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1.  How Is Emotional Awareness Related to Emotion Regulation Strategies and Self-Reported Negative Affect in the General Population? 
PLoS ONE  2014;9(3):e91846.
The Levels of Emotional Awareness Scale (LEAS) as a performance task discriminates between implicit or subconscious and explicit or conscious levels of emotional awareness. An impaired awareness of one's feeling states may influence emotion regulation strategies and self-reports of negative emotions. To determine this influence, we applied the LEAS and self-report measures for emotion regulation strategies and negative affect in a representative sample of the German general population.
Sample and Methods
A short version of the LEAS, the Hospital Anxiety and Depression Scale (HADS) and the Emotion Regulation Questionnaire (ERQ), assessing reappraisal and suppression as emotion regulation strategies, were presented to N = 2524 participants of a representative German community study. The questionnaire data were analyzed with regard to the level of emotional awareness.
LEAS scores were independent from depression, but related to self-reported anxiety. Although of small or medium effect size, different correlational patters between emotion regulation strategies and negative affectivity were related to implict and explict levels of emotional awareness. In participants with implicit emotional awareness, suppression was related to higher anxiety and depression, whereas in participants with explicit emotional awareness, in addition to a positive relationship of suppression and depression, we found a negative relationship of reappraisal to depression. These findings were independent of age. In women high use of suppression and little use of reappraisal were more strongly related to negative affect than in men.
Our first findings suggest that conscious awareness of emotions may be a precondition for the use of reappraisal as an adaptive emotion regulation strategy. They encourage further research in the relation between subconsious and conscious emotional awareness and the prefarance of adaptive or maladaptive emotion regulation strategies The correlational trends found in a representative sample of the general population may become more pronounced in clinical samples.
PMCID: PMC3956759  PMID: 24637792
2.  Age and gender effect on alexithymia in large, Japanese community and clinical samples: a cross-validation study of the Toronto Alexithymia Scale (TAS-20) 
The construct validity of alexithymia and its assessment using the 20-item Toronto Alexithymia Scale (TAS-20) in Japan is unknown. Low reliability has been found for the third factor of the TAS-20 in some cultures, and the factor structure for psychosomatic disorder patients has not been adequately investigated. Although alexithymia most likely has certain developmental aspects, this has infrequently been investigated.
The newly-developed Japanese TAS-20 was administered to a normative sample (n = 2,718; 14–84 y.o.), along with the NEO Five-Factor Inventory (NEO-FFI) for cross validation. Psychosomatic patients (n = 1,924, 12–87 y.o.) were tested to evaluate the factor structure in a clinical sample. College students (n = 196) were used for a test-retest study. Internal reliability and consistency were assessed, and the factorial structure was evaluated using confirmatory and exploratory factor analyses for both the normative and the clinical samples. The correlations between the TAS-20 and the NEO-FFI factor scores were evaluated. Age-related and gender differences in the TAS-20 were explored using analysis of variance in the normative sample.
The original three-factor model of the TAS-20 was confirmed to be valid for these Japanese samples, although a 4-factor solution that included negatively keyed items (NKI) as an additional factor was more effective. Significant correlations of the TAS-20 with the NEO-FFI were found, as has been previously reported. Factor analyses of the normative and patient samples showed similar patterns. The TAS-20 total, difficulty in identifying feelings (DIF), and difficulty in describing feelings (DDF) scores were high for teenagers, decreased with age, and from 30s did not change significantly. In contrast, externally oriented thinking (EOT) scores showed an almost linear positive correlation with age. DIF scores were higher for females, while EOT scores were higher for males, without any interaction between gender and age differences.
The original three-factor concept of the TAS-20 was generally supported for practical use. Age-related differences in TAS-20 scores indicate developmental aspects of alexithymia. Alexithymia is made up of two components with different developmental paths: DIF/DDF and EOT.
PMCID: PMC1838425  PMID: 17371586
3.  Association between trait emotional awareness and dorsal anterior cingulate activity during emotion is arousal-dependent 
NeuroImage  2008;41(2):648.
The dorsal anterior cingulate cortex (dACC) is commonly thought to subserve primarily cognitive functions, but has been strongly implicated in the allocation of attention to emotional information. In a previous positron emission tomography (PET) study, we observed that women with higher emotional awareness as measured by the Levels of Emotional Awareness Scale (LEAS) showed greater changes in regional cerebral blood flow (rCBF) in dACC induced by emotional films and recall. In the current study, we tested whether these effects were due to the processing of any non-neutral stimulus, or were specific to conditions of high emotional arousal. Our results extend the previous finding by demonstrating a positive correlation between emotional awareness and dACC activity only in the context of viewing highly arousing pictures. No such relationship was observed when comparing pleasant or unpleasant pictures to neutral or to each other. We also observed that the relationship between LEAS and dACC activity was present in both sexes but stronger in women than men. These results reinforce the concept that greater trait awareness of one's own emotional experiences is associated with greater engagement of the dACC during emotional arousal, which we suggest may reflect greater attentional processing of emotional information.
PMCID: PMC2821667  PMID: 18406175
4.  Deficits in emotional awareness in schizophrenia and their relationship with other measures of functioning 
Conscious awareness of emotion is adaptive and its disruption in schizophrenia can impact social functioning. This study assessed levels of emotional awareness for self and others in social scenarios (LEAS) in 21 individuals with schizophrenia spectrum disorders (SSD) and 20 healthy individuals. Individuals with SSD had lower levels of emotional awareness for others in complex social scenarios, but not simple social scenarios; no difference was found in emotional awareness for self. Higher levels of emotional awareness were associated with better quality of life in patients. Patients also reported higher social anhedonia. Healthy individuals’ higher levels of emotional awareness for self were associated with lower anhedonia, but this relationship was not found in SSD patients. Individuals with schizophrenia have particular difficulty anticipating others’ emotional responses in complex social situations. Further, this deficit is independent of anhedonia in SSD patients, indicating a systemic disruption in the integration of emotional processing.
PMCID: PMC2779570  PMID: 19752644
emotion awareness; levels of emotional awareness scale; schizophrenia; emotion; anhedonia
5.  Alexithymia, emotional empathy, and self-regulation in Anorexia Nervosa 
During starvation, individuals with Anorexia Nervosa (AN) experience poor awareness of personal emotions (alexithymia), difficulty understanding others’ mental states (cognitive empathy), and poor regulation of personal emotions (self-regulation). Despite its important role in social interaction and interpersonal relationships, emotional empathy has not been measured in AN. Furthermore, how weight affects relationships among alexithymia, empathy, and self-regulation has not been investigated.
Women with AN were tested longitudinally during starvation (N=26) and after weight restoration (N=20) and compared to 16 age-matched healthy women at comparable time-points. The Toronto Alexithymia Scale 20 (TAS-20) assessed alexithymia and the Interpersonal Reactivity Index (IRI) measured empathy. Self-regulation was assessed by a subset of 37 items from the MMPI 2.
Relative to comparison participants, AN participants at starvation and weight restoration reported greater alexithymia and personal distress (a domain of emotional empathy measuring vicarious negative arousal to others’ suffering). Among AN participants, personal distress was positively correlated with alexithymia and negatively correlated with self-regulation, when accounting for depression.
This study provides evidence that alexithymia and personal distress may represent vulnerability features of AN. Higher levels of personal distress in AN may be related to poor self-regulation and emotional awareness.
PMCID: PMC3880788  PMID: 23638441
Anorexia Nervosa; social cognition; alexithymia; empathy; self-regulation; weight effects
6.  Alexithymia and emotional regulation: A cluster analytical approach 
BMC Psychiatry  2011;11:33.
Alexithymia has been a familiar conception of psychosomatic phenomenon. The aim of this study was to investigate whether there were subtypes of alexithymia associating with different traits of emotional expression and regulation among a group of healthy college students.
1788 healthy college students were administered with the Chinese version of the 20-item Toronto Alexithymia Scale (TAS-20) and another set of questionnaires assessing emotion status and regulation. A hierarchical cluster analysis was conducted on the three factor scores of the TAS-20. The cluster solution was cross-validated by the corresponding emotional regulation.
The results indicated there were four subtypes of alexithymia, namely extrovert-high alexithymia (EHA), general-high alexithymia (GHA), introvert-high alexithymia (IHA) and non-alexithymia (NA). The GHA was characterized by general high scores on all three factors, the IHA was characterized by high scores on difficulty identifying feelings and difficulty describing feelings but low score on externally oriented cognitive style of thinking, the EHA was characterized by high score on externally oriented cognitive style of thinking but normal score on the others, and the NA got low score on all factors. The GHA and IHA were dominant by suppressive character of emotional regulation and expression with worse emotion status as compared to the EHA and NA.
The current findings suggest there were four subtypes of alexithymia characterized by different emotional regulation manifestations.
PMCID: PMC3050802  PMID: 21345180
7.  451 The Relationship Between Emotional Cognition and the Symptom Gap in Patients with Bronchial Asthma: the Effects of Alexithymia and Empathy 
When symptoms are poorly controlled, patients with bronchial asthma may show a symptom gap: a cognitive divergence between the true severity of symptoms and the severity evaluated by the patients themselves. The aim of this study was to determine which factors (emotional cognition of the self and others) are associated with this symptom gap.
Forty-two patients with bronchial asthma, who were found with the Comprehensive Asthma Inventory (a bronchial asthma symptom questionnaire) to have psychosocial factors associated with a deep concern about the onset of asthma attacks, were studied by means of validated scales for alexithymia (the Toronto Alexithymia Scale-20) and for empathy (the Interpersonal Reactivity Index: IRI) and questions about how patients evaluate the severity of asthma.
Of the patients, 42.5% showed a cognitive divergence regarding asthma symptoms. The scores for “perspective taking” on the IRI were significantly higher in patients who felt symptoms were less severe than they actually than in patients who felt symptoms were more severe than they actually were. No association was found between alexithymia and the symptom gap.
The results show that empathy, the ability to understand the emotions of others, is associated with a symptom gap in patients with bronchial asthma and that high scores for “perspective taking” on the IRI may indicate problems of treatment and symptom control in asthma.
PMCID: PMC3512663
8.  The NEO-FFI in Multiple Sclerosis: Internal Consistency, Factorial Validity and Correspondence Between Self and Informant Reports 
Assessment  2010;18(1):39-49.
Personality assessment is a potentially important component of clinical and empirical work with neurological patients because (1) individual differences in personality may be associated with different neurological outcomes and (2) central nervous system changes may give rise to alteration in personality. In order for personality assessment to be useful to clinicians and researchers, the tests must be reliable and valid, as self-report measures require certain baseline levels of comprehension and insight, both of which can be compromised by cerebral disease. In this study, we examined the psychometric properties of the widely used NEO Five Factor Inventory (NEO-FFI) in a group of 419 patients with multiple sclerosis (MS). Our objective was to determine if the NEO-FFI is reliable and valid in this population. Results showed adequate estimates of internal consistency, factorial validity and self-informant correlation that support its use with MS patients. Implications, limitations of the current study and directions for future research are discussed.
PMCID: PMC2953584  PMID: 20484711
personality assessment; psychometrics; reliability; validity; NEO-FFI; Five Factor Model of Personality; multiple sclerosis
9.  Characterization of Two Soybean (Glycine max L.) LEA IV Proteins by Circular Dichroism and Fourier Transform Infrared Spectrometry 
Plant and Cell Physiology  2010;51(3):395-407.
Late embryogenesis-abundant (LEA) proteins, accumulating to a high level during the late stages of seed development, may play a role as osmoprotectants. However, the functions and mechanisms of LEA proteins remained to be elucidated. Five major groups of LEA proteins have been described. In the present study, we report on the characterization of two members of soybean LEA IV proteins, basic GmPM1 and acidic GmPM28, by circular dichroism and Fourier transform infrared spectroscopy. The spectra of both proteins revealed limited defined secondary structures in the fully hydrated state. Thus, the soybean LEA IV proteins are members of ‘natively unfolded proteins’. GmPM1 or GmPM28 proteins showed a conformational change under hydrophobic or dry conditions. After fast or slow drying, the two proteins showed slightly increased proportions of defined secondary structures (α-helix and β-sheet), from 30 to 49% and from 34 to 42% for GmPM1 and GmPm28, respectively. In the dehydrated state, GmPM1 and GmPM28 interact with non-reducing sugars to improve the transition temperature of cellular glass, with poly-l-lysine to prevent dehydration-induced aggregation and with phospholipids to maintain the liquid crystal phase over a wide temperature range. Our work suggests that soybean LEA IV proteins are functional in the dry state. They are one of the important components in cellular glasses and may stabilize desiccation-sensitive proteins and plasma membranes during dehydration.
PMCID: PMC2835872  PMID: 20071374
Circular dichroism; Fourier transform infrared; LEA protein; Molecular chaperone; Natively unfolded proteins; Protein secondary structure
10.  Overexpression of TaLEA Gene from Tamarix androssowii Improves Salt and Drought Tolerance in Transgenic Poplar (Populus simonii × P. nigra) 
PLoS ONE  2013;8(6):e67462.
Late embryogenesis abundant (LEA) genes were confirmed to confer resistance to drought and water deficiency. An LEA gene from Tamarixandrossowii (named TaLEA) was transformed into Xiaohei poplar (Populussimonii × P. nigra) via Agrobacterium. Twenty-five independent transgenic lines were obtained that were resistant to kanamycin, and 11 transgenic lines were randomly selected for further analysis. The polymerase chain reaction (PCR) and ribonucleic acid (RNA) gel blot indicated that the TaLEA gene had been integrated into the poplar genome. The height growth rate, malondialdehyde (MDA) content, relative electrolyte leakage and damages due to salt or drought to transgenic and non-transgenic plants were compared under salt and drought stress conditions. The results showed that the constitutive expression of the TaLEA gene in transgenic poplars could induce an increase in height growth rate and a decrease in number and severity of wilted leaves under the salt and drought stresses. The MDA content and relative electrolyte leakage in transgenic lines under salt and drought stresses were significantly lower compared to those in non-transgenic plants, indicating that the TaLEA gene may enhance salt and drought tolerance by protecting cell membranes from damage. Moreover, amongst the lines analyzed for stress tolerance, the transgenic line 11 (T11) showed the highest tolerance levels under both salinity and drought stress conditions. These results indicated that the TaLEA gene could be a salt and drought tolerance candidate gene and could confer a broad spectrum of tolerance under abiotic stresses in poplars.
PMCID: PMC3696074  PMID: 23840708
11.  A LEA Gene Regulates Cadmium Tolerance by Mediating Physiological Responses 
In this study, the function of a LEA gene (TaLEA1) from Tamrix androssowii in response to heavy metal stress was characterized. Time-course expression analyses showed that NaCl, ZnCl2, CuSO4, and CdCl2 considerably increased the expression levels of the TaLEA1 gene, thereby suggesting that this gene plays a role in the responses to these test stressors. To analyze the heavy metal stress-tolerance mechanism regulated by TaLEA1, TaLEA1-overexpressing transgenic poplar plants (Populus davidiana Dode × P. bollena Lauche) were generated. Significant differences were not observed between the proline content of the transgenic and wild-type (WT) plants before and after CdCl2 stress. However, in comparison with the WT plants, the TaLEA1-transformed poplar plants had significantly higher superoxide dismutase (SOD) and peroxidase (POD) activities, and lower malondialdehyde (MDA) levels under CdCl2 stress. Further, the transgenic plants showed better growth than the WT plants did, indicating that TaLEA1 provides tolerance to cadmium stress. These results suggest that TaLEA1 confers tolerance to cadmium stress by enhancing reactive oxygen species (ROS)-scavenging ability and decreasing lipid peroxidation. Subcellular-localization analysis showed that the TaLEA1 protein was distributed in the cytoplasm and nucleus.
PMCID: PMC3382805  PMID: 22754308
LEA gene; cadmium stress; stress tolerance; gene transformation; physiological response
12.  Adult attachment and emotional awareness impairment: a multimethod assessment 
Our objective was to explore the relationships between adult attachment and various aspects of emotional awareness, including alexithymia and level of emotional awareness. Participants were 112 university students who completed the Attachment Style Questionnaire, the Bermond–Vorst Alexithymia Questionnaire (BVAQ), and the Level of Emotional Awareness Scale. We found that alexithymia was positively related to the avoidant attachment style and negatively with the anxious attachment style. Anxious style-but not avoidance-was also related to the level of emotional awareness. An analysis of the four attachment categories revealed subtle differences regarding the subscales of the BVAQ. Findings are discussed with reference to internal working models of self and others, highlighting the relationship between emotional awareness impairment and interpersonal behaviour.
PMCID: PMC3960018
alexithymia; emotional awareness; attachment; internal working model; BVAQ; LEAS
13.  Personality and Medical Illness Burden Among Older Adults in Primary Care 
Psychosomatic medicine  2007;69(3):10.1097/PSY.0b013e3180313975.
To examine the association between Five Factor Model personality traits (Neuroticism, Extraversion, Openness to experience, Agreeableness, Conscientiousness) and physician-quantified aggregate morbidity in a sample of older adults in primary care.
A total of 449 primary care patients, ranging in age from 65 to 97 years (75 ± 6.9 (mean ± standard deviation)), completed the Neo-Five Factor Inventory (NEO-FFI) and extensive interviews. A physician-investigator completed the Cumulative Illness Rating Scale (CIRS), a well-validated measure of aggregate morbidity based on a review of medical records.
Bivariate analyses demonstrated that all five domains of the NEO-FFI were associated with CIRS scores. Multivariate regression controlling for age, gender, education, depression, smoking, hypertension, total cholesterol, alcohol or substance misuse, and other personality traits showed that greater Conscientiousness was independently associated with lower CIRS scores (β = −0.10, t(435) = −1.96, p = .05). Other independent predictors of less morbidity were younger age, absence of hypertension, and lower levels of depression.
Our results point toward the necessity of considering Conscientiousness and other personality traits in studies of risk factors for aggregate morbidity. More detailed characterization of at-risk populations will increase the likelihood of constructing informed and effective prevention, intervention, and policy initiatives.
PMCID: PMC3807736  PMID: 17401059
personality; older adults; medical illnesses; primary care
14.  Reliability and Validity of the 20-Item Toronto Alexithymia Scale in Korean Adolescents 
Psychiatry Investigation  2009;6(3):173-179.
Adolescence is a period of developing emotional regulation. However, alexithymia has rarely been examined during this period. The objective of this study is to examine the factor structure and internal consistency of the Korean version of the 20-item Toronto Alexithymia Scale (TAS-20K) in normal adolescents in South Korea.
The TAS-20K was administered to a sample of 290 adolescents aged from 12 to 16 years old. Internal reliability, test-retest reliability, and factorial validity were evaluated.
The three factors of the TAS-20K were confirmed by confirmatory factor analysis. The internal consistency, measured using Cronbach's alpha coefficient was acceptable for difficulty in identifying feelings, good for difficulty in describing feelings, and acceptable for externally oriented thinking.
Our study indicates that the TAS-20K is an appropriate instrument to assess alexithymia in Korean adolescents.
PMCID: PMC2796065  PMID: 20046392
Toronto alexithymia scale; Alexithymia; Adolescents
15.  Confidence in Emotion Perception in Point-Light Displays Varies with the Ability to Perceive Own Emotions 
PLoS ONE  2012;7(8):e42169.
One central issue in social cognitive neuroscience is that perceiving emotions in others relates to activating the same emotion in oneself. In this study we sought to examine how the ability to perceive own emotions assessed with the Toronto Alexithymia Scale related to both the ability to perceive emotions depicted in point-light displays and the confidence in these perceptions. Participants observed video scenes of human interactions, rated the depicted valence, and judged their confidence in this rating. Results showed that people with higher alexithymia scores were significantly less confident about their decisions, but did not differ from people with lower alexithymia scores in the valence of their ratings. Furthermore, no modulating effect of social context on the effect of higher alexithymia scores was found. It is concluded that the used stimuli are fit to investigate the kinematic aspect of emotion perception and possibly separate people with high and low alexithymia scores via confidence differences. However, a general difference in emotion perception was not detected in the present setting.
PMCID: PMC3425494  PMID: 22927921
16.  Developing and Validating a Risk Score for Lower-Extremity Amputation in Patients Hospitalized for a Diabetic Foot Infection 
Diabetes Care  2011;34(8):1695-1700.
Diabetic foot infection is the predominant predisposing factor to nontraumatic lower-extremity amputation (LEA), but few studies have investigated which specific risk factors are most associated with LEA. We sought to develop and validate a risk score to aid in the early identification of patients hospitalized for diabetic foot infection who are at highest risk of LEA.
Using a large, clinical research database (CareFusion), we identified patients hospitalized at 97 hospitals in the U.S. between 2003 and 2007 for culture-documented diabetic foot infection. Candidate risk factors for LEA included demographic data, clinical presentation, chronic diseases, and recent previous hospitalization. We fit a logistic regression model using 75% of the population and converted the model coefficients to a numeric risk score. We then validated the score using the remaining 25% of patients.
Among 3,018 eligible patients, 21.4% underwent an LEA. The risk factors most highly associated with LEA (P < 0.0001) were surgical site infection, vasculopathy, previous LEA, and a white blood cell count >11,000 per mm3. The model showed good discrimination (c-statistic 0.76) and excellent calibration (Hosmer-Lemeshow, P = 0.63). The risk score stratified patients into five groups, demonstrating a graded relation to LEA risk (P < 0.0001). The LEA rates (derivation and validation cohorts) were 0% for patients with a score of 0 and ~50% for those with a score of ≥21.
Using a large, hospitalized population, we developed and validated a risk score that seems to accurately stratify the risk of LEA among patients hospitalized for a diabetic foot infection. This score may help to identify high-risk patients upon admission.
PMCID: PMC3142050  PMID: 21680728
17.  Validity issues in the assessment of alexithymia related to the developmental stages of emotional cognition and language 
We examined developmental aspects of the emotional awareness of adolescents by evaluating their responses to a self-reported questionnaire based on the Toronto Alexithymia Scale-20 (TAS-20).
The items of the TAS-20 were modified to make them more understandable by adolescents, and nine new items related to a limited capacity for imagination were added. The Japanese Linguistic Ability Test and the multi-dimensional empathy scale for adolescents were administered to examine concurrent validity. Two hundred and two normative young adolescents and thirty-two adolescent patients with psychosomatic and/or behavioral problems participated in the study. Eighty junior high school students also participated in a separate examination of test-retest reliability.
Thirteen items were extracted after exploratory and confirmatory factor analyses, and four core factors were identified in the resulting scale: Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), Externally-Oriented Thinking (EOT) and Constricted Imaginal Capacities (CIC). Interestingly, scores on the multi-dimensional empathy scale correlated positively with DIF and DDF, but negatively with EOT and CIC. Higher DDF scores were associated with higher Japanese linguistic abilities. DIF/DDF scores were higher for females than males, irrespective of linguistic ability. Test-retest reliability coefficients were significant. The patient group showed significantly higher DIF scores than the normative students.
The present findings indicated that subjective difficulties in identifying and describing feelings are associated with empathetic and linguistic abilities. The developmental aspect to emotional awareness herein described suggests that self-reported questionnaires for alexithymia must be carefully constructed and examined, even for adults.
PMCID: PMC2777913  PMID: 19886981
18.  Temperament and personality: the German version of the Adult Temperament Questionnaire (ATQ) 
The psychobiological orientation inherent in temperament concepts permits a close tie between temperament and the rapidly proliferating research areas of neurosciences and behavioural genetics. Based on developmental and psychobiological studies, the Adult Temperament Questionnaire (ATQ) by Rothbart measures self-regulatory processes in addition to constitutionally based individual reactivity. The purpose of this paper is to validate a German version of the short form of the ATQ with 77 items. 213 psychosomatic inpatients and outpatients and 116 control subjects took part in this study. The study included standardized measures of personality and symptoms. The German version reliably measures the four dimensions negative affect, extraversion, orienting sensitivity and effortful control; subscales were moderately correlated. We found a consistent pattern of correlation to personality (NEO-FFI) and interpersonal problems (IIP), negative affect strongly correlated with neuroticism; effortful control correlated with conscientiousness, orienting sensitivity with openness, and extraversion correlated with the corresponding scale of the NEO-FFI. According to our hypothesis, negative affect was positively correlated with higher distress and physical complaints, while effortful control was negatively correlated with them. When negative affect and effortful control were combined, effortful control had a moderating effect on distress. Clinical and non-clinical samples differed significantly on all dimensions; the ATQ appears to be suitable for differentiating subgroups of patients according to self-regulation.
PMCID: PMC2736500  PMID: 19742070
temperament; personality; Adult Temperament Questionnaire; validation
19.  A major quantitative trait locus for cold-responsive gene expression is linked to frost-resistance gene Fr-A2 in common wheat 
Breeding Science  2013;63(1):58-67.
Low temperature induces expression of Cor (cold-responsive)/Lea (late embryogenesis-abundant) gene family members through C-repeat binding factor (CBF) transcription factors in common wheat. However, the relationship between the genetic loci controlling cold-responsive gene expression and freezing tolerance is unclear. In expression quantitative trait locus (eQTL) analysis, accumulated transcripts of Cor/Lea and CBF genes were quantified in recombinant inbred lines derived from a cross between two common wheat cultivars with different levels of freezing tolerance. Four eQTLs controlling five cold-responsive genes were found, and the major eQTL with the greatest effect was located on the long arm of chromosome 5A. At least the 1D and 5A eQTLs played important roles in development of freezing tolerance in common wheat. The chromosomal location of the 5A eQTL, controlling four cold-responsive genes, coincided with a region homoeologous to a frost-tolerance locus (Fr-Am2) reported as a CBF cluster region in einkorn wheat. The 5A eQTL plays a significant role through Cor/Lea gene expression in cold acclimation of wheat. In addition, our results suggest that one or more CBF copies at the Fr-2 region positively regulate other copies, which might amplify the positive effects of the CBF cluster on downstream Cor/Lea gene activation.
PMCID: PMC3621446  PMID: 23641182
Triticum aestivum L.; cold acclimation; freezing tolerance; recombinant inbred lines; transcript accumulation
20.  Adult Discrimination Performance for Pediatric Acuity Test Optotypes 
Pediatric acuity tests have a variety of optotype designs. Adult performance when discriminating these targets indicated that acuity estimates collected from children are likely to vary based solely on target design.
To compare adult discrimination performance on nine pediatric visual acuity tests to determine the consistency of optotype design.
After their binocular acuity was measured with each test, eight adult observers (mean age, 27 years ± 6.3 SD; three emmetropes and five corrected myopes) were shown isolated single optotypes from the Allen figures, HOTV, Landolt C, Lea Numbers, Lea Symbols, Lighthouse, Patti Pics, Precision Vision numbers, and Tumbling E tests. A one-interval, two-alternative forced-choice protocol was used at a single distance, and each optotype was paired with all optotypes from the same chart. Confusion matrices were generated for each test and Luce's (1963) biased-choice model was fit to each matrix to derive measures of pairwise similarity between the optotypes.
The acuities from the Allen figures (P < 0.001) and HOTV (P = 0.029) were the only ones to differ significantly from the reference Landolt C. The choice-model analyses of the confusion matrices revealed that the Allen figures, HOTV, Lighthouse, Patti Pics, and Precision Vision numbers tests all had significant differences in discriminability of optotypes within the test.
Pediatric acuity test optotypes are not all equally discriminable to adult observers with normal vision and no ocular disorders. The current data suggest that care must be taken when presenting limited numbers of optotypes, as is done with young patients.
PMCID: PMC3175947  PMID: 21436270
21.  Vesicle Size and Stability of Biomimetic Liposomes from 3’-Sulfo-Lewis a (SuLea)-Containing Glycolipids 
We report on the use of a natural Lewis type saccharide ligand, 3’-sulfo-Lewis a (SuLea) for glycocalyx-mimetic surface modification of liposomes. Two SuLea–containing glycolipids, monovalent SuLea-lipid and trivalent SuLea (TSuLea)-lipid, were synthesized, and used with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol to prepare unilaminar vesicles (ULVs) by a freeze-thaw and extrusion method. The effects of the glycolipid concentrations and the pore sizes of extrusion membranes on vesicle size and stability were investigated by photon correlation spectroscopy (PCS). Glycoliposomes, with 5% SuLea- or TSuLea-lipids obtained by 50 nm extrusion, had 25-30% more vesicles less than 100 nm in diameter compared with the 100 nm extrusion. TSuLea-liposomes always produced larger vesicle size than SuLea-liposomes, which we attribute to the larger TSuLea headgroup. Both SuLea- and TSuLea-liposomes increased their vesicle size with increasing glycolipid concentration from 5% to 15%, and demonstrated good stability at room temperature for over one month. Further increasing the glycolipid concentration to 20% resulted in large vesicle aggregation after 5 days for TSuLea-liposomes, while the SuLea-liposomes remained stable for 10 days. SuLea- and TSuLea-liposomes with 15% glycolipids demonstrated better stability due to the electrostatic effect from the negatively charged SuLea and TSuLea headgroups. The results indicate that the biomimetic liposomes with SuLea- and TSuLea-lipids with 5 to 15% incorporation are sufficiently stable for the potential applications in targeted drug delivery.
PMCID: PMC2041829  PMID: 17499486
Liposomes; saccharides; 3’-sulfo-Lewis a; glycolipids; vesicle size
22.  Triglycerides and Amputation Risk in Patients With Diabetes 
Diabetes Care  2011;34(3):635-640.
To determine the association between triglyceride levels and lower-extremity amputation (LEA) risk in a large diabetic cohort.
This is a 10-year survey follow-up study (from 1995–2006) of 28,701 diabetic patients with a baseline triglyceride measure. All patients were fully insured members of the Kaiser Permanente Medical Care Program and responded to a survey at baseline that included information on ethnicity, socioeconomic status, education, behavioral factors, and information required to determine type of diabetes. The relationship between triglycerides and time to incident nontraumatic LEA, defined by primary hospitalization discharge or procedures, was evaluated using Cox proportional hazards models.
Triglyceride level was an independent, stepwise risk factor for nontraumatic LEAs within this large diabetic cohort: triglycerides 150–199 mg/dL, hazard ratio (HR) 1.10 (95% CI 0.92–1.32); 200–499 mg/dL, 1.27 (1.10–1.47); >500 mg/dL, 1.65 (1.30–2.10) (reference <150 mg/dL).
Hypertriglyceridemia is a significant risk factor for LEA in diabetic patients even after controlling for known socioeconomic, health behavioral, and clinical factors. This previously unrecognized clinical risk needs to be further investigated to determine if treatment of triglycerides can reduce amputation risk.
PMCID: PMC3041196  PMID: 21285390
23.  The Prognostic Value of Peripheral Artery Diseases in Patients with ST-Segment Elevation Myocardial Infarction 
Disease Markers  2013;35(6):877-882.
Hypothesis. To evaluate the clinical and prognostic role of haemodynamically insignificant stenosis of the extracranial arteries (ECA) and lower extremity arteries (LEA) among patients with ST-segment elevation myocardial infarction (STEMI). Patients and Methods. The study sample consisted of 423 patients with STEMI who were consecutively admitted to the Kemerovo Cardiological Centre. Results. The prevalence of polyvascular diseases (PVD), as defined by an increased intima-media thickness (IMT) of the common carotid artery or by stenosis of the ECA or LEA, was 95%. Among patients with ECA or LEA, the case fatality rate of those with stenosis with occlusion of less than 30% of the vessel lumen was 5.7%, whereas the case fatality rate among patients with stenosis with occlusion of more than 30% of the vessel lumen was 15.1% (χ2 = 13.68, P = 0.003). Using the GRACE score model, together with the determination of additional factors (congestive heart failure, PVD, prior stroke, and smoking status), we developed an improved model (KemScore) for death risk stratification for a 12-month period. The value of the AUC for our model (KemScore) was 0.83 (95% CI = 0.76–0.90), which was significantly higher than the initial GRACE score value of 0.71 (95% CI = 0.63–0.79).
PMCID: PMC3874939  PMID: 24415828
24.  LEA polypeptide profiling of recalcitrant and orthodox legume seeds reveals ABI3-regulated LEA protein abundance linked to desiccation tolerance 
Journal of Experimental Botany  2013;64(14):4559-4573.
In contrast to orthodox seeds that acquire desiccation tolerance during maturation, recalcitrant seeds are unable to survive drying. These desiccation-sensitive seeds constitute an interesting model for comparative analysis with phylogenetically close species that are desiccation tolerant. Considering the importance of LEA (late embryogenesis abundant) proteins as protective molecules both in drought and in desiccation tolerance, the heat-stable proteome was characterized in cotyledons of the legume Castanospermum australe and it was compared with that of the orthodox model legume Medicago truncatula. RNA sequencing identified transcripts of 16 homologues out of 17 LEA genes for which polypeptides are detected in M. truncatula seeds. It is shown that for 12 LEA genes, polypeptides were either absent or strongly reduced in C. australe cotyledons compared with M. truncatula seeds. Instead, osmotically responsive, non-seed-specific dehydrins accumulated to high levels in the recalcitrant cotyledons compared with orthodox seeds. Next, M. truncatula mutants of the ABSCISIC ACID INSENSITIVE3 (ABI3) gene were characterized. Mature Mtabi3 seeds were found to be desiccation sensitive when dried below a critical water content of 0.4g H2O g DW–1. Characterization of the LEA proteome of the Mtabi3 seeds revealed a subset of LEA proteins with severely reduced abundance that were also found to be reduced or absent in C. australe cotyledons. Transcripts of these genes were indeed shown to be ABI3 responsive. The results highlight those LEA proteins that are critical to desiccation tolerance and suggest that comparable regulatory pathways responsible for their accumulation are missing in both desiccation-sensitive genotypes, revealing new insights into the mechanistic basis of the recalcitrant trait in seeds.
PMCID: PMC3808335  PMID: 24043848
abi3; Castanospermum australe; desiccation tolerance; late embryogenesis abundant proteins; Medicago truncatula; proteomics; recalcitrant seed; RNAseq.
25.  Personality and EQ-5D scores among individuals with chronic conditions 
Personality is associated with self-rated health, but prior studies have not examined associations with preference-based measures. We hypothesized similar associations would exist with preference-based health.
We analyzed baseline data from chronically ill individuals enrolled in a self-management intervention. We conducted regression analyses with the EQ-5D summary index score and dimension scores (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) as dependent variables, The key independent variables were NEO-Five Factor Inventory (NEO-FFI) personality factors (Neuroticism, Conscientiousness, Extraversion, Openness, Agreeableness), adjusting for age, gender, educational level, minority status, and chronic conditions.
Of 415 participants, 245 (59%) had ≥2 chronic conditions, 384 (94%) completed the NEO-FFI and 397 (96%) the EQ-5D. After adjustment, Neuroticism was associated with EQ-5D summary index scores [−0.04 per 1 SD increase in Neuroticism (95% CI −0.06, −0.01)]. Neuroticism [AOR 2.99 (95% CI 2.06, 4.35; P < 0.001)] and Openness [1.32 (95% CI 1.00, 1.75; P = 0.05)] were associated with worse anxiety/depression scores, while Conscientiousness was associated with better usual activities scores [0.66 (95% CI 0.49, 0.89; P = 0.01)].
The associations between personality factors and self-rated health appear to extend to preference-based measures. Future studies should explore whether personality affects preference-based health estimates in cost-effectiveness analyses.
PMCID: PMC2894523  PMID: 18839336
Bias; Chronic disease; Health status; Personality; Quality of life

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