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1.
J Prev Alzheimers Dis ; 11(1): 22-37, 2024.
Article in English | MEDLINE | ID: mdl-38230714

ABSTRACT

Many risk factors for dementia, identified from observational studies, are potentially modifiable. This raises the possibility that targeting key modifiable dementia risk factors may reduce the prevalence of dementia, which has led to the development of dementia risk reduction and prevention strategies, such as intervention trials or dementia prevention guidelines. However, what has rarely been considered in the studies that inform these strategies is the extent to which modifiable dementia risk factors can (1) be identified by individuals, and (2) be readily modified by individuals. Characteristics of modifiable dementia risk factors such as readiness of identification and targeting, as well as when they should be targeted, can influence the design, or success of strategies for reducing dementia risk. This review aims to develop a framework for classifying the degree of modifiability of dementia risk factors for research studies. The extent to which these modifiable dementia risk factors could be modified by an individual seeking to reduce their dementia risk is determined, as well as the resources that might be needed for both risk factor identification and modification, and whether modification may be optimal in early-life (aged <45 years), midlife (aged 45-65 years) or late-life (aged >65 years). Finally, barriers that could influence the ability of an individual to engage in risk factor modification and, ultimately, dementia risk reduction are discussed.


Subject(s)
Dementia , Risk Reduction Behavior , Humans , Risk Factors , Research Design , Prevalence , Dementia/epidemiology , Dementia/prevention & control , Dementia/etiology
2.
Article in English | MEDLINE | ID: mdl-38085524

ABSTRACT

BACKGROUND AND OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory itchy skin condition. Genomic- and epigenetic wide association studies provide insights into the genetic susceptibility and potential underlying disease pathogenesis. This study sought to functionally characterise an AD-associated single nucleotide polymorphism (SNP) located deep intronic of the tight junction protein 2 (TJP2) gene (9q21.11 locus), identified through a genome-wide association study (GWAS). METHODS: The association between the 9q21.11 locus (rs7872806) and AD was identified through a GWAS of 956 cases and 723 controls. TJP2 expression in peripheral blood mononuclear cells (PBMCs) was assessed against the rs7872806 genotypes. Allele-specific methylation was evaluated at CpG sites 10kb up- and down-stream of the 9q21.11 locus. Effects of DNA methylation on TJP2 expression was validated via in vitro methylation and 5-aza-2'-deoxycytidine-induced transcriptional activation studies. Trans-epidermal water loss measurements were used to determine skin barrier function. RESULTS: The major allele of rs7872806 was determined to increase AD risk by 2.64-fold (adjusted p-value=2.40 x 10-18, OR=0.38), associated with increased methylation levels at cg13920460 site (p<0.001) and lower TJP2 expression in PBMCs (Pearson's p=1.09 x 10-6, Pearson's R=-0.313, p<0.001). Methylation inhibition by 5-aza-2'-deoxycytidine increased TJP2 promoter activity by up to 85%. Elimination of the cg13920460 methylation site increased expression by approximately 25%. The rs7872806 major allele was also found to be associated with increased trans-epidermal water loss (p<0.001). CONCLUSION: Epigenetic influence at CpG site cg13920460 is associated with rs7872806 located deep intronic at 9q21.11. The SNP confers susceptibility to AD through altering TJP2 expression and promoting trans-epidermal water loss.

3.
J Prev Alzheimers Dis ; 10(4): 800-809, 2023.
Article in English | MEDLINE | ID: mdl-37874102

ABSTRACT

BACKGROUND: S-adenosyl methionine (SAMe) is a pivotal metabolite in multiple pathways required for neuronal homeostasis, several of which are compromised in Alzheimer's disease (AD). Correction of the SAMe deficiency that is characteristic of the AD brain may attenuate or prevent pathological processes driving AD-associated neurodegeneration including aberrant tau hyperphosphorylation and DNA hypomethylation. OBJECTIVES: The primary aim is to test the hypothesis that daily treatment with 400 mg oral SAMe for 180 days will lead to a greater reduction from baseline in plasma levels of p-tau181 compared to placebo in patients with mild cognitive impairment or dementia due to AD. DESIGN, SETTING, PARTICIPANTS: This is a phase II, randomized, multi-center, double-blind, placebo-controlled trial among 60 participants with mild cognitive impairment or dementia due to AD. Participants will be randomized in a 1:1 ratio to receive either SAMe or matching placebo, to be taken as an adjunct to their AD standard of care. MEASUREMENTS AND RESULTS: The primary outcome is change in plasma p-tau181 concentration between baseline and following 180 days of treatment, which will be compared between the active and placebo group. Secondary outcomes are the safety of SAMe administration (incidence of serious adverse events), change from baseline in cognitive performance (as measured by the Repeatable Battery for the Assessment of Neuropsychological Status), and epigenetic changes in DNA methylation. CONCLUSION: Demonstration of effective and safe lowering of plasma p-tau181 with SAMe in this phase II trial would pave the way for an exciting field of translational research and a larger phase III trial.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/psychology , Cognitive Dysfunction/drug therapy , Brain , Double-Blind Method , Methionine/therapeutic use , Randomized Controlled Trials as Topic , Multicenter Studies as Topic , Clinical Trials, Phase II as Topic
4.
J Prev Alzheimers Dis ; 9(1): 178-183, 2022.
Article in English | MEDLINE | ID: mdl-35098989

ABSTRACT

Sensitive cognitive assessments accurately detect and track cognitive decline in Alzheimer's disease. The Cogstate battery was used to measure cognitive change in cognitively normal participants and in individuals with mild cognitive impairment and mild Alzheimer's disease enrolled in the Australian Imaging, Biomarker and Lifestyle Rate of Change Substudy. Over 18 months, verbal episodic memory performance declined for mild cognitive impairment and mild Alzeheimer's disease groups when compared to cognitively normal participants. Frequent assessments of episodic memory may facilitate early detection of cognitive decline due to Alzheimer's disease.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/complications , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Australia , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Disease Progression , Humans , Neuropsychological Tests
5.
J Appl Microbiol ; 127(1): 59-67, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31006174

ABSTRACT

AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound. METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin. CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.


Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Diarylheptanoids/pharmacology , Diarylheptanoids/toxicity , Gram-Positive Bacteria/drug effects , Zingiber officinale/chemistry , Animals , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/isolation & purification , Borneo , Cell Death/drug effects , Cell Line, Tumor , Cells, Cultured , Curcumin/pharmacology , Diarylheptanoids/adverse effects , Diarylheptanoids/isolation & purification , Humans , Microbial Sensitivity Tests , Permeability/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology
6.
J Appl Microbiol ; 123(5): 1148-1159, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28869803

ABSTRACT

AIMS: The potential of Dicranopteris linearis leaves' extract and its bioactive components were investigated for the first time for its disrupting ability against Staphylococcus aureus biofilms. METHODS AND RESULTS: The leaves of D. linearis were subjected to sonication-assisted extraction using hexane (HEX), dichloromethane, ethyl acetate and methanol (MeOH). It was found that only the MeOH fraction exhibited antimicrobial activity using broth microdilution assay; while all four fractions do not exhibit biofilm inhibition activity against S. aureusATCC 6538P, S. aureusATCC 43300, S. aureusATCC 33591 and S. aureusATCC 29213 using crystal violet assay. Among the four fractions tested, only the HEX fraction showed biofilm disrupting ability, with 60-90% disruption activity at 5 mg ml-1 against all four S. aureus strains tested. Bioassay-guided purification of the active fraction has led to the isolation of α-tocopherol. α-Tocopherol does not affect the cells within the biofilms but instead affects the biofilm matrix in order to disrupt S. aureus biofilms. CONCLUSIONS: α-Tocopherol was identified to be the bioactive component of D. linearis with disruption activity against S. aureus biofilm matrix. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of α-tocopherol as a biofilm disruptive agent might potentially be useful to treat biofilm-associated infections in the future.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Ferns/chemistry , Plant Extracts/pharmacology , Staphylococcus aureus/drug effects , alpha-Tocopherol/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Humans , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Leaves/chemistry , Staphylococcal Infections/microbiology , Staphylococcus aureus/physiology , alpha-Tocopherol/chemistry , alpha-Tocopherol/isolation & purification
7.
J Appl Microbiol ; 123(4): 810-818, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28708293

ABSTRACT

AIMS: To investigate the antimicrobial properties of Etlingera coccinea and Etlingera sessilanthera and to isolate and identify the antimicrobial compounds. METHODS AND RESULTS: Extracts were obtained via sequential solvent extraction method using hexane, dichloromethane, ethyl acetate, methanol and water. Antimicrobial activity testing was done using broth microdilution assay against 17 strains of bacteria. The leaf hexane extract of E. coccinea and rhizome hexane extract of E. sessilanthera showed best antimicrobial activities, with minimum inhibitory concentration (MIC) values ranging from 0·016 to 1 mg ml-1 against Gram-positive bacteria. From these active extracts, two antimicrobials were isolated and identified as trans-2-dodecenal and 8(17),12-labdadiene-15,16-dial with MIC values ranging from 4 to 8 µg ml-1 against Bacillus cereus, Bacillus subtilis and Staphylococcus aureus. CONCLUSION: Etlingera coccinea and E. sessilanthera demonstrated good antimicrobial activities against clinically relevant bacteria strains. The antimicrobial compounds isolated showed low MIC values, hence suggesting their potential use as antimicrobial agents. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to identify the potent antimicrobials from these gingers. The antimicrobials isolated could potentially be developed further for use in treatment of bacterial infections. Also, this study warrants further research into other Etlingera species in search for more antimicrobial compounds.


Subject(s)
Anti-Bacterial Agents/pharmacology , Plant Extracts/pharmacology , Zingiber officinale/chemistry , Anti-Bacterial Agents/chemistry , Bacillus cereus/drug effects , Bacillus cereus/growth & development , Borneo , Microbial Sensitivity Tests , Plant Extracts/chemistry , Plant Leaves/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development
8.
Clin Radiol ; 72(3): 207-216, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27932250

ABSTRACT

AIM: To determine the frequency of and reasons for false-negative breast magnetic resonance imaging (MRI) examinations in high-risk women undergoing annual screening. MATERIALS AND METHODS: The family history clinic database was interrogated and women at high risk of breast cancer who had undergone screening MRI and been diagnosed with breast cancer within 2 years of the MRI examination were identified. All available MRI examinations were reviewed and classified by two radiologists. RESULTS: Of 32 women diagnosed with breast cancer, 23 had MRI images available for review. Fourteen were diagnosed at MRI, four at interim mammography, two symptomatically, one incidentally on ultrasound, and two at risk-reducing mastectomy. Ten women (43%) had potentially avoidable delays in diagnosis. The preceding MRIs were classified as false-negative screens in five women (one prevalent, four incident), false-negative assessment in seven and minimal signs in three (three women were assigned dual classifications). Common reasons for diagnostic delay included small enhancing masses that were overlooked, areas of non-mass enhancement that showed little or no change between screens, false reassurance from normal conventional imaging at assessment, and overreliance on short-interval repeat MRI. CONCLUSION: Small enhancing foci, masses, and areas of segmental non-mass enhancement are common MRI features of early breast cancer. Lack of change of non-mass enhancement on serial examinations does not exclude malignancy. Double reading of both screening and assessment examinations is recommended. Ready access to MRI biopsy is essential. Short-interval repeat MRI should be limited to reassessing low suspicion areas likely to be benign glandular enhancement. Annual mammography remains important in these women.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/epidemiology , Early Detection of Cancer/statistics & numerical data , Magnetic Resonance Imaging/statistics & numerical data , Medical History Taking/statistics & numerical data , Adult , Age Distribution , Breast Neoplasms/genetics , False Negative Reactions , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Middle Aged , Prevalence , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , United Kingdom/epidemiology
9.
Clin Radiol ; 71(6): 551-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27040801

ABSTRACT

AIM: To compare the acceptability, safety, and feasibility of vacuum-assisted biopsy (VAB) and core needle biopsy (CNB) of axillary lymph nodes in women with breast cancer. MATERIALS AND METHODS: This parallel, non-blinded, randomised study was approved by the National Research Ethics Service. Following written informed consent, women with abnormal appearing axillary lymph nodes and radiologically malignant breast masses were randomised 1:1 to lymph node sampling under local anaesthetic with either 14 G CNB or 13 G VAB in a single UK centre. Primary outcomes were study uptake rate and patient willingness to undergo a repeat procedure if necessary. Procedure duration, immediate and post-procedure pain scores, diagnostic yield, complications, and surgical histopathology were recorded. RESULTS: Ninety-five women were approached; 81 (85.3%) consented and were randomised. Forty underwent CNB; 40 underwent VAB; one was excluded. Median age was 57 years. The median procedure time was 2 minutes for both techniques. The median number of samples obtained was three for CNB and four for VAB. Median pain scores for the procedure and first 3 days were 1/10 and 1/10 for CNB and 1/10 and 2/10 for VAB (p=0.11 and 0.04). More women were prepared to undergo repeat CNB compared to VAB, but the difference was not significant (38/39 versus 33/39; p=0.11). Two patients developed a haematoma after VAB. One CNB and six VABs failed to yield adequate tissue (p=0.11), but the sensitivity was similar at 79% and 78%. CONCLUSION: Study uptake was high. Acceptability of the two procedures was similar, but VAB was associated with more post-procedure pain. The sensitivity appears to be similar.


Subject(s)
Biopsy, Large-Core Needle/methods , Breast Neoplasms/pathology , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Needles/classification , Sentinel Lymph Node Biopsy/instrumentation , Sentinel Lymph Node/pathology , Adult , Aged , Aged, 80 and over , Axilla , Biopsy, Large-Core Needle/adverse effects , Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects , Feasibility Studies , Female , Humans , Lymphatic Metastasis , Middle Aged , Pilot Projects , Reproducibility of Results , Sensitivity and Specificity , Sentinel Lymph Node Biopsy/methods , Vacuum
10.
Aliment Pharmacol Ther ; 43(7): 831-7, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26847417

ABSTRACT

BACKGROUND: Marked epidemiological changes in upper gastrointestinal diseases and Helicobacter pylori infection have taken place in the Asian Pacific region. In particular, differences with respect to race in the multiracial Asian population in Malaysia have been important and interesting. AIM: A time trend study of upper gastrointestinal disease and H. pylori infection in three time periods: 1989-1990, 1999-2000 and 2009-2010 spanning a period of 20 years was carried out. METHODS: Consecutive first time gastroscopies carried out on patients attending the University of Malaya Medical Center were studied. Diagnoses and H. pylori infection status were carefully recorded. RESULTS: A steady decline in prevalence of duodenal ulcer (DU) and gastric ulcer (GU) from 21.1% to 9.5% to 5.0% and from 11.9% to 9.4% to 9.9% while an increase in erosive oesophagitis (EO) from 2.0% to 8.4% to 9.5% (chi-square for trend; P < 0.001) for the periods 1989-1990, 1999-200 and 2009-2010 were observed. The overall prevalence of H. pylori had also decreased from 51.7% to 30.3% to 11.1% for the same periods of time. The proportion of H. pylori positive ulcers had also decreased: DU (90.1%-69.8%-28.9%) and GU (86.6-56.8%-18.9%) (P < 0.001). This was observed in Malays, Chinese and Indians but the difference over time was most marked in Malays. There was a steady decline in the proportion of patients with gastric and oesophageal cancers. CONCLUSIONS: Peptic ulcers have declined significantly over a 20-year period together with a decline in H. pylori infection. In contrast, a steady increase in erosive oesophagitis was observed. Gastric and oesophageal squamous cell cancers have declined to low levels.


Subject(s)
Asian People/ethnology , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/ethnology , Helicobacter Infections/diagnosis , Helicobacter Infections/ethnology , Helicobacter pylori/isolation & purification , Adult , Aged , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/ethnology , Carcinoma, Squamous Cell/microbiology , Duodenal Ulcer/diagnosis , Duodenal Ulcer/ethnology , Duodenal Ulcer/microbiology , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/ethnology , Esophageal Neoplasms/microbiology , Esophageal Squamous Cell Carcinoma , Female , Gastrointestinal Diseases/microbiology , Humans , Malaysia/ethnology , Male , Middle Aged , Peptic Ulcer/diagnosis , Peptic Ulcer/ethnology , Peptic Ulcer/microbiology , Population Surveillance , Stomach Ulcer/diagnosis , Stomach Ulcer/ethnology , Stomach Ulcer/microbiology , Time Factors
11.
Mol Psychiatry ; 20(7): 860-6, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25070537

ABSTRACT

The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.


Subject(s)
Cognition Disorders/epidemiology , Diet , Aged , Aging/genetics , Aging/psychology , Apolipoprotein E4/genetics , Australia , Cognition Disorders/genetics , Cohort Studies , Executive Function , Female , Follow-Up Studies , Humans , Linear Models , Male , Neuropsychological Tests , Principal Component Analysis , Surveys and Questionnaires
12.
Mol Psychiatry ; 20(11): 1322-8, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25288138

ABSTRACT

Accumulation of ß-amyloid (Aß) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4(+)], ɛ4 non-carrier[ɛ4(-)]) and brain-derived neurotrophic factor (BDNF(Val/Val), BDNF(Met)) in the extent to which they moderate Aß-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aß neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aß positron emission tomography neuroimaging was used to classify participants as Aß(-) or Aß(+). Relative to Aß(-)ɛ4(-), Aß(+)ɛ4(+) individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while Aß(+)ɛ4(-) individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aß(-)ɛ4(-) and Aß(-)ɛ4(+) groups. Among Aß(+) individuals, ɛ4(+)/BDNF(Met) participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4(-)/BDNF(Val/Val) participants (d=0.90-1.02). At least two genetic loci affect the rate of Aß-related cognitive decline. Aß(+)ɛ4(+)/BDNF(Met) individuals can expect to show clinically significant memory impairment after 3 years, whereas Aß(+)ɛ4(+)/BDNF(Val/Val) individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aß(-) and Aß(+) ɛ4(-) groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials.


Subject(s)
Alzheimer Disease/complications , Amyloid beta-Peptides/metabolism , Apolipoproteins E/genetics , Brain-Derived Neurotrophic Factor/genetics , Cognition Disorders , Polymorphism, Single Nucleotide/genetics , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Aniline Compounds/metabolism , Cognition Disorders/etiology , Cognition Disorders/genetics , Cognition Disorders/metabolism , Female , Follow-Up Studies , Genetic Engineering , Genotype , Humans , Male , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography , Psychiatric Status Rating Scales , Thiazoles/metabolism
13.
Clin Exp Dermatol ; 39(3): 368-75, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24635081

ABSTRACT

BACKGROUND: Vitamin D receptor (VDR) is expressed in dermal papilla cells and in the epidermis of the hair follicle. Patients with alopecia areata (AA) and alopecia universalis (AU) have VDR mutations. AIMS: We investigated expression of VDR in isolated hair follicles and epidermal keratinocytes from patients with AA or AU, and assessed changes in the expression of Wnt signalling regulation factors to determine the relationship between the occurrence of AA or AU and decreased expression of VDR. METHODS: Immunohistochemistry was performed for canonical Wnt signalling molecules, VDR, and proliferation and differentiation markers in the skin tissue of patients with AA or AU. After VDR small interfering RNA or Dickkopf-1 (DKK1) treatment of follicle dermal papilla (DP) cells, expression of VDR and Wnt signalling molecules was determined. DKK1 was used to treated keratinocytes and DP cells in a transwell coculture system. Western blotting analysis was performed to assay for VDR and ß-catenin. RESULTS: Expression of Wnt/ß-catenin signals and VDR was decreased in AA or AU lesions compared with nonlesional skin. Inhibition of Wnt/ß-catenin signals and VDR influenced differentiation and proliferation of epidermis and hair follicles. In the transwell coculture system, DKK1 reduced the expression of VDR and ß-catenin in cells in a dose-dependent manner. CONCLUSIONS: This study demonstrates that the decreased expression of VDR in AA and AU lesions is related to decreased expression of Wnt/ß-catenin signals, which inhibits proliferation and differentiation of hair follicles and epidermal cells.


Subject(s)
Alopecia/metabolism , Receptors, Calcitriol/metabolism , Wnt Proteins/metabolism , Adult , Female , Hair Follicle/metabolism , Humans , Keratinocytes/metabolism , Middle Aged , Scalp/metabolism , Signal Transduction/physiology
14.
Clin Exp Dermatol ; 38(7): 758-67, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23581888

ABSTRACT

BACKGROUND: Alopecia areata (AA) is characterized by rapid and complete hair loss in one or multiple areas of the scalp. Stress is an important triggering factor in AA. AIM: To identify the inhibitory effect of tianeptine on catagen induction in C57BL/6 mice with AA-like lesions induced by ultrasonic wave stress (UWS). METHODS: The mice were divided into four groups. Group 1 received oral tianeptine before and after UWS; group 2 received oral tianeptine only after UWS; group 3 was given UWS treatment only; and group 4 (negative control group) was not given any treatment. Phototrichigraphy and dermatoscopy were used for assessment. Histological analysis was performed using haematoxylin and eosin, toluidine blue, Masson trichrome and Verhoeff-van Gieson stains. Immunohistochemical analysis was also performed. The level of apoptosis and expression of neuropeptides in the skin were assessed by terminal deoxynucleotidyl transferase dUTP nick end labelling and immunofluorescence assays. RESULTS: Mice in group 1 had an increased rate of hair growth and greater hair-shaft thickness compared with mice in groups 2 and 3. In addition, mice in group 1 had a higher number of anagen hair follicles, increased synthesis of collagen and elastic fibres, decreased mast-cell degranulation, reduction in cell apoptosis in hair follicles, and recovery of vitamin D receptor expression. Expression of neuropeptides (substance P, calcitonin gene-related peptide) was not altered. CONCLUSIONS: Tianeptine might play a role in suppressing catagen induction in a stress-induced AA mouse model.


Subject(s)
Alopecia Areata/drug therapy , Antidepressive Agents, Tricyclic/therapeutic use , Cell Cycle/drug effects , Stress, Psychological/drug therapy , Thiazepines/therapeutic use , Alopecia Areata/psychology , Animals , Antidepressive Agents, Tricyclic/pharmacology , Disease Models, Animal , Female , Hair Follicle/drug effects , Immunohistochemistry , Mice , Mice, Inbred C57BL , Stress, Psychological/complications , Thiazepines/pharmacology
15.
Clin Radiol ; 66(12): 1129-39, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21851932

ABSTRACT

Incidental renal masses are common findings on cross-sectional imaging. Most will be readily identified as simple cysts, but with an inexorable rise in abdominal imaging, [particularly computed tomography (CT)], coupled with a rise in the incidence of renal cancer, the likelihood of detecting a malignant mass is increasing. This review informs the radiologist which lesions can be safely ignored, which will require further imaging for accurate categorization, and which require referral for consideration of treatment. For the small proportion of lesions that are indeterminate, careful attention to imaging technique, and the use of unenhanced and contrast-enhanced CT or magnetic resonance imaging (MRI) in all but a few specific instances will accurately characterize such lesions. The figures have been chosen to illustrate specific imaging features of common renal lesions. Management options for malignant, or presumed malignant, renal masses include active surveillance, percutaneous ablation, laparoscopic or open, partial or total nephrectomy. Biopsy has a role in determining the nature of masses that remain indeterminate on cross-sectional imaging, prior to definitive treatment. Common pitfalls in assessing incidental renal lesions are emphasized; some of these are due to sub-optimal imaging techniques and others to errors in interpretation.


Subject(s)
Incidental Findings , Kidney Diseases/diagnosis , Biopsy , Female , Follow-Up Studies , Humans , Kidney Diseases/pathology , Kidney Neoplasms/diagnosis , Magnetic Resonance Imaging , Male , Tomography, X-Ray Computed , Ultrasonography, Doppler
16.
Diabet Med ; 27(6): 685-90, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20546288

ABSTRACT

AIM: To explore the impact of sharing personalized written clinical information with diabetes outpatients on patient involvement in the clinical consultation. METHODS: One hundred and six patients attending diabetes outpatient clinics for a review visit were allocated to receive either a patient information sheet containing personalized clinical information (prior to their consultation) or no information sheet. Both groups were compared by observing the number of patients raising any of the 17 topics included on the patient information sheet, the number of topics raised by each individual and the proportion of the total consultation time in which the patient was involved in conversation. A mean patient score was calculated by summing the number of topics raised by each patient. RESULTS: Patients in the intervention group were more likely to initiate a conversation on all 17 topics during the consultation than those in the control group. These differences were significant for all topics except glycated haemoglobin (HbA(1c)) and diabetes complications. The mean patient score was significantly higher in the intervention group (5 vs. 1, P < 0.005), with the highest patient score in the intervention group being 14 compared with 4 in the control group. The mean patient conversation time for the intervention group was significantly longer than for the control group (6.34 vs. 3.34 min, P < 0.01). The overall consultation time did not significantly differ between groups. CONCLUSIONS: Providing patients with personalized clinical information in a routine clinical setting can increase patients' involvement in the consultation without significantly increasing the length of the consultation.


Subject(s)
Diabetes Complications/psychology , Diabetes Mellitus/psychology , Patient Satisfaction , Physician-Patient Relations , Adolescent , Adult , Aged , Aged, 80 and over , Ambulatory Care Facilities , Case-Control Studies , Child , Child, Preschool , Communication , Diabetes Complications/physiopathology , Diabetes Mellitus/physiopathology , Female , Glycated Hemoglobin , Humans , Infant , Male , Middle Aged , Patient Education as Topic , Pilot Projects , Statistics as Topic , Young Adult
17.
Singapore Med J ; 51(3): 247-52, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20428748

ABSTRACT

INTRODUCTION: The aim of this study was to identify factors associated with poor academic achievement during the early school years. METHODS: This was a cross-sectional study of urban Primary Two children. Sociodemographic and medical data were obtained from questionnaires and interviews. Achievement was based on marks obtained in the core subjects of the Primary One examination. All students underwent the Raven's Standard Progressive Matrices test as a general measure of cognitive ability, audiometry and visual tests, and standardised measurements of weight and height. RESULTS: Out of 1,470 eligible children, 206 (14 percent) had poor academic achievement. Of the 919 children who participated in the study, 111 (12.1 percent) had poor achievement compared with 95 (17.2 percent) of the 551 non-participants. Using logistic regression analysis, the factors that were found to be independently associated with poor academic achievement were lower mean Raven scores (p-value is less than 0.001), lower mean socioeconomic status scores (p-value is less than 0.001), larger sibship size (p-value is 0.031), male gender (odds ratio [OR] 1.7; 95 percent confidence interval [CI] 1.1-2.65) and a history of prematurity (OR 14; 95 percent CI 2-97.8). CONCLUSION: Cognitive ability, gender, prematurity and social factors contribute to poor academic achievement during the early school years. The higher proportion of poor achievers among non-participants warrants further attention.


Subject(s)
Educational Measurement , Schools , Students , Audiometry , Child , Child Welfare , Cognition , Confidence Intervals , Cross-Sectional Studies , Educational Status , Female , Humans , Intelligence Tests , Logistic Models , Malaysia , Male , Odds Ratio , Regression Analysis , Risk Factors , Sex Factors , Socioeconomic Factors , Surveys and Questionnaires , Urban Population , Vision Tests
18.
Singapore Med J ; 47(1): 8-13, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16397714

ABSTRACT

In 2001, the Health Promotion Board (HPB) developed HPB Online, an internet-based health education portal to disseminate health messages. The objective of this article is to describe the structure of HPB Online, review its reach as a tool to deliver health information in Singapore, and discuss the advantages of using the internet to complement traditional media such as the television, newspapers and radio. Since its inception in 2001, the numbers of page-views, monthly visits and repeat visitors have increased markedly. The most popular webpages have consistently been Food Info Search. The average length of visit also showed a gradual increase during the study period, from about 11.0 minutes in January 2002 to 18.5 minutes in December 2004. The key advantage of using the HPB Online is that it allows quick delivery of information to the public and this is ideal for time-sensitive issues. It helps Singaporeans to make better informed decisions to maintain and to improve their health. With its high utilisation, the HPB will continue to use the internet as part of its multichannel marketing strategy to disseminate health information.


Subject(s)
Health Education/methods , Information Services/statistics & numerical data , Internet/statistics & numerical data , Patient Education as Topic/methods , Humans , Information Services/trends , Internet/trends , Regression Analysis , Singapore
19.
Clin Radiol ; 61(1): 86-90, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16356821

ABSTRACT

AIM: To determine the impact on diagnostic and interventional radiology services when imaging patients with severe pancreatitis on intensive therapy (ITU) and high-dependency units (HDU) in a tertiary referral centre. MATERIAL AND METHODS: One hundred and sixty-nine patients admitted to ITU/HDU over a 9-year period (1996-2004) with severe acute pancreatitis were reviewed. There were 109 admissions to the ITU with length of stay of 0.2-81.6 days (mean 19.7 days) and 92 admissions to the HDU with length of stay of 0.4-12.8 days (mean 4.9 days). RESULTS: One hundred and seventy-nine computed tomography (CT) and 199 ultrasound (US) examinations were performed on the ITU patients in whom interventional procedures were required in 24% of patients undergoing CT examinations and in 32% of patients undergoing US. Sixty-two CT and 60 US examinations were performed in the HDU patients. The percentage of interventional procedures performed in HDU patients was similar to that in ITU patients, i.e., 18% CT-guided and 35% US-guided. The proportion of patients that underwent investigations and interventions has gradually increased over the period of the study. Inpatient mortalities were 29% and 5.4%, respectively, in ITU and HDU patients. CONCLUSIONS: This study demonstrates the huge input and increasing workload undertaken by radiologists when managing patients with severe acute pancreatitis in an ITU/HDU setting. We believe this is partly due to the implementation of the British Society of Gastroenterology (BSG) guidelines on management of acute pancreatitis and partly due to the more intensive non-surgical management offered to patients being referred into a specialist tertiary referral unit.


Subject(s)
Critical Care/methods , Pancreatitis/diagnostic imaging , Workload , Acute Disease , Biopsy, Fine-Needle , Drainage , Female , Humans , Intensive Care Units/organization & administration , Male , Radiology, Interventional/methods , Tomography, X-Ray Computed/methods , Ultrasonography
20.
J Colloid Interface Sci ; 255(2): 425-7, 2002 Nov 15.
Article in English | MEDLINE | ID: mdl-12505092

ABSTRACT

The rate of autooxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) in the presence of micelles formed from mixing equal concentrations of [Cu(C(12)-tmed)Br(2)] (where C(12)-tmed is N,N,N'-trimethyl-N'-dodecylethylenediamine) and several amino acids has been investigated. It was found that the rate in air-saturated solution is very much dependent on pH, which affects the availability of copper(II) coordination site for the catechol and the degree of micellization. At a given pH, the rates in [Cu(C(12)-tmed)Br(2)] micellar media are greatly enhanced in the presence sodium halide.


Subject(s)
Amino Acids/chemistry , Catechols/chemistry , Copper , Surface-Active Agents , Hydrogen-Ion Concentration , Kinetics , Oxidation-Reduction
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