Biosynthesis of tumorigenic HER2 C-terminal fragments by alternative initiation of translation.
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The overactivation of the HERs, a family of tyrosine kinase receptors, leads to the development of cancer. Although the canonical view contemplates HER receptors restricted to the secretory and endocytic pathways, full-length HER1, HER2 and HER3 have been detected in the nucleoplasm. Furthermore, limited proteolysis of HER4 generates nuclear C-terminal fragments (CTFs). Using cells expressing a panel of deletion and point mutants, here we show that HER2 CTFs are generated by alternative initiation of translation from methionines located near the transmembrane domain of the full-length molecule. In vitro and in vivo, HER2 CTFs are found in the cytoplasm and nucleus. Expression of HER2 CTFs to levels similar to those found in human tumors induces the growth of breast cancer xenografts in nude mice. Tumors dependent on CTFs are sensitive to inhibitors of the kinase activity but do not respond to therapeutic antibodies against HER2. Thus, the kinase domain seems necessary for the activity of HER2 CTFs and the presence of these HER2 fragments could account for the resistance to treatment with antibodies. (+info)
Research subjects with limited English proficiency: ethical and legal issues.
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In this article, we examine Institutional Review Board (IRB) policies, international guidelines, and federal regulations and guidance for dealing with Limited English Proficiency (LEP) research subjects. We show that federal and international guidance concerning this topic is insufficient, and there is considerable variation in IRB policies. While some IRBs have thorough and useful policies, others do not. Many IRBs do not provide researchers and IRB member with answers to several important questions relating to language barriers in research. We recommend that federal agencies, international organizations, IRBs, and researchers take steps to fill in the gaps in guidance and policy to help insure that LEP populations will receive equitable and ethical treatment in research. (+info)
Japanese version of the Dermatology Life Quality Index: validity and reliability in patients with acne.
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BACKGROUND: Patient-reported quality of life is strongly affected by some dermatologic conditions. We developed a Japanese version of the Dermatology Life Quality Index (DLQI-J) and used psychometric methods to examine its validity and reliability. METHODS: The Japanese version of the DLQI was created from the original (English) version, using a standard method. The DLQI-J was then completed by 197 people, to examine its validity and reliability. Some participants completed the DLQI-J a second time, 3 days later, to examine the reproducibility of their responses. In addition to the DLQI-J, the participants completed parts of the SF-36 and gave data on their demographic and clinical characteristics. Their physicians provided information on the location and clinical severity of the skin disease. RESULTS: The participants reported no difficulties in answering the DLQI-J items. Their mean age was 24.8 years, 77.2% were female, and 78.7% had acne vulgaris. The mean score of DLQI was 3.99(SD: 3.99). The responses were found to be reproducible and stable. Results of principal-component and factor analysis suggested that this scale measured one construct. The correlations of DLQI-J scores with sex or age were very poor, but those with SF-36 scores and with clinical severity were high. CONCLUSION: The DLQI-J provides valid and reliable data despite having only a small number of items. (+info)
Cross-cultural adaptation of the Burns Specific Pain Anxiety Scale--BSPAS to be used with Brazilian burned patients.
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This study aimed at translating and adapting the Burns Specific Pain Anxiety Scale--BSPAS and the Impact of Event Scale--IES into Portuguese; making available two simple, short and easily applicable instruments and describing the study participants according to their scores on the Visual Analogue Scale and the Trait-State Anxiety Inventory. The cross-cultural adaptation process involved the following steps: translation of the scales; reaching a consensus in Portuguese; evaluation by an expert committee; back-translation; obtaining a consensus in Dutch; comparing the original versions with the consensus in Dutch; semantic analysis and pretest of the Portuguese versions. The results showed that both scales present high values of internal consistency between the scale items. Participants' average pain scores were higher after bathing and wound dressing. Participants' average anxiety scores were low or medium. (+info)
Quality of life in aphasia: Greek adaptation of the stroke and aphasia quality of life scale - 39 item (SAQOL-39).
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AIM: Health-related quality of life (HRQL) measures are becoming increasingly popular in evaluating health care interventions and services. The stroke and aphasia quality of life scale-39 item (SAQOL-39) is an English questionnaire that measures HRQL in people with aphasia. There is currently no measure to assess the HRQL of Greek-speaking people with aphasia. This study began the cross-cultural adaptation of the SAQOL-39 into Greek, by translating and linguistically validating the instrument. METHODS: The Mapi approach to linguistic validation was followed. The SAQOL-39 was forward translated into Greek and back-translated into English. The pilot version was produced by comparing the forward and backward translations. The resulting instrument was then reviewed by an expert professional and pilot tested with a sample of 10 people with aphasia. RESULTS: Sixty-seven percent of back-translated items matched those in the original instrument. Only 20% of the items in the consensus version needed amendments for the pilot version. The pilot testing showed that the SAQOL-39 had good accessibility (no missing data), acceptability (maximum endorsement frequencies, MEF=or>70%; 9 out of 10 participants had no difficulty) and content validity (8 participants had nothing to add to the questionnaire). CONCLUSIONS: By employing the Mapi approach to linguistic validation, a close matching between the original and the Greek version of the SAQOL-39 was ensured. The Greek SAQOL-39 is accessible and acceptable to people with aphasia. Further research is needed on the psychometric properties of the Greek SAQOL-39 and on its appropriateness as a clinical outcome measure. (+info)
Cross-cultural validation of the Brief Social Phobia Scale for use in Portuguese and the development of a structured interview guide.
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OBJECTIVE: To present the translation and validation of the Brief Social Phobia Scale for use in Brazilian Portuguese, to develop a structured interview guide in order to systemize its use and to perform a preliminary study of inter-rater reliability. METHOD: The instrument was translated and adapted to Portuguese by specialists in anxiety disorders and rating scales. A structured interview guide was created with the aim of covering all of the items of the instrument and grouping them into six categories. Specialists in mental health evaluated the guide. These professionals also watched the videotaped interviews of patients with and without social anxiety disorders, and, based on the interview guide, they rated the scale to evaluate its reliability. RESULTS: No semantic or linguistic adjustments were needed. For the complete scale, the general evaluation showed a percentage of agreement of 0.84 and intraclass coefficient of 0.91. The mean inter-rater correlation was 0.84. CONCLUSIONS: The Portuguese-language version of the Brief Social Phobia Scale is available for use in the Brazilian population, with rather acceptable indicators of inter-rater reliability. The interview guide was useful in providing these values. Further studies are needed in order to improve the reliability and to study other psychometric properties of the instrument. (+info)
Translation into Brazilian Portuguese, cultural adaptation and validation of the oral health impact profile (OHIP-49).
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The aim of this study is to develop a Portuguese version of the OHIP-49 to be used in Brazil. The adopted methodology involves translation, back-translation, revision of the first version, cultural adaptation and evaluation of its measurement properties. The questionnaire was administered in interviews with 60 year-old and older Brazilian people. The Kendall-tau correlation coefficient was used to assess reproducibility; the Cronbach alpha coefficient was used to verify internal consistency and the Kruskal-Wallis and Mann-Whitney U tests were used to assess validity. Reproducibility was shown to be statistically significant, with coefficients ranging from 0.72 to 0.74 between dimensions of three interviews. The Cronbach alpha coefficients were 0.96 and 0.90 respectively for the dimensions of the interviews and for total items. Constructive validity, demonstrated through a comparison between the questionnaire dimensions and the clinical parameters, showed statistical significance for "presence of carious lesion" (p < 0.05). Significant correlations between similar dimensions of the OHIP-49 and the SF-36 were also identified (p < 0.05). In the present sample, the Portuguese version of the OHIP-49 presented results similar to those found in the literature and proved to be a reproducible and valid parameter for evaluating the impact of oral conditions on the quality of life of Brazilians. (+info)
An examination of the psychometric structure of the Multidimensional Pain Inventory in temporomandibular disorder patients: a confirmatory factor analysis.
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BACKGROUND: This paper seeks to analyse the psychometric and structural properties of the Multidimensional Pain Inventory (MPI) in a sample of temporomandibular disorder patients. METHODS: The internal consistency of the scales was obtained. Confirmatory Factor Analysis was carried out to test the MPI structure section by section in a sample of 114 temporomandibular disorder patients. RESULTS: Nearly all scales obtained good reliability indexes. The original structure could not be totally confirmed. However, with a few adjustments we obtained a satisfactory structural model of the MPI which was slightly different from the original: certain items and the Self control scale were eliminated; in two cases, two original scales were grouped in one factor, Solicitous and Distracting responses on the one hand, and Social activities and Away from home activities, on the other. CONCLUSION: The MPI has been demonstrated to be a reliable tool for the assessment of pain in temporomandibular disorder patients. Some divergences to be taken into account have been clarified. (+info)