Physical health and lifestyle predictors for significant cognitive impairment in community-dwelling Chinese older adults in Hong Kong

published_or_final_versio

Association between vascular risk factors and incident significant cognitive impairment in Chinese older people in Hong Kong in a six-year study

Objective: This study aimed to examine the association between vascular risk factors, namely hypertension, diabetes mellitus and hypercholesterolemia, and incident significant cognitive impairment in community-dwelling Chinese older people in Hong Kong. Methods: Community-dwelling Chinese older people aged 65 years and above who attended Nam Shan Elderly Health Centre in 2005 with no history of dementia or stroke constituted the baseline sample. Retrospective data retrieval for the presence of vascular risk factors at baseline was conducted. Annual clinical assessment on cognition was offered in the 6-year study period. Significant cognitive impairment was defined by presence of dementia in accordance with DSM-IV-TR, scoring below the cut-off point on the Cantonese version of the Mini-Mental State Examination, and / or a global Clinical Dementia Rating score of 1-3. Results: A total of 1925 subjects were recruited into our study; 161 (8.4%) subjects developed significant cognitive impairment in the 6-year study period. Subjects with incident significant cognitive impairment was older (75 vs. 73 years; Mann-Whitney U test, p < 0.001) with lower education attainment (30.4% vs. 23.9% of illiteracy; χ2 test, p = 0.06). However, there was no statistically significant difference in the point prevalence of pre-existing hypertension (χ2 test, p = 0.68), diabetes mellitus (χ2 test, p = 0.21), and hypercholesterolemia (χ2 test, p = 0.31) between subjects who developed significant cognitive impairment and those who remained cognitively stable. Interestingly, baseline pulse pressure, but not systolic or diastolic blood pressure, was found to be higher among subjects with incident significant cognitive impairment (70 mm Hg vs. 66 mm Hg; Mann-Whitney U test, p = 0.03). Conclusions: This study did not have evidence to show that hypertension, diabetes mellitus, and hypercholesterolemia were associated with incident significant cognitive impairment in the Chinese older people in Hong Kong. Further studies are needed to examine the role of pulse pressure in contributing to cognitive decline in late life.published_or_final_versio

Higher dementia incidence in older adults with type 2 diabetes and large reduction in HbA1c

BACKGROUND: although type 2 diabetes increases risk of dementia by 2-fold, whether optimizing glycemic level in late life can reduce risk of dementia remains uncertain. We examined if achieving the glycemic goal recommended by the American Diabetes Association (ADA) within a year was associated with lower risk of dementia in 6 years. METHODS: in this population-based observational study, we examined 2246 community-living dementia-free Chinese older adults with type 2 diabetes who attended the Elderly Health Centres in Hong Kong at baseline and followed their HbA1c level and cognitive status for 6 years. In line with the ADA recommendation, we defined the glycemic goal as HbA1c < 7.5%. The study outcome was incident dementia in 6 years, diagnosed according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) or Clinical Dementia Rating of 1-3. RESULTS: those with HbA1c ≥ 7.5% at baseline and HbA1c < 7.5% in 1 year were associated with higher rather than lower incidence of dementia, independent of severe hypoglycemia, glycemic variability and other health factors. Sensitivity analyses showed that a relative reduction of ≥10%, but not 5-10%, in HbA1c within a year was associated with higher incidence of dementia in those with high (≥8%) and moderate (6.5-7.9%) HbA1c at baseline. CONCLUSION: a large reduction in HbA1c could be a potential predictor and possibly a risk factor for dementia in older adults with type 2 diabetes. Our findings suggest that optimizing or intensifying glycemic control in this population requires caution

Risk of incident dementia varies with different onset and courses of depression

Background: This study aims to examine if risk of dementia differs between adult- and late-onset depression. Methods: 16,608 community-living dementia-free older adults were followed for 6 years to the outcome of incident dementia. Depression was diagnosed according to international diagnostic guidelines. Depression in adulthood or late life was categorized using age 65 as cutoff. Hazard ratio for dementia was estimated using Cox regression analysis. Results: People with depression in adulthood only did not have higher dementia incidence, suggesting those in remission from adult-onset depression are not at greater risk of dementia. Conversely, having depression in both adulthood and late life was associated with higher dementia risk, and improvement in depression in late life was associated with lower risk, suggesting persistent or recurrent lifetime depression is a risk factor for dementia. Those with depression in late life only were not associated with higher dementia risk after controlling for the longitudinal changes in depressive symptoms, consistent with late-onset depression being a prodrome of dementia. Limitations: Reverse causation is a potential limitation. This was minimized by careful ascertainment of depression and dementia cases, exclusion of individuals with suspected dementia at baseline and those who developed dementia within 3 years after baseline, and controlling for various important confounders. Conclusions: Risk of incident dementia varies with presence and resolution of depression at different ages. Further studies are needed to test whether treating adult-onset depression may prevent dementia. Older adults with a history of depression present for an extended time should be monitored for cognitive decline

TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells

The TP53induced glycolysis and apoptosis regulator (TIGAR) is the protein product of the p53 target gene, C12orf5. TIGAR blocks glycolysis and promotes cellular metabolism via the pentose phosphate pathway; it promotes the production of cellular nicotinamide adenine dinucleotide phosphate (NADPH), which leads to enhanced scavenging of intracellular reactive oxygen species, and inhibition of oxidative stressinduced apoptosis in normal cells. Our previous study identified a novel nucleoside analog that inhibited cellular growth and induced apoptosis in nasopharyngeal carcinoma (NPC) cell lines via downregulation of TIGAR expression. Furthermore, the growth inhibitory effects of cMet tyrosine kinase inhibitors were ameliorated by the overexpression of TIGAR in the NPC cell lines. These results indicate a significant role for TIGAR expression in the survival of NPCs. The present study aimed to further define the function of TIGAR expression in NPC cells. In total, 36 formalinfixed, paraffinembedded NPC tissue samples were obtained for the immunohistochemical determination of TIGAR expression. The effects of TIGAR expression on cell proliferation, NADPH production and cellular invasiveness were also assessed in NPC cell lines. Overall, TIGAR was overexpressed in 27/36 (75%) of the NPC tissues compared with the adjacent noncancer epithelial cells. Similarly, TIGAR overexpression was also observed in a panel of six NPC cell lines compared with normal NP460 hTert and Het1A cell lines. TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness of the NPC cell lines, whereas a knockdown of TIGAR expression resulted in significant inhibition of cellular growth and invasiveness. The expression of the two mesenchymal markers, fibronectin and vimentin, was increased by TIGAR overexpression, but reduced following TIGARknockdown. The present study revealed that TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness, and the maintenance of a mesenchymal phenotype, in NPC tissues.published_or_final_versio

“Cheating” In a Fast by Exercising After a Snack

As the prevalence of chronic diseases has increased, research has emerged supporting the utility of intermittent fasting in managing certain health conditions. Despite potential benefits, adhering to a fasting regimen can be difficult. PURPOSE: The purpose of this study was twofold. The first purpose was to describe how consuming a modest snack prior to exercise influences plasma glucose, beta-hydroxybutyrate and hunger in reference to fasting with and without exercise. The second purpose was to examine how exercising in a fasted state influences plasma glucose, beta-hydroxybutyrate and hunger. METHODS: A randomized crossover design with counterbalanced treatment conditions was used to compare the influence of fasting alone (control), fasting with exercise (exercise), and fasting with the addition of a snack immediately prior to exercise (snack/exercise). The effects of these interventions on beta-hydroxybutyrate levels, blood glucose, hunger, and mood were assessed. RESULTS: BHB was significantly higher in the exercise condition than control starting at 24 hrs to the end of the study (p \u3c 0.05). BHB levels between control and snack/exercise conditions were not different. Immediately after participants had exercised, blood glucose levels were higher in both the exercise and snack/exercise conditions than control (p \u3c 0.001). With the exception of one time point, there were no additional differences. In the exercise and snack/exercise conditions, hunger was significantly lower than control right after exercise (p = .0043 and p = .0003, respectively). Hunger was not different between the exercise and snack/exercise conditions at any time point. Mood was not different between conditions. CONCLUSIONS: Exercising after modest caloric intake produces BHB and glucose levels that are similar to fasting alone. Exercising without a snack briefly interrupts the fast but elevates BHB production starting around three hours after the exercise bout. Finally, mood was not different between any conditions and calls into question the assumption that a snack/exercise fasting protocol is in fact easier to adhere to

Sexualidade da pessoa com deficiência intelectual - Atitudes de pais e profissionais

Dissertação de Mestrado em Psicologia Educacional, apresentada ao ISPA - Instituto UniversitárioTendo em conta que as atitudes dos pais e profissionais face à sexualidade das pessoas com deficiência intelectual têm um papel preponderante na disponibilização de oportunidades de vivências e experiências sexuais e na passagem de informação correcta acerca da sexualidade (Brown & Pirtle, 2008), o presente estudo pretende conhecer e analisar as atitudes e necessidades que ambos têm, bem como verificar se existem diferenças estatisticamente significativas entre elas. Tendo sido utilizada uma abordagem mista através da utilização do questionário ASQ-ID- Attitudes to Sexuality Questionnaire (Individuals with an Intellectual Disability) e de uma entrevista semi-estruturada, o presente estudo contou com uma amostra de 130 participantes (80 profissionais e 50 pais), dos quais três mães e três profissionais foram entrevistados. Os resultados obtidos confirmaram a nossa hipótese de que existem diferenças estatisticamente significativas nas atitudes dos pais e profissionais, demonstrando que os profissionais têm atitudes mais liberais. Através das entrevistas, verificámos que os profissionais têm necessidades de formação no que toca à capacidade para intervirem de forma adequada nas várias manifestações sexuais dos seus clientes, tendo sido enfatizada a necessidade do envolvimento da família neste processo, a consideração das diferenças individuais e a promoção de contextos favoráveis nas instituições para as vivências e experiências sexuais desta população. Por fim, atestou-se ainda através do discurso dos inquiridos, a falta de um consenso dentro das instituições acerca daquilo que devem fazer em situações onde os clientes necessitam de resposta.ABSTRACT: Given that the attitudes of parents and professionals towards sexuality of people with intellectual disabilities have a role in providing opportunities for experiences and sexual experiences and pass correct information about sexuality (Brown & Pirtle, 2008), this study seeks to examine and analyze the attitudes and needs that both have and see if there are statistically significant differences between them. Having used a mixed approach by using the questionnaire ASQ-ID-Attitudes to Sexuality Questionnaire (Individuals with an Intellectual Disability) and a semi-structured interview, this study involved a sample of 130 participants (80 professionals and 50 parents), of which three mothers and three professionals were interviewed. The results confirmed our hypothesis that there are significant differences in the attitudes of parents and professionals, demonstrating that professionals have more liberal attitudes. Through the interviews, we found that professionals have training needs in relation to the ability to intervene appropriately in various sexual manifestations of its customers, having emphasized the need to involve the family in this process, consideration of individual differences and promoting favorable contexts in institutions for sexual experiences and the experiences of this population. Finally, it is also attested by the discourse of the respondents, the lack of consensus within institutions about what they should do in situations where customers need to be answered

Preclinical activity of gefitinib in non-keratinizing nasopharyngeal carcinoma cell lines and biomarkers of response

This study evaluated the preclinical activity and molecular predictors of response to gefitinib (Iressa®, Astra Zeneca Inc, UK) in nasopharyngeal carcinoma (NPC). The activity of gefitinib was evaluated in four human NPC cell lines-HK1, HONE-1, CNE2, C666-1. A representative gefitinib-sensitive (HK1, IC50 = 250 nM) and gefitinib-resistant cell line (HONE-1, IC 50 > 15 μM) were selected and compared for expression of epidermal growth factor receptor (EGFR) and related ligands, and activation of downstream proteins. Gefitinib induced G1 cycle arrest, apoptosis and inhibited cell invasion more significantly in HK1 than HONE-1 cells. HK1 expressed higher levels of p-EGFR, lower p-AKT and phospho-signal transducer and activator of transcription 3 (p-STAT3) than other cell lines. EGFR gene was found to be amplified in HK1. Gefitinib at IC50 concentrations significantly suppressed EGF-induced activation of p-EGFR, phospho-mitogen-activated protein kinase (p-MAPK) and p-STAT3, but p-AKT showed persistent activation in HK1 and HONE-1 cells. There was no difference in EGFR-ligand expression between the 4 NPC cell lines. In NPC samples derived from non-responders to gefitinib, 50% and 60% showed cytoplasmic and nuclear pi-EGFR expression, respectively, and 33% showed p-AKT expression. EGFR or KRAS mutations were not detected. This study suggests that most NPC cell lines are intrinsically resistant to gefitinib (except HK1 cells), and further studies are needed to confirm whether EGFR gene amplification and persistent AKT activation may influence response to gefitinib in NPC. © 2009 Springer Science+Business Media, LLC.published_or_final_versionSpringer Open Choice, 01 Dec 201

Clinical significance of frizzled homolog 3 protein in colorectal cancer patients

2013-2014 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Gene mapping of familial amyotrophic lateral sclerosis

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by gradual death of motor neurons in cerebral cortex, brain stem, and spinal cord. The pathogenetic mechanism remains unclear for the vast majority of cases. About 10% of ALS cases are familial (FALS). Cu/Zn superoxide dismutase (SOD1) gene accounts for about 10% of autosomal dominant FALS and the gene(s) responsible for the rest of ALS/ FALS remain(s) to be found. METHOD: We recruited a large Chinese kindred without SOD1 mutation for linkage analysis. Peripheral blood samples were collected and DNA were extracted from peripheral lymphocyte. We screened the family with ~ 400 polymorphic microsatellite markers. The genotyping data were subjected to model-based and model-free linkage analysis. RESULT: Using MLINK of LINKAGE (Ver 5.2) package, we found a maximum LOD score of 4.357, ?[m=f]=0.0 at a microsatellite marker located at distal long arm of chromosome 8. Multipoint analysis by GENEHUNTER (Ver 1.2) revealed a maximum multipoint LOD score of 3.909 and NPL score 9.209. Haplotype analyses revealed a critical region which spanned 10.18-cM on chromosome 8. CONCLUSION: We identified a 10.18-cM critical FALS region on chromosome 8. Further analyses using positional cloning and candidate gene approach are indicated to delineate the underlying genetic defect for FALS in this family.published_or_final_versio