A preliminary validation of the pediatric adaptation of the Insomnia Severity Index.

INTRODUCTION: The prevalence of insomnia in children aged 5 to 12 years old is 20% to 31%. Currently, there is no well-validated questionnaire assessing all the components of insomnia in school-aged children. The present study aims to introduce an adaptation of the Insomnia Severity Index for this purpose. METHOD: Fifty-nine children aged 8- to 12-years-old with at least one anxiety disorder were recruited from youth mental health care settings. Their parents completed the pediatric adaptation of the Insomnia Severity Index which includes two scales used to report insomnia symptoms in children and their impact on the child (ISI-Child) and parents (ISI-Parent), My Child's Sleep Habits questionnaire, and the Child Behavior Checklist. RESULTS: Both the ISI-Child and the ISI-Parent scales presented adequate factorial structure (RMSEA ≤ 0.05) and internal consistency (ISI-Child: α=0.87; ISI-Parent: α=0.88). Furthermore, the results of the two scales were strongly correlated (r=0.91, P<0.001). The convergent validity was assessed using the Waking During the Night scale of the My Child's Sleep Habits questionnaire and was adequate for the ISI-Child (r=0.52, P<0.001) and the ISI-Parent (r=0.53, P<0.001). Finally, the Rule-Breaking Behavior (r ≤ 0.26, P ≥ 0.05) and Aggressive Behavior (r ≤ 0.19, P ≥ 0.19) scales of the Child Behavior Checklist showed small correlations with both subscales, indicating good divergent validity. CONCLUSION: The pediatric adaptation of the Insomnia Severity Index is a potentially reliable and valid measure for screening and assessing insomnia in children.

[Distress tolerance and experience of chronic pain]. / Tolérance à la détresse et expérience de la douleur chronique.

INTRODUCTION: Chronic pain is a highly prevalent condition that is associated with distressing somatic and emotional experiences. Consequently, an individual's distress tolerance, the perceived capacity to tolerate negative psychological and physical states, may influence their pain experience. This effect could be explained in part by a reduction in the catastrophic interpretation of pain which is associated with increased pain intensity and interference in everyday activities. AIMS: The first aim of this study was to explore the association between the components of the 5-factor model of distress tolerance and (1) pain intensity and (2) pain interference in everyday activities. The secondary aim was to assess the potential mediating effect of pain catastrophizing in the eventual association between components of distress tolerance and (1) pain intensity or (2) pain interference in everyday activities. METHOD: This is a cross-sectional study of adult (18 years or older) university students and staff with chronic pain (3 months). They were invited to complete the online questionnaire through an email invitation. Pain intensity and interference in everyday functioning were assessed with the corresponding subscales of the Brief Pain Inventory. The following instruments were used to assess the components of the 5-factor model of distress tolerance: Ambiguity Tolerance Scale (tolerance to ambiguity), Intolerance to Uncertainty Scale (reversed score: tolerance to uncertainty), Discomfort Intolerance Scale (reversed score: discomfort tolerance), Distress Tolerance Scale (tolerance to negative emotions), Frustration Discomfort Scale (tolerance to frustration). Participants also completed the Pain Catastrophizing Scale. RESULTS: Eighty participants were recruited (57 % women, mean age=33.09; standard deviation=12,87). Tolerance to negative emotions was the only component of distress tolerance that was associated with pain (ß=-0.04; 95% CI): -0.07--0.01; t (78)=-3.06, p<0.01) or pain interference in everyday functioning (ß=-0.07; 95% CI: -0.10--0.03; t (78)=-3.97, p<0.01), independently of the others. Combined with age, these factors explained 16.2 % of the variance in pain intensity and 19.4 % of the variance in pain interference. Pain catastrophizing partially mediated the association between tolerance to negative emotions and pain interference in everyday functioning, but it was not involved in the association between tolerance to negative emotions and pain intensity. CONCLUSION: Tolerance to negative emotions appears to be the most relevant aspect of distress tolerance in the context of chronic pain and is a potential clinical target that is independent and complementary from pain catastrophizing.

CO(2) rebreathing: an undergraduate laboratory to study the chemical control of breathing.

The Read CO2 rebreathing method (Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med 16: 20-32, 1967) provides a simple and reproducible approach for studying the chemical control of breathing. It has been widely used since the modifications made by Duffin and coworkers. Our use of a rebreathing laboratory to challenge undergraduate science students to investigate the control of breathing provided 8 yr of student-generated data for comparison with the literature. Students (age: 19-22 yr, Research Ethics Board approval) rebreathed from a bag containing 5% CO2 and 95% O2 (to suppress the peripheral chemoreflex to hypoxia). Rebreathing was performed, and ventilation measured, after hyperventilation to deplete tissue CO2 stores and enable the detection of the central chemoreflex threshold. We analyzed 43 data sets, of which 10 were rejected for technical reasons. The mean threshold and ventilatory sensitivity to CO2 were 43.3 ± 3.8 mmHg and 4.60 ± 3.04 l·min(-1)·mmHg(-1) (means ± SD), respectively. Threshold values were normally distributed, whereas sensitivity was skewed to the left. Both mean values agreed well with those in the literature. We conclude that the modified rebreathing protocol is a robust method for undergraduate investigation of the chemical control of breathing.

Development of ELIP to Assess Physical Literacy for Emerging Adults: A Methodological and Epistemological Challenge.

Purpose: Following increased interest in physical literacy (PL), development of appropriate tools for assessment has become an important next step for its operationalization. To forward the development of such tools, the objective of this study was to build the foundations of the Évaluation de la Littératie Physique (ELIP), designed to help reduce existing tensions in approaches to PL assessment that may be resulting in a low uptake into applied settings. Methods: We followed two steps: (1) the development of the first version of ELIP by deploying a Delphi method (n = 30); and (2) the modification of items through cognitive interviews with emerging adults (n = 32). Results: The expert consensus highlighted four dimensions of PL to be assessed-physical; affective; cognitive; and social-with new perspectives, including a preference for broad motor tests over fitness. Conclusion: Results offer new insights into the assessment of emerging adults' PL, but ELIP still requires further work concerning validity, reliability, and sensitivity.

Sensitization to the cytotoxicity of melphalan by ethacrynic acid and hyperthermia in drug-sensitive and multidrug-resistant Chinese hamster ovary cells.

The ability of physical and pharmacological modulators to increase the cytotoxicity of melphalan was investigated in Chinese hamster ovary cells using a clonogenic cell survival assay. Hyperthermia has potential for use in cancer treatment, particularly as an adjuvant to chemotherapy or radiotherapy. Ethacrynic acid is a glutathione S-transferase inhibitor and also undergoes conjugation with glutathione. Interactions between hyperthermia (41-43 degrees C), ethacrynic acid and melphalan were evaluated in multidrug-resistant (CH(R)C5) cells with overexpression of P-glycoprotein (33.69-fold), and in drug-sensitive (AuxB1) cells. GST alpha was expressed at a higher level (3.65-fold) in CH(R)C5 cells than in sensitive cells, whereas levels of isoforms pi and mu were the same. GST pi was the most highly expressed isoform in the two cell populations. Ethacrynic acid was cytotoxic at elevated temperatures, while it caused little or no cytotoxicity at 37 degrees C. This effect occurred in drug-resistant and drug-sensitive cells, and attributes thermosensitizing properties to ethacrynic acid. Ethacrynic acid (20 microM) alone did not alter the cytotoxicity of melphalan at 37 degrees C. Hyperthermia potentiated drug cytotoxicity in cells, both with and without ethacrynic acid treatment. Ethacrynic acid could be useful in cancer treatment by acting as a thermosensitizer when combined with heat and by enhancing the cytotoxicity of melphalan at elevated temperatures. A major advantage arising from the use of regional hyperthermia is the ability to target drug cytotoxicity to the tumor volume. A useful finding is that ethacrynic acid, heat and/or melphalan are also effective against multidrug-resistant cells with overexpression of P-glycoprotein.

Platelet-activating factor stimulates interleukin-6 production by human endothelial cells and synergizes with tumor necrosis factor for enhanced production of granulocyte-macrophage colony stimulating factor.

The interaction between human endothelial cells (EC) and leukocytes during inflammation is in part mediated through the release of soluble factors. Since platelet-activating factor (PAF) is a potent mediator of inflammatory responses, we investigated the potential of PAF to modulate IL-6 and GM-CSF production by EC. Exposure of these cells to PAF resulted in a concentration-dependent increase in IL-6 production, with a maximum at 10(-10) M PAF. Sequential incubation of EC with PAF and TNF alpha resulted in a synergistic increase of IL-6 production. This effect was specific for PAF since it was prevented by preincubation with the PAF receptor antagonist, WEB 2086. Northern blot analysis revealed enhanced IL-6 mRNA expression in PAF-treated EC. However, the synergy observed in protein synthesis between PAF and TNF alpha was not reflected in IL-6 mRNA accumulation, suggesting a post-translational modulation. Pretreatment of EC with the protein synthesis inhibitor cycloheximide before their exposure to PAF resulted, after washout of the cycloheximide, in a markedly augmented production of IL-6, suggesting a synergy between augmented IL-6 mRNA accumulation by PAF and IL-6 mRNA superinduction by cycloheximide. GM-CSF production by EC was also stimulated by the combined effects of PAF and TNF alpha, but PAF alone did not affect GM-CSF production. Taken together, our data suggest that PAF can stimulate EC to synthesize cytokines, including IL-6 and GM-CSF, which may contribute to local and, possibly, systemic responses during inflammation.

Validation of an electronic version of the Mini Asthma Quality of Life Questionnaire.

BACKGROUND: The Mini Asthma Quality of Life Questionnaire (MiniAQLQ) is a validated disease-specific quality of life (QOL) paper (p) questionnaire. Electronic (e) versions enable inclusion of asthma QOL in electronic medical records and research databases. PURPOSE: To validate an e-version of the MiniAQLQ, compare time required for completion of e- and p-versions, and determine which version participants prefer. METHODS: Adults with stable asthma were randomized to complete either the e- or p-MiniAQLQ, followed by a 2-h rest period before completing the other version. Agreement between versions was measured using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. RESULTS: Two participants with incomplete p-MiniAQLQ responses were excluded. Forty participants (85% female; age 47.7 +/- 14.9 years; asthma duration 22.6 +/- 16.1 years; FEV(1) 87.1 +/- 21.6% predicted) with both AQLQ scores <6.0 completed the study. Agreement between e- and p-versions for the overall score was acceptable (ICC=0.95) with no bias (difference (Delta) p-e=0.1; P=0.21). ICCs for the symptom, activity limitation, emotional function and environmental stimuli domains were 0.94, 0.89, 0.90, and 0.91 respectively. A small but significant bias (Delta=0.3; P=0.004) was noted in the activity limitation domain. Completion time was significantly longer for the e-version (3.8 +/- 1.9min versus 2.7 +/- 1.1min; P<0.0001). The majority of patients (57.5%) preferred the e-MiniAQLQ; 35% had no preference. CONCLUSION: This e-version of the MiniAQLQ is valid and was preferred by most participants despite taking slightly longer to complete. Generalizabilty may be limited in younger (12-17) and older (>65) adults.

The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types.

In addition to new tumour antigens, new prognostic and diagnostic markers are needed for common cancers. In this study, we report the expression of Dickkopf-1 (DKK1) in multiple common cancers. This constitutes a comprehensive analysis of the DKK1 expression profile. Dickkopf-1 expression was evaluated by classical and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbant assay for protein determination, in cancer lines and clinical specimens of several cancer origins. For breast cancer, expression was correlated with clinicopathological parameters. Dickkopf-1 expression was confirmed in several cancer cell lines derived from breast and other common cancers. Dickkopf-1 protein secretion was documented in breast, prostate and lung cancer lines, but was negligible in melanoma. Analysis of DKK1 expression in human cancer specimens revealed DKK1 expression in breast (21 out of 73), lung (11 out of 23) and kidney cancers (six out of 20). Interestingly, DKK1 was preferentially expressed in oestrogen and progesterone receptor-negative tumours (ER(-)/PR(-); P=0.005) and in tumours from women with a family history of breast cancer (P=0.024). Importantly, DKK1 protein production was confirmed in multiple breast cancer specimens that were positive by RT-PCR. This work establishes DKK1 as a potential prognostic and diagnostic marker for cohorts of breast cancer patients with poor prognosis. Dickkopf-1 may also become a relevant candidate target for immunotherapy of different cancers.

Adhesion-independent synergy of monocytes and endothelial cells in cytokine production: regulation of IL-6 and GM-CSF production by PAF.

Co-Cultures of monocytes (MO) and endothelial cells (EC) were studied for their capacity to synergize in the production of interleukin-6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), two cytokines potentially important in vascular physiopathology. Resting monocytes produced detectable amounts of IL-6 but no GM-CSF, whereas confluent EC produced significant quantities of GM-CSF, but minimal IL-6. In co-cultures without stimuli, additive synthesis of both cytokines was observed. When EC were pretreated, however, with either PAF, TNF or both stimuli, before addition of MO, synergistic production of IL-6 was observed. In contrast, GM-CSF production was not enhanced by coculture of monocytes with activated EC. When either cell population was fixed with paraformaldehyde or killed by freeze-thawing before addition to the co-culture, cytokine levels reverted to those produced by the unaffected population alone. On the other hand, separating the two cell populations by a cell-impermeable membrane in transwell cultures did not affect the synergistic production of the cytokines. Taken together, our data suggest that EC and MO can synergize in response to stimuli by producing IL-6 and that this synergy is dependent on the integrity of both cell populations, but independent of cell-cell contact.

Human PAF receptor gene expression: induction during HL-60 cell differentiation.

Platelet-activating factor is a potent lipid mediator of inflammation and immune regulation. Its numerous biological activities are mediated through specific receptors on the plasma membranes of responsive cells. The expression of such receptors may be modulated by various agents, including those responsible for cell differentiation. Here, we demonstrate that differentiation of the human promyelocytic leukemia cell line HL-60 by 1 alpha,25(OH)2 vitamin D3 towards the macrophage phenotype is associated with induction of PAF receptor gene expression: PAF receptor mRNA accumulation correlates with the induction and development of specific PAF responsiveness as assayed by [Ca2+]i fluxes. Our studies suggest that PAF responsiveness parallels macrophage differentiation and that PAF receptor expression can be regulated at the transcriptional level.

Priming of human monocytes with leukotriene B4 enhances their sensitivity in IL-2-driven tumor necrosis factor-alpha production. Transcriptional and post-transcriptional up-regulation of IL-2 receptors.

Cytotoxic activity of monocytes may be mediated by their production of TNF-alpha, and IL-2 has been shown to induce TNF-alpha production in monocytes and alveolar macrophages. Unstimulated human monocytes constitutively express the beta-chain of the IL-2R (IL-2R beta), but little or no IL-2R alpha. When monocytes were pretreated with leukotriene (LT) B4, they responded to IL-2 with both enhanced production of TNF-alpha (two- to threefold) and, more strikingly, with augmented sensitivity (1000-fold) to IL-2. Treatment of monocytes with LTB4 induced IL-2R alpha gene transcription at 30 min and augmented expression of IL-2R alpha gene transcripts by 3 h, maximal at 10(-8) M LTB4. LTB4 induced increased shedding of the IL-2R alpha in the culture supernatants and a modest induction of IL-2R alpha protein expression on monocytes. On the other hand, although LTB4 could stimulate the cell membrane expression of IL-2R beta and the accumulation of IL-2R beta mRNA, LTB4 did not significantly affect IL-2R beta gene transcription. The augmented expression of IL-2R on monocytes was associated with augmented binding of 125I-labeled IL-2 to LTB4-pretreated monocytes. Our data present direct evidence that the inflammatory lipid mediator LTB4 can induce the expression of IL-2R alpha in human monocytes by activating IL-2R alpha gene transcription; it can also stimulate the expression of IL-2R beta, through post-transcriptional regulation; this augmented expression of both alpha- and beta-chains of the IL-2R is associated with enhanced sensitivity of monocytes to IL-2 in terms of TNF-alpha production and may be relevant to the proinflammatory actions of LTB4.

Immune regulation by platelet-activating factor. I. Induction of suppressor cell activity in human monocytes and CD8+ T cells and of helper cell activity in CD4+ T cells.

Platelet-activating factor (PAF) is a powerful mediator of inflammation. We have recently described a potential role for PAF in immune reactions, as it inhibits T cell proliferation and IL-2 production in response to mitogens. To further define the mechanism through which this inhibition is exerted, we used a coculture system in which PBML are preincubated with increasing concentrations of PAF for 24 h, followed by washing, treatment with mitomycin C and addition to fresh autologous PBML stimulated with PHA. In this context, a significant (40 to 60%) inhibition of proliferation was observed. In parallel, PAF-pre-treated cells induced a reduction (30 to 50%) of IL-2 production by PHA-stimulated lymphocytes. The PAF receptor antagonist BN52021 could partially block the PAF-induced suppressor cell activity, but also showed some suppressor cell-inducing properties of its own (20 to 30%). The expression of suppressor cell function during the co-culture could be partially abrogated by the inclusion of indomethacin, suggesting that cycloxygenase metabolites of arachidonic acid were involved in this phase of suppression. When PBML were fractionated into monocytes, lymphocytes, or T cell subsets before pre-incubation with PAF, indomethacin-sensitive suppressor cell function was generated in the monocyte population. Monocyte-depleted lymphocytes showed slight helper effect, whereas CD8+ T cells were induced to become indomethacin-resistant suppressor cells. CD4+ T cells, in contrast, were activated to exert very marked helper effect. When incubated with PAF for 24 h, monocyte-depleted lymphocytes showed a 30% decrease in CD4+ T cell numbers and a 50% increase in CD8+ T cell numbers. Our data suggest a novel immunoregulatory role for PAF and potentially important interactions of this lipid mediator of inflammation with lymphocyte and monocyte functions.

Application of Raman spectroscopy to metal-sulfide surface analysis.

The surface products of electrochemically oxidized pyrite (FeS(2)) are investigated as a function of applied potential by using Raman spectroscopy. The parameters necessary for sulfur formation on the pyrite surface were determined. An optical multichannel apparatus, consisting of an argon laser, a triple spectrograph, and a charge-coupled-device detector, was utilized for the Raman measurements. The advantages of this system for surface characterization include high resolution and high sensitivity as well as the capability of identifying compounds and making in-situ measurements.

Critérios de elegibilidade e plano mínimo de acompanhamento integrado no serviço de assistência domiciliar do Campo Limpo: relato de experiência

Introdução: a avaliação inicial de usuários em situação de dependência funcional é complexa, implicando na avaliação de fatores diversos, de ordens bio-psico-sociais, dificultando a utilização de dados quantitativos e dando margem à interpretação do observador. Entretanto, a conformação de instrumentos de avaliação inicial e o dimensionamento do serviço a partir de escores e dos recursos disponíveis mostram-se úteis às atividades de planejamento e avaliação de serviços de assistência domiciliar. Numa ótica de otimização de recursos, o Serviço de Assistência Domiciliar do Campo Limpo (SAD-CL) criou um instrumento de avaliação inicial pontuada para determinar a elegibilidade do usuário ao serviço e criou uma padronização de plano mínimo de acompanhamento integrado a partir da pontuação obtida na avaliação. Objetivo: o objetivo deste trabalho é apresentar o instrumento de avaliação inicial pontuado utilizado pelo SAD-CL e a criação da padronização do plano mínimo de acompanhamento integrado de cuidados domiciliares.

Critérios de elegibilidade e plano mínimo de acompanhamento integrado no serviço de assistência domiciliar do Campo Limpo: relato de experiência / Eligibility criteria and minimum follow-up plan in integrated home care service Limpo: experience report

Introdução: a avaliação inicial de usuários em situação de dependência funcional é complexa, implicando na avaliação de fatores diversos, de ordens bio-psico-sociais, dificultando a utilização de dados quantitativos e dando margem à interpretação do observador. Entretanto, a conformação de instrumentos de avaliação inicial e o dimensionamento do serviço a partir de escores e dos recursos disponíveis mostram-se úteis às atividades de planejamento e avaliação de serviços de assistência domiciliar. Numa ótica de otimização de recursos, o Serviço de Assistência Domiciliar do Campo Limpo (SAD-CL) criou um instrumento de avaliação inicial pontuada para determinar a elegibilidade do usuário ao serviço e criou uma padronização de plano mínimo de acompanhamento integrado a partir da pontuação obtida na avaliação. Objetivo: o objetivo deste trabalho é apresentar o instrumento de avaliação inicial pontuado utilizado pelo SAD-CL e a criação da padronização do plano mínimo de acompanhamento integrado de cuidados domiciliares.