Isolation and characterization of a human heart cDNA encoding a new member of the small heat shock protein family — HSPL27

AbstractA novel cDNA clone was isolated from a human adult heart cDNA library. This cDNA clone is similar to the small heat shock protein (smhsp) in both DNA and amino acid sequences, especially in the conserved region. Sequence analysis has shown that the putative novel smhsp, named 27 kDa heat-shock-protein-like protein (HSPL27) is a protein of 241 amino acids with a deduced molecular mass of 26.7 kDa and a deduced pI of 8.0. We have expressed the HSPL27 in E. coli and the expressed protein was found to be present in the soluble fraction of the bacterial cell lysate. Chromosomal mapping data shows that the HSPL27 gene is located at human chromosome 5q11.2

Treatment of Chinese adolescents with anorexia nervosa in Hong Kong: The gap between treatment expectations and outcomes.

BACKGROUND AND OBJECTIVE: Anorexia nervosa (AN) is one of the most difficult-to-treat psychiatric disorders. AN is associated with individual vulnerability, societal and family factors. There has been limited research in Asia regarding the patients or their families' perceptions on its treatment. This study explored the perceived treatment outcomes among Chinese families having adolescents with AN. METHODS: Qualitative interviews were conducted on parents of adolescents with AN recruited through an eating disorder association in Hong Kong to understand their views and experiences regarding the help-seeking and treatment process. RESULTS: The parents expressed dissatisfaction towards help-seeking and treatment outcomes, including relationships with health professionals, hospitalization, health professionals' knowledge of AN, understanding of the treatment model and parents' role, amount of psychological support, and coordination among health professionals. The parents were unclear about the treatment plan as they received little explanation from the health professionals. The parents perceived that the AN treatment only focused on weight restoration with limited psychological support. Home diet monitoring was seen as a harsh task which worsened the relationship with their children. The parents often needed to take up the coordinator role and search around for different health professionals and integrate their advices by themselves. CONCLUSIONS: The study shows that limited psychoeducation, communication and coordination in the treatment for AN are major problems in a Chinese context. Open communication between the health professionals and the parents about the expected treatment outcomes and limitations is needed to enhance their mutual trust. Besides, treatment should emphasize not only family involvement but also empower them to fight against AN

The predictive value of G8 and the Cancer and aging research group chemotherapy toxicity tool in treatment-related toxicity in older Chinese patients with cancer

Introduction: Older patients experience a higher risk of treatment-related toxicity (TRT). The G8 screening tool was developed to separate cancer older patients fit to receive standard treatment from those who are frail and experiencing functional decline due to reduced organ function and multiple comorbidities. The Cancer and Aging Research Group chemotherapy toxicity tool (CARG-tt) questionnaire was developed to predict chemotherapy toxicity in geriatric patients. This prospective observational study evaluated the performance of G8 and CARG-tt in predicting severe TRT in older Chinese cancer patients. Methods: Chinese patients aged ≥65 with a diagnosis of solid malignancy and scheduled to receive anti-cancer treatment (chemotherapy or targeted therapy) were enrolled from March 2016 to July 2017 at the Department of Clinical Oncology at Queen Mary Hospital in Hong Kong. All patients completed the G8 and CARG-tt screening and pre-treatment assessments before starting treatment. Patients were monitored for any severe TRT, which was defined by grades 3–5 using the National Cancer Institute's Common Terminology Criteria for Adverse Events v4.03, treatment discontinuation, or unexpected hospitalization from starting to 30 days after treatment. Results: A total of 259 patients (male: 154, 59.5%; median age: 73.4, age range: 65–93) were enrolled in the study. Two hundred and ten (81.1%) patients received chemotherapy while the rest (n = 49, 18.9%) received targeted therapy. Overall, 146 patients (56.8%) experienced severe TRT. The mean G8 score was 12.4 (SD: 2.8). The G8 score had a significant association with unexpected admission (cutoff: 14, 41.3% vs. 26.5%, p = 0.03) but not significant in other types of TRTs. The mean CARG-tt score was 7.67 (SD: 3.7); it was not associated with severe TRTs. Conclusions: The G8 and CARG-tt demonstrated a weak prediction of severe TRT in older Chinese cancer patients. Future studies need to develop predictive tools for TRT in patients receiving novel antineoplastic therapies, with a focus on subgroup analysis for different populations

Gene Expression Profiling on the Molecular Action of Danshen-Gegen Formula in a Randomized Placebo-Controlled Trial of Postmenopausal Women with Hypercholesterolemia

The Danshen-Gegen formula (DG) is a traditional Chinese herbal formula which has long been used to treat cardiovascular disease. DG was found to be a cardiovascular tonic in our recent research. However, a comprehensive investigation of the molecular mechanism of DG in cardiovascular disease has not been performed. The aim of this study was to clarify the transcriptional profiling of genes modulated by DG on postmenopausal women by using DNAmicroarray technology. We obtained 29 whole blood samples both from DG-treated and placebo-treated subjects. Blood lipid profile and intima-media thickness (IMT) were measured. Affymetrix GeneChip was used to identify differentially expressed genes (DEGs), followed by validation by the real-time PCR method. The results showed that DG-treated group has a significant improvement in IMT and lipid profile as compared to placebo-treated group. For the genomic study, the DG-treated group has a higher number of DEGs identified as compared to the placebo-treated group. Two important biological processes of “regulation of systemic arterial blood pressure by hormone” and “regulation of smooth muscle proliferation” have been identified by GePS in the DG-treated group. No significant biological process and cellular components were identified in the placebo-treated group. This genomic study on the molecular action of DG in postmenopausal women gathered sufficient molecular targets and pathways to reveal that DG could improve neointima thickening and hypertension

Social Europe. No 2/87

BACKGROUND: DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. RESULTS: Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. CONCLUSION: Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0408-0) contains supplementary material, which is available to authorized users

A 2-year prospective evaluation of the Prostate Health Index in guiding biopsy decisions in a large cohort

Objectives: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real-life setting for men with a prostate-specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. Patients and Methods: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow-up plan was then decided via shared decision-making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. Results: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score &lt;35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score &lt;35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score &lt;35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score &lt;35 group (13%) with a median follow-up of 2.4 years. Conclusion: In a real-life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high-grade prostate cancer detection rate when compared to PSA-driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow-up visits.</p

An update on genomic-guided therapies for pediatric solid tumors

YesCurrently, out of the 82 US FDA-approved targeted therapies for adult cancer treatments, only three are approved for use in children irrespective of their genomic status. Apart from leukemia, only a handful of genomic-based trials involving children with solid tumors are ongoing. Emerging genomic data for pediatric solid tumors may facilitate the development of precision medicine in pediatric patients. Here, we provide an up-to-date review of all reported genomic aberrations in the eight most common pediatric solid tumors with whole-exome sequencing or whole-genome sequencing data (from cBioPortal database, Pediatric Cancer Genome Project, Therapeutically Applicable Research to Generate Effective Treatments) and additional non-whole-exome sequencing studies. Potential druggable events are highlighted and discussed so as to facilitate preclinical and clinical research in this area.Seed Grant of Strategic Research Theme for Cancer, The University of Hong Kong of AKSC. VWY Lui is funded by the Research Grant Council, Hong Kong (#17114814, #17121616, General Research Fund; T12–401/13-R, Theme-based Research Scheme), and the Start-up Fund, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong. W Piao is funded by the Faculty Postdoctoral Fellowship Scheme, Faculty of Medicine, the Chinese University of Hong Kong

Old Technique -New Evidence: Topical agents for musculo-skeletal injuries

The popular use of topical agents for the treatment of musculoskeletal injuries has persisted for centuries but not much scientific evaluations have been done. Since medicinal herbs are particularly popular in Asia, we started a systematic exploration on their choices, and their pharmacological activities; whether transcutaneous transport of bioactive components occur and above all, whether quality clinical evidences could be generated. We found that a search on the vast literature pool would reveal the favourable choices of herbal agents. Biological screening of those selected herbs showed that they probably follow three major common pathways to help with healing after injury, viz, anti-inflammation, pro-angiogenesis and cellular proliferation. Using a simple formula of selected herbs with the ideal bioactivities, evidence based clinical trials could be organized to further prove the efficacy. We have created two such formulae to be put on clinical trial. Our early pilot clinical trials on two minor injuries on the foot and one chronic inflammatory condition have yielded positive data on the value of such topical agents on pain and oedema control, as well as functional maintenance. There was also suggestion of more rapid bone healing. Although limitations exist clear with the small number of study subjects, the positive data and safe application support more studies

Incidence rates and management of urinary tract infections among children in Dutch general practice: results from a nation-wide registration study

BACKGROUND: We aimed to investigate incidence rates of urinary tract infections in Dutch general practice and their association with gender, season and urbanisation level, and to analyse prescription and referral in case of urinary tract infections. METHOD: During one calendar year, 195 general practitioners in 104 practices in the Netherlands registered all their patient contacts. This study was performed by the Netherlands Institute for Health Services Research (NIVEL) in 2001. Of 82,053 children aged 0 to 18 years, the following variables were collected: number of episodes per patient, number of contacts per episode, month of the year in which the diagnosis of urinary tract infection was made, age, gender, urbanisation level, drug prescription and referral. RESULTS: The overall incidence rate was 19 episodes per 1000 person years. The incidence rate in girls was 8 times as high as in boys. The incidence rate in smaller cities and rural areas was 2 times as high as in the three largest cities. Throughout the year, incidence rates varied with a decrease in summertime for children at the age of 0 to 12 years. Of the prescriptions, 66% were in accordance with current guidelines, but only 18% of the children who had an indication were actually referred. CONCLUSION: This study shows that incidence rates of urinary tract infections are not only related to gender and season, but also to urbanisation. General practitioners in the Netherlands frequently do not follow the clinical guidelines for urinary tract infections, especially with respect to referral