCSM4 simulations are compared to observations, where relevant, and to the standard 1° CCSM4. Both the halfdegree and 1° resolutions are coupled to a nominal 1° ocean. North American and South Asian/Indian monsoon regimes are highlighted because these regimes demonstrate improvements due to highermore » resolution, primarily because of better-resolved topography. Agriculturally sensitive areas are analyzed and include Southwest, Central, and Southeast U.S., Southern Europe, and Australia. Both mean and extreme precipitation is discussed for convective and large-scale precipitation processes. Convective precipitation tends to decrease with increasing resolution and large-scale precipitation tends to increase. Improvements for the half-degree agricultural regions can be found for mean and extreme precipitation in the Southeast U.S., Southern Europe, and Australian regions. Climate change responses differ between the model resolutions for the U.S. Southwest/Central regions and are seasonally dependent in the Southeast and Australian regions. Both resolutions project a clear drying signal across Southern Europe due to increased greenhouse warming. As a result, differences between resolutions tied to the representation of convective and large-scale precipitation play an important role in the character of the climate change and depend on regional influences.« less

A Large Array of Small Antennas to Support Future NASA Missions

NASA Astrophysics Data System (ADS)

Jones, D. L.; Weinreb, S.; Preston, R. A.

2001-01-01

A team of engineers and scientists at JPL is currently working on the design of an array of small radio antennas with a total collecting area up to twenty times that of the largest existing (70 m) DSN antennas. An array of this size would provide obvious advantages for high data rate telemetry reception and for spacecraft navigation. Among these advantages are an order-of-magnitude increase in sensitivity for telemetry downlink, flexible sub-arraying to track multiple spacecraft simultaneously, increased reliability through the use of large numbers of identical array elements, very accurate real-time angular spacecraft tracking, and a dramatic reduction in cost per unit area. NASA missions in many disciplines, including planetary science, would benefit from this increased DSN capability. The science return from planned missions could be increased, and opportunities for less expensive or completely new kinds of missions would be created. The DSN array would also bean immensely valuable instrument for radio astronomy. Indeed, it would be by far the most sensitive radio telescope in the world. Additional information is contained in the original extended abstract.

Fourier transform ion cyclotron resonance mass spectrometry

NASA Astrophysics Data System (ADS)

Marshall, Alan G.

1998-06-01

As for Fourier transform infrared (FT-IR) interferometry and nuclear magnetic resonance (NMR) spectroscopy, the introduction of pulsed Fourier transform techniques revolutionized ion cyclotron resonance mass spectrometry: increased speed (factor of 10,000), increased sensitivity (factor of 100), increased mass resolution (factor of 10,000-an improvement not shared by the introduction of FT techniques to IR or NMR spectroscopy), increased mass range (factor of 500), and automated operation. FT-ICR mass spectrometry is the most versatile technique for unscrambling and quantifying ion-molecule reaction kinetics and equilibria in the absence of solvent (i.e., the gas phase). In addition, FT-ICR MS has the following analytically important features: speed (~1 second per spectrum); ultrahigh mass resolution and ultrahigh mass accuracy for analysis of mixtures and polymers; attomole sensitivity; MSn with one spectrometer, including two-dimensional FT/FT-ICR/MS; positive and/or negative ions; multiple ion sources (especially MALDI and electrospray); biomolecular molecular weight and sequencing; LC/MS; and single-molecule detection up to 108 Dalton. Here, some basic features and recent developments of FT-ICR mass spectrometry are reviewed, with applications ranging from crude oil to molecular biology.

A front end readout electronics ASIC chip for position sensitive solid state detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kravis, S.D.; Tuemer, T.O.; Visser, G.J.

1998-12-31

A mixed signal Application Specific Integrated Circuit (ASIC) chip for front end readout electronics of position sensitive solid state detectors has been manufactured. It is called RENA (Readout Electronics for Nuclear Applications). This chip can be used for both medical and industrial imaging of X-rays and gamma rays. The RENA chip is a monolithic integrated circuit and has 32 channels with low noise high input impedance charge sensitive amplifiers. It works in pulse counting mode with good energy resolution. It also has a self triggering output which is essential for nuclear applications when the incident radiation arrives at random. Different,more » externally selectable, operational modes that includes a sparse readout mode is available to increase data throughput. It also has externally selectable shaping (peaking) times.« less

Modeling Olfactory Bulb Evolution through Primate Phylogeny

PubMed Central

Heritage, Steven

2014-01-01

Adaptive characterizations of primates have usually included a reduction in olfactory sensitivity. However, this inference of derivation and directionality assumes an ancestral state of olfaction, usually by comparison to a group of extant non-primate mammals. Thus, the accuracy of the inference depends on the assumed ancestral state. Here I present a phylogenetic model of continuous trait evolution that reconstructs olfactory bulb volumes for ancestral nodes of primates and mammal outgroups. Parent-daughter comparisons suggest that, relative to the ancestral euarchontan, the crown-primate node is plesiomorphic and that derived reduction in olfactory sensitivity is an attribute of the haplorhine lineage. The model also suggests a derived increase in olfactory sensitivity at the strepsirrhine node. This oppositional diversification of the strepsirrhine and haplorhine lineages from an intermediate and non-derived ancestor is inconsistent with a characterization of graded reduction through primate evolution. PMID:25426851

Thirty-year survey on airborne pollen concentrations in Genoa, Italy: relationship with sensitizations, meteorological data, and air pollution.

PubMed

Negrini, Arsenio Corrado; Negrini, Simone; Giunta, Vania; Quaglini, Silvana; Ciprandi, Giorgio

2011-01-01

Pollen allergy represents a relevant health issue. Betulaceae sensitization significantly increased in Genoa, Italy, in the last decades. This study investigated possible relationships among pollen count, meteorological changes, air pollution, and sensitizations in this city during a 30-year period. Betulaceae, Urticaceae, Gramineae, and Oleaceae pollen counts were measured from 1981 to 2010 in Genoa. Sensitization to these pollens was also considered in large populations of allergic patients. Meteorological parameters and pollutants were also measured in the same area. Betulaceae sensitization increased over time. All pollen species significantly increased over this time. Pollen season advanced for Betulaceae and Urticaceae. Only Urticaceae season significantly increased. Temperature increased while rainfall decreased over the time. Pollutants significantly decreased. There were some relationships between pollen changes and climatic and air pollution parameters. This 30-year study conducted in an urbanized area provided evidence that Betulaceae sensitization significantly increased, pollen load significantly augmented, and climate and air pollution changed with a possible influence on pollen release.

Understanding Socio-Hydrology System in the Kissimmee River Basin

NASA Astrophysics Data System (ADS)

Chen, X.; Wang, D.; Tian, F.; Sivapalan, M.

2014-12-01

This study is to develop a conceptual socio-hydrology model for the Kissimmee River Basin. The Kissimmee River located in Florida was channelized in mid-20 century for flood protection. However, the environmental issues caused by channelization led Floridians to conduct a restoration project recently, focusing on wetland recovery. As a complex coupled human-water system, Kissimmee River Basin shows the typical socio-hydrology interactions. Hypothetically, the major reason to drive the system from channelization to restoration is that the community sensitivity towards the environment has changed from controlling to restoring. The model developed in this study includes 5 components: water balance, flood risk, wetland area, crop land area, and community sensitivity. Furthermore, urban population and rural population in the basin have different community sensitivities towards the hydrologic system. The urban population, who live further away from the river are more sensitive to wetland restoration; while the rural population, who live closer to the river are more sensitive to flood protection. The power dynamics between the two groups and its impact on management decision making is described in the model. The model is calibrated based on the observed watershed outflow, wetland area and crop land area. The results show that the overall focus of community sensitivity has changed from flood protection to wetland restoration in the past 60 years in Kissimmee River Basin, which confirms the study hypothesis. There are two main reasons for the community sensitivity change. Firstly, people's flood memory is fading because of the effective flood protection, while the continuously shrinking wetland and the decreasing bird and fish population draw more and more attention. Secondly, in the last 60 years, the urban population in Florida drastically increased compared with a much slower increase of rural population. As a result, the community sensitivity of urban population towards wetland restoration has more weight than the rural population's towards flood protection.

Trends in mass spectrometry instrumentation for proteomics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Richard D.

2002-12-01

Mass spectrometry has become a primary tool for proteomics due to its capabilities for rapid and sensitive protein identification and quantitation. It is now possible to identify thousands of proteins from microgram sample quantities in a single day and to quantify relative protein abundances. However, the needs for increased capabilities for proteome measurements are immense and are now driving both new strategies and instrument advances. These developments include those based on integration with multi-dimensional liquid separations and high accuracy mass measurements, and promise more than order of magnitude improvements in sensitivity, dynamic range, and throughput for proteomic analyses in themore » near future.« less

Coated Fused Silica Fibers for Enhanced Sensitivity Torsion Pendulum

NASA Technical Reports Server (NTRS)

Numata, Kenji; Horowitz, Jordan; Camp, Jordan

2007-01-01

In order to investigate the fundamental thermal noise limit of a torsion pendulum using a fused silica fiber, we systematically measured and modeled the mechanical losses of thin fused silica fibers coated by electrically conductive thin metal films. Our results indicate that it is possible to achieve a thermal noise limit for coated silica lower by a factor between 3 and 9, depending on the silica diameter, compared to the best tungsten fibers available. This will allow a corresponding increase in sensitivity of torsion pendula used for weak force measurements, including the gravitational constant measurement and ground-based force noise testing for the Laser Interferometer Space Antenna (LISA) mission.

Barium Tagging from nEXO Using Resonance Ionization Spectroscopy

NASA Astrophysics Data System (ADS)

Twelker, K.; Kravitz, S.

nEXO is a 5-ton liquid enriched-xenon time projection chamber (TPC) to search for neutrinoless double-beta decay, designed to have the sensitivity to completely probe the inverted mass hierarchy of Majorana neutrinos. The detector will accommodate-as a background reduction technique-a system to recover and identify the barium decay product. This upgrade will allow a background-free measurement of neutrinoless double-beta decay and increase the half-life sensitivity of the experiment by at least one order of magnitude. Ongoing research and development includes a system to test barium extraction from liquid xenon using surface adsorption and Resonance Ionization Spectroscopy (RIS).

Evaluating alternative approaches to modeling terrestrial C and N interactions using observations of ecosystem response to nitrogen deposition and experimental fertilization

NASA Astrophysics Data System (ADS)

Thomas, R. Q.; Bonan, G. B.; Goodale, C. L.

2012-12-01

In many forest ecosystems, nitrogen deposition is increasing carbon storage and reducing climate warming from fossil fuel emissions. Accurately modeling the forest carbon sequestration response to elevated nitrogen deposition using global biogeochemical models coupled to climate models is therefore important. Here, we use observations of the forest carbon response to both nitrogen fertilization experiments and nitrogen deposition gradients to test and improve a global biogeochemical model (CLM-CN 4.0). We introduce a series of model modifications to the CLM-CN that 1) creates a more closed nitrogen cycle with reduced nitrogen fixation and N gas loss and 2) includes buffering of plant nitrogen uptake and buffering of soil nitrogen available for plants and microbial processes. Overall, the modifications improved the comparison of the model predictions to the observational data by increasing the carbon storage response to historical nitrogen deposition (1850-2004) in temperate forest ecosystems by 144% and reducing the response to nitrogen fertilization. The increased sensitivity to nitrogen deposition was primarily attributable to greater retention of nitrogen deposition in the ecosystem and a greater role of synergy between nitrogen deposition and rising atmospheric CO2. Based on our results, we suggest that nitrogen retention should be an important attribute investigated in model inter-comparisons. To understand the specific ecosystem processes that contribute to the sensitivity of carbon storage to nitrogen deposition, we examined sensitivity to nitrogen deposition in a set of intermediary models that isolate the key differences in model structure between the CLM-CN 4.0 and the modified version. We demonstrate that the nitrogen deposition response was most sensitive to the implementation of a more closed nitrogen cycle and buffered plant uptake of soil mineral nitrogen, and less sensitive to modifications of the canopy scaling of photosynthesis, soil buffering of available nitrogen, and plant buffering of labile nitrogen. By comparing carbon storage sensitivity to observational data from both nitrogen deposition gradients and nitrogen fertilization experiments, we show different observed estimates of sensitivity between these two approaches could be explained by differences in the magnitude and time-scale of nitrogen additions.

Diffusion-weighted and T2-weighted MR imaging for colorectal liver metastases detection in a rat model at 7 T: a comparative study using histological examination as reference.

PubMed

Wagner, Mathilde; Maggiori, Léon; Ronot, Maxime; Paradis, Valérie; Vilgrain, Valérie; Panis, Yves; Van Beers, Bernard E

2013-08-01

To compare diffusion-weighted (DW) and T2-weighted MR imaging in detecting colorectal liver metastases in a rat model, using histological examination as a reference method. Eighteen rats had four liver injections of colon cancer cells. MR examinations at 7 T included FSE-T2-weighted imaging and SE-DW MR imaging (b = 0, 20 and 150 s/mm(2)) and were analysed by two independent readers. Histological examination was performed on 0.4-mm slices. McNemar's test was used to compare the sensitivities and the Wilcoxon matched pairs test to compare the average number of false-positives per rat. One hundred and sixty-six liver metastases were identified on histological examination. The sensitivity in detecting liver metastases was significantly higher on DW MR than on T2-weighted images (99/166 (60 %) (reader 1) and 92/166 (55 %) (reader 2) versus 77/166 (46 %), P ≤ 0.001), without an increase in false-positives per rat (P = 0.773/P = 0.850). After stratification according to metastasis diameter, DW MR imaging had a significantly higher sensitivity than T2-weighted imaging only for metastases with a diameter (0.6-1.2 mm) similar to that of the spatial resolution of MR imaging in the current study. This MR study with histological correlations shows the higher sensitivity of DW relative to T2-weighted imaging at 7 T for detecting liver metastases, especially small ones. • Diffusion weighted (DW) sequences are increasingly used in magnetic resonance imaging (MRI). • DW has higher sensitivity for liver metastases than T2-weighted imaging at 7 T. • This increase in sensitivity is especially marked for small liver metastasis detection. • This higher sensitivity is confirmed in an animal model with histological correlation. • DW imaging has the potential for earlier diagnosis of small liver metastases.

Induced sensitivity of Bacillus subtilis colony morphology to mechanical media compression

PubMed Central

Polka, Jessica K.

2014-01-01

Bacteria from several taxa, including Kurthia zopfii, Myxococcus xanthus, and Bacillus mycoides, have been reported to align growth of their colonies to small features on the surface of solid media, including anisotropies created by compression. While the function of this phenomenon is unclear, it may help organisms navigate on solid phases, such as soil. The origin of this behavior is also unknown: it may be biological (that is, dependent on components that sense the environment and regulate growth accordingly) or merely physical. Here we show that B. subtilis, an organism that typically does not respond to media compression, can be induced to do so with two simple and synergistic perturbations: a mutation that maintains cells in the swarming (chained) state, and the addition of EDTA to the growth media, which further increases chain length. EDTA apparently increases chain length by inducing defects in cell separation, as the treatment has only marginal effects on the length of individual cells. These results lead us to three conclusions. First, the wealth of genetic tools available to B. subtilis will provide a new, tractable chassis for engineering compression sensitive organisms. Second, the sensitivity of colony morphology to media compression in Bacillus can be modulated by altering a simple physical property of rod-shaped cells. And third, colony morphology under compression holds promise as a rapid, simple, and low-cost way to screen for changes in the length of rod-shaped cells or chains thereof. PMID:25289183

Sensitivity analysis of conservative and reactive stream transient storage models applied to field data from multiple-reach experiments

USGS Publications Warehouse

Gooseff, M.N.; Bencala, K.E.; Scott, D.T.; Runkel, R.L.; McKnight, Diane M.

2005-01-01

The transient storage model (TSM) has been widely used in studies of stream solute transport and fate, with an increasing emphasis on reactive solute transport. In this study we perform sensitivity analyses of a conservative TSM and two different reactive solute transport models (RSTM), one that includes first-order decay in the stream and the storage zone, and a second that considers sorption of a reactive solute on streambed sediments. Two previously analyzed data sets are examined with a focus on the reliability of these RSTMs in characterizing stream and storage zone solute reactions. Sensitivities of simulations to parameters within and among reaches, parameter coefficients of variation, and correlation coefficients are computed and analyzed. Our results indicate that (1) simulated values have the greatest sensitivity to parameters within the same reach, (2) simulated values are also sensitive to parameters in reaches immediately upstream and downstream (inter-reach sensitivity), (3) simulated values have decreasing sensitivity to parameters in reaches farther downstream, and (4) in-stream reactive solute data provide adequate data to resolve effective storage zone reaction parameters, given the model formulations. Simulations of reactive solutes are shown to be equally sensitive to transport parameters and effective reaction parameters of the model, evidence of the control of physical transport on reactive solute dynamics. Similar to conservative transport analysis, reactive solute simulations appear to be most sensitive to data collected during the rising and falling limb of the concentration breakthrough curve. ?? 2005 Elsevier Ltd. All rights reserved.

Environmental pollution and lung effects in children.

PubMed

Searing, Daniel A; Rabinovitch, Nathan

2011-06-01

Studies over the last 2 years have added important new information on the relationship between air pollution and asthma incidence and severity. Outdoor air pollution has been associated with asthma exacerbations, including emergency department visits and hospitalizations, as well as with the onset of asthma. Possible mechanisms mediating both incidence and severity effects include the induction of oxidative stress, and/or allergic sensitization, as well as increased susceptibility to viral infections. Some of these mechanisms may be occurring in utero including epigenetic changes that may increase risk for development of asthma. Factors related to increased susceptibility for air pollution-related asthma severity include age, season and genetic polymorphisms related to antioxidant enzymes. Ambient pollution levels may be associated with both asthma incidence and severity. Susceptibility to air pollution may be higher in children with genetic polymorphisms related to the 'oxidant stress pathways'. Potential interventions for susceptible children at risk for asthma development and/or severity include decreased exposure on high air pollution days, especially in the summer months, and antioxidant supplementation. On the population level, changes in school and home zoning to increase distance from busy roadways may help reduce both asthma incidence and severity.

Food deprivation increases the low-dose locomotor stimulant response to ethanol in Drosophila melanogaster.

PubMed

Kliethermes, Christopher L

2013-10-01

Acute and chronic states of food deprivation result in increased sensitivity to a variety of natural reinforcers as well as to drugs of abuse. Food deprived animals show increased locomotor activity during periods of food deprivation, as well as increased locomotor stimulant responses to drugs of abuse, including cocaine, amphetamine, morphine, and ethanol, implying that drugs of abuse act in part on neural systems that underlie responses towards food. To determine whether this effect extends to an invertebrate, highly genetically tractable animal, the locomotor stimulant effects of low dose ethanol were assessed under a variety of feeding conditions in the fruit fly, Drosophila melanogaster. Food deprivation resulted in strain specific increases in ethanol-stimulated locomotor activity in most strains tested, although elevated baseline activity confounded interpretation in some strains. Experiments conducted with Canton S flies found that the effects of food deprivation on the locomotor stimulant response to ethanol increased with the duration of deprivation, and could be blocked by refeeding the flies with standard food or sucrose, but not yeast, immediately prior to the ethanol exposure. Life-span extending dietary depletion procedures or previous periods of food deprivation did not affect the response to ethanol, indicating that only animals in an acutely food deprived state are more sensitive to the stimulant effects of ethanol. These results suggest that increased sensitivity to the stimulant effects of some drugs of abuse might reflect an evolutionarily conserved neural mechanism that underlies behavioral responses to natural reinforcers and drugs of abuse. The identification of this mechanism, and the genes that underlie its development and function, will constitute a novel approach towards the study of alcohol abuse and dependence. © 2013.

Seasonality, Rather than Nutrient Addition or Vegetation Types, Influenced Short-Term Temperature Sensitivity of Soil Organic Carbon Decomposition

PubMed Central

He, Feng-Peng; Wang, Wei

2016-01-01

The response of microbial respiration from soil organic carbon (SOC) decomposition to environmental changes plays a key role in predicting future trends of atmospheric CO2 concentration. However, it remains uncertain whether there is a universal trend in the response of microbial respiration to increased temperature and nutrient addition among different vegetation types. In this study, soils were sampled in spring, summer, autumn and winter from five dominant vegetation types, including pine, larch and birch forest, shrubland, and grassland, in the Saihanba area of northern China. Soil samples from each season were incubated at 1, 10, and 20°C for 5 to 7 days. Nitrogen (N; 0.035 mM as NH4NO3) and phosphorus (P; 0.03 mM as P2O5) were added to soil samples, and the responses of soil microbial respiration to increased temperature and nutrient addition were determined. We found a universal trend that soil microbial respiration increased with increased temperature regardless of sampling season or vegetation type. The temperature sensitivity (indicated by Q10, the increase in respiration rate with a 10°C increase in temperature) of microbial respiration was higher in spring and autumn than in summer and winter, irrespective of vegetation type. The Q10 was significantly positively correlated with microbial biomass and the fungal: bacterial ratio. Microbial respiration (or Q10) did not significantly respond to N or P addition. Our results suggest that short-term nutrient input might not change the SOC decomposition rate or its temperature sensitivity, whereas increased temperature might significantly enhance SOC decomposition in spring and autumn, compared with winter and summer. PMID:27070782

Alfalfa

MedlinePlus

... your health provider.Medications that increase sensitivity to sunlight (Photosensitizing drugs)Some medications can increase sensitivity to sunlight. Large doses of alfalfa might also increase your ...

New imaging systems in nuclear medicine. Final report, January 1, 1993--December 31, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-12-31

The aim of this program has been to improve the performance of positron emission tomography (PET) to achieve high resolution with high sensitivity. Towards this aim, the authors have carried out the following studies: (1) explored new techniques for detection of annihilation radiation including new detector materials and system geometries, specific areas that they have studied include--exploration of factors related to resolution and sensitivity of PET instrumentation including geometry, detection materials and coding, and the exploration of technique to improve the image quality by use of depth of interaction and increased sampling; (2) complete much of the final testing ofmore » PCR-II, an analog-coded cylindrical positron tomograph, developed and constructed during the current funding period; (3) developed the design of a positron microtomograph with mm resolution for quantitative studies in small animals, a single slice version of this device has been designed and studied by use of computer simulation; (4) continued and expanded the program of biological studies in animal models. Current studies have included imaging of animal models of Parkinson`s and Huntington`s disease and cancer. These studies have included new radiopharmaceuticals and techniques involving molecular biology.« less

Pregnancy eating attributes study (PEAS): a cohort study examining behavioral and environmental influences on diet and weight change in pregnancy and postpartum.

PubMed

Nansel, Tonja R; Lipsky, Leah M; Siega-Riz, Anna Maria; Burger, Kyle; Faith, Myles; Liu, Aiyi

2016-01-01

The rising prevalence of maternal overweight/obesity and excessive gestational weight gain poses a serious public health concern due to the contribution of these factors to increased risk of negative health outcomes for both mother and child. Scant intervention research has indicated moderate short-term improvement in maternal diet and gestational weight gain, with little evidence of long-term behavior change, in parallel with findings from interventions outside of pregnancy. Recent laboratory-based findings from neuroscience implicate aberrant reward processing of food at the brain level ("food reward sensitivity," the between-individual variation in the response to food stimuli) as a contributor to eating beyond energy needs. However, scant research has examined the influence of these processes on weight change in population-based settings, and the relevance of these processes to pregnancy-related weight change has not been explored. The purpose of the Pregnancy Eating Attributes Study (PEAS) is to examine the role of food reward sensitivity in maternal diet and weight change during pregnancy and postpartum. The study examines the interplay of food reward sensitivity with behavioral control, home food environment, and related aspects of eating behavior in the context of weight-related biomedical, psychosocial, genetic and behavioral factors including physical activity, stress, sleep and depression. Women of varying baseline weight status (n = 450) are enrolled early in pregnancy and followed, along with their infants, until 1 year postpartum. Assessments occur during each trimester of pregnancy, and postpartum at approximately 2 months, 6 months, 9 months and 12 months. Maternal food reward, self-control, home food environment, eating behaviors, dietary intake, health behaviors, and anthropometrics are assessed along with maternal and infant clinical and biological data, infant anthropometrics, and feeding practices. Primary exposures of interest include food reward sensitivity, behavioral control, and home food environment. Primary outcomes include gestational weight gain, postpartum weight retention and maternal diet quality. With increasing evidence suggesting the relevance of food reward sensitivity for understanding eating behavior, PEAS aims to advance understanding of the determinants of eating behavior during pregnancy, informing future interventions for improving maternal diet and weight change, and leading to improved maternal and child health and weight trajectories. Clinicaltrials.gov, NCT02217462. Date of registration: August 13, 2014.

Ventricular dilation and electrical dyssynchrony synergistically increase regional mechanical nonuniformity but not mechanical dyssynchrony: a computational model.

PubMed

Kerckhoffs, Roy C P; Omens, Jeffrey H; McCulloch, Andrew D; Mulligan, Lawrence J

2010-07-01

Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97+/-0.004, 0.010+/-0.002, and 78+/-1 milliseconds, respectively. With dilation alone, CURE decreased 2.0+/-0.07%, ISF increased 58+/-47%, and WTpeak increased 31+/-3%. With dyssynchronous activation alone, CURE decreased 15+/-0.6%, ISF increased 14-fold (+/-3), and WTpeak increased 121+/-4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23+/-0.8%, ISF increased 20-fold (+/-5), and WTpeak increased 147+/-5%. Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.

Selective effects of 5-HT2C receptor modulation on performance of a novel valence-probe visual discrimination task and probabilistic reversal learning in mice.

PubMed

Phillips, Benjamin U; Dewan, Sigma; Nilsson, Simon R O; Robbins, Trevor W; Heath, Christopher J; Saksida, Lisa M; Bussey, Timothy J; Alsiö, Johan

2018-04-22

Dysregulation of the serotonin (5-HT) system is a pathophysiological component in major depressive disorder (MDD), a condition closely associated with abnormal emotional responsivity to positive and negative feedback. However, the precise mechanism through which 5-HT tone biases feedback responsivity remains unclear. 5-HT2C receptors (5-HT2CRs) are closely linked with aspects of depressive symptomatology, including abnormalities in reinforcement processes and response to stress. Thus, we aimed to determine the impact of 5-HT2CR function on response to feedback in biased reinforcement learning. We used two touchscreen assays designed to assess the impact of positive and negative feedback on probabilistic reinforcement in mice, including a novel valence-probe visual discrimination (VPVD) and a probabilistic reversal learning procedure (PRL). Systemic administration of a 5-HT2CR agonist and antagonist resulted in selective changes in the balance of feedback sensitivity bias on these tasks. Specifically, on VPVD, SB 242084, the 5-HT2CR antagonist, impaired acquisition of a discrimination dependent on appropriate integration of positive and negative feedback. On PRL, SB 242084 at 1 mg/kg resulted in changes in behaviour consistent with reduced sensitivity to positive feedback. In contrast, WAY 163909, the 5-HT2CR agonist, resulted in changes associated with increased sensitivity to positive feedback and decreased sensitivity to negative feedback. These results suggest that 5-HT2CRs tightly regulate feedback sensitivity bias in mice with consequent effects on learning and cognitive flexibility and specify a framework for the influence of 5-HT2CRs on sensitivity to reinforcement.

Risk Factors for Hearing Decrement Among U.S. Air Force Aviation-Related Personnel.

PubMed

Greenwell, Brandon M; Tvaryanas, Anthony P; Maupin, Genny M

2018-02-01

The purpose of this study was to analyze historical hearing sensitivity data to determine factors associated with an occupationally significant change in hearing sensitivity in U.S. Air Force aviation-related personnel. This study was a longitudinal, retrospective cohort analysis of audiogram records for Air Force aviation-related personnel on active duty during calendar year 2013 without a diagnosis of non-noise-related hearing loss. The outcomes of interest were raw change in hearing sensitivity from initial baseline to 2013 audiogram and initial occurrence of a significant threshold shift (STS) and non-H1 audiogram profile. Potential predictor variables included age and elapsed time in cohort for each audiogram, gender, and Air Force Specialty Code. Random forest analyses conducted on a learning sample were used to identify relevant predictor variables. Mixed effects models were fitted to a separate validation sample to make statistical inferences. The final dataset included 167,253 nonbaseline audiograms on 10,567 participants. Only the interaction between time since baseline audiogram and age was significantly associated with raw change in hearing sensitivity by STS metric. None of the potential predictors were associated with the likelihood for an STS. Time since baseline audiogram, age, and their interaction were significantly associated with the likelihood for a non-HI hearing profile. In this study population, age and elapsed time since baseline audiogram were modestly associated with decreased hearing sensitivity and increased likelihood for a non-H1 hearing profile. Aircraft type, as determined from Air Force Specialty Code, was not associated with changes in hearing sensitivity by STS metric.Greenwell BM, Tvaryanas AP, Maupin GM. Risk factors for hearing decrement among U.S. Air Force aviation-related personnel. Aerosp Med Hum Perform. 2018; 89(2):80-86.

CABOZANTINIB IS EFFECTIVE IN A SUBSET OF XENOGRAFT GBM TUMORS AND AFFECTS MULTIPLE SIGNALING PATHWAYS

PubMed Central

Mikkelsen, Tom; deCarvalho, Ana C.; Arnold, Kimberly; Mueller, Claudius; Petricoin, Emanuel F; Poisson, Laila M.; Irtenkauf, Susan; Hasselbach, Laura

2014-01-01

BACKGROUND: (blind field). METHODS: Neurospheres enriched in CSCs were cultured from resected GBM tumors. Sensitivity to cabozantinib was determined in vitro. Cells were treated (IC40) in triplicate, and cell lysates were analyzed by reverse phase protein microarrays (RPPAs). GBM CSCs were implanted intracranially into nude mice. Cabozantinib was administered by oral gavage at a dose of 60 mg/kg for 4 weeks (5 days/week) as a single agent or in combination with 40 mg/kg TMZ. Tumor growth and response to treatment were monitored by non-invasive in vivo bioluminescence imaging (BLI) using the Xenogen IVIS System (Caliper Life Sciences), and overall survival. RESULTS: Sensitivity to cabozantinib treatment varied for the different GBM CSCs. From 70 proteins and phosphoproteins measured, 29 distributed among several signaling pathways were significantly altered after treatment in both resistant and sensitive GBM CSCs, including Met, Ret, AKT, MAPK/ERK. Cabozantinib single agent treatment reduced GBM tumor growth and increased mouse survival in two xenograft lines. Cabozantinib monotherapy reduced tumor size, as measured by BLI, but had no significant effect on overall survival for another xenograft line, however, the combination treatment resulted in sensitization of these xenografts to TMZ treatment. RPPA confirmed downregulation of the described targets for XL184, including activated Met, VEGFR2 and Ret (in vitro). CONCLUSIONS: Consistent with the clinical experience, both sensitive and resistant GBMs are represented in our CSC xenografts. More extensive evaluation will likely identify baseline biomarkers which might be valuable in identifying potentially sensitive sub-populations for subsequent clinical trials. RPPA and next-gen sequencing (NGS) on terminal tumors is underway. SECONDARY CATEGORY: Tumor Biology.

Acetylsalicylic acid-triggered 15-HETE generation by peripheral leukocytes for identifying ASA sensitivity.

PubMed

Korosec, Peter; Tisler, Ursa; Bajrovic, Nissera; Silar, Mira; Mrhar, Ales; Kosnik, Mitja

2011-10-01

Exposure to acetylsalicylic acid (ASA) may exacerbate respiratory or skin diseases or induce anaphylactoid reactions in apparently healthy individuals. We wanted to evaluate the clinical and diagnostic utility of measuring ASA-induced 15-hydroxyeicosatetraenoic acid (15-HETE) generation. We performed a prospective single-blind study with 26 subjects undergoing clinical evaluation and/or ASA provocation testing. We also included 12 control subjects. Peripheral blood leukocytes were incubated with 500 μM ASA and 15-HETE release was measured by competitive ELISA. We found that 18 subjects were ASA-tolerant and 8 were ASA-intolerant. The mean increase in 15-HETE in intolerant subjects was 34% and this was comparable to the mean increase of 30% observed in ASA-tolerant subjects. A similar mean increase was also observed in control subjects. The ROC calculation showed that the optimal diagnostic threshold would be an increase of greater than 33%. However, the sensitivity of this increase was only 63% and the specificity was 50%. Our data suggest that further studies are needed before the ASA-induced 15-HETE test can be used in clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detecting climate change oriented and human induced changes in stream temperature across the Southeastern U.S.

NASA Astrophysics Data System (ADS)

Zhang, X.; Voisin, N.; Cheng, Y.; Niemeyer, R. J.; Nijssen, B.; Yearsley, J. R.; Zhou, T.

2017-12-01

In many areas, climate change is expected to alter the flow regime and increase stream temperature, especially during summer low flow periods. During these low flow periods, water management increases flows in order to sustain human activities such as water for irrigation and hydroelectric power generation. Water extraction from rivers during warm season can increase stream temperature while reservoir regulation may cool downstream river temperatures by releasing cool water from deep layers. Thus, it is reasonable to hypothesize that water management changes the sensitivity of the stream temperature regime to climate change when compared to unmanaged resources. The time of emergence of change refers to the point in time when observations, or model simulations, show statistically significant changes from a given baseline period, i.e. above natural variability. Here we aim to address two questions by investigating the time of emergence of changes in stream temperature in the southeastern United States: what is the sensitivity of stream temperature under regulated flow conditions to climate change and what is the contribution of water management in increasing or decreasing stream temperature sensitivity to climate change. We simulate regulated flow by using runoff from the Variable Infiltration Capacity (VIC) macroscale hydrological model as input into a large scale river routing and reservoir model MOSART-WM. The River Basin Model (RBM), a distributed stream temperature model, includes a two-layer thermal stratification module to simulate stream temperature in regulated river systems. We evaluate the timing of emergence of changes in flow and stream temperature based on climate projections from two representative concentration pathways (RCPs; RCP4.5 and RCP8.5) from the Coupled Model Intercomparison Project Phase 5 (CMIP5). We analyze the difference in emergence of change between natural and regulated streamflow. Insights will be provided toward applications for multiple sectors of activities including electrical resources adequacy studies over the southeastern U.S.

IgE sensitization in relation to preschool eczema and filaggrin mutation.

PubMed

Johansson, Emma Kristin; Bergström, Anna; Kull, Inger; Lind, Tomas; Söderhäll, Cilla; van Hage, Marianne; Wickman, Magnus; Ballardini, Natalia; Wahlgren, Carl-Fredrik

2017-12-01

Eczema (atopic dermatitis) is associated with an increased risk of having IgE antibodies. IgE sensitization can occur through an impaired skin barrier. Filaggrin gene (FLG) mutation is associated with eczema and possibly also with IgE sensitization. We sought to explore the longitudinal relation between preschool eczema (PSE), FLG mutation, or both and IgE sensitization in childhood. A total of 3201 children from the BAMSE (Children Allergy Milieu Stockholm Epidemiology) birth cohort recruited from the general population were included. Regular parental questionnaires identified children with eczema. Blood samples were collected at 4, 8, and 16 years of age for analysis of specific IgE. FLG mutation analysis was performed on 1890 of the children. PSE was associated with IgE sensitization to both food allergens and aeroallergens up to age 16 years (overall adjusted odds ratio, 2.30; 95% CI, 2.00-2.66). This association was even stronger among children with persistent PSE. FLG mutation was associated with IgE sensitization to peanut at age 4 years (adjusted odds ratio, 1.88; 95% CI, 1.03-3.44) but not to other allergens up to age 16 years. FLG mutation and PSE were not effect modifiers for the association between IgE sensitization and PSE or FLG mutation, respectively. Sensitized children with PSE were characterized by means of polysensitization, but no other specific IgE sensitization patterns were found. PSE is associated with IgE sensitization to both food allergens and aeroallergens up to 16 years of age. FLG mutation is associated with IgE sensitization to peanut but not to other allergens. Sensitized children with preceding PSE are more often polysensitized. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Relative Severity of Single Hazards within a Multi-Hazard Framework

NASA Astrophysics Data System (ADS)

Gill, Joel C.; Malamud, Bruce D.

2013-04-01

Here we present a description of the relative severity of single hazards within a multi-hazard framework, compiled through examining, quantifying and ranking the extent to which individual hazards trigger or increase the probability of other hazards. Hazards are broken up into six major groupings (geophysical, hydrological, shallow earth processes, atmospheric, biophysical and space), with the interactions for 21 different hazard types examined. These interactions include both one primary hazard triggering a secondary hazard, and one primary hazard increasing the probability of a secondary hazard occurring. We identify, through a wide-ranging review of grey- and peer-review literature, >90 interactions. The number of hazard-type linkages are then summed for each hazard in terms of their influence (the number of times one hazard type triggers another type of hazard, or itself) and their sensitivity (the number of times one hazard type is triggered by other hazard types, or itself). The 21 different hazards are then ranked based on (i) influence and (ii) sensitivity. We found, by quantification and ranking of these hazards, that: (i) The strongest influencers (those triggering the most secondary hazards) are volcanic eruptions, earthquakes and storms, which when taken together trigger almost a third of the possible hazard interactions identified; (ii) The most sensitive hazards (those being triggered by the most primary hazards) are identified to be landslides, volcanic eruptions and floods; (iii) When sensitivity rankings are adjusted to take into account the differential likelihoods of different secondary hazards being triggered, the most sensitive hazards are found to be landslides, floods, earthquakes and ground heave. We believe that by determining the strongest influencing and the most sensitive hazards for specific spatial areas, the allocation of resources for mitigation measures might be done more effectively.

Early morning urine collection to improve urinary lateral flow LAM assay sensitivity in hospitalised patients with HIV-TB co-infection.

PubMed

Gina, Phindile; Randall, Philippa J; Muchinga, Tapuwa E; Pooran, Anil; Meldau, Richard; Peter, Jonny G; Dheda, Keertan

2017-05-12

Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB. 123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined. This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.

[Validity of expired carbon monoxide and urine cotinine using dipstick method to assess smoking status].

PubMed

Park, Su San; Lee, Ju Yul; Cho, Sung-Il

2007-07-01

We investigated the validity of the dipstick method (Mossman Associates Inc. USA) and the expired CO method to distinguish between smokers and nonsmokers. We also elucidated the related factors of the two methods. This study included 244 smokers and 50 ex-smokers, recruited from smoking cessation clinics at 4 local public health centers, who had quit for over 4 weeks. We calculated the sensitivity, specificity and Kappa coefficient of each method for validity. We obtained ROC curve, predictive value and agreement to determine the cutoff of expired air CO method. Finally, we elucidated the related factors and compared their effect powers using the standardized regression coefficient. The dipstick method showed a sensitivity of 92.6%, specificity of 96.0% and Kappa coefficient of 0.79. The best cutoff value to distinguish smokers was 5-6 ppm. At 5 ppm, the expired CO method showed a sensitivity of 94.3%, specificity of 82.0% and Kappa coefficient of 0.73. And at 6 ppm, sensitivity, specificity and Kappa coefficient were 88.5%, 86.0% and 0.64, respectively. Therefore, the dipstick method had higher sensitivity and specificity than the expired CO method. The dipstick and expired CO methods were significantly increased with increasing smoking amount. With longer time since the last smoking, expired CO showed a rapid decrease after 4 hours, whereas the dipstick method showed relatively stable levels for more than 4 hours. The dipstick and expired CO methods were both good indicators for assessing smoking status. However, the former showed higher sensitivity and specificity and stable levels over longer hours after smoking, compared to the expired CO method.

Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease.

PubMed

Wormser, Gary P; Schriefer, Martin; Aguero-Rosenfeld, Maria E; Levin, Andrew; Steere, Allen C; Nadelman, Robert B; Nowakowski, John; Marques, Adriana; Johnson, Barbara J B; Dumler, J Stephen

2013-01-01

For the diagnosis of Lyme disease, the 2-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice. Copyright © 2013 Elsevier Inc. All rights reserved.

Nursing home director of nursing leadership style and director of nursing-sensitive survey deficiencies.

PubMed

McKinney, Selina H; Corazzini, Kirsten; Anderson, Ruth A; Sloane, Richard; Castle, Nicholas G

2016-01-01

Nursing homes are becoming increasingly complex clinical environments because of rising resident acuity and expansion of postacute services within a context of historically poor quality performance. Discrete quality markers have been linked to director of nursing (DON) leadership behaviors. However, the impact of DON leadership across all measured areas of DON jurisdiction has not been tested using comprehensive domains of quality deficiencies. The aim of this study was to examine the effects of DON leadership style including behaviors that facilitate the exchange of information between diverse people on care quality domains through the lens of complexity science. Three thousand six hundred nine DONs completed leadership and intent-to-quit surveys. Quality markers that were deemed DON sensitive included all facility survey deficiencies in the domains of resident behaviors/facility practices, quality of life, nursing services, and quality of care. Logistic regression procedures estimated associations between variables. The odds of deficiencies for all DON sensitive survey domains were lower in facilities where DONs practiced complexity leadership including more staff input and shared decisional authority. DON quit intentions were aligned with higher odds of facility deficiencies across all domains. Results supported the hypotheses that DONs using complexity leadership approaches by interacting more freely with staff, discussing resident issues, and sharing decision making produced better care outcomes from every DON sensitive metric assessed by Centers for Medicare and Medicaid Services. The mechanism linking poor quality with high DON quit intentions is an area for future research. Encouraging DON use of complexity leadership approaches has the potential to improve a broad swath of quality outcomes.

Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis.

PubMed

van der Waaij, Laurens A; van Dullemen, Hendrik M; Porte, Robert J

2005-09-01

Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts (PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the value of cyst fluid analysis in the differential diagnosis of benign (SCA, PC) vs. premalignant or malignant (MCA, MCAC) lesions. A search in PubMed was performed with the search terms cyst, pancrea, and fluid. Articles about cyst fluid analysis of pancreatic lesions that contained the individual data of at least 7 patients were included in the study. Data of all individual patients were combined and were plotted in scatter grams. Cutoff levels were determined. Twelve studies were included, which comprised data of 450 patients. Cysts with an amylase concentration <250 U/L were SCA, MCA, or MCAC (sensitivity 44%, specificity 98%) and, thus, virtually excluded PC. A carcinoembryonic antigen (CEA) <5 ng/mL suggested a SCA or PC (sensitivity 50%, specificity 95%). A CEA >800 ng/mL strongly suggested MCA or MCAC (sensitivity 48%, specificity 98%). A carbohydrate-associated antigen (CA) 19-9 <37 U/mL strongly suggested PC or SCA (sensitivity 19%, specificity 98%). Cytologic examination revealed malignant cells in 48% of MCAC (n = 111). Most pancreatic cystic tumors should be resected without the need for cyst fluid analysis. However, in asymptomatic patients, in patients with an increased surgical risk, and, in patients in whom there is a diagnostic uncertainty about the presence of a PC, cyst fluid analysis helps to determine the optimal therapeutic strategy.

Survey of metal tolerance in moderately halophilic eubacteria.

PubMed

Nieto, J J; Fernández-Castillo, R; Márquez, M C; Ventosa, A; Quesada, E; Ruiz-Berraquero, F

1989-09-01

The tolerance patterns, expressed as MICs, for 250 moderately halophilic eubacteria to 10 heavy metals were surveyed by using an agar dilution method. The moderate halophiles tested included 12 culture collection strains and fresh isolates representative of Deleya halophila (37 strains), Acinetobacter sp. (24 strains), Flavobacterium sp. (28 strains), and 149 moderately halophilic gram-positive cocci included in the genera Marinococcus, Sporosarcina, Micrococcus, and Staphylococcus. On the basis of the MICs, the collection strains showed, overall, similar responses to silver, cobalt, mercury, nickel, lead, and zinc. All were sensitive to silver, mercury, and zinc and tolerant of lead. The response to arsenate, cadmium, chromium, and copper was very heterogeneous. The metal susceptibility levels of the 238 freshly isolated strains were, in general, very heterogeneous among the four taxonomic groups as well as within the strains included in each group. The highest toxicities were found with mercury, silver, and zinc, while arsenate showed the lowest activity. All these strains were tolerant of nickel, lead, and chromium and sensitive to silver and mercury. Acinetobacter sp. strains were the most heavy-metal tolerant, with the majority of them showing tolerance of eight different metal ions. In contrast, Flavobacterium sp. strains were the most metal sensitive. The influence of salinity and yeast extract concentrations of the culture medium on the toxicity of the heavy metals tested for some representative strains was also studied. Lowering the salinity, in general, led to enhanced sensitivity to cadmium and, in some cases, to cobalt and copper. However, increasing the salinity resulted in only a slight decrease in the cadmium, copper, and nickel toxicities.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of chronic psychosocial stress in explaining racial differences in stress reactivity and pain sensitivity

PubMed Central

Gordon, Jennifer L.; Johnson, Jacqueline; Nau, Samantha; Mechlin, Beth; Girdler, Susan S.

2016-01-01

Objective To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. Methods Participants included 133 AA and non-Hispanic White (nHW) individuals (mean (SD) age = 37 (9)) matched for age, sex and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. Results Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g. r = −.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. Conclusion Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs’ increased pain sensitivity in laboratory settings. PMID:27669431

Nonoxidative free fatty acid disposal is greater in young women than men.

PubMed

Koutsari, Christina; Basu, Rita; Rizza, Robert A; Nair, K Sreekumaran; Khosla, Sundeep; Jensen, Michael D

2011-02-01

Large increases in systemic free fatty acid (FFA) availability in the absence of a corresponding increase in fatty acid oxidation can create a host of metabolic abnormalities. These adverse responses are thought to be the result of fatty acids being shunted into hepatic very low-density lipoprotein-triglyceride production and/or intracellular lipid storage and signaling pathways because tissues are forced to increase nonoxidative FFA disposal. The objective of the study was to examine whether variations in postabsorptive nonoxidative FFA disposal within the usual range predict insulin resistance and hypertriglyceridemia. We measured: systemic FFA turnover using a continuous iv infusion of [9-10, (3)H]palmitate; substrate oxidation with indirect calorimetry combined with urinary nitrogen excretion; whole-body and peripheral insulin sensitivity with the labeled iv glucose tolerance test minimal model. the study was conducted at the Mayo Clinic General Clinical Research Center. Participants included healthy, postabsorptive, nonobese adults (21 women and 21 men). There were no interventions. Nonoxidative FFA disposal (micromoles per minute), defined as the FFA disappearance rate minus fatty acid oxidation. Women had 64% greater nonoxidative FFA disposal rate than men but a better lipid profile and similar insulin sensitivity. There was no significant correlation between nonoxidative FFA disposal and whole-body sensitivity, peripheral insulin sensitivity, or fasting serum triglyceride concentrations in men or women. Healthy nonobese women have greater rates of nonoxidative FFA disposal than men, but this does not appear to relate to adverse health consequences. Understanding the sex-specific interaction between adipose tissue lipolysis and peripheral FFA removal will help to discover new approaches to treat FFA-induced abnormalities.

The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating agents.

PubMed

Chen, Clark C; Taniguchi, Toshiyasu; D'Andrea, Alan

2007-05-01

DNA alkylating agents including temozolomide (TMZ) and 1,3-bis[2-chloroethyl]-1-nitroso-urea (BCNU) are the most common form of chemotherapy in the treatment of gliomas. Despite their frequent use, the therapeutic efficacy of these agents is limited by the development of resistance. Previous studies suggest that the mechanism of this resistance is complex and involves multiple DNA repair pathways. To better define the pathways contributing to the mechanisms underlying glioma resistance, we tested the contribution of the Fanconi anemia (FA) DNA repair pathway. TMZ and BCNU treatment of FA-proficient cell lines led to a dose- and time-dependent increase in FANCD2 mono-ubiquitination and FANCD2 nuclear foci formation, both hallmarks of FA pathway activation. The FA-deficient cells were more sensitive to TMZ/BCNU relative to their corrected, isogenic counterparts. To test whether these observations were pertinent to glioma biology, we screened a panel of glioma cell lines and identified one (HT16) that was deficient in the FA repair pathway. This cell line exhibited increased sensitivity to TMZ and BCNU relative to the FA-proficient glioma cell lines. Moreover, inhibition of FA pathway activation by a small molecule inhibitor (curcumin) or by small interference RNA suppression caused increased sensitivity to TMZ/BCNU in the U87 glioma cell line. The BCNU sensitizing effect of FA inhibition appeared additive to that of methyl-guanine methyl transferase inhibition. The results presented in this paper underscore the complexity of cellular resistance to DNA alkylating agents and implicate the FA repair pathway as a determinant of this resistance.

The Role of Chronic Psychosocial Stress in Explaining Racial Differences in Stress Reactivity and Pain Sensitivity.

PubMed

Gordon, Jennifer L; Johnson, Jacqueline; Nau, Samantha; Mechlin, Beth; Girdler, Susan S

To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. Participants included 133 AA and non-Hispanic white (nHW) individuals (mean [SD] age, 37 [9]) matched for age, sex, and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g., r = -.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs' increased pain sensitivity in laboratory settings.

Section 1: Interfacial reactions and grain growth in ferroelectric SrBi{sub 2}Ta{sub 2}O (SBT) thin films on Si substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dickerson, B.D.; Zhang, X.; Desu, S.B.

1997-04-01

Much of the cost of traditional infrared cameras based on narrow-bandgap photoelectric semiconductors comes from the cryogenic cooling systems required to achieve high detectivity. Detectivity is inversely proportional to noise. Generation-recombination noise in photoelectric detectors increases roughly exponentially with temperature, but thermal noise in photoelectric detectors increases only linearly with temperature. Therefore `thermal detectors perform far better at room temperature than 8-14 {mu}m photon detectors.` Although potentially more affordable, uncooled pyroelectric cameras are less sensitive than cryogenic photoelectric cameras. One way to improve the sensitivity to cost ratio is to deposit ferroelectric pixels with good electrical properties directly on mass-produced,more » image-processing chips. `Good` properties include a strong temperature dependence of the remanent polarization, P{sub r}, or the relative dielectric constant, {epsilon}{sub r}, for sensitive operation in pyroelectric or dielectric mode, respectively, below or above the Curie temperature, which is 320 C for SBT. When incident infrared radiation is chopped, small oscillations in pixel temperature produce pyroelectric or dielectric alternating currents. The sensitivity of ferroelectric thermal detectors depends strongly on pixel microstructure, since P{sub r} and {epsilon}{sub r} increase with grain size during annealing. To manufacture SBT pixels on Si chips, acceptable SBT grain growth must be achieved at the lowest possible oxygen annealing temperature, to avoid damaging the Si chip below. Therefore current technical progress describes how grain size, reaction layer thickness, and electrical properties develop during the annealing of SBT pixels deposited on Si.« less

Combined Effects of Gamma Radiation and High Dietary Iron on Peripheral Leukocyte Distribution and Function

NASA Technical Reports Server (NTRS)

Crucian, Brian E.; Morgan, Jennifer L. L.; Quiriarte, Heather A.; Sams, Clarence F.; Smith, Scott M.; Zwart, Sara R.

2012-01-01

Both radiation and increased iron stores can independently increase oxidative damage, resulting in protein, lipid and DNA oxidation. Oxidative stress increases the risk of many health problems including cancer, cataracts, and heart disease. This study, a subset of a larger interdisciplinary investigation of the combined effect of iron overload on sensitivity to radiation injury, monitored immune parameters in the peripheral blood of rats subjected to gamma radiation, high dietary iron or both. Specific immune measures consisted of: (1) peripheral leukocyte distribution, (2) plasma cytokine levels and (3) cytokine production profiles following whole blood mitogenic stimulation

Performance of an improved thermal neutron activation detector for buried bulk explosives

NASA Astrophysics Data System (ADS)

McFee, J. E.; Faust, A. A.; Andrews, H. R.; Clifford, E. T. H.; Mosquera, C. M.

2013-06-01

First generation thermal neutron activation (TNA) sensors, employing an isotopic source and NaI(Tl) gamma ray detectors, were deployed by Canadian Forces in 2002 as confirmation sensors on multi-sensor landmine detection systems. The second generation TNA detector is being developed with a number of improvements aimed at increasing sensitivity and facilitating ease of operation. Among these are an electronic neutron generator to increase sensitivity for deeper and horizontally displaced explosives; LaBr3(Ce) scintillators, to improve time response and energy resolution; improved thermal and electronic stability; improved sensor head geometry to minimize spatial response nonuniformity; and more robust data processing. The sensor is described, with emphasis on the improvements. Experiments to characterize the performance of the second generation TNA in detecting buried landmines and improvised explosive devices (IEDs) hidden in culverts are described. Performance results, including comparisons between the performance of the first and second generation systems are presented.

The Prevalence and Natural History of Food Allergy.

PubMed

Kattan, Jacob

2016-07-01

Numerous studies have demonstrated that the prevalence of food allergy is increasing. Not only are more children being diagnosed with food allergies, but studies suggest that when people outgrow their food allergies, it is taking longer than was previously thought. Studies in recent years have noted factors that may lead to a lower likelihood of developing a food allergy, including the early introduction of common food allergens, having a sufficient vitamin D level, or having a higher maternal intake of peanut early in pregnancy. Given a recent report that sensitization to common food allergens did not increase from the late 1980s/early 1990s to the mid-2000s, further studies will need to examine if the rise in food allergy prevalence is due to a change in the relationship between sensitization and clinical allergy or changes in the recognition and diagnosis of food allergy.

Warping Armchair Graphene Nanoribbon Curvature Effect on Sensing Properties: A Computational Study

NASA Astrophysics Data System (ADS)

Sakina, S. H.; Johari, Zaharah; Auzar, Zuriana; Alias, N. Ezaila; Mohamad, Azam; Zakaria, N. Aini

2018-02-01

The aim of this paper is to investigate the interaction between gas molecules and warped armchair graphene nanoribbons (AGNRs) using Extended-Huckel Theory. There are two types of warping known as inward and upward. The sensing properties including binding energy, charge transfer and sensitivity were examined for both warped AGNR cases for 3m+1 configuration and were compared with previous work. Through simulation, it was found that a substantial increase in binding energy by more than 50% was achieved when warped at a higher angle. It is also showed that there was a significant difference in sensitivity for both warping cases when reacting with O2 and NH3 molecules. Interestingly, the ability of the inward warped in sensing O2 and NH3 considerably increases upon warping angle. By applying back gate bias, this shows that current conductivity of the inward warped is twice as high as the upward warped AGNR.

Pathophysiology and Treatment of Resistant Hypertension: The Role of Aldosterone and Amiloride-Sensitive Sodium Channels

PubMed Central

Judd, Eric K.; Calhoun, David A.; Warnock, David G.

2015-01-01

Summary Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. The pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Existing dogma attributes the increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects in the distal nephron. However, emerging research, which has identified and has begun to define the function of amiloride-sensitive sodium channels and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. This review integrates these findings to better define the role of the vasculature and aldosterone in the pathophysiology of resistant hypertension. In addition, a brief guide to the treatment of resistant hypertension is presented. PMID:25416662

Pathophysiology and treatment of resistant hypertension: the role of aldosterone and amiloride-sensitive sodium channels.

PubMed

Judd, Eric K; Calhoun, David A; Warnock, David G

2014-01-01

Resistant hypertension is a clinically distinct subgroup of hypertension defined by the failure to achieve blood pressure control on optimal dosing of at least 3 antihypertensive medications of different classes, including a diuretic. The pathophysiology of hypertension can be attributed to aldosterone excess in more than 20% of patients with resistant hypertension. Existing dogma attributes the increase in blood pressure seen with increases in aldosterone to its antinatriuretic effects in the distal nephron. However, emerging research, which has identified and has begun to define the function of amiloride-sensitive sodium channels and mineralocorticoid receptors in the systemic vasculature, challenges impaired natriuresis as the sole cause of aldosterone-mediated resistant hypertension. This review integrates these findings to better define the role of the vasculature and aldosterone in the pathophysiology of resistant hypertension. In addition, a brief guide to the treatment of resistant hypertension is presented.

Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells.

PubMed

Zhang, S; Zhang, Y; Qu, J; Che, X; Fan, Y; Hou, K; Guo, T; Deng, G; Song, N; Li, C; Wan, X; Qu, X; Liu, Y

2017-11-13

Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.

Neuroprotective role of ATP-sensitive potassium channels in cerebral ischemia

PubMed Central

Sun, Hong-shuo; Feng, Zhong-ping

2013-01-01

ATP-sensitive potassium (KATP) channels are weak, inward rectifiers that couple metabolic status to cell membrane electrical activity, thus modulating many cellular functions. An increase in the ADP/ATP ratio opens KATP channels, leading to membrane hyperpolarization. KATP channels are ubiquitously expressed in neurons located in different regions of the brain, including the hippocampus and cortex. Brief hypoxia triggers membrane hyperpolarization in these central neurons. In vivo animal studies confirmed that knocking out the Kir6.2 subunit of the KATP channels increases ischemic infarction, and overexpression of the Kir6.2 subunit reduces neuronal injury from ischemic insults. These findings provide the basis for a practical strategy whereby activation of endogenous KATP channels reduces cellular damage resulting from cerebral ischemic stroke. KATP channel modulators may prove to be clinically useful as part of a combination therapy for stroke management in the future. PMID:23123646

Dietary sodium and health: more than just blood pressure.

PubMed

Farquhar, William B; Edwards, David G; Jurkovitz, Claudine T; Weintraub, William S

2015-03-17

Sodium is essential for cellular homeostasis and physiological function. Excess dietary sodium has been linked to elevations in blood pressure (BP). Salt sensitivity of BP varies widely, but certain subgroups tend to be more salt sensitive. The mechanisms underlying sodium-induced increases in BP are not completely understood but may involve alterations in renal function, fluid volume, fluid-regulatory hormones, the vasculature, cardiac function, and the autonomic nervous system. Recent pre-clinical and clinical data support that even in the absence of an increase in BP, excess dietary sodium can adversely affect target organs, including the blood vessels, heart, kidneys, and brain. In this review, the investigators review these issues and the epidemiological research relating dietary sodium to BP and cardiovascular health outcomes, addressing recent controversies. They also provide information and strategies for reducing dietary sodium. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Untoward penicillin reactions

PubMed Central

Guthe, T.; Idsöe, O.; Willcox, R. R.

1958-01-01

The literature on untoward reactions following the administration of penicillin is reviewed. These reactions, including a certain number of deaths which have been reported, are of particular interest to health administrations and to WHO in view of the large-scale programmes for controlling the treponematoses which are now under way—programmes affecting millions of people in many parts of the world. The most serious problems are anaphylactic sensitivity phenomena and superinfection or cross-infection with penicillin-resistant organisms, and the reactions involved range in intensity from the mildest to the fatal; the incidence of the latter is estimated at 0.1-0.3 per million injections. The authors point out that with increasing use of penicillin, more persons are likely to become sensitized and the number of reactions can therefore be expected to rise. The best prevention against such an increase is the restriction of the unnecessary use of penicillin. PMID:13596877

Stormwater Volume Control to Prevent Increases in Lake Flooding and Dam Failure Risk

NASA Astrophysics Data System (ADS)

Potter, K. W.

2017-12-01

Urban expansion is not often considered a major factor contributing to dam failure. But if urbanization occurs without mitigation of the hydrologic impacts, the risk of dam failure will increase. Of particular concern are increases in the volume of storm runoff resulting from increases in the extent of impervious surfaces. Storm runoff volumes are not regulated for much the U.S, and where they are, the required control is commonly less than 100%. Unmitigated increases in runoff volume due to urbanization can pose a risk to dams. A recent technical advisory committee of Dane County has recommended that the county require 100% control of stormwater volumes for new developments. The primary motivation was to prevent increases in the water levels in the Yahara Lakes, slowly draining lakes that are highly sensitive to runoff volume. The recommendations included the use of "volume trading" to achieve efficient compliance. Such recommendations should be considered for other slowly draining lakes, including those created by artificial structures.

Acute Inactivity Impairs Glycemic Control but Not Blood Flow to Glucose Ingestion

PubMed Central

Reynolds, Leryn J; Credeur, Daniel P; Holwerda, Seth W; Leidy, Heather J; Fadel, Paul J; Thyfault, John P

2014-01-01

Purpose Insulin-stimulated increases in skeletal muscle blood flow play a role in glucose disposal. Indeed, 7 days of aerobic exercise in type 2 diabetes patients increased blood flow responses to an oral glucose tolerance test (OGTT) and improved glucose tolerance. More recent work suggests that reduced daily physical activity impairs glycemic control (GC) in healthy individuals. Herein, we sought to determine if an acute reduction in daily activity (from >10,000 to <5,000 steps/day) for 5 days (RA5) in healthy individuals reduced insulin-stimulated blood flow and GC in parallel and if a 1 day return to activity (RTA1) improved these outcomes. Methods OGTTs were performed as a stimulus to increase insulin in 14 healthy, recreationally active men (24±1.1 yrs) at baseline, RA5, and RTA1. Measures of insulin sensitivity (Matsuda index) and femoral and brachial artery blood flow were made during the OGTT. Free living measures of GC including peak postprandial glucose (peak PPG) were also made via continuous glucose monitoring. Results Femoral and brachial artery blood flow increased during the OGTT but neither was significantly impacted by changes in physical activity (p>0.05). However, insulin sensitivity was decreased by RA5 (11.3±1.5 to 8.0±1.0; p<0.05). Likewise, free living GC measures of peak post prandial blood glucose (113±3 to 123±5 mg/dL; p<0.05) was significantly increased at RA5. Interestingly, insulin sensitivity and GC as assessed by peak PPG were not restored after RTA1 (p>0.05). Conclusions Thus, acute reductions in physical activity impaired GC and insulin sensitivity; however blood flow responses to an OGTT were not affected. Further, a 1 day return to activity was not sufficient to normalize GC following 5 days of reduced daily physical activity. PMID:25207931

Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2

PubMed Central

Fedier, A; Ruefenacht, U B; Schwarz, V A; Haller, U; Fink, D

2002-01-01

A large fraction of human tumours carries mutations in the p53 gene. p53 plays a central role in controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack of p53 function impairs these cellular processes, and this may be the basis of resistance to chemotherapeutic regimens. By virtue of the involvement of DNA mismatch repair in modulating cytotoxic pathways in response to DNA damaging agents, we investigated the effects of loss of Pms2 on the sensitivity to a panel of widely used anticancer agents in E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient in Pms2. We report that lack of the Pms2 gene is associated with an increased sensitivity, ranging from 2–6-fold, to some types of anticancer agents including the topoisomerase II poisons doxorubicin, etoposide and mitoxantrone, the platinum compounds cisplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, and the antimetabolite gemcitabine. In contrast, no change in sensitivity was found after treatment with 5-fluorouracil. Cell cycle analysis revealed that both, Pms2-deficient and -proficient cells, retain the ability to arrest at the G2/M upon cisplatin treatment. The data indicate that the concomitant loss of Pms2 function chemosensitises p53-deficient cells to some types of anticancer agents, that Pms2 positively modulates cell survival by mechanisms independent of p53, and that increased cytotoxicity is paralleled by increased apoptosis. Tumour-targeted functional inhibition of Pms2 may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers. British Journal of Cancer (2002) 87, 1027–1033. doi:10.1038/sj.bjc.6600599 www.bjcancer.com © 2002 Cancer Research UK PMID:12434296

Theoretical study on sensitivity enhancement in energy-deficit region of chemically amplified resists used for extreme ultraviolet lithography

NASA Astrophysics Data System (ADS)

Kozawa, Takahiro; Santillan, Julius Joseph; Itani, Toshiro

2017-10-01

The role of photons in lithography is to transfer the energy and information required for resist pattern formation. In the information-deficit region, a trade-off relationship is observed between line edge roughness (LER) and sensitivity. However, the sensitivity can be increased without increasing LER in the energy-deficit region. In this study, the sensitivity enhancement limit was investigated, assuming line-and-space patterns with a half-pitch of 11 nm. LER was calculated by a Monte Carlo method. It was unrealistic to increase the sensitivity twofold while keeping the line width roughness (LWR) within 10% critical dimension (CD), whereas the twofold sensitivity enhancement with 20% CD LWR was feasible. The requirements are roughly that the sensitization distance should be less than 2 nm and that the total sensitizer concentration should be higher than 0.3 nm-3.

Toward a culturally sensitive conceptualization of resilience: Participatory research with war-affected communities in northern Uganda.

PubMed

Vindevogel, Sofie; Ager, Alastair; Schiltz, Julie; Broekaert, Eric; Derluyn, Ilse

2015-06-01

Resilience research with war-affected populations has long conceptualized resilience as the absence of psychopathology and operationalized it by use of standardized measures. However, literature on resilience increasingly highlights the importance of also including indicators of positively valued functioning as well as contextually sensitive indicators of resilience. This study used a participatory approach to examine the contextual conceptualization of youth resilience in the aftermath of war in northern Uganda, as defined by groups of stakeholders (youths, parents, elders, leaders, teachers) in four communities. The results identify 40 indicators covering a multiplicity of domains of functioning. The rationales behind these indicators were clustered into the broad themes: progress, self-reliance, social connectedness, morality, health, and comfort. The findings suggest that positively and negatively valued aspects of functioning are both key to conceptualizing resilience, and indicate the importance of including contextually distinguished indicators. The findings further point to the role of individual and collective processes in the construction of resilience, and to the need to take into account the contexts wherein resilience is conceptualized and observed. This study generated contextually sensitive indicators of young people's resilience, which can be used, complementary to existing measures of functioning, to provide a more comprehensive and culturally sensitive view of youths' resilience in the wake of war adversity. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Cocoa butter and safflower oil elicit different effects on hepatic gene expression and lipid metabolism in rats.

PubMed

Gustavsson, Carolina; Parini, Paolo; Ostojic, Jovanca; Cheung, Louisa; Hu, Jin; Zadjali, Fahad; Tahir, Faheem; Brismar, Kerstin; Norstedt, Gunnar; Tollet-Egnell, Petra

2009-11-01

The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for 3 days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic beta-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by 3 days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavorable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet.

Cyclopentenyl cytosine increases gemcitabine radiosensitisation in human pancreatic cancer cells

PubMed Central

van Bree, C; Rodermond, H M; Leen, R; Medema, J P; van Kuilenburg, A B P

2008-01-01

The deoxycytidine analogue 2′,2′-difluoro-2′-deoxycytidine (dFdC, gemcitabine) is a potent radiosensitiser, but has limited efficacy in combination with radiotherapy in patients with pancreatic cancer due to acute toxicity. We investigated whether cyclopentenyl cytosine (CPEC), targetting the ‘de novo' biosynthesis of cytidine triphosphate (CTP), could increase dFdC cytotoxicity alone or in combination with irradiation in a panel of human pancreatic cancer cells (Panc-1, Miapaca-2, BxPC-3). To investigate the role of deoxycytidine kinase (dCK), the rate-limiting enzyme in the activation of dFdC, human lung cancer cells without (dFdC-resistant SWg) and with an intact dCK gene (dFdC-sensitive SWp) were included. We found that CPEC (100–1000 nmol l−1) specifically reduced CTP levels in a dose-dependent manner that lasted up to 72 h in all cell lines. Preincubation with CPEC resulted in a dose-dependent increase in dFdC incorporated into the DNA only in dFdC-sensitive cells. Consequently, CPEC increased the effectiveness of dFdC (300 nmol l−1 for 4 h) only in dFdC-sensitive cells, which was accompanied by an increase in apoptosis. We also found that CPEC enhanced the radiosensitivity of cells treated with dFdC (30–300 nmol l−1 for 4 h). These results indicate that CPEC enhances the cytotoxicity of dFdC alone and in combination with irradiation in several human tumour cell lines with an intact dCK gene. PMID:18349845

The influence of extratropical cloud phase and amount feedbacks on climate sensitivity

NASA Astrophysics Data System (ADS)

Frey, William R.; Kay, Jennifer E.

2018-04-01

Global coupled climate models have large long-standing cloud and radiation biases, calling into question their ability to simulate climate and climate change. This study assesses the impact of reducing shortwave radiation biases on climate sensitivity within the Community Earth System Model (CESM). The model is modified by increasing supercooled cloud liquid to better match absorbed shortwave radiation observations over the Southern Ocean while tuning to reduce a compensating tropical shortwave bias. With a thermodynamic mixed-layer ocean, equilibrium warming in response to doubled CO2 increases from 4.1 K in the control to 5.6 K in the modified model. This 1.5 K increase in equilibrium climate sensitivity is caused by changes in two extratropical shortwave cloud feedbacks. First, reduced conversion of cloud ice to liquid at high southern latitudes decreases the magnitude of a negative cloud phase feedback. Second, warming is amplified in the mid-latitudes by a larger positive shortwave cloud feedback. The positive cloud feedback, usually associated with the subtropics, arises when sea surface warming increases the moisture gradient between the boundary layer and free troposphere. The increased moisture gradient enhances the effectiveness of mixing to dry the boundary layer, which decreases cloud amount and optical depth. When a full-depth ocean with dynamics and thermodynamics is included, ocean heat uptake preferentially cools the mid-latitude Southern Ocean, partially inhibiting the positive cloud feedback and slowing warming. Overall, the results highlight strong connections between Southern Ocean mixed-phase cloud partitioning, cloud feedbacks, and ocean heat uptake in a climate forced by greenhouse gas changes.

Increased antidepressant sensitivity after prefrontal cortex glucocorticoid receptor gene deletion in mice.

PubMed

Hussain, Rifat J; Jacobson, Lauren

2015-01-01

Our laboratory has previously shown that antidepressants regulate glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC). To determine if PFC GR are involved in antidepressant effects on behavior or hypothalamic-pituitary-adrenocortical (HPA) axis activity, we treated floxed GR male mice with saline or 15 or 30 mg/kg/d imipramine after PFC injection of adeno-associated virus 2/9 vectors transducing expression of Cre recombinase, to knock-down GR (PFC-GRKD), or green fluorescent protein (PFC-GFP), to serve as a control. The pattern of virally transduced GR deletion, common to all imipramine treatment groups, included the infralimbic, prelimbic, and medial anterior cingulate cortex at its largest extent, but was confined to the prelimbic and anterior cingulate cortex at its smallest extent. PFC GR knock-down increased behavioral sensitivity to imipramine, with imipramine-treated PFC-GRKD but not PFC-GFP mice exhibiting significant decreases in depression-like immobility during forced swim. PFC GR deletion did not alter general locomotor activity. The 30 mg/kg dose of imipramine increased plasma corticosterone levels immediately after a 5-min forced swim, but PFC GR knock-down had no significant effect on plasma corticosterone under these experimental conditions. We conclude that PFC GR knock-down, likely limited to the medial prelimbic and anterior cingulate cortices, can increase behavioral sensitivity to antidepressants. These findings indicate a novel role for PFC GR in influencing antidepressant response. Copyright © 2014 Elsevier Inc. All rights reserved.