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Angeliki Bogosian Rona Moss‐Morris Felicity L. Bishop Julie Hadwin 《British journal of health psychology》2011,16(2):430-444
Objectives. The aim of this study was to explore how adolescents with a parent with multiple sclerosis (MS) adjust to their parents' illness. Design. We used an inductive qualitative approach with open ended questions as this was appropriate to facilitate the development of a broad and child‐centred understanding of how adolescents adjust and which resources they use to cope with the challenges that are associated with parental MS. Methods. Fifteen semi‐structured face‐to‐face interviews were conducted. Interviews were audiotaped, transcribed, and analysed using inductive thematic analysis. Results. Adolescents described both positive and negative experiences related to having a parent with MS. Benefits to having a parent with MS included reports of feeling more empathetic to others and more grown‐up. Negative impacts included family tension, less time to spend with friends, and worries about the future. The support from the well parent, siblings, and friends were found to facilitate adolescents' adjustment. Adolescents assuming a parenting role and illness characteristics, such as illness deterioration, relapses and fatigue, challenged adolescents' adjustment to having a parent with MS. Conclusions. Some adolescents described adjusting well to having a parent with MS, while others appeared to have more difficulty. Whilst the severity of the parent's deterioration and symptoms appeared to play a role in adjustment, other potentially modifiable factors such as the lack of well parent's support, adolescents' increased parenting responsibilities, and family tension also posed barriers to adolescents' adjustment. Support interventions may be helpful for vulnerable adolescents, which consider both family and individual factors. 相似文献
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995.
Namjou B Kothari PH Kelly JA Glenn SB Ojwang JO Adler A Alarcón-Riquelme ME Gallant CJ Boackle SA Criswell LA Kimberly RP Brown E Edberg J Stevens AM Jacob CO Tsao BP Gilkeson GS Kamen DL Merrill JT Petri M Goldman RR Vila LM Anaya JM Niewold TB Martin J Pons-Estel BA Sabio JM Callejas JL Vyse TJ Bae SC Perrino FW Freedman BI Scofield RH Moser KL Gaffney PM James JA Langefeld CD Kaufman KM Harley JB Atkinson JP 《Genes and immunity》2011,12(4):270-279
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors have a role. Rare mutations in the TREX1 gene, the major mammalian 3'-5' exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurological condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. A total of 40 single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene, were evaluated in ~8370 patients with SLE and ~7490 control subjects. Stringent quality control procedures were applied, and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P-values, false-discovery rate q values, and odds ratios (OR) with 95% confidence intervals (CI) were calculated. The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient, whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (minor allele frequency (MAF)>10%) revealed a relatively common risk haplotype in European SLE patients with neurological manifestations, especially seizures, with a frequency of 58% in lupus cases compared with 45% in normal controls (P=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (P=2.99E-13, OR=5.2, 95% CI=3.18-8.56). Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis. 相似文献
996.
Sarah B Brien Felicity L Bishop Kirsty Riggs David Stevenson Victoria Freire George Lewith 《The British journal of general practice》2011,61(583):e89-e96
Background
Complementary and alternative medicine (CAM) is popular with patients, yet how patients use CAM in relation to orthodox medicine (OM) is poorly understood.Aim
To explore how patients integrate CAM and OM when self-managing chronic illness.Design of study
Qualitative analysis of interviews.Method
Semi-structured interviews were conducted with individuals attending private CAM practices in the UK, who had had a chronic benign condition for 12 months and were using CAM alongside OM for more than 3 months. Patients were selected to create a maximum variation sample. The interviews were analysed using framework analysis.Results
Thirty five patient interviews were conducted and seven categories of use were identified: using CAM to facilitate OM use; using OM to support long-term CAM use; using CAM to reduce OM; using CAM to avoid OM; using CAM to replace OM; maximising relief using both CAM and OM; and returning to OM. Participants described initiating CAM use following a perceived lack of suitable orthodox treatment. Participants rejecting OM for a specific condition never totally rejected OM in favour of CAM.Conclusion
Patients utilise CAM and OM in identifiably different ways, individualising and integrating both approaches to manage their chronic conditions. To support patients and prevent potential adverse interactions, open dialogue between patients, OM practitioners, and CAM practitioners must be improved. 相似文献997.
998.
Visnyei K Onodera H Damoiseaux R Saigusa K Petrosyan S De Vries D Ferrari D Saxe J Panosyan EH Masterman-Smith M Mottahedeh J Bradley KA Huang J Sabatti C Nakano I Kornblum HI 《Molecular cancer therapeutics》2011,10(10):1818-1828
Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells among which a tumor-initiating and treatment-resistant subpopulation, here termed GBM stem cells, have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GBM stem cells. The paradigm uses a tissue culture model to enrich for GBM stem cells derived from human GBM resections and combines a phenotype-based screen with gene target-specific screens for compound identification. We used 31,624 small molecules from 7 chemical libraries that we characterized and ranked based on their effect on a panel of GBM stem cell-enriched cultures and their effect on the expression of a module of genes whose expression negatively correlates with clinical outcome: MELK, ASPM, TOP2A, and FOXM1b. Of the 11 compounds meeting criteria for exerting differential effects across cell types used, 4 compounds showed selectivity by inhibiting multiple GBM stem cells-enriched cultures compared with nonenriched cultures: emetine, n-arachidonoyl dopamine, n-oleoyldopamine (OLDA), and n-palmitoyl dopamine. ChemBridge compounds #5560509 and #5256360 inhibited the expression of the 4 mitotic module genes. OLDA, emetine, and compounds #5560509 and #5256360 were chosen for more detailed study and inhibited GBM stem cells in self-renewal assays in vitro and in a xenograft model in vivo. These studies show that our screening strategy provides potential candidates and a blueprint for lead compound identification in larger scale screens or screens involving other cancer types. 相似文献
999.
AIMS: To assess: (1) the prevalence of reporting of atypical ductal hyperplasia (ADH) and intraductal atypia of uncertain significance (AUS) in a series of core biopsies from mammographically detected lesions, (2) the proportion of cases where excision revealed breast carcinoma, and (3) whether any diagnoses should be revised on review. METHODS: Breast core biopsy reports from the Sir Charles Gairdner Hospital Breast Assessment Centre for the years 1999-2000 were retrieved. Slides from cases reported as ADH or AUS were reviewed as well as slides from the excision biopsies. RESULTS: There were 1048 core biopsies from 911 women. Breast carcinoma was diagnosed in 197 samples (18.8%) including 88 with invasive carcinoma (8.4%), 109 with ductal carcinoma in situ (DCIS) (10.4%). Three biopsies (0.3%) 'suspicious' of invasive carcinoma proved to be so. Of 52 samples (5.0%) with a diagnosis of ADH or AUS, 46 were excised, showing seven invasive carcinomas, 15 DCIS, 11 ADH, two lobular carcinoma in situ (LCIS), nine fibrocystic change (FCC), one mucocoele-like lesion and one fibroadenoma. The 22 malignancies represented 47.8% of the excised lesions. On review, seven of the 52 original core diagnoses were downgraded to benign hyperplasia. Five underwent excision, revealing two FCC, one complex sclerosing lesion, and two incidental lesions unrelated to the mammographic abnormality, including a microscopic tubular carcinoma and a focus of LCIS. In one case reviewed as unsatisfactory, excision showed invasive carcinoma. Lesions of particular interest included a case of high-grade DCIS with local regression in the core biopsy (so-called 'bumt out DCIS'), and one case diagnosed on excision as micropapillary ADH, where the review diagnosis was micropapillary DCIS. CONCLUSIONS: ADH and AUS were reported in 5.0% of biopsies. There was a high rate of carcinoma (47.8%) in subsequent excisions. Very few diagnoses were revised on review. Current protocols for excision of lesions with a 14-gauge core biopsy diagnosis of ADH/AUS appear justified. Literature review suggests that vacuum-assisted core sampling with 11-gauge needles will not remove the need for excision. Further study of local regression of DCIS and micropapillary lesions will be worthwhile. 相似文献
1000.
Benjamin F. Bruner Joel M. Guthridge Rufei Lu Gabriel Vidal Jennifer A. Kelly Julie M. Robertson Diane L. Kamen Gary S. Gilkeson Barbara R. Neas Morris Reichlin R. Hal Scofield John B. Harley Judith A. James 《Arthritis \u0026amp; Rheumatology》2012,64(11):3677-3686