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Background There is limited work on the impact of chemotherapy‐induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin‐cyclophosphamide (AC)–treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients’ QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. Materials and Methods This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index–emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included “no significant nausea” (NSN), “significant nausea” (SN), “no vomiting” (NoV), “vomiting” (V), and complete response (CR). Results Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p, This article focuses on chemotherapy‐induced nausea and vomiting and quality of life of breast cancer patients through multiple cycles of treatment.

Purpose To determine whether point-of-care clinical decision support can effectively reduce inappropriate medical imaging of patients who present to the emergency department (ED) with low-back pain (LBP). Materials and Methods This was a prospective, single-center study of lumbar imaging referrals made by 43 emergency physicians at a major acute care center. Each physician saw at least 10 LBP cases in both pre- and post-intervention periods. A point-of-care checklist of accepted red flags for LBP was designed by a working group of physicians and embedded in the computerized order entry form for lumbar imaging. We compared imaging rates of LBP and physician variation in imaging ordering before and after the implementation of the checklist. We then measured the potential harms of reduced imaging. Results After intervention, the proportion of LBP patients with an imaging order fell significantly (median: 22% to 17%; mean: 23% to 18%; P = .0002) compared with pre-intervention baseline. The percentage of patients without imaging who were later imaged at a hospital outpatient clinic within 30 days was 2.3% before intervention and 2.2% after ( P = .974). In addition, the proportion of patients discharged from the ED without imaging who returned to the ED within 30 days was 8.2% before intervention and 6.9% after ( P = .170). One minor thoracic spine compression fracture was missed, but management was not impacted. No serious diagnoses were missed. Conclusion Clinical decision support integrated in electronic order entry forms can safely and effectively reduce imaging orders for LBP patients in the ED.

Purpose The psychological and social factors associated with smoking initiation and continuation are different for young and adult smokers. Before 2005, there were no population-based smoking cessation interventions targeting young smokers in Hong Kong, China. This study describes the processes and outcomes of an individualized "Youth Quitline" service for young Hong Kong Chinese smokers over a 10-year period. Methods A retrospective population-based study was conducted to evaluate the effectiveness of the Quitline and identify the predictors of quitting. Telephone records were used to obtain information of each call. Young smokers of the Quitline completed a questionnaire at baseline and 6-month follow-up. Data were collected between August 2005 and August 2015. Results Over the 10-year period, the Youth Quitline received 7,720 telephone inquiries and provided smoking cessation counseling to 1,684 young smokers. At the 6-month follow-up, 16.9% had reduced cigarette consumption by more than 50%, 33.8% had tried quitting, and 23.6% had successfully quit smoking. Logistic regression analyses indicated that 7 factors, including (1) age; (2) daily cigarette consumption; (3) level of nicotine dependence; (4) intention to quit; (5) having made at least one quit attempt; (6) level of self-efficacy; and (7) adherence to telephone counseling, significantly predicted smoking cessation at 6 months. Conclusions During the first 10 years of the Youth Quitline, we trained many youths to become smoking cessation peer counselors. The Youth Quitline successfully increased youths' awareness of the risks of smoking and smoking cessation services and provided individualized smoking cessation counseling services to young smokers.

ObjectivesThis is a prospective study evaluating NEPA in patients with breast cancer (the NEPA group), who received (neo)adjuvant AC chemotherapy (consisting of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). The primary objectives were to assess the efficacy and safety of NEPA in controlling chemotherapy-induced nausea and vomiting (CINV). The secondary objectives were to compare CINV between the NEPA group and historical controls (the APR group) who received aprepitant in an earlier prospective randomised study.Patients and methods60 patients participated in the NEPA group; 62 were in the APR group. Eligibility criteria of both groups were similar, that is, Chinese patients with breast cancer who were treated with (neo)adjuvant AC. NEPA group received NEPA and dexamethasone; APR group received aprepitant, ondansetron and dexamethasone. Individuals filled in self-reported diary, visual analogue scale for nausea and Functional Living Index-Emesis questionnaire.ResultsWithin the NEPA group, 70.0%, 85.7% and 60.0%, respectively reported complete response in the acute, delayed and overall phases in cycle 1 AC. When compared with the historical APR group during cycle 1 AC, NEPA group achieved significantly higher rates of complete response, complete protection, total control, ‘no significant nausea’ and ‘no nausea’ in the delayed phase; similar findings were noted in the overall phase with significantly better quality of life. Superior efficacy of NEPA was maintained over multiple cycles. Both antiemetic regimens were well tolerated.ConclusionIn this study on Chinese patients with breast cancer who were uniformly receiving AC, NEPA was effective in controlling CINV.Trial registration numberNCT03386617.

Thalassemias and hemophilias are the most important inherited hematological diseases in Hong Kong and China. Prenatal diagnosis has significantly decreased the burden of these diseases. For thalassemia major, adequate transfusion and iron chelation therapy have dramatically improved patient outlook. Hematopoietic stem cell transplantation is curative for thalassemia major and is increasingly adopted. The efficacy of arsenic trioxide in acute promyelocytic leukemia (APL) was discovered in China. An oral formulation of arsenic trioxide was developed in Hong Kong for newly diagnosed and relapsed APL patients. With combination chemotherapy containing non-P-glycoprotein-dependent drugs and L-asparaginase, durable remission can be achieved in the most patients.

Objectives There is limited literature describing the effect exercise may have on depression and an individual’s health-related quality of life (HRQoL) in Parkinson’s Disease (PD). We aim to quantify this effect. Methods A cross-sectional questionnaire was administered to 60 PD subjects. The Parkinson’s Disease Questionnaire-39 (PDQ-39) summary index and the Geriatric Depression Scale-30 were used to quantify HRQoL and depression, respectively. Data were obtained on exercise habits. ANOVA and multivariate linear regression analysis were used to calculate mean differences in HRQoL. Results Depression was consistently related to HRQoL ( p Discussion Exercising and depression may interact to affect HRQoL. Thus, coordination of mental health evaluation and exercise regimens in persons with PD may improve HRQoL.

AIMS AND OBJECTIVES To explore the relationship between smoking and other risk behaviours among Chinese young people in Hong Kong. BACKGROUND There is growing concern about coexisting risk behaviours in young smokers. Information about smoking and other risk behaviours is crucial for developing interventions to promote smoking abstinence and adoption of healthy lifestyles. The relationship between smoking and other risk behaviours among Chinese young people in Hong Kong has not been explored. DESIGN This is a mixed-method retrospective population-based study. METHODS A retrospective population-based study was conducted with 1,147 young smokers through Youth Quitline between November 2011-July 2016. Attitudes, behaviours and experiences related to smoking and risk behaviours among Chinese young smokers were examined in semi-structured qualitative interviews with 30 participants randomly selected from the retrospective population-based study. RESULTS In total, 45.5% participants reported engaging in at least one other risk behaviour. The interviews revealed that drinking alcohol may have a significant impact on quitting smoking. In addition, smoking may be a gateway for more serious risk behaviours during adolescence. Low health awareness may explain the unhealthy lifestyles among young smokers. CONCLUSIONS This study bridges a gap in existing literature by exploring relationships between smoking and other risk behaviours among young people in Hong Kong. RELEVANCE TO CLINICAL PRACTICE Given the interrelationships between smoking and other risk behaviours, a holistic approach should be used to promote smoking cessation and healthy lifestyles among young smokers. If young smokers improve their health and quit smoking at the same time, their physical and mental development will benefit as a secondary outcome.

The National Comprehensive Cancer Network (NCCN) guidelines are the gold standard in hereditary cancer risk assessment, screening, and treatment. A minority of physicians follow NCCN guidelines for BRCA1 or BRCA2 mutations. This study assesses the impact of an interventional educational program on HBOC in terms of knowledge. Physicians were sent an invite to join either an intervention survey (web-training offered prior to the knowledge survey) or control survey (web-training offered after the knowledge survey). Sixty-nine physicians in the intervention arm and 67 physicians in the control arm completed the survey. The interventional group regularly answered items correctly at a higher frequency than the control group. For example, 64.71% (n = 44) of physicians in the intervention group knew that multi-gene testing does not have to include only highly penetrant genes compared to 32.84% (n = 22) of the control group (p

Purpose The Knowledge Exchange–Decision Support (KE-DS) Model provides a framework outlining essential components of knowledge generation and exchange. The purpose of this research was to illustrate how the Model makes explicit the different contextual aspects implicit in the planning and implementation of two cancer navigation programs in Canada. Methods The KE-DS Model guided the collection and analysis of interviews with program personnel and narrative data. A qualitative thematic analysis was conducted wherein we compared and contrasted the planning and implementation of these two navigation programs. Results The planning and implementation of these two programs was conceptualized differently and adapted to meet local contingencies. The KE-DS Model highlighted three factors that influenced program delivery. First, the structure of health services was shaped by the interaction of professionals and services operating in the region, and the existing health services influenced the program’s approach to navigation. Second, while there were similarities in the professional roles and responsibilities of the navigators, these roles and responsibilities also reflected local context in their approaches to patient assessment, referral, education, coordination of services, and advocacy. Third, these two distinct approaches to navigation have responded to the needs of diverse populations being served by improving access to care. Conclusions Evidence generated using the KE-DS Model could ensure a more robust and structured approach to the planning and implementation of future navigation programs. The Model prompts users to make explicit the different types of evidence utilized during program planning and implementation. The systematic collection of new information on program implementation using the KE-DS Model in future initiatives will contribute to an improved understanding of the science of knowledge exchange.

Objectives To determine haematological parameters in fetuses affected by homozygous α0-thalassemia. Methods This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous α0-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. Results There were significant differences in the haematological parameters between homozygous α0-thalassemia (n = 183) and control (n = 363) which were either heterozygous α0-thalassemia (alpha thalassemia trait) or normal. In homozygous α0-thalassemia, the median Hb level, proportion of Hb Bart's (γ4) and Hb Portland 1(ζ2γ2) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. Conclusion Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 (ζ2γ2) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia. Copyright © 2010 John Wiley & Sons, Ltd.

Objective To evaluate in maternal plasma, the efficacy of detecting the paternal β-gene mutation and informative single nucleotide polymorphisms (SNPs) linked to the paternal-mutant or -normal allele in non-invasive prenatal diagnosis (NIPND). Study design In 20 at-risk pregnancies, using the allele-specific arrayed primer extension (AS-APEX) technology of the previously published “Thalassemia” array, cyanine-5-deoxycytosine triphosphate (Cy5-dCTP) was incorporated into the extended strands to matched PCR-amplified maternal plasma DNA templates, to detect both the paternal β-gene mutation and informative paternal SNPs. Results Sensitivity experiment showed that 5 pg DNA as starting template gave detectable signals on the array. In 13 cases (65%), the paternal-derived β-gene mutation and/or informative mutant-associated SNP were detected. A subsequent invasive procedure was required to determine if the fetus had a β-thalassemia (thal) major or minor genotype. In 3 cases (15%), absence of the paternal mutant or mutant-associated SNP excluded a β-thal major fetus; while in 4 cases (20%), this approach was non-discriminative as both parents carry the same mutation without any informative SNP. Conclusion This approach was useful in 16 out of 20 (80%) pregnancies at risk for β-thal in southern Chinese.

Bone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major susceptibility loci for peak spine BMD has been mapped to chromosome 1q21-q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case-control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD.

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Chromosome 14q has previously been linked to BMD variation in several genome-wide linkage scans in Caucasian populations.Our objective was to replicate and identify the novel candidate genes in the quantitative trait loci (QTL) at chromosome 14q QTL.Eighteen microsatellite markers were genotyped for a 117-cM interval in 306 Southern Chinese pedigrees with 1459 subjects. Successful replication of the QTL was confirmed within this region for trochanter and total hip BMD. Using a gene prioritization approach as implemented in the Endeavour program, we genotyped 65 single-nucleotide polymorphisms in the top five ranking candidate genes within the linkage peak in 706 and 760 case-control subject pairs with extremely high and low trochanter and total hip BMD, respectively.Single-marker and haplotype analyses revealed that ESR2 and latent TGF-beta binding protein 2 (LTBP2) had significant associations with trochanter and total hip BMD. Multiple logistic regression revealed a strong genetic association between LTBP2 gene locus and total hip BMD variation (P=0.0004) and prevalent fracture (P=0.01). Preliminary in vitro study showed differential expression of LTBP2 gene in MC3T3-E1 mouse preosteoblastic cells in culture.Apart from ESR2, LTBP2 is a novel positional candidate gene in chromosome 14q QTL for BMD variation and fracture.

Background The need to identify priorities to help shape future directions for research and practice increases as the knowledge translation (KT) field advances. Since many KT trainees are developing their research programs, understanding their concerns and KT research and practice priorities is important to supporting the development and advancement of KT as a field. Our purpose was to identify research and practice priorities in the KT field from the perspectives of KT researcher/practitioner trainees. Findings Survey response rate was 62 % (44/71). Participants were mostly Canadian graduate students, post-doctoral fellows, residents, and learners from various disciplines; the majority was from Ontario (44 %) and Quebec (20 %). Seven percent (5/71) were from other countries including USA, UK, and Switzerland. Seven main KT priority themes were identified: determining the effectiveness of KT strategies, technology use, increased key stakeholder involvement, context, theory, expand ways of inquiry, and sustainability. Conclusions Overall, the priorities identified by the trainees correspond with KT literature and with KT experts’ views. The trainees appeared to push the boundaries of current KT literature with respect to creative use of communication technologies research. Electronic supplementary material The online version of this article (doi:10.1186/s13012-015-0282-5) contains supplementary material, which is available to authorized users.

Background: Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. Objective: Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. Methods: This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. Results: Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators’ posts (median 60, IQR 25 vs median 32, IQR 7; P =.05) and participants’ posts (median 35, IQR 50 vs median 6, IQR 9; P =.07) than their Facebook counterparts, but the difference was insignificant. Conclusions: The intervention via the WhatsApp social group was effective in reducing relapse probably because of enhanced discussion and social support. Inactive discussion in the Facebook social group might have attributed to the lower effectiveness. ClinicalTrial: Clinicaltrials.gov NCT02007369; https://clinicaltrials.gov/show/NCT02007369 (Archived by WebCite® at http://www.webcitation.org/6c3RbltQG) [J Med Internet Res 2015;17(10):e238]

Knowledge translation (KT) refers to the process of moving evidence into healthcare policy and practice. Understanding the experiences and perspectives of individuals who develop careers in KT is important for designing training programs and opportunities to enhance capacity in KT research and practice. To date, however, limited research has explored the challenges that trainees encounter as they develop their careers in KT.The purpose of this study is to identify the challenges that KT trainees face in their KT research or practice.An online survey was conducted with a sample of trainees associated with the Knowledge Translation Trainee Collaborative or the KT Canada Summer Institutes, with written responses thematically analyzed.A total of 35 individual responses were analyzed, resulting in the identification of six interrelated themes, listed in descending order of prevalence: limited availability of KT-specific resources (54%), difficulty inherent in investigating KT (34%), KT not recognized as a distinct field (23%), colleagues' limited knowledge and understanding of KT (20%), competing priorities and limited time (20%), and difficulties in relation to collaboration (14%).KT trainees experience specific challenges in their work: limited understanding of KT in other stakeholder groups; limited structures or infrastructure to support those who do KT; the inherently interdisciplinary and applied nature of KT; and the resultant complexities of scientific inquiry in this field, such as designing and testing multifaceted, multilevel implementation strategies and accounting for contextual factors.KT training and capacity-building efforts are needed to better position health systems to routinely adopt knowledge into healthcare policy and practice.

Chromosome 1q has previously been linked to bone mineral density (BMD) variation in the general population in several genome-wide linkage studies in both humans and mouse model. The aim of present study is to replicate and fine map the QTL influencing BMD in chromosome 1q in southern Chinese. Twelve microsatellite markers were genotyped for a 57 cMu region in the chromosome 1q in 306 southern Chinese families with 1,459 subjects. Each of these families was ascertained through a proband with BMD Z-scores less than -1.3 at the hip or spine. BMD (g/cm2) at the L1-4 lumbar spine, femoral neck (FN), trochanter and total hip was measured by dual-energy X-ray absortiometry. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software. Four markers (D1S2878, D1S196, D1S452, and D1S218) achieved a LOD score greater than 1.0 with spine BMD, with the maximum multipoint LOD score of 2.36 at the marker D1S196. We did not detect a LOD score greater than 1.0 for BMD at the FN, trochanter, or total hip in multipoint linkage analyses. Our results present the first evidence for the presence of an osteoporosis susceptibility gene on chromosome 1q in non-Caucasian subjects. Further analyses of candidate genes are warranted to identify QTL genes and variants underlying the variations of BMD in this region.

Seventeen non-transfusion-dependent Chinese haemoglobin H (Hb H) disease patients (age 29-76 years) with serum ferritin900 microg/l were treated with deferiprone for up to 18 months. One patient withdrew and data from 16 patients were analysed. Sixteen other Hb H patients with ferritin900 microg/l, matched for age and genotype, acted as controls. Treatment was well tolerated except for mild arthralgia. Serum ferritin fell with treatment, reaching significance at 6 and 18 months (from 1492.3 +/- 901.4 to 519.4 +/- 405.4 microg/l at 18 months, P = 0.0008). Nine of 16 patients had levels below 397 microg/l before 18 months. Serum ferritin remained stable 6 months after stopping treatment. In contrast, there was no change in ferritin levels in the control group. Magnetic resonance imaging was used for measurement of liver iron content. Spin echo T(1)-signal intensity ratio (T(1)-SIR) and gradient echo T(2)-signal intensity ratio (T(2)-SIR) increased with treatment. T(2)-SIR rose from 0.17 +/- 0.08 pretreatment to 0.58 +/- 0.50 at 2 years (P = 0.0055). Improvement occurred in 12 of 16 patients, reaching normal in three patients. Using echocardiography, peak early diastolic : late diastolic blood flow (E/A) remained unchanged with treatment, but isovolumic relaxation time (IVRT) was prolonged at 2 years indicating mild impairment of diastolic function. All systolic function parameters were normal. A longer treatment period is desirable to demonstrate improvement in cardiac function.

Background: Chromosome 11q has not only been found to contain mutations responsible for the several Mendelian disorders of the skeleton, but it has also been linked to bone mineral density (BMD) variation in several genome-wide linkage studies. Furthermore, quantitative trait loci (QTL) affecting BMD in inbred mice and baboons have been mapped to a region syntenic to human chromosome 11q. The aim of the present study is to determine whether there is a QTL for BMD variation on chromosome 11q in the Chinese population. Methods: Nineteen microsatellite markers were genotyped for a 75 cM region on 11q13-25 in 306 Chinese families with 1,459 subjects. BMD (g/cm2) was measured by DXA. Linkage analyses were performed using the variance component linkage analysis method implemented in Merlin software. Results: For women, a maximum LOD score of 1.62 was achieved at 90.8 cM on 11q21 near the marker D11S4175 for femoral neck BMD; LOD scores greater than 1.0 were observed on 11q13 for trochanter BMD. For men, a maximum LOD score of 1.57 was achieved at 135.8 cM on 11q24 near the marker D11S4126 for total hip BMD. Conclusion: We have not only replicated the previous linkage finding on chromosome 11q but also identified two sex-specific QTL that contribute to BMD variation in Chinese women and men.

Thyrotoxic (hypokalemic) periodic paralysis (TPP) is a frequent complication of thyrotoxicosis among Chinese men. To determine the genetic association of TPP, we studied 97 male TPP patients, 77 Graves' disease patients without TPP, and 100 normal male subjects. Mutations of the voltage-dependent calcium channel (Ca(v)1.1), sodium channel (Na(v)1.4), and potassium channel (K(v)3.4), and association of the microsatellite markers on chromosome 1 in the region of the Na/K-ATPase subunits alpha1, alpha2, and beta1 were studied. None of the TPP patients carried the known mutations in Ca(v)1.1, Na(v)1.4, and K(v)3.4 genes. There was no association of TPP with the microsatellite markers that mapped to 1p13, 1q21-23, and 1q22-25. We detected 12 single nucleotide polymorphisms (SNPs) in Ca(v)1.1 in our population, of which three were novel. Significant differences in the SNP genotype distribution between TPP compared with Graves' disease controls and normal controls were seen at the 5' flanking region nucleotide (nt) -476 (P = 0.02), intron 2 nt 57 (P0.01), and intron 26 nt 67 (P0.001). Because these SNPs lie at or near the thyroid hormone responsive element, it is possible that they may affect the binding affinity of the thyroid hormone responsive element and modulate the stimulation of thyroid hormone on the Ca(v)1.1 gene.

Two tri-axial accelerometers were placed on the wrists (one on each hand) of the patients with Parkinson's disease (PD) and a non-PD control group. Subjects were asked to perform three of the upper extremity motor function tasks from the Unified Parkinson's Disease Rating Scale (UPDRS) test. The tasks were: 1) finger tapping, 2) opening and closing of palms, and 3) pronation-supination movements of the forearms. The inertia signals were wirelessly received and stored on a computer for further off-line analysis. Various features such as range, standard deviation, entropy, time to accomplish the task, and maximum frequency present in the signal were extracted and compared. The results showed that among the studied population, "standard deviation", "range", "entropy", "time" and "max frequency" are the best to worst features, respectively, to distinguish between the non-PD and PD subjects. Furthermore, using the mentioned features, it is more probable to distinguish between the non-PD and PD subjects from tasks 2 and 3 as opposed to task 1.

Adolescent idiopathic scoliosis (ALS) is one of the most common orthopedic disorders, affecting up to 4% of schoolchildren worldwide. We studied seven unrelated multiplex families of southern Chinese descent with AIS, consisting of 25 affected members. A genomewide scan with >400 fluorescent microsatellite markers was performed. Multipoint linkage analysis by GENEHUNTER revealed significant linkage of the abnormal phenotype to the distal short arm of chromosome 19, with both a maximum multipoint LOD score and a nonparametric LOD score of 4.93. Two-point linkage analysis by MLINK gave a LOD score of 3.63 (recombination fraction θ [m=f] = 0.00) at D19S216. Further high-density mapping and informative recombinations defined the AIS critical region in the vicinity of D19S216, flanked by D19S894 and D19S1034, spanning 5.2 cM on the sex-averaged genetic map on chromosome 19p13.3., published_or_final_version

Objective To examine if there were changes in the proportion of hardcore smokers and factors associated with hardcore smoking before and after implementation of smoke-free legislation, and warning labels on cigarette packets in Hong Kong in January 2007. Study design Repeated cross-sectional surveys of the general population in Hong Kong. Methods Data from all daily smokers aged ≥15 years in the population-based Thematic Household Surveys from 2005 ( n = 3740) and 2008 ( n = 2958) were used to estimate the prevalence of hardcore smokers before and after implementation of smoke-free legislation. A logistic regression model was used to identify the factors associated with hardcore smoking, and to examine if there were any changes in their associations with the likelihood of hardcore smoking after implementation of smoke-free legislation. Results The proportion of hardcore smokers among current daily smokers increased significantly from 22.5% [95% confidence interval (CI) 21.1–23.8%] in 2005 to 28.3% (95% CI 26.7–29.9%) in 2008. Change in the strength of the association of hardcore smoking with three factors was observed. The strength of the association between hardcore smoking and ‘necessity in social functions’ [odds ratio (OR) 0.54, 95% CI 0.31–0.95) and ‘necessity for killing time’ (OR 0.56, 95% CI 0.36–0.89) decreased, while the association between hardcore smoking and ‘necessity as refreshment’ increased (OR 3.02, 95% CI 1.43–6.39) after implementation of smoke-free legislation and warning labels on cigarette packets. ‘Smoking had become a habit’ was the factor associated most strongly with hardcore smoking (OR 4.88, 95% CI 4.02–5.93). Conclusions The proportion of hardcore smokers remained stable in Hong Kong from 2005 to 2008. While the implementation of the two tobacco control measures may have provided an environment to reduce social smoking in hardcore smokers, addiction appeared to be the most important factor associated with hardcore smoking. More effective and tailor-made cessation services that target this group of smokers are needed.

The study aim was to evaluate the association between genetics referrals, training in medical school, residency, or continuing medical education and physician knowledge of hereditary breast and ovarian cancer (HBOC). A survey of 55 questions was administered to 140 physicians evaluating knowledge and practice patterns regarding HBOC. Physicians with genetics training during residency were more likely to recognize that most instances of ovarian cancer are not hereditary (odds ratio (OR) = 3.16; 95 % confidence interval (CI) 1.32, 7.58). Physicians with continuing medical education (CME) training on genetics were more likely to identify that screening can be improved for those with a hereditary mutation (OR = 4.28; 95 % CI 1.32, 13.90). Primary care physicians who frequently referred for genetics were more likely to recognize that maternal history is not more important than paternal history (OR = 2.51; 95 % CI 1.11, 5.66), that screening can be improved for those with hereditary risk (OR = 4.06; 95 % CI 1.08, 15.22), and that females with a hereditary breast cancer risk would have different recommendations for screening than someone without this risk (OR = 4.91; 95 % CI 1.04, 23.25). Our data suggest that training and frequency of genetics referrals may be associated with knowledge of general risk assessment for HBOC.

Sequential effects are ubiquitous in decision-making, but no more than in the absolute identification task where participants must identify stimuli from a set of items that vary on a single dimension. A number of competing explanations for these sequential effects have been proposed, and recently Matthews and Stewart [(2009a). The effect of inter-stimulus interval on sequential effects in absolute identification. The Quarterly Journal of Experimental Psychology, 62, 2014–2029] showed that manipulations of the time between decisions is useful in discriminating between these accounts. We use a Bayesian hierarchical regression model to show that inter-trial interval has an influence on behaviour when it varies across different blocks of trials, but not when it varies from trial to trial. We discuss the implications of both our and Matthews and Stewart's results on the effect of inter-trial interval for theories of sequential effects.

Identification of founder mutations in various ethnic groups is important to improve genetic screening and cancer risk assessment because it makes a more specific approach for molecular testing that targets the founder allele possible, thus resulting in reduced cost of genetic testing and faster turnaround time. The high frequency of founder mutations in a given population provides a large patient cohort not only for robust information regarding penetrance but also accurate assessment of the effectiveness of preventive measures. Previously, our laboratory identified and reported a recurrent BRCA2 mutation in 4 unrelated probands in a cohort of 119 high-risk women [1]. All these probands were from Chinese ancestry and 81.5% were from Guangdong province of Southern China. The recurrent mutation c.3109C[T (p.Gln1037X) was located in exon 11 of BRCA2. By prediction, this mutation resulted in the creation of an early termination codon and a truncated BRCA2 protein product. The haplotype analysis confirmed the mutation to be a founder mutation of Southern Chinese. To date, BRCA mutations are scattered over all exons and thus genetic tests for these BRCA1/2 genes require a mutation screening method of the entire coding regions of the genes. In our laboratory, we currently offer BRCA1/2 mutation screening in Hong Kong to Chinese women with breast or ovarian cancer at age 45 years and below, or with a history of BRCA related cancer such as breast, ovarian, colon, prostate in the family using full gene sequencing. This BRCA1/2 mutation detection procedure is time-consuming and labor intensive. Recently, increasing numbers of reports use high-resolution melting (HRM) as a promising pre-screening method of gene scanning for rapid identification of BRCA1/2 variants [2–7]. HRM analysis is a new and useful method for fast genotyping and high-throughput mutation scanning of disease-associated genes in genome diagnostics [8–10]. To date, little is known about the penetrance of BRCA founder mutation in Chinese population. So far, apart from our recently identified BRCA2 founder mutation, only one other founder mutation in BRCA1 (1081delG) found in Southern Chinese population has been reported [11]. Thus, using our recently developed HRM assays, we determined the frequency of these two BRCA1/2 founder mutations in Southern Chinese population. Between March 2007 and September 2009, a total of 709 Chinese patients with breast and/or ovarian cancer were recruited from the Hong Kong Hereditary Breast Cancer Family Registry to perform BRCA1/2 genetic testing. Of these 709 patients, 705 are only breast cancer patients and 14 are both breast and ovarian cancer patients. The mean age at diagnosis of breast cancer was 44.6 years old (range 18–83) and that of ovarian cancer was A. Kwong E. K. O. Ng H. N. Wong V. W. Chan Division of Breast Surgery, Queen Mary and Tung Wah Hospital, The University of Hong Kong, Hong Kong, China

Natural killer (NK) cell lymphomas are a group of rare but highly aggressive malignancies. Clinically, they can be divided into nasal NK cell lymphomas, nonnasal NK cell lymphomas, and aggressive NK cell lymphoma/leukemia. To determine the patterns of genetic deletions in these tumors, we performed loss of heterozygosity (LOH) analysis on 15 cases (11 nasal and four nonnasal), and fluorescence in situ hybridization on three cases of aggressive lymphoma/leukemia. A panel of 41 microsatellite loci on chromosomes 6q, 11q, 13q, and 17p were investigated. LOH at chromosomes 6q and 13q was frequently detected in NK cell lymphomas, being found in 80 and 66.7% of cases, respectively. LOH at chromosomes 11q and 17p was less common, being found in 28.6 and 30.8% of cases, respectively. Most tumors showed multiple loci deletions at different chromosomal regions, but several patterns of LOH could be defined. LOH at chromosome 6q was found in 90.9% of nasal NK cell lymphomas, but only in 50% of nonnasal NK cell lymphomas. LOH at chromosome 13q was found in 63.6% of nasal NK cell lymphomas and 75% of nonnasal NK cell lymphomas. For nasal NK cell lymphomas, LOH at 13q was found in 33.3% of cases at presentation, but 100% of cases at relapse. Five tumors showed LOH in only one chromosomal region, involving 6q in three cases (two nasal and one nonnasal), and 13q in two cases (both nonnasal). For the three cases of aggressive NK cell lymphoma/leukemia studied by fluorescence in situ hybridization, DNA loss at 13q14 and 17p13 regions were demonstrated. 17p13 seemed to be more commonly involved in aggressive than nasal and nonnasal NK cell lymphomas. Our results suggested that consistent patterns of LOH could be defined in NK cell malignancies. These deleted loci may contain genes important in the initiation and progression of this lymphoma.

Carrier detection and prenatal testing for haemophilia B in Oriental populations have been hampered by the lack of informative markers within the factor IX (FIX) gene. We detected a T/C nucleotide variation at nucleotide 32770 in the poly-A region of the FIX gene in the mother of a haemophilia B child. Analysis of 139 unrelated alleles revealed a heterozygosity rate of 0.193, thus offering an additional marker for linkage analysis. Together with two other polymorphic sites (5' MseI and 3' HhaI) found in Chinese and Thai populations, these polymorphisms were useful in 66% of the families studied.

Background: A bioelectronic detection platform has recently been developed that facilitates the detection and characterization of nucleic acids. The DNA chip platform is compatible with homogeneous assays because separate labeling and wash steps are not required. A one-step, bioelectronic detection assay was developed to genotype patient samples with respect to the H63D polymorphism of the Hfe gene, associated with hereditary hemochromatosis. Methods and Results: Electrode arrays were modified with DNA capture probes that were perfectly matched to the wild-type or mutant allele of H63D. Amplicons containing the polymorphic site were hybridized with the capture probes on the electrode arrays in the presence of electronically labeled reporter (signaling) probes. Voltammetric analysis of the electrode arrays was conducted first at ambient temperature and then at elevated temperature. The electronic signal was preferentially diminished at elevated temperature from electrodes that hybridized with mismatched target amplicons. Conclusion: An assay for bioelectronic genotyping of the H63D polymorphism was developed and used with six patient specimens to show the feasibility of this system as a model for point mutation detection.

Purpose A program of cord blood stem cell (CBSC) transplants for patients with beta-thalassemia major was initiated in conjunction with the prenatal diagnostic service in 1994. Two patients who received HLA-matched related CBSC transplants with posttransplant fetal hemoglobin (HbF) expression are described and the literature is reviewed. Patients and methods After screening 12 pregnancies, matched sibling CBSC transplants were performed for 2 girls with beta-thalassemia major when they were 3.8 and 2.2 years old, respectively. Their HbF was assayed serially. Results The nucleated cell counts/kg were 11.4 x 10(7) and 6.2 x 10(7), which engrafted on days 19 and 24, respectively. The children are now transfusion-independent at 3 years and 1.2 years posttransplant. Their HbF levels showed a rapid rise posttransplant and reached peak levels of 37.2% and 42.2% on day 83 and day 88, respectively. The HbF levels declined to 1.0% and 3.8% on day 581 and day 305, respectively. Nine other sibling CBSC transplants for thalassemias have been reported with an engraftment rate of approximately 50%. Graft rejection was related to insufficient CBSC number in one. Conclusions HbF levels in patients with beta-thalassemia major after CBSC transplants could be influenced by many factors, including reactivation of HbF synthesis, intrinsic rate of Hb switching of CBSC, and mixed chimerism.

A 37-year-old untransfused, non-drinking man with Hemoglobin H-CS disease presented with insulin-dependent diabetes mellitus, markedly elevated serum ferritin level, and marked iron deposition in hepatocytes. He did not carry either of the two common mutations of the HLA-H gene for hereditary hemochromatosis, namely, Cys282Tyr and His68Asp, nor did he have the associated HLA marker (HLA-A3, B7 nor B-14) for the disease. Patient with HbH disease should be monitored for iron overload.

The molecular defect in two unique cases of Hb H hydrops fetalis has been characterized. Both cases are due to co-inheritance of a 'non-deletion' defect affecting the alpha2 gene: at codon 30 delta GAG, Glu) and codon 59 (G --> A, Gly --> Asp) respectively, and a zeta-alpha thalassaemia (thal) 1 or alpha thal 1 genotype. These two non-deletion defects, unlike previously described cases, resulted in severe anaemia of the fetuses and emphasize the importance of performing prenatal diagnosis for these families.

Exocyst-positive organelle (EXPO) is a double-membrane organelle mediating unconventional protein secretion in plants. The Arabidopsis exocyst subunit AtExo70E2 is essential for the recruitment of other exocyst subunits to EXPO and plays a key role in EXPO formation in both plant and animal cells., In contrast to a single copy of Exo70 in yeast and mammals, the Arabidopsis genome contains 23 paralogues of Exo70 (AtExo70). Using AtExo70E2 and its GFP fusion as probes, we recently identified a novel double-membrane organelle termed exocyst-positive organelle (EXPO) that mediates an unconventional protein secretion in plant cells. Here we further demonstrate that AtExo70E2 is essential for exocyst subunit recruitment and for EXPO formation in both plants and animals. By performing transient expression in Arabidopsis protoplasts, we established that a number of exocyst subunits (especially the members of the Sec family) are unable to be recruited to EXPO in the absence of AtExo70E2. The paralogue AtExo70A1 is unable to substitute for AtExo70E2 in this regard. Fluorescence resonance energy transfer assay and bimolecular fluorescence complementation analyses confirm the interaction between AtExo70E2 and Sec6 and Sec10. AtExo70E2, but not its yeast counterpart, is also capable of inducing EXPO formation in an animal cell line (HEK293A cells). Electron microscopy confirms the presence of double-membraned, EXPO-like structures in HEK293A cells expressing AtExo70E2. Inversely, neither human nor yeast Exo70 homologues cause the formation of EXPO in Arabidopsis protoplasts. These results point to a specific and crucial role for AtExo70E2 in EXPO formation.

Background: Knowledge about hereditary colorectal cancer (CRC) can aid cancer screening and prevention in high-risk patients. Genetic testing, once conducted primarily at academic centers, is now routinely performed in a variety of clinics. Nonacademic physicians may not be aware of hereditary CRC standards of care. Methods: From August to November 2012, a survey was administered to predominantly primary care physicians evaluating academic center affiliation, past training in genetics and knowledge regarding hereditary CRC. Results: One hundred forty physicians completed the survey. Knowledge of hereditary CRC was neither associated with academic affiliation nor with training during medical school or residency, but with continuing medical education (CME) training. Those with CME training were more likely to know that screening could be enhanced for patients with a hereditary cancer risk (OR = 4.49, 95% CI = 1.40-14.38) and that an individual with hereditary CRC would have different screening recommendations (OR = 7.49, 95% CI = 1.37-40.81). Residency training and CME training were associated with more frequent hereditary risk assessment. Conclusion: Genetics training may be associated with physicians' knowledge and assessment of hereditary CRC. Training at the CME level in particular may be integral to the delivery of genetic services in clinical practice.

A clonal-specific polymerase chain reaction technique to detect T-cell receptor delta gene rearrangement in acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) was evaluated. It was applied to detect minimal residual disease. A sensitive and specific technique to detect minimal residual disease for T-cell malignancies was explored. Southern analysis and polymerase chain reaction (PCR) were used to detect the rearranged V-D-J segment of T-cell receptor delta (TCR delta) gene from malignant cell specimens of patients with leukemia and lymphoma of T-cell lineage. The PCR product was sequenced and from the DNA sequences of the V-D-J region, a 3' anti-sense primer was designed and synthesized for clonal specific PCR (CS-PCR). T-cell receptor delta (TCR-delta) gene rearrangement was studied in 40 cases of acute leukaemia and lymphoma of T-cell lineage at diagnosis. Using Southern analysis, the positive rates were 28 and 32% for the 18 T-lymphoma and 22 T-ALL, respectively. A one stage Polymerase Chain Reaction (PCR) technique was used to detect the rearrangement in Southern positive cases and the PCR positive rates were 80 and 86%, respectively. The PCR technique had a sensitivity of 0.1%. Serial follow-up marrow specimens were available from 4 T-ALL patients following chemotherapy for monitoring of minimal residual disease. Their PCR products were DNA sequenced. A 3' primer was designed for each case for a clonal specific (CS) PCR. The technique had a sensitivity of 0.003%. It was applied to detect minimal residual disease in serial follow-up marrow samples. The first patient had persistent negative CS-PCR results and enjoyed continuous remission for more than 3 years. The second patient with negative one stage PCR but positive CS-PCR results had eventual relapse of leukaemia. The other two patients never achieved a morphological remission. These preliminary results appeared to support the usefulness of these PCR techniques in detecting minimal residual disease and predicting relapses for ALL. However, further clinical correlation in larger populations of patients is necessary.

Translocations involving chromosome band 11q23 are frequently found in infant acute leukemia and involve rearrangement of the MLL gene. In this study, 29 cases of adult acute myeloid leukemia (AML) were analyzed to determine the frequency of MLL gene rearrangement. Of these, 19 cases were karyotyped and none showed cytogenetic evidence of 11q23 aberration. MLL rearrangements were demonstrable in four cases, giving a frequency of 14% (429). Only one of the four cases with MLL rearrangement showed features typical of leukemia with 11q23 aberration; other cases were indistinguishable from those without MLL rearrangement. There was no apparent difference in presentation blast count, remission, and survival duration when cases with or without MLL rearrangement were compared. Clinicopathologic features of adult AML with MLL rearrangements may be heterogenous.

Introduction: We aim to develop a simple and sensitive array-based method for the detection of epidermal growth factor receptor ( EGFR ) gene mutations in the plasma of non–small-cell lung cancer patients and determine its use in the follow-up of those on tyrosine-kinase inhibitor (TKI) therapy. Method: DNA from 100 μl of plasma was amplified in the presence of peptide nucleic acid clamp to provide single-stranded template for the allele-specific arrayed primer extension reaction, incorporating cyanine-5-deoxycytidine triphosphate in the newly synthesized strands. The fluorescent product was visualized by laser at 670 nm. Results: Eleven different types of EGFR TKI drug-sensitive mutants (SM) were identified in plasma-DNA from 46 of 51 patients. Five patients carried only wild-type sequence. Plasma-DNA finding was concordant in 36 of 37 cases with tumor-sequencing data. This method could detect as little as 62.5 copies of mutant L858R; 125 copies of E709K + G719A or 625 copies of del 746–750 in the presence of 100,000 copies of wild-type EGFR. In 21 patients on longitudinal follow-up for up to 18 months, SM was found in all initial plasma samples, except for three samples collected after recent chemotherapy. Nine of 16 patients (56%) who responded to TKI had undetectable plasma EGFR mutant. SM was present concurrently with drug-resistant mutant in 44% of patients with disease progression while on TKI, the remaining 56% might have other mechanisms of resistance. Conclusion: The EGFR array provides a sensitive, inexpensive, and robust method for monitoring non–small-cell lung cancer patients' response to TKI, and obviates the need of repeated lung biopsy.

Trainees (e.g., graduate students, residents, fellows) are increasingly identifying knowledge translation as their research discipline. In Canada, a group of trainees have created a trainee-initiated and trainee-led national collaborative to provide a vehicle for trainees to examine the diversity of knowledge translation research and practice, and to link trainees from diverse geographical areas and disciplines. The aim of this paper is to describe our experience and lessons learned in creating the Knowledge Translation Trainee Collaborative. In this meeting report, we outline the process, challenges, and opportunities in planning and experiencing the collaborative's inaugural meeting as participant organizers, and present outcomes and learnings to date.

Objective To develop a comprehensive hepatitis B virus (HBV) array providing simultaneous analysis of 8 genotypes, 47 mutations of reverse-transcriptase polymerase gene and 18 mutations of S gene. Method Oligonucleotides corresponding to various HBV-normal and -mutant sequences were spotted onto pre-treated glass slides. Single-stranded templates of the HBV gene fragment were prepared from serum-DNA of HBV-infected patients by 2-staged PCR and subjected to allele-specific arrayed-primer extension with Cy5-dCTP. Fluorescein-labelled products were scanned at 670 nm. Results Comparative analysis of 100 unrelated samples using the array and a commercial kit, revealed 44 with additional mutations from the array, these were confirmed by sequencing. Analysis of 381 samples from 45 patients during 1–3 years of anti-viral therapy showed improved sensitivity with detection of drug-resistant mutations months before clinical relapse. The lower detection limit was 28 copies/mL. Conclusion The array is better than many existing methods as it provides both mutations and genotype data in a single analysis.

Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations. © 2011 by The American Society of Hematology., link_to_subscribed_fulltext

Initial screening for the common beta-thalassaemia mutations with allele-specific oligonucleotide probes in an at-risk family suggested non-paternity. Subsequent DNA fingerprinting of the members proved otherwise. The mother had a codon 41/42 frameshift mutation and the father's defect, determined by direct sequencing of PCR-amplified beta gene, was a codon 43 nonsense mutation. In the affected children, the close proximity of these two defects resulted in the absence of a hybridization signal to the normal probe in that region and a wrong assumption of homozygosity for the codon 41/42 mutation. The non-reactivity of the father's amplified DNA to the codon 41/42 thalassaemic probe accounted for the initial wrong conclusion of non-paternity. Since prior screening for beta-thalassaemia mutations is done in all prenatal diagnosis programmes and concomitant inheritance of these two defects is relatively common in the Chinese, this 'artefact' of false non-paternity is worth noting.

Seminested polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity-determining region 3 of the immunoglobulin (Ig) gene heavy chain from the malignant cell specimens of patients with leukemias and lymphomas of B-cell lineage. Two different pairs of primers were used sequentially. Twenty of the 27 (74%) acute lymphoblastic leukemia (ALL) patients, 14 of 19 (74%) chronic lymphocytic leukemia (CLL) patients and eight of 20 (40%) non-Hodgkin's lymphoma (NHL) patients, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by the seminested PCR. False-negative results appeared to occur more commonly in cases of lymphoma. The PCR analysis was also less likely to be positive if one-stage PCR studies with either pair of primers were both negative. The seminested PCR technique was found to have a high sensitivity of detecting malignant cells at the level of 0.02%. The clinical application of this assay needs to be investigated further.

This is a report on our attempt to use polymerase chain reaction (PCR) to detect rearrangement of the immunoglobulin gene in the tissue specimens obtained from 30 patients with non-Hodgkin's lymphomas. There were 20 B-cell lymphomas and 10 T-cell. All 20 B-cell lymphomas but none of the 10 T-cell lymphomas had JH rearrangement by Southern analysis. Two pairs of primers (V670/OL-4 and VH26/OL-4) were designed to amplify the CDR3 region of the immunoglobulin gene heavy chain. The PCR analysis was positive using either one or both pairs of primers in 11 of the the 20 cases (55 per cent) of B-cell lymphomas which all had positive rearrangement by Southern analysis. The two pairs of primers seemed to produce complementary results as the specimens may be positive to one pair but negative to the other. The false negative rate of 45 per cent is however much higher than the respective figures of 18 per cent and 0 per cent observed in our patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia in a previous study. Peripheral blood and bone marrow biopsy specimens obtained at the time of initial diagnosis were available from 10 patients with B-cell lymphomas whose lymph node biopsy specimens at the time of diagnosis were positive by both Southern analysis and PCR. All these peripheral blood and marrow specimens had no microscopic evidence of involvement by lymphoma cells and JH rearrangement was not detected by Southern analysis. However, rearranged bands identical to that of the lymph node biopsy specimen were detected by PCR in the peripheral and marrow blood of one of them. This PCR technique has been shown to have a sensitivity of 0.1 per cent in our previous report and may be more useful than morphology alone or Southern analysis in detecting minimal lymphomatous involvement in the peripheral blood and bone marrow at the time of initial diagnosis. Further clinical correlation is required to confirm the finding.

Hepatocellular carcinoma (HCC) is a lethal malignancy for which there are no effective therapies. To develop rational therapeutic approaches for treating this disease, we are performing proof-of-principle studies targeting molecules crucial for the development of HCC. Here, we show that cadherin-17 (CDH17) adhesion molecule is up-regulated in human liver cancers and can transform premalignant liver progenitor cells to produce liver carcinomas in mice. RNA interference-mediated knockdown of CDH17 inhibited proliferation of both primary and highly metastatic HCC cell lines in vitro and in vivo. The antitumor mechanisms underlying CDH17 inhibition involve inactivation of Wnt signaling, because growth inhibition and cell death were accompanied by relocalization of β-catenin to the cytoplasm and a concomitant reduction in cyclin D1 and an increase in retinoblastoma. Conclusion: Our results identify CDH17 as a novel oncogene in HCC and suggest that CDH17 is a biomarker and attractive therapeutic target for this aggressive malignancy. Copyright © 2009 by the American Association for the Study of Liver Diseases., link_to_subscribed_fulltext

The common restriction fragment length polymorphisms (RFLPs) associated with the FIX gene: 5' BamH I, Dde I, BamH I (2), Taq I and 3' Hha I were absent or of low incidence in Southern Chinese and are therefore not useful for linkage analysis. No deletion was detected amongst seven consecutive unrelated haemophilia B patients, but one had an insertion of a 15 kb Pvu II fragment containing exon d. Using an alternate strategy of polymerase chain reaction (PCR) amplification and direct sequencing, the molecular defect in the other six patients was defined. The four novel mutations characterized were: nucleotide (nt) 6410 G----C (Gly12----Ala); nt 31261 delta T (stop codon 31 bp downstream); nt 31260 C----G (Thr380----Ser) and nt 31122 C----A (Ala34----Asp). Two patients had the same mutation at nt 6365, G----A (Arg-4----Gln), identical to one previously described in other ethnic groups, suggesting that this is a hotspot for mutation. Each of the mutations was found to affect an enzyme recognition site and could thus be identified by direct visualization of abnormal restriction fragments in amplified genomic DNA. This allows rapid and accurate DNA diagnosis of haemophilia B in an ethnic group which otherwise shows little or no polymorphism for the common RFLP sites.

Background: hRad9 is a cell cycle checkpoint gene that is up-regulated in breast cancer. We have previously shown that the mRNA up-regulation correlated with tumor size and local recurrence. Immunohistochemical studies were made to better define the role of hRad9 in breast carcinogenesis. Methods: Localisation of hRad9 protein were performed on paired tumor and normal breast tissues. Immunoblotting with and without dephosphorylation was used to define the protein isolated from breast cancer cells. Results: Increased hRad9 protein was observed in breast cancer cells nucleus compared to non-tumor epithelium. This nuclear protein existed in hyperphosphorylated forms which may be those of the hRad9-hRad1-hHus1 complex. Conclusion: Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth. © 2008 Chan et al; licensee BioMed Central Ltd., published_or_final_version

The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T-cell receptor (TCR), and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement, and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage, which is similar to reports in the white population. However, the incidence of bcl-2 gene rearrangement in follicular B-cell lymphoma is lower than that reported in the US but comparable with that in Japan.

This descriptive study was undertaken to investigate patients' perceptions of the seven content areas commonly included in cardiac teaching in terms of how important and how realistic they were for being learned following the experience of an acute myocardial infarction (MI). Lazarus's stress-coping theory was used as a framework for the study. A sample of 30 MI subjects were interviewed before discharge and during early convalescence. Before discharge, subjects rated six out of the seven content areas as "important" for learning. Although the information was considered important, it was not rated as equally realistic to learn. During early convalescence, mean scores under 'important to learn' were slightly lower, but all seven content areas were rated as significantly more realistic to be learned (P less than 0.05). Little variation in patients' perceptions of the importance of teaching content was noted over time. However, there was major variation between their perceptions of how important and how realistic it was to learn the material before discharge. Both dimensions, how important and how realistic, are therefore crucial to consider in cardiac teaching.