bluuebunny/crossref_metadata_2025_split huggingface dataset:
Congenital heart disease in 111 225 births in Belgium: birth prevalence, treatment and survival in the 21st century
Authors: Moons Philip , Sluysmans Thierry , De Wolf Daniel , Massin Martial , Suys Bert , Benatar Abraham , Gewillig Marc 
Published: December 2008

AbstractAim: To investigate the birth prevalence, treatment modalities and short‐term survival of children with congenital heart disease who were born in 2002.Methods: We undertook a retrospective review of medical records of all patients who were born in 2002, and were diagnosed, treated and/or followed‐up in one of the seven‐paediatric cardiology programmes in Belgium.Results: In 111 225 births, 921 children with congenital heart disease were detected, yielding a birth prevalence of 8.3 per 1000. The most frequently occurring conditions were ventricular septal defects (VSDs) (33%), ostium secundum atrial septal defects (18%) and pulmonary valve abnormalities (10%). Thirty‐nine percent of the children either had a cardiosurgical operation or catheter intervention. In this study, 4% of the children died. The actuarial survival at 6 months and 1 year of age was 97% and 96%, respectively and remained stable after then. Compared to other heart defects, mortality was higher in univentricular physiology, pulmonary atresia with VSD, left ventricle outflow obstruction and tetralogy of Fallot.Conclusion: Survival of congenital heart disease is excellent and continued to improve in the early 21st century. New therapeutic options are increasingly used. This study provides baseline data for the longitudinal follow‐up of this cohort.
Correlation between severity of mucopolysaccharidoses and combination of the residual enzyme activity and efficiency of glycosaminoglycan synthesis
Authors: Piotrowska Ewa , Jakóbkiewicz‐Banecka Joanna , Tylki‐Szymańska Anna , Czartoryska Barbara , Węgrzyn Alicja , Węgrzyn Grzegorz 
Published: December 2008

AbstractAim: To develop a method for prediction of severity and clinical course of mucopolysaccharidoses (MPS), a group of inherited metabolic diseases.Methods: Various biochemical and clinical parameters (including estimation of the level of clinical severity, presence of specific mutations, residual enzyme activity, urinary glycosaminoglycan (GAG) excretion, storage of GAG in fibroblasts and efficiency of GAG synthesis) of patients suffering from MPS types II, IIIA and IIIB were determined. Correlations between genetic, biochemical and clinical parameters were tested.Results: We found that efficiency of GAG synthesis may contribute to the level of severity of MPS. It appears that (i) combination of low or average efficiency of GAG synthesis and the presence of residual activity of the enzyme is responsible for an attenuated phenotype, (ii) a lack of detectable residual enzyme activity causes a severe phenotype, irrespective of the efficiency of GAG synthesis and (iii) high efficiency of GAG synthesis leads to a severe phenotype, even if residual enzyme activity is detected. This correlation was found to be valid in 15 out of 17 patients tested.Conclusion: Analysis of efficiency of GAG synthesis and residual activity of the enzyme may be considered for prediction of severity of MPS patients’ clinical phenotypes.
SOCIAL ROLES FOR OLDER WOMEN
Authors: Pilcher Ann Jackson 
Published: December 2008

AbstractThis article addresses a concern with the lack of real life positions for older adults. It suggests that, unlike other real life positions, older adult has not been sufficiently defined in a normative sense. Consequently there are few established or structural roles for the aged. Four broad social role categories are proposed for older adults and possible activities described within each. Also identified are the particular theories on ageing which support each role category, and the implications of each are discussed for social work practice.
AUSTRALIAN LITERATURE IN SOCIAL GERONTOLOGY: A CONTENT ANALYSIS OF TRENDS SINCE 1980
Authors: Minichiello V. , Alexander L. , Jones D. 
Published: December 2008

AbstractAustralian social gerontology entered a new stage of development in the 1980s with the establishment of a number of research projects and educational programmes. The aim of this paper is to make a systematic review of the recent research literature and identify research achievements and knowledge gaps. A total of 158 research articles published in overseas and Australian academic journals are reviewed in terms of source of publication, author institutional affiliation, content and theoretical orientation, and research approaches. The findings show a steady increase In the volume of published material but a number of theoretical and methodological issues need further analysis. Notable gaps are in the psychological aspects of ageing, research by allied health professionals, studying ageing from a political economy perspective, and multi‐disciplinary and multi‐method approaches.
TRY, TRY AGAIN: IMPROVING OLDER ADULTS‘ MEMORY THROUGH PRACTICE
Authors: Luszcz M. , Hinton M. 
Published: December 2008

ABSTRACTOlder, relative to younger, adults may be disadvantaged on typical laboratory memory tasks because of limited experience with them. This study provided task experience over four serial memory trials, on the expectation that practice would be more beneficial for older (mean age 73) than younger (mean age 23) adults, giving them the opportunity to gain task knowledge and devise strategies to enhance memory. Results confirmed these hypotheses. Although older adults remembered less throughout the trials, their memory and strategies improved. Individual differences in strategy use and educational background also predicted performance. Findings challenge the assumption that older adults cannot actively improve their memory.
INTERGENERATIONAL HELP GIVING AND RECEIVING: ATTITUDES OF SIX AUSTRALIAN COMMUNITIES
Authors: Legge V. , Westbrook M. 
Published: December 2008

ABSTRACTA survey of 371 health practitioners from the Arabic speaking, Chinese, German, Greek, Italian and Anglo Australian communities investigated perceptions of the help aged people within these communities receive from, and give to, their families as well as community attitudes regarding such transfers. Positive and negative aspects of intergenerational relationships within the communities were also examined. Highly significant community differences were observed in responses to 22 of the 29 questions asked.
A Psychogeriatric Outreach Service to Nursing Homes in Sydney
Authors: Draper Brian , Meares Susanne , McIntosh Helen 
Published: December 2008

Objective: To describe nursing home referrals to a multidisciplinary psychogeriatric outreach service.Methods: Retrospective case note audit of all nursing home referrals to a psychogeriatric outreach service in Sydney during 1996.Results: Of 106 referrals (mean age 76.9 years) from 22 nursing homes, 101 (95%) were assessed in the home. Behavioural problems were identified in 87 referrals (82%), usually being associated with chronic organic brain syndromes including dementia (n = 75, 86%). Aggressive behaviours (45%), agitation (32%), uncooperativeness (17%) and vocally disruptive behaviour (16%) were the most frequently identified problems. Depression was diagnosed in 33 referrals (31%), often comorbid with dementia (n = 16). Multiple diagnoses were present in 58 (55%) referrals. The most frequent treatment recommendations related to the use of nursing interventions (73%), psychotropic medication (70%), behavioural programs (29%) and family involvement (29%). Admission to the acute psychogeriatric ward occurred in 18 cases (17%).Conclusion: Psychogeriatric services should provide adequately staffed outreach teams to nursing homes.
The impact of age on antithrombotic use in elderly patients with non‐valvular atrial fibrillation
Authors: Bajorek B.V. , Krass I. , Ogle S.J. , Duguid M.J. , Shenfield G.M. 
Published: December 2008

Aim of study: To investigate the use of antithrombotic therapy in elderly patients with atrial fibrillation (AF). Methods: Data were collected retrospectively from the medical records of 262 AF patients >65 years, who were admitted to a Sydney teaching hospital over a 12‐month period.Results: Overall, 202 (79%) patients were discharged on some antithrombotic therapy. Patients <80 years were as likely to receive antithrombotic therapy as those <80 years (75.8% versus 81.9%, P=0.23), but a significantly lower proportion received warfarin than did those <80 years (25.5% versus 61.5%, P < 0.0001). Definite contraindications to anticoagulation were a significant influence on antithrombotic agent selection (P=0.04), but multivariate analysis indicated that ‘old age’ was the largest contributing factor: patients >80 years were 5.46 times more likely to receive aspirin in preference to warfarin than their younger counterparts (P<0.0001).Conclusion: Warfarin is being withheld in AF patients ≥80 years for reasons other than recognised contraindications and is, therefore, potentially underutilised in the target elderly population. Further studies are necessary to determine whether this is appropriate.
Crushing or altering medications: what's happening in residential aged‐care facilities?
Authors: Paradiso L M. , Roughead E. E. , Gilbert A. L. , Cosh D. , Nation R. L. , Barnes L. , Cheek J. , Ballantyne A. 
Published: December 2008

Objectives: To determine the extent to which medications are altered or crushed prior to administration to residents of aged‐care facilities, the medications involved and the methods employed.Method: Observation of medication rounds at a representative sample of South Australian aged‐care facilities.Results: At least one medication was altered in 34% of the 1207 occasions of medication administration observed within ten residential aged‐care facilities in South Australia. 17% of medicines which were altered, had the potential, because of the alteration, to cause increased toxicity, decreased efficacy, unpalatability, safety or stability concerns. The process of altering medicines was found to be problematic. In all occasions where more than one medicine was altered, they were crushed together within the same vessel. In 59% of occasions where the same vessel was shared amongst residents, the vessel was not cleaned between residents and in 70% of cases where medicines were altered, spillage, and thus potential loss of dosage, was observed.Conclusions: Guidelines outlining best practice for the alteration and administration of medications in residential aged‐care facilities are required. In addition, accurate and up‐to‐date information needs to be available for carers and health practitioners in residential aged‐care facilities detailing those medications which should not be altered, the potential risks of alternating medicines and other options.
Water neutrality: A first quantitative framework for investing in water in South Africa
Authors: Nel D.C. , Marais C , Blignaut J.N. 
Published: December 2008

AbstractThe concept of water neutrality, based on its carbon equivalent, was first coined during the World Summit on Sustainable Development in 2002. Since then the term has been loosely used, with little quantitative validation. Here we present a first quantitative framework for a water‐neutral scheme that allows a private water user to balance its water account through both demand‐ and supply‐side interventions. Such innovative voluntary mechanisms can provide benefits in a chronically water stressed and developing country, such as South Africa. This scheme seeks to harness private sector investment in water security, by allowing investors to balance quantitatively their water account based on sound scientific rationale. Investors are required to engage in a three‐step process of: reviewing their water usage, implementing a reduction strategy, and replenishment of water to hydrological systems through the investment in watershed services, equivalent to their water usage. Initially, the scheme allows participants to replenish quantitatively their water usage through investment in the clearing of water‐intensive invasive alien plants. The project, however, encourages the innovation and development of further quantitative mechanisms for investing in watershed services, and proposes an operational model for the promotion of a water‐neutral market in South Africa.
Literary appreciation for medical students at International Medical University, Kuala Lumpur: the learner’s experience
Authors: DMani S S 
Published: December 2008

Background:A literature in medicine module was offered to second-year undergraduate medical students at the International Medical University. The general aim of this educational initiative was to enhance the selected medical students' understanding of medical practice through literature.Objective:This study was carried out to discover the selected students' learning experience through the literature in medicine module.Methods:A qualitative study was conducted by using two different semi-structured questionnaires which were administered respectively at the beginning and end of the course. The data were explored using grounded theory and by coding responses for emerging themes.Results:Students identified the following key benefits that enhanced their learning experience: “opportunity to identify, explore and develop self”; “gained patient's perspective of suffering and emotional needs”; “abilities to understand the mechanics and influences of society”.Conclusion:The literature in medicine selective has directed the selected students towards developing self, reflecting on the profession and understanding the dynamics of society. By diversifying the design and delivery of the module, the students have gained a holistic medical education. Therefore, this module has the potential for development, exploration and implementation within this region.
ODC1 Is a Critical Determinant of MYCN Oncogenesis and a Therapeutic Target in Neuroblastoma
Authors: Hogarty Michael D. , Norris Murray D. , Davis Kimberly , Liu Xueyuan , Evageliou Nicholas F. , Hayes Candace S. , Pawel Bruce , Guo Rong , Zhao Huaqing , Sekyere Eric , Keating Joanna , Thomas Wayne , Cheng Ngan Ching , Murray Jayne , Smith Janice , Sutton Rosemary , Venn Nicola , London Wendy B. , Buxton Allen , Gilmour Susan K. , Marshall Glenn M. , Haber Michelle 
Published: December 2008

Abstract
Neuroblastoma is a frequently lethal childhood tumor in which MYC gene deregulation, commonly as MYCN amplification, portends poor outcome. Identifying the requisite biopathways downstream of MYC may provide therapeutic opportunities. We used transcriptome analyses to show that MYCN-amplified neuroblastomas have coordinately deregulated myriad polyamine enzymes (including ODC1, SRM, SMS, AMD1, OAZ2, and SMOX) to enhance polyamine biosynthesis. High-risk tumors without MYCN amplification also overexpress ODC1, the rate-limiting enzyme in polyamine biosynthesis, when compared with lower-risk tumors, suggesting that this pathway may be pivotal. Indeed, elevated ODC1 (independent of MYCN amplification) was associated with reduced survival in a large independent neuroblastoma cohort. As polyamines are essential for cell survival and linked to cancer progression, we studied polyamine antagonism to test for metabolic dependence on this pathway in neuroblastoma. The Odc inhibitor α-difluoromethylornithine (DFMO) inhibited neuroblast proliferation in vitro and suppressed oncogenesis in vivo. DFMO treatment of neuroblastoma-prone genetically engineered mice (TH-MYCN) extended tumor latency and survival in homozygous mice and prevented oncogenesis in hemizygous mice. In the latter, transient Odc ablation permanently prevented tumor onset consistent with a time-limited window for embryonal tumor initiation. Importantly, we show that DFMO augments antitumor efficacy of conventional cytotoxics in vivo. This work implicates polyamine biosynthesis as an arbiter of MYCN oncogenesis and shows initial efficacy for polyamine depletion strategies in neuroblastoma, a strategy that may have utility for this and other MYC-driven embryonal tumors. [Cancer Res 2008;68(23):9735–45]
A Polymorphism in the TC21 Promoter Associates with an Unfavorable Tamoxifen Treatment Outcome in Breast Cancer
Authors: Rokavec Matjaž , Schroth Werner , Amaral Sandra M.C. , Fritz Peter , Antoniadou Lydia , Glavač Damjan , Simon Wolfgang , Schwab Matthias , Eichelbaum Michel , Brauch Hiltrud 
Published: December 2008

Abstract
Tamoxifen therapy is a standard in the treatment of estrogen receptor (ER)-positive breast cancer; however, its efficacy varies widely among patients. In addition to interpatient differences in the tamoxifen-metabolizing capacity, there is growing evidence that crosstalk between ER and growth factor signaling contributes to tamoxifen resistance. We focused on TC21, a member of the Ras superfamily, to investigate the influence of the TC21 −582C&gt;T promoter polymorphism on TC21 expression and treatment outcome. Immunohistochemical analyses of breast tumors revealed a higher TC21 expression in ER-negative compared with ER-positive tumors. Expression in ER-positive tumors was higher in carriers of the T allele in an allele dose–dependent manner. Quantitative real-time PCR analyses showed that TC21 mRNA expression is decreased after transfection of ERα in ER-negative breast cancer cells MDA-MB-231, UACC893, and BT-20. In MCF7 ER-positive cells, TC21 expression decreased with 17β-estradiol treatment and increased after treatment with tamoxifen metabolites, 4-OH-tamoxifen, or endoxifen. In patients treated with adjuvant mono tamoxifen, high cytoplasmic TC21 tumor expression or the carriership of the −582T allele conferred increased recurrence rates [n = 45: hazard ratio (HR), 3.06; 95% confidence interval (95% CI), 1.16–8.05; n = 206: HR, 1.79; 95% CI, 1.08–3.00, respectively]. A combined analysis with the data of the known tamoxifen predictor CYP2D6 showed an improvement of outcome prediction compared with CYP2D6 or TC21 genotype status alone (per mutated gene HR, 2.35; 95% CI, 1.34–4.14). Our functional and patient-based results suggest that the TC21 −582C&gt;T polymorphism improves prediction of tamoxifen treatment outcome in breast cancer. [Cancer Res 2008;68(23):9799–808]
ICAM-1 Has a Critical Role in the Regulation of Metastatic Melanoma Tumor Susceptibility to CTL Lysis by Interfering with PI3K/AKT Pathway
Authors: Hamaï Ahmed , Meslin Franck , Benlalam Houssem , Jalil Abdelali , Mehrpour Maryam , Faure Florence , Lecluse Yann , Vielh Philipe , Avril Marie-Françoise , Robert Caroline , Chouaib Salem 
Published: December 2008

Abstract
Human primary melanoma cells (T1) were found to be more susceptible to lysis by a Melan-A/MART-1–specific CTL clone (LT12) than their metastatic derivative (G1). We show that this differential susceptibility does not involve antigen presentation by target cells, synapse formation between the metastatic target and CTL clone, or subsequent granzyme B (GrB) polarization. Although PI-9, an inhibitor of GrB, was found to be overexpressed in metastatic G1 cells, knockdown of the PI-9 gene did not result in the attenuation of G1 resistance to CTL-induced killing. Interestingly, we show that whereas T1 cells express high levels of intercellular adhesion molecule-1 (ICAM-1), a dramatically reduced expression was noted on G1 cells. We also showed that sorted ICAM-1+ G1 cells were highly sensitive to CTL-induced lysis compared with ICAM-1− G1 cells. Furthermore, incubation of metastatic G1 cells with IFN-γ resulted in the induction of ICAM-1 and the potentiation of their susceptibility to lysis by LT12. More importantly, we found that the level of ICAM-1 expression by melanoma cells correlated with decreased PTEN activity. ICAM-1 knockdown in T1 cells resulted in increased phosphorylation of PTEN and the subsequent activation of AKT. We have additionally shown that inhibition of the phosphatidylinositol (3,4,5)-triphosphate kinase (PI3K)/AKT pathway by the specific inhibitor wortmannin induced a significant potentiation of susceptibility of G1 and ICAM-1 small interfering RNA–treated T1 cells to CTL-induced lysis. The present study shows that a shift in ICAM-1 expression, which was associated with an activation of the PI3K/AKT pathway, can be used by metastatic melanoma cells to escape CTL-mediated killing. [Cancer Res 2008;68(23):9854–64]
Evidence that Resistance to Nilotinib May Be Due to BCR-ABL, Pgp, or Src Kinase Overexpression
Authors: Mahon François-Xavier , Hayette Sandrine , Lagarde Valérie , Belloc Francis , Turcq Béatrice , Nicolini Franck , Belanger Coralie , Manley Paul W. , Leroy Cédric , Etienne Gabriel , Roche Serge , Pasquet Jean-Max 
Published: December 2008

Abstract
Targeting the tyrosine kinase activity of Bcr-Abl is an attractive therapeutic strategy in chronic myeloid leukemia (CML) and in Bcr-Abl–positive acute lymphoblastic leukemia. Whereas imatinib, a selective inhibitor of Bcr-Abl tyrosine kinase, is now used in frontline therapy for CML, second-generation inhibitors of Bcr-Abl tyrosine kinase such as nilotinib or dasatinib have been developed for the treatment of imatinib-resistant or imatinib-intolerant disease. In the current study, we generated nilotinib-resistant cell lines and investigated their mechanism of resistance. Overexpression of BCR-ABL and multidrug resistance gene (MDR-1) were found among the investigated mechanisms. We showed that nilotinib is a substrate of the multidrug resistance gene product, P-glycoprotein, using verapamil or PSC833 to block binding. Up-regulated expression of p53/56 Lyn kinase, both at the mRNA and protein level, was found in one of the resistant cell lines and Lyn silencing by small interfering RNA restored sensitivity to nilotinib. Moreover, failure of nilotinib treatment was accompanied by an increase of Lyn mRNA expression in patients with resistant CML. Two Src kinase inhibitors (PP1 and PP2) partially removed resistance but did not significantly inhibit Bcr-Abl tyrosine kinase activity. In contrast, dasatinib, a dual Bcr-Abl and Src kinase inhibitor, inhibited the phosphorylation of both BCR-ABL and Lyn, and induced apoptosis of the Bcr-Abl cell line overexpressing p53/56 Lyn. Such mechanisms of resistance are close to those observed in imatinib-resistant cell lines and emphasize the critical role of Lyn in nilotinib resistance. [Cancer Res 2008;68(23):9809–16]
SMAD6 Contributes to Patient Survival in Non–Small Cell Lung Cancer and Its Knockdown Reestablishes TGF-β Homeostasis in Lung Cancer Cells
Authors: Jeon Hyo-Sung , Dracheva Tatiana , Yang Sei-Hoon , Meerzaman Daoud , Fukuoka Junya , Shakoori Abbas , Shilo Konstantin , Travis William D. , Jen Jin 
Published: December 2008

Abstract
The malignant transformation in several types of cancer, including lung cancer, results in a loss of growth inhibition by transforming growth factor-β (TGF-β). Here, we show that SMAD6 expression is associated with a reduced survival in lung cancer patients. Short hairpin RNA (shRNA)–mediated knockdown of SMAD6 in lung cancer cell lines resulted in reduced cell viability and increased apoptosis as well as inhibition of cell cycle progression. However, these results were not seen in Beas2B, a normal bronchial epithelial cell line. To better understand the mechanism underlying the association of SMAD6 with poor patient survival, we used a lentivirus construct carrying shRNA for SMAD6 to knock down expression of the targeted gene. Through gene expression analysis, we observed that knockdown of SMAD6 led to the activation of TGF-β signaling through up-regulation of plasminogen activator inhibitor-1 and phosphorylation of SMAD2/3. Furthermore, SMAD6 knockdown activated the c-Jun NH2-terminal kinase pathway and reduced phosphorylation of Rb-1, resulting in increased G0-G1 cell arrest and apoptosis in the lung cancer cell line H1299. These results jointly suggest that SMAD6 plays a critical role in supporting lung cancer cell growth and survival. Targeted inactivation of SMAD6 may provide a novel therapeutic strategy for lung cancers expressing this gene. [Cancer Res 2008;68(23):9686–92]