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The twenty-item Toronto Alexithymia Scale--I. Item selection and cross-validation of the factor structure.

Addressing shortcomings of the self-report Toronto Alexithymia Scale (TAS), two studies were conducted to reconstruct the item domain of the scale. The first study resulted in the development of a new twenty-item version of the scale--the TAS-20. The TAS-20 demonstrated good internal consistency and test-retest reliability, and a three-factor structure theoretically congruent with the alexithymia construct. The stability and replicability of this three-factor structure were demonstrated in the second study with both clinical and nonclinical populations by the use of confirmatory factor analysis.

Adult

Dimensions of pain-related cognitive coping: cross-validation of the factor structure of the Coping Strategy Questionnaire.

Previous research has demonstrated a relationship between cognitive pain coping activity and adjustment in pain patients. The empirically derived dimensions of coping activity, as measured by scales from the Coping Strategy Questionnaire (CSQ), however, have varied across investigations. The purpose of this investigation was to determine both the content and number of dimensions of the CSQ and to explore the potential moderating influence that sociodemographic and patient history variables may have on the latent structure of the CSQ. A total of 620 patients from 5 different chronic pain patient samples were used to assess the generalizability of the dimensions across samples. Confirmatory factor analytic procedures identified a 3-factor solution in most of the samples that was robust across various demographic characteristics. Two factors appeared particularly robust: one reflected conscious use of cognitive coping strategies (with high loadings on ignoring pain and coping self-statements) and another reflected self-efficacy beliefs concerning pain (with high loadings on ability to control and decrease pain). A third factor, which was somewhat less stable, appeared to reflect avoidance of pain by attention to non-pain-related mental activity (with high loadings on diverting attention and praying and hoping). Scales reflecting catastrophizing cognitions and behavioral coping strategies did not consistently load on the above dimensions. Issues concerning the conceptualization and measurement of pain-related cognitive coping dimensions are discussed.

Adaptation, Psychological

The matrix method of metabolic control analysis: its validity for complex pathway structures.

The sensitivities of the variables of a metabolic system (such as fluxes and concentrations) to variations in enzyme concentration are expressed in metabolic control analysis as control coefficients. The matrix method is a system of writing matrix equations that generate expressions for the control coefficients in terms of the characteristics of the components (principally the enzymes). Previously, the matrix method has been considered in terms of simple pathway structures; here we justify its applicability to complex pathways, such as those with multiple branches. It is shown that this requires modification of the branch point relationship to take account of changes of flux along the limbs of the branch and of stoichiometric factors. The method of deriving the flux control coefficients with respect to different fluxes in the system is extended to cope with these circumstances.

Animals

Structure of the tetraheme cytochrome from Desulfovibrio desulfuricans ATCC 27774: X-ray diffraction and electron paramagnetic resonance studies.

The three-dimensional X-ray structure of cytochrome c3 from a sulfate reducing bacterium, Desulfovibrio desulfuricans ATCC 27774 (107 residues, 4 heme groups), has been determined by the method of molecular replacement [Frazão et al. (1994) Acta Crystallogr. D50, 233-236] and refined at 1.75 A to an R-factor of 17.8%. When compared with the homologous proteins isolated from Desulfovibrio gigas, Desulfovibrio vulgaris Hildenborough, Desulfovibrio vulgaris Miyazaki F, and Desulfomicrobium baculatus, the general outlines of the structure are essentialy kept [heme-heme distances, heme-heme angles, His-His (axial heme ligands) dihedral angles, and the geometry of the conserved aromatic residues]. The three-dimensional structure of D. desulfuricans ATCC 27774 cytochrome c3Dd was modeled on the basis of the crystal structures available and amino acid sequence comparisons within this homologous family of multiheme cytochromes [Palma et al. (1994) Biochemistry 33, 6394-6407]. This model is compared with the refined crystal structure now reported, in order to discuss the validity of structure prediction methods and critically evaluate the steps used to predict protein structures by homology modeling. The four heme midpoint redox potentials were determined by using deconvoluted electron paramagnetic resonance (EPR) redox titrations. Structural criteria (electrostatic potentials, heme ligand orientation, EPR g values, heme exposure, data from protein-protein interaction studies) are invoked to assign the redox potentials corresponding to each specific heme in the three-dimensional structure.

Crystallography, X-Ray

[Validity of videolaryngoscopy in detecting laryngeal structural changes].

STUDY OBJECTIVE: To determinate the validity of videolaryngoscopy on diagnose of laryngeal diseases versus other laryngoscopic methods. DESIGN: Retrospective study covering 2 years (1992 and 1993). SETTING: 267 were the consulting patients because of dysphony. This collective was ranged in 2 groups. Group A included those hoarse individuals in whom was detected a growth, confirmed afterwards by means of direct laryngoscopy, biopsy and pathologists examination of a smear. Group B was formed for dysphonics with no organic changes seen through indirect laryngoscopy. INTERVENTIONS: All patients underwent indirect laryngoscopy (laryngeal mirror) and videolaryngoscopy. Patients showing an organic lesion underwent, also, suspension direct laryngoscopy, biopsy and histopathological control (reference's measurement). In all laryngoscopic procedures were determinated presence or absence of laryngeal changes (organic or functional) and the glottic area involved. RESULTS: In 156 patients direct laryngoscopies were performed. Organic lesion could be confirmed in 154 cases. The relative sensibility of videolaryngoscopy versus laryngeal mirror account for 0.4 and its negative predictive value for 0.26. The correlation videolaryngoscopy direct laryngoscopy results in 1. CONCLUSIONS: Videolaryngoscopy is a method with major sensibility and negative predictive value as indirect laryngoscopy with mirror. But the latter is indispensable in diagnosis of laryngeal organic lesions and must be done prior to microlaryngoscopie direct examination.

Humans

Effects of proximal intra-atrial Wenckebach on distal atrioventricular nodal, and His-Purkinje, block with special reference to the theory of alternating Wenckebach periods.

Intra-atrial Wenckebach patterns of stimulus-to-response intervals coexisting with distal, A-V nodal, and His-Purkinje, blocks occurred in eight patients during high right atrial stimulation at rapid rates. In two patients with 2:1 St-H block and in two patients with 4:1 St-V block, an increase in the degree of block occurred when the proximal intra-atrial Wenckebach cycle was completed with the stimulus which otherwise would have been propagated to the distal levels. However, the degree of block did not increase when the intra-atrial Wenckebach terminated in distally blocked stimuli. In one patient progression of 4:1 into 5:1 St-V block was due to the association of intra-atrial Wenckebach with alternating 2:1 block at the A-V nodal, and His-Purkinje, levels. Contrasting with most reports dealing with the mechanisms of alternating Wenckebach in a single structure, this study permitted the determination of the boundaries between proximal and more distal levels. It also showed that alternating Wenckebach cycles (of St-H intervals) ending with two consecutively blocked stimuli could result from the association of proximal intra-atrial Wenckebach with distal, A-V nodal Wenckebach, or abortive AW, cycles. The electrophysiology of documented two, or three, level block in different structures has validated previously made assumptions regarding multilevel block in a single structure.

Atrioventricular Node

[Effects of intra-arterial Wenckebach's periods on the nodal and intranodal A-V 2:1 and 4:1 (their significance in the electrogenesis of the so-called alternating Wenckebach's periods)].

Intra-atrial Wenckebach patterns coexisting with distal, A-V nodal, and His-Purkinje blocks occurred in eight patients during high atrial stimulation at rapid rates. In two patients with 2:1 St-H block and in two patients with 4:1 St-V block, an increase in the degree of block occurred when the proximal intraatrial Wenckebach cycle was completed with the stimulus which otherwise would have been propagated to the distal levels. However, the degree of block did not increase when the intraatrial Wenckebach terminated in distally blocked stimuli. In one patient progression of 4:1 into 5:1 St-V block was due to the association of intraatrial Wenckebach with alternating 2:1 block at the A-V nodal, and His-Purkinje levels. Contrasting with most reports dealing with the mechanisms of alternating Wenckebach in a single structure, this study permitted the determination of the boundaries between proximal and more distal levels. The electrophysiology of documented two or three level block in different structures has validated previously made assumptions regarding multilevel block in a single structure.

Bundle-Branch Block

Validation and coding of the NIC taxonomy structure. Iowa Intervention Project. Nursing Interventions Classification.

Processes for validation and coding of the taxonomy for the Nursing Interventions Classification (NIC) are described. A sample of nurses expert in theory development rated the NIC taxonomy using five criteria. Following identification of a stable structure, the taxonomy was coded with each intervention receiving a unique number. A coded and valid taxonomic structure facilitates use of the classification in computerization and makes possible the collection of comparable data. A coded classification can also be used in reimbursement systems.

Cluster Analysis

Cross validation of the Hypnotic Induction Profile factor structure: simultaneous confirmatory factor analysis of two published samples.

This study cross-validated factor structure and psychometric characteristics of the Hypnotic Induction Profile (HIP). Earlier studies identified two constructs of the HIP, but their methodology did not allow empirical confirmation of the number of factors. I have used a new methodology, confirmatory factor analysis, and submitted the data from the previous studies to a simultaneous, multisample, factor analysis. The results showed that the HIP indeed consists of two factors. Although the HIP two-factor model is statistically adequate, 7 of the 10 scales have very low item reliability. Issues of measurement error and clinical implications of the study are also discussed in relation to the current findings.

Factor Analysis, Statistical

An examination of the factor structure and convergent and discriminant validity of the SCL-90R in an outpatient clinic population.

This study investigated the factor structure of the SCL-90R using an outpatient psychology clinic population. Six relatively homogeneous and stable factors were identified: Depression, Somatization, Anger-Hostility, Paranoid-Psychoticism, Phobic Anxiety, and Obsessive-Compulsive. However, a principal component analysis revealed that the first factor accounted for a large percentage of the variance, suggesting that this instrument measures a general dimension of psychopathology. In addition, significant correlations between the SCL-90R symptom dimensions and both the BDI and several MMPI scales were found. The results of the study lead to questions regarding the utility of the SCL-90R.

Adolescent

Multitargeted comparative evaluation suggests 2-Aoeobenoxmide shows favourable in silico binding compared to Tucatinib against ERα, HER2, AKT1, EGFR, and PIK3CA in breast cancer.

Breast cancer is a leading cause of cancer-related morbidity and mortality globally, with the WHO reporting approximately 2.3 million new cases and 685,000 deaths annually. Drug resistance in breast cancer complicates treatment, with mutations in critical proteins contributing to therapy failure. Key oncogenic proteins involved in breast cancer progression-namely ERα (a ligand-activated nuclear receptor; PDB: 1A52) and the kinase domains of HER2 (PDB ID: 3PP0), AKT1 (PDB ID: 4EJN), EGFR (PDB ID: 4I23) and PIK3CA (PDB ID: 7R9V)-are pivotal in tumour progression and resistance mechanisms. Targeting these proteins using multitargeted therapeutic strategies may overcome resistance by disrupting key signalling pathways involved in cell proliferation, survival, and metastasis. Such combinatorial approaches promise to improve treatment efficacy and patient outcomes in cases of resistant breast cancer. In this study, we performed multitarget docking on prepared and validated protein structures against the ZINC natural compound library using HTVS, SP, and XP, with pose validation using MM-GBSA. We identified 2-Aoeobenoxmide (2-[1-(2-amino-2-oxo-ethoxy)-6-oxo-benzo[c]chromen-3-yl]oxyacetamide, ZINC134008) with docking and MM-GBSA scores ranging from -8.162 to -10.327 kcal/mol and from -47.18 to -57.62 kcal/mol, respectively, and compared the results with the FDA-approved drug Tucatinib, which exhibited lower binding affinity scores. We further evaluated pharmacokinetic properties using QikProp and electronic properties using DFT (Jaguar) and compared the descriptors of 2-Aoeobenoxmide with those of Tucatinib and with accepted reference ranges. We also performed the WaterMap for 5 nanoseconds (ns), computed various energies, interactions and hydration sites, and the comparison suggests that 2-Aoeobenoxmide shows more favourable hydration-site displacement and binding interactions than Tucatinib. Additionally, a 100 ns MD Simulation has resulted in far less deviation, fluctuations, and intermolecular interactions than Tucatinib, suggesting stable protein-ligand interactions, while the binding free energy and total complex energy computed across 0-1000 frames of the MD trajectories indicate that 2-Aoeobenoxmide is a promising in silico candidate. Importantly, because the entire study is computational, the findings should be interpreted as in silico hypotheses, and experimental validation through in vitro and in vivo assays is warranted before any clinical translation is considered.

Humans

Valid and invalid implementations of GOR secondary structure predictions.

GOR algorithms have long been a standard methodology for predicting protein secondary structure from primary sequence. We have developed two short validation sequences for the GOR I and GOR II algorithms. Use of these sequences with seven commercial and non-commercial implementations of these algorithms demonstrated that several were incorrect implementations, including two of the three commercial modules implementing the GOR I algorithm. This may be due to an easy misinterpretation of the GOR I algorithm and related data tables. We present the validation sequences and discuss implications of this widely propagated error on secondary and tertiary structure prediction, using several proteins of known structure in three different structural classes as examples. A valid GOR I implementation predicts secondary structure increases the accuracy of predictions by from 1-13 percentage points over an invalid implementation based on the easy misinterpretation. A valid implementation of the GOR I and GOR II algorithms is available from the authors.

Algorithms

Quality of life after intensive care with the sickness impact profile.

OBJECTIVES: a) to validate the structure of the Sickness Impact Profile scale (SIP) when applied to intensive care patients after discharge from the hospital; b) to explore the influence of age upon the various components of quality of life. DESIGN: Prospective study. SETTING: Patients admitted to 36 Dutch ICUs. METHODS: 6,247 patients out of 13,000 consecutive admissions to the ICUs answered a SIP questionnaire 6 months after discharge from the hospital. The 3,655 returned questionnaire were analyzed after aggregating the respondents into 6 age groups: from group 1: 17-29 up to group 4: > 70 years of age. INTERVENTION: Self-administration of SIP one year after discharge, measuring 5 independent categories (IC) and two dimensions: physical (PD) and psychosocial (PSD). RESULTS: The total SIP-score oscillated between 5.8 +/- 8.2 (group I) and 10.5 +/- 9.5 (group 4). Group 3 had also a high score (9.4 +/- 11.2). Overall, the quality of life of patients was dominated by dysfunction on the categories composing the physical dimension, with exception of patients with ages between 30 and 50 years, in which dysfunction on the categories composing the psychosocial dimension was dominant. The structure of the SIP in the study was similar to that described to the original instrument. CONCLUSIONS: The study validated the use of the SIP QOL-instrument on patients after intensive care. Age influenced consistently the various components of quality of life.

Activities of Daily Living

The Beck Depression Inventory: testing and cross-validating a second-order factorial structure for Swedish nonclinical adolescents.

The intent of the present study was to test for the validity and equivalency of a second-order factorial structure of the Beck Depression Inventory for and across three independent samples (n1 = 661; n2 = 239; n3 = 196) of nonclinical Swedish adolescents. The model under study derived from a cross-validated study of Canadian high school adolescents. Model fitting, testing and equating were based on the analysis of covariance structures within the framework of a confirmatory factor analytic model. Of major importance was the tenability of the hypothesized model for Swedish adolescents. Only minor differences where found among samples, which involved correlated errors and one cross-loading (Sample 2). Results are expected to be of substantial interest to both researchers and clinicians whose concerns focus on depression as it bears on this population.

Adolescent

Regional cerebral blood flow in pigs estimated by microspheres.

Regional cerebral blood flow in anaesthetized pigs is determined with the microsphere method. Five regions of cortical grey matter and three white subcortical areas in each hemisphere are examined together with anatomically classic structures. The validity of the biopsies was confirmed by freeze drying of the tissue. Three flow measurements in a group of six animals showed large interindividual variations whereas regions with the same structure in the particular animal showed a high degree of uniformity. Symmetrical regions in the two hemispheres were similar with a coefficient of variation between sides of less than 5%. The coefficient of variation of the particular flow measurements were 15%. The different brain structures have four discernible flow levels. White subcortical matter has three different flow values and forms together with medulla oblongata and hippocampus the low flow area. Flow in grey cortical matter is of the same magnitude as in unanaesthetized animals and constitutes together with thalamus, mesencephalon, pons and cerebellar hemispheres the intermediate flow level. The high flow areas are nucleus caudatus and lentiformis together with the cerebellar vermis. The choroid plexus, pituitary gland and pineal gland all have very high flow values and seem, in contrast to the rest of the brain, insensitive to the CO2-tension in arterial blood and global cerebral metabolism. Microsphere estimation of regional blood flow seems to be an appropriate technique for evaluating regional cerebral blood with a high degree of spatial resolution in repeated flow measurements.

Animals