BACKGROUND

The Dynamic Gait Index (DGI) has emerged as a valid indicator of functional gait abilities for people with balance and vestibular disorders. Recent Rasch-based analyses have indicated possible concerns for multidimensionality and a ceiling effect within the DGI.

OBJECTIVE

The aim of this study was to evaluate the DGI in a sample of patients from a dizziness and balance clinic to determine whether patient features such as dizziness or fall history influence the measurement characteristics of the DGI.

METHODS

This study used a retrospective design.

METHODS

A sample of 117 patients' charts was reviewed, and patients were grouped according to a primary impairment of dizziness only or imbalance and were categorized based on a history of falls. A one-parameter Rasch-Andrich rating scale model was used with thorough analyses, including rating scale analysis, item-difficulty hierarchy, scale unidimensionality, and differential item functioning (DIF).

RESULTS

The DGI demonstrated an effective rating scale design and was found to be a unidimensional measurement of dynamic gait. The DGI displayed a modest ceiling effect, primarily with patients with higher functional levels displaying symptoms of dizziness. Three items ("vertical head nods," "gait on level surface," and "stepping over obstacles") demonstrated DIF based on categories of patient characteristics, although the effects on measurement were negligible.

CONCLUSIONS

Functional categories were based on impairments and not underlying medical diagnoses derived from a retrospective chart review, whereas the limited sample size may have underestimated statistically significant DIF.

CONCLUSIONS

Results from this study offer additional evidence supporting the validity of the DGI as a measure of gait ability. The present findings also are in agreement with prior research that has shown a ceiling effect for the DGI in people with balance or vestibular disorders. Effects of DIF were found to be negligible, yet the presence of DIF within the present sample helped to explain some differences in DGI item-difficulty hierarchies from prior studies. Continued research is needed to determine how population differences may affect performance on the DGI and to develop and test assessments capable of measuring a broader range of gait abilities.

The aim of this study was to translate, culturally adapt and evaluate the psychometric properties of the Pain Self-Efficacy Questionnaire (PSEQ) in a population of patients with fibromyalgia in Denmark. The study sample included 102 patients diagnosed with fibromyalgia referred to a specialist clinic. The PSEQ was translated and adapted to a Danish setting using a standard stepwise forward-backward translation procedure, followed by initial testing and focus group interview. Reliability was examined by analysing internal consistency and test-retest agreement. Construct validity was examined by investigating dimensionality, targeting, local independence, category functioning and differential item functioning (DIF). Reliability was high: Cronbach's alpha 0.88, test-retest correlation 0.93, intraclass correlation coefficient (ICC) 0.89 and item-total correlations 0.44-0.70. Factor analyses and item response (IRT) models indicated unidimensionality, and the PSEQ-DK was well targeted to the sample. High interitem correlation was observed between two items, indicating local dependence, and item misfit and DIF were observed for a few items. However, the overall fit of the scale to a single-factor model and IRT models supported acceptable construct validity. The PSEQ-DK showed acceptable psychometric properties and can therefore represent a reliable and valid measure for evaluating self-efficacy in patients with fibromyalgia in Denmark.

A trial of antepartum dexamethasone therapy was carried out in 55 mothers in whom premature delivery threatned between 28 to 36 weeks gestation in the hope of reducing the incidence of respiratory distress syndromes (RDS). The control group was made up of 62 mothers who delivered prematurely in the same gestational age without any treatment. In the treated group isoxsuprine was used to delay delivery when necessary. The respiratory dif infants (8.3 per cent) than in the controls (35.2 per cent; p less than 0.001). The difference was more marked in babies of under 32 weeks gestation. Considering only cases with intact membranes the incidence of RDS was significantly (p less than 0.01) lower in the treated group. Early neonatal mortality was 6.6 per cent in the treated group and 38 per cent (p less than 0.0001) in the controls. In 12 cases the L/S ratio was measured during dexamethasone administration and in the majority of these the L/S ratio rose sharply to mature values following treatment. This rise was observed as soon as 48 hours after beginning of dexamethasone. Antepartum isoxsuprine in the treated group had no apparent effect on the incidence of RDS. No adverse effects of steroid therapy were observed. This trial confirms the studies of others that antepartum glucocorticoid can significantly reduce the incidence of RDS in premature infants.

BACKGROUND

The aims of the current study were to calibrate the item parameters of the Dutch-Flemish PROMIS Pain Behavior item bank using a sample of Dutch patients with chronic pain and to evaluate cross-cultural validity between the Dutch-Flemish and the US PROMIS Pain Behavior item banks. Furthermore, reliability and construct validity of the Dutch-Flemish PROMIS Pain Behavior item bank were evaluated.

METHODS

The 39 items in the bank were completed by 1042 Dutch patients with chronic pain. To evaluate unidimensionality, a one-factor confirmatory factor analysis (CFA) was performed. A graded response model (GRM) was used to calibrate the items. To evaluate cross-cultural validity, Differential item functioning (DIF) for language (Dutch vs. English) was evaluated. Reliability of the item bank was also examined and construct validity was studied using several legacy instruments, e.g. the Roland Morris Disability Questionnaire.

RESULTS

CFA supported the unidimensionality of the Dutch-Flemish PROMIS Pain Behavior item bank (CFI = 0.960, TLI = 0.958), the data also fit the GRM, and demonstrated good coverage across the pain behavior construct (threshold parameters range: -3.42 to 3.54). Analysis showed good cross-cultural validity (only six DIF items), reliability (Cronbach's α = 0.95) and construct validity (all correlations ≥0.53).

CONCLUSIONS

The Dutch-Flemish PROMIS Pain Behavior item bank was found to have good cross-cultural validity, reliability and construct validity. The development of the Dutch-Flemish PROMIS Pain Behavior item bank will serve as the basis for Dutch-Flemish PROMIS short forms and computer adaptive testing (CAT).

To determine the mechanism by which differentiation-inducing factor-1 (DIF-1), a morphogen of Dictyostelium discoideum, inhibits tumor cell proliferation, we examined the effect of DIF-1 on the gene expression of cyclin D1. DIF-1 strongly reduced the expression of cyclin D1 mRNA and correspondingly decreased the amount of beta-catenin in HeLa cells and squamous cell carcinoma cells. DIF-1 activated glycogen synthase kinase-3beta (GSK-3beta) and inhibition of GSK-3beta attenuated the DIF-1-induced beta-catenin degradation, indicating the involvement of GSK-3beta in this effect. Moreover, DIF-1 reduced the activities of T-cell factor (TCF)/lymphoid enhancer factor (LEF) reporter plasmid and a reporter gene driven by the human cyclin D1 promoter. Eliminating the TCF/LEF consensus site from the cyclin D1 promoter diminished the effect of DIF-1. These results suggest that DIF-1 inhibits Wnt/beta-catenin signaling, resulting in the suppression of cyclin D1 promoter activity.

The sesquiterpene synthase germacradiene-4-ol synthase (GdolS) from Streptomyces citricolor is one of only a few known high-fidelity terpene synthases that convert farnesyl diphosphate (FDP) into a single hydroxylated product. Crystals of unliganded GdolS-E248A diffracted to 1.50 Å and revealed a typical class 1 sesquiterpene synthase fold with the active site in an open conformation. The metal binding motifs were identified as D(80)DQFD and N(218)DVRSFAQE. Some bound water molecules were evident in the X-ray crystal structure, but none were obviously positioned to quench a putative final carbocation intermediate. Incubations in H2(18)O generated labeled product, confirming that the alcohol functionality arises from nucleophilic capture of the final carbocation by water originating from solution. Site-directed mutagenesis of amino acid residues from both within the metal binding motifs and without identified by sequence alignment with aristolochene synthase from Aspergillus terreus generated mostly functional germacradien-4-ol synthases. Only GdolS-N218Q generated radically different products (∼50% germacrene A), but no direct evidence of the mechanism of incorporation of water into the active site was obtained. Fluorinated FDP analogues 2F-FDP and 15,15,15-F3-FDP were potent noncompetitive inhibitors of GdolS. 12,13-DiF-FDP generated 12,13-(E)-β-farnesene upon being incubated with GdolS, suggesting stepwise formation of the germacryl cation during the catalytic cycle. Incubation of GdolS with [1-(2)H2]FDP and (R)-[1-(2)H]FDP demonstrated that following germacryl cation formation a [1,3]-hydride shift generates the final carbocation prior to nucleophilic capture. The stereochemistry of this shift is not defined, and the deuteron in the final product was scrambled. Because no clear candidate residue for binding of a nucleophilic water molecule in the active site and no significant perturbation of product distribution from the replacement of active site residues were observed, the final carbocation may be captured by a water molecule from bulk solvent.

BACKGROUND

Randomized trials stochastically answer the question. "What would be the effect of treatment on outcome if one turned back the clock and switched treatments in the given population?" Generalizations to other subjects are reliable only if the particular trial is performed on a random sample of the target population. By considering an unobserved binary variable, we graphically investigate how randomized trials can also stochastically answer the question, "What would be the effect of treatment on outcome in a population with a possibly different distribution of an unobserved binary baseline variable that does not interact with treatment in its effect on outcome?"

METHODS

For three different outcome measures, absolute difference (DIF), relative risk (RR), and odds ratio (OR), we constructed a modified BK-Plot under the assumption that treatment has the same effect on outcome if either all or no subjects had a given level of the unobserved binary variable. (A BK-Plot shows the effect of an unobserved binary covariate on a binary outcome in two treatment groups; it was originally developed to explain Simpsons's paradox.)

RESULTS

For DIF and RR, but not OR, the BK-Plot shows that the estimated treatment effect is invariant to the fraction of subjects with an unobserved binary variable at a given level.

CONCLUSIONS

The BK-Plot provides a simple method to understand generalizability in randomized trials. Meta-analyses of randomized trials with a binary outcome that are based on DIF or RR, but not OR, will avoid bias from an unobserved covariate that does not interact with treatment in its effect on outcome.

Cutaneous macroglobulinosis is a rare skin manifestation of Waldenstrom macroglobulinemia. It is characterized by the deposition of eosinophilic, immunoglobulin-derived material in the dermis. It typically presents as pink or skin-colored papules favoring the extensor surfaces of the extremities. There are 11 reported cases of cutaneous macroglobulinosis in the literature. In our consultative dermatopathology practice we encountered three additional cases. In Case 1, a 41-year-old female with a monoclonal immunoglobulin M (IgM)-kappa gammopathy developed skin-colored papules on her extensor extremities, forehead and back. Histopathologic and immunohistochemical analyses revealed periodic acid-Schiff (PAS)-positive pink material in the dermis that stained with IgM. In Case 2, an 83-year-old female with a monoclonal IgM-lambda paraproteinemia developed non-blanching papules and plaques on the lower extremities and cheeks. Skin biopsies showed a striking occlusion of the vessels with a PAS-positive eosinophilic precipitate, which was also found in the extravascular spaces and stained with IgM using direct immunofluorescence (DIF) and immunohistochemical stains. In Case 3, an 80-year-old male with Waldenstrom macroglobulinemia developed ulcerated papules and nodules on the lower extremities. The biopsy findings were similar to those of Case 2. We present a series of three patients with cutaneous macroglobulinosis and explore variations in the clinical and histopathological findings of this uncommon entity.

BACKGROUND

In previous studies, the Irritable Bowel Syndrome Quality of Life (IBS-QOL) instrument has been determined to have good measurement properties for general irritable bowel syndrome (IBS) and the diarrheal IBS (IBS-d) subtype in clinical trials.

OBJECTIVE

This article aims to extend the true-score analyses that have been previously conducted to evaluate the IBS-QOL in IBS-d patients.

METHODS

Item response theory analysis was conducted by fitting models to responses from 753 patients with severe IBS-d from a recent clinical trial. Three item response theory models, the constrained graded response model (CGRM), the unconstrained GRM (UGRM), and the testlet response model (TRM), were fit to the 34 items of the IBS-QOL questionnaire. Subsequently, differential item functioning (DIF) for patient sex was assessed by fitting nested models by applying likelihood ratio tests. Model latent trait estimates were then compared with the IBS-QOL score and the IBS Symptom Severity Score.

RESULTS

Model fits improved with complexity, with the TRM model fitting best compared with the CGRM and UGRM. The DIF evaluation for patient sex flagged 17 items for the CGRM and 9 items for the UGRM; however, these items were not found to have much effect on the overall estimation of the latent trait. Differential testlet functioning was not indicated, and no items exhibited potential DIF under the TRM because likelihood ratio tests were not statistically significant. Comparison of latent trait estimates to the IBS Symptom Severity Score and IBS-QOL questionnaire revealed high Spearman correlations (0.47 and ≥0.99, respectively).

CONCLUSIONS

Previous true-score approach results were supported by the IBS-QOL item-level analysis. Further, the IBS-QOL total score was found to be a valid measure of perceived quality of life for IBS-d patients when compared with more sophisticated model-based estimates of perceived quality of life. ClinicalTrials.gov identifier: NCT01130272.

BACKGROUND

The HCL-32 is a widely-used screening questionnaire for hypomania. We aimed to use a Rasch analysis approach to (i) evaluate the measurement properties, principally unidimensionality, of the HCL-32, and (ii) generate a score table to allow researchers to convert raw HCL-32 scores into an interval-level measurement which will be more appropriate for statistical analyses.

METHODS

Subjects were part of the Bipolar Disorder Research Network (BDRN) study with DSM-IV bipolar disorder (n=389). Multidimensionality was assessed using the Rasch fit statistics and principle components analysis of the residuals (PCA). Item invariance (differential item functioning, DIF) was tested for gender, bipolar diagnosis and current mental state. Item estimates and reliabilities were calculated.

RESULTS

Three items (29, 30, 32) had unacceptable fit to the Rasch unidimensional model. Item 14 displayed significant DIF for gender and items 8 and 17 for current mental state. Item estimates confirmed that not all items measure hypomania equally.

CONCLUSIONS

This sample was recruited as part of a large ongoing genetic epidemiology study of bipolar disorder and may not be fully representative of the broader clinical population of individuals with bipolar disorder.

CONCLUSIONS

The HCL-32 is unidimensional in practice, but measurements may be further strengthened by the removal of four items. Re-scored linear measurements may be more appropriate for clinical research.

The photodegradation of two fluoroquinolone veterinary antibiotics, difloxacin (DIF) and sarafloxacin (SARA) has been explored for the first time in aqueous systems. The study was performed to evaluate the influence of pH, inorganics, humic substances, and other additives. The drugs followed first-order degradation kinetics in matrix free aqueous medium with a rate constant 'k' value of 0.82 and 0.26 h(-1) for DIF and SARA, respectively. Studies performed at various pH revealed that the photolysis rates dropped sharply at pH >7 for DIF, while SARA dissipated faster with increasing pH. Humic substances acted as light barriers by attenuating the light intensity, to retard the drug degradation process. However, rapid drug dissipation was observed in the presence of additives like acetone, hydrogen peroxide, and phosphates, while inorganics such as fluoride, nitrate, and sulfate did not influence the drug photodegradation. Studies on the photolysis of DIF and SARA in river water revealed that both the drugs degraded rapidly under conditions that were relevant to natural systems, following direct photolysis mechanism. It was observed that SARA was the primary photoproduct of DIF and showed relatively a higher persistence than DIF. The findings were also substantiated by the quantum yield (Phi(c)) calculations. The analytical measurements were carried out with LC-MS/MS.

Human macrophage differentiation inducing factor (DIF) can induce differentiation of human myeloid leukemic cells into macrophage-like cells in vitro. A procedure is described for purification of DIF from serum-free human monocytic leukemia THP-1 cell-conditioned medium. The procedure included concentration of a conditioned medium by ultrafiltration, lentil lectin-Sepharose affinity chromatography, and fast protein liquid chromatography using Mono S and Mono Q. DIF-A of pI 9.0 and DIF-B of pI 8.8 were obtained after a final purification with a Mono Q column, and both DIF gave a single peak with a molecular weight of approximately 51,000 determined by gel chromatography. NH2-terminal amino acid analysis of DIF-A showed a noticeable homology with murine leukemia inhibitory factor. Human DIF-A was found to induce maturation of human and murine leukemic cells into both macrophage-like cells with nitro blue tetrazolium reducing activity and phagocytic cells, but was found to suppress proliferation of these leukemic cells.

BACKGROUND

Autoimmune blistering diseases are a group of bullous disorders characterized by pathogenic antibodies directed at the target antigens, which are components of the desmosomes or adhesion complex at the dermoepidermal junction. Direct immunofluorescence (DIF) is invaluable in the diagnosis of these lesions.

OBJECTIVE

The aim of this study was to evaluate the sensitivity of DIF in immunobullous dermatoses and to study the pattern of DIF. The study also aims to correlate DIF with clinical and histologic findings and to analyze discrepancies.

METHODS

Total 100 biopsies received over a period of 2 years in the Department of Pathology were analyzed. DIF, histopathology and clinical data were reviewed.

RESULTS

Out of 100, 89 cases showed DIF patterns concordant with clinical/histologic diagnosis. The sensitivity of DIF was 94.44% (51/58) in the pemphigus and 84% (21/25) in the bullous pemphigoid (BP) group, 100% each in dermatitis herpetiformis (2/2) and linear IgA disease (1/1). A total of 11 histologically proven cases of immunobullous lesions were DIF negative-four (three of pemphigus vulgaris and one of BP) due to having no epidermis, three (cases of BP) owing to sampling/technical errors and the remaining four (cases of pemphigus vulgaris) due to being on treatment.

CONCLUSIONS

Immunofluorescence helps confirm the diagnosis of bullous lesions in which there is clinical and the histopathologic overlap. Sampling errors contributed to false negative (FN) results.

Desmin intermediate filaments (DIFs) form an intricate meshwork that organizes myofibers within striated muscle cells. The mechanisms that regulate the association of desmin to sarcomeres and their role in desminopathy are incompletely understood. Here we compare the effect nebulin binding has on the assembly kinetics of desmin and three desminopathy-causing mutant desmin variants carrying mutations in the head, rod, or tail domains of desmin (S46F, E245D, and T453I). These mutants were chosen because the mutated residues are located within the nebulin-binding regions of desmin. We discovered that, although nebulin M160-164 bound to both desmin tetrameric complexes and mature filaments, all three mutants exhibited significantly delayed filament assembly kinetics when bound to nebulin. Correspondingly, all three mutants displayed enhanced binding affinities and capacities for nebulin relative to wild-type desmin. Electron micrographs showed that nebulin associates with elongated normal and mutant DIFs assembled in vitro. Moreover, we measured significantly delayed dynamics for the mutant desmin E245D relative to wild-type desmin in fluorescence recovery after photobleaching in live-cell imaging experiments. We propose a mechanism by which mutant desmin slows desmin remodeling in myocytes by retaining nebulin near the Z-discs. On the basis of these data, we suggest that for some filament-forming desmin mutants, the molecular etiology of desminopathy results from subtle deficiencies in their association with nebulin, a major actin-binding filament protein of striated muscle.

BACKGROUND

The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used patient reported outcome in osteoarthritis. An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items exhibit differential item functioning (DIF). That is, if respondents have the same underlying level of an attribute, does the item give the same score in different subgroups or is it biased towards one subgroup or another. The aim of the study was to explore DIF in the Likert format WOMAC for the first time in a UK osteoarthritis population with respect to demographic, social, clinical and psychological factors.

METHODS

The sample comprised a community sample of 763 people with osteoarthritis who participated in the Somerset and Avon Survey of Health. The WOMAC was explored for DIF by gender, age, social deprivation, social class, employment status, distress, body mass index and clinical factors. Ordinal regression models were used to identify DIF items.

RESULTS

After adjusting for age, two items were identified for the physical functioning subscale as having DIF with age identified as the DIF factor for 2 items, gender for 1 item and body mass index for 1 item. For the WOMAC pain subscale, for people with hip osteoarthritis one item was identified with age-related DIF. The impact of the DIF items rarely had a significant effect on the conclusions of group comparisons.

CONCLUSIONS

Overall, the WOMAC performed well with only a small number of DIF items identified. However, as DIF items were identified in for the WOMAC physical functioning subscale it would be advisable to analyse data taking into account the possible impact of the DIF items when weight, gender or especially age effects, are the focus of interest in UK-based osteoarthritis studies. Similarly for the WOMAC pain subscale in people with hip osteoarthritis it would be worthwhile to analyse data taking into account the possible impact of the DIF item when age comparisons are of primary interest.

This study addresses several important issues in assessment of differential item functioning (DIF). It starts with the definition of DIF, effectiveness of using item fit statistics to detect DIF, and linear modeling of DIF in dichotomous items, polytomous items, facets, and testlet-based items. Because a common metric over groups of test-takers is a prerequisite in DIF assessment, this study reviews three such methods of establishing a common metric: the equal-mean-difficulty method, the all-other-item method, and the constant-item (CI) method. A small simulation demonstrates the superiority of the CI method over the others. As the CI method relies on a correct specification of DIF-free items to serve as anchors, a method of identifying such items is recommended and its effectiveness is illustrated through a simulation. Finally, this study discusses how to assess practical significance of DIF at both item and test levels.

OBJECTIVE

The major aims were to evaluate responsiveness and clinical/research applicability of the Revised Oswestry Disability Questionnaire (ODQ) and the Dallas Pain Questionnaire (DPQ). Construct and content validity were assessed. Patient characteristics and outcomes were also documented.

METHODS

Longitudinal observational study.

METHODS

College outpatient clinics.

METHODS

Six hundred sixty-three consecutive new patients accepted for treatment of low back pain (LBP) at the clinics over a 1-yr period, age 18 or older.

METHODS

Treatment of low back pain by senior interns under the supervision of staff clinicians.

METHODS

ODQ and DPQ administered at baseline, 2 wk, 1 month, and monthly up to 6 months. Responsiveness: mean standardized change score (delta' = mudif/sigma dif), relative efficiency ([RE = delta' ODQ/delta DPQ']2), and improvement rates (IR). Applicability: instrument completion rates. Construct validity: correlation with VAS for pain intensity.

RESULTS

ODQ responsiveness was generally consistent over time (delta' = .70-.83) and negligibly better than the DPQ activities of daily living scale (RE = 1.00-1.35); most patients self-reporting improvement showed positive outcomes (IR = 97%). For large samples (n>> 100): delta' = .47-.63 and IR = 81% for the DPQ work/leisure scale; delta' = .17-.40 and IR = 54% for the DPQ anxiety/depression and social dimensions. Completion rates: 65%-78% of all instruments; 81%-100% of individual scales. Construct validity: r = .44-.68 for the ODQ, DPQ activities of daily living, and DPQ work/leisure scales; r = .20-.40 for the anxiety/depression scale.

CONCLUSIONS

The ODQ and the activities of daily living and work/leisure scales from the DPQ appear appropriate for monitoring LBP patients returning for care to chiropractic teaching clinics. The social and anxiety/depression dimensions of the DPQ do not appear to be responsive in this population. The latter scale may be unsuitable on the grounds of misinterpretations.

OBJECTIVE

The Multidimensional Health Locus of Control (MHLC) scales are widely used to measure beliefs about determinants of persons' health. We evaluated the scales over the largest-ever disease-specific sample of subjects using a combined-method psychometric approach.

METHODS

We performed a secondary analysis of data from 1,206 subjects from three osteoarthritis studies, using Rasch analysis and confirmatory factor analysis simultaneously. Differential item functioning (DIF) by gender and data source, scale dimensionality, and item fit were examined. The Rasch model fit the data if Rasch residual principal components analysis (PCA) corroborated three distinct dimensions and item fit statistics fell between 0.80 and 1.20. The confirmatory factor (CFA) model fit the data if factor loadings exceeded 0.50 for all items.

RESULTS

DIF by gender or data source was not materially evident for any items. PCA supported existence of three dimensions in the data. Both Rasch and CFA models fit the data for 16 items; two items were detected as misperforming. When these items were removed, fit of both models improved.

CONCLUSIONS

Results of this large-sample evaluation of the MHLC scales corroborated earlier findings that removal of certain items improves the scales. The combined Rasch-CFA approach provided better insight to scale performance problems than either method alone provided.

The Center for Epidemiological Studies-Depression (CES-D) scale is a widely used measure of depressive symptoms, but its psychometric properties have not been adequately evaluated among adults with HIV/AIDS. This study used an item response theory approach (Rasch analysis) to evaluate the CES-D's validity and reliability in relation to key demographic and clinical variables in adults with HIV/AIDS. A convenience sample of 347 adults with HIV/AIDS (231 males, 93 females, and 23 transgenders; age range 22-77 years) completed the CES-D. A Rasch model application was used to analyze the CES-D's rating scale functioning, internal scale validity, person-response validity, person-separation validity, internal consistency, differential item functioning (DIF), and differential test functioning. CES-D scores were generally high and associated with several demographic and clinical variables. The CES-D distinguished 3 distinct levels of depression and had acceptable internal consistency but lacked unidimensionality, five items demonstrated poor fit to the model, 15% of the respondents demonstrated poor fit, and eight items demonstrated DIF related to gender, race, or AIDS diagnosis. Removal of misfitting items resulted in minimal improvement in the CES-D's substantive and structural validity. CES-D scores should be interpreted with caution in adults with HIV/AIDS, particularly when comparing scores across gender and racial groups.

In bacteria, the FtsK/Xer/dif (chromosome dimer resolution site) system is essential for faithful vertical genetic transmission, ensuring the resolution of chromosome dimers during their segregation to daughter cells. This system is also targeted by mobile genetic elements that integrate into chromosomal dif sites. A central question is thus how Xer/dif recombination is tuned to both act in chromosome segregation and stably maintain mobile elements. To explore this question, we focused on pathogenic Neisseria species harboring a genomic island in their dif sites. We show that the FtsK DNA translocase acts differentially at the recombination sites flanking the genomic island. It stops at one Xer/dif complex, activating recombination, but it does not stop on the other site, thus dismantling it. FtsK translocation thus permits cis discrimination between an endogenous and an imported Xer/dif recombination complex.

OBJECTIVE

Differentiation-inducing factors (DIFs) are chlorinated alkylphenones found in the cellular slime mold Dictyostelium discoideum. DIF derivatives exhibit antiproliferative activities and promote glucose consumption in mammalian cells in vitro. In this study, we assessed the ability of DIFs to regulate the immune system and investigated their mechanisms of action.

METHODS

We examined the effects of 30 DIF derivatives on concanavalin A-induced IL-2 production (CIIP) in Jurkat T-cells. We also examined the effects of some DIF derivatives on the activity of AP-1 (activator protein-1), NFAT (nuclear factor of activated T-cells), and NFkappaB (nuclear factor kappa B), which are transcription factors required for CIIP.

RESULTS

Of the derivatives tested, some compounds suppressed CIIP as well as the known immunosuppressants cyclosporine A and FK506. A reporter gene assay revealed that 4 DIF derivatives tested suppressed CIIP, at least in part, by inhibiting the activity of AP-1, NFAT, and/or NFkappaB. Unlike cyclosporine A and FK506, the DIF derivatives had little effect on concanavalin A-induced interferon-gamma production in Jurkat cells.

CONCLUSIONS

The present results suggest that DIF derivatives could be developed as novel immunosuppressive drugs.

The aim of this study was to evaluate the prevalence of suicide in Turkish male substance dependents, and to investigate the relationship of suicide attempt history with childhood abuse and neglect, alexithymia, and temperament and character dimensions of personality. Participants were 154 consecutively admitted male substance dependents. Patients were investigated with the Childhood Abuse and Neglect Questionnaire, Toronto Alexithymia Scale (TAS-20) and Temperament and Character Inventory (TCI). Among substance-dependent patients, 28.6% was considered a group with suicide attempt history (SAH). Current age was lower and rate of being single was higher in the group with SAH. There were no significant differences between groups in terms of employment, educational status and duration of education. Rates of physical, emotional abuse and neglect, self-mutilation and being alexithymic were higher and ages at first substance use and regular substance use were lower in the group with SAH. Mean scores of "difficulty in identifying feelings" (DIF) and "difficulty in describing feelings" (DDF) subscale EOT of the TAS-20 were higher in the SAH group. Among temperament and character dimensions of the TCI, only "Self-directedness" and "Cooperativeness" were lower in SAH and there were no significant differences between groups in terms of other subscales. Age and Self-directedness score of TCI were determinants for suicide attempt. In particular, young drug users with low Self-directedness scores could be the target population in order to prevent suicidal behavior. This study also suggests that in substance-dependent patients, in the background of all suicidal behavior, childhood abuse and neglect must be evaluated.

BACKGROUND

The Positive Mental Health (PMH) instrument was developed and validated to assess the level of PMH and its six dimensions in a multi-ethnic general population sample. This cross-sectional study examines the psychometric properties of the instrument for assessing the level of PMH among help-seeking patients with mental disorders.

METHODS

The PMH instrument was tested among 360 out-patients with schizophrenia, depression or anxiety spectrum disorders, seeking treatment at a tertiary psychiatric hospital and its affiliated clinics in Singapore. All participants completed the PMH instrument along with measures of life satisfaction, mental and overall health and happiness. Reliability (internal consistency), construct (Exploratory Structural Equation Modeling (ESEM)) and criterion (convergent and divergent) validity of the PMH instrument were tested in this population. Items were also tested for item response theory and differential item functioning (IRT-DIF).

RESULTS

ESEM on the PMH instrument showed good fit with the model reflecting six factors (general coping, personal growth and autonomy, spirituality, interpersonal skills, emotional support, and global affect). Internal consistency was high (Cronbach's alpha >0.85) for the instrument and its six subscales. The PMH instrument fulfilled expected correlations with related constructs and demonstrated adequate item discrimination and difficulty estimates; however, significant DIF was noted for few items for age, gender and ethnicity groups.

CONCLUSIONS

The PMH instrument is a reliable and valid instrument for measuring PMH dimensions in patients with mental disorders. Further studies in larger samples are needed to assess the impact of DIF on PMH scores. The implications for the shift in focus from just the negative aspects of mental disorders to including positive components in the assessment of patients with mental disorders are immense, and can be applied in routine mental health practice and policy making.

BACKGROUND

Differential Item Functioning (DIF) is investigated to ensure that each item displays a consistent pattern of responses irrespective of the characteristics of the respondents. Assessing DIF helps to understand the nature of instruments, to assess the quality of a measure and to interpret results. This study aimed to examine whether the items of the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Short-Form 12 (SF-12) exhibit DIF.

METHODS

A total of 124 outpatients diagnosed with substance dependence participated in a cross-sectional, multicenter study. In addition to the Q-LES-Q-SF and SF-12 results, demographic data such as age, sex, type of substance dependence and education level were collected. Rasch analysis was conducted (using RUMM2020 software) to assess DIF of the Q-LES-Q-SF and SF-12 items.

RESULTS

For SF-12, significant age-related uniform DIF was found in two of the 12 items, and sex-related DIF was found in one of the 12 items. All of the observed DIF effects in SF-12 were found among the mental health items. Three items showed DIF on the Q-LES-Q-SF; however, the impact of DIF item on the delta score calculation for the comparisons of self-reported health status between the groups was minimal in the SF-12 and small in the Q-LES-Q-SF.

CONCLUSIONS

These results indicated that no major measurement bias affects the validity of the self-reported health status assessed using the Q-LES-Q-SF or SF-12. Thus, these questionnaires are largely robust measures of self-reported health status among substance users.