於香港一所大學醫院推行以畸變產物耳聲發射檢查為新生兒進行聽覺普查計劃之可行性

OBJECTIVE: To assess the feasibility of implementing a universal neonatal hearing screening programme using distortion product otoacoustic emission detection at a major teaching hospital in Hong Kong. DESIGN: Descriptive study and questionnaire. SETTING. Teaching hospital, Hong Kong. METHODS: A total of 1064 infants, together with their mothers, were successfully recruited for the study. The participation rate was 99.3%. A three-stage hearing screening protocol using distortion product otoacoustic emission detection was adopted. Each of the participating infants was screened on three separate occasions (day 1-4, day 5-14, and day 21-30 after birth), irrespective of the test results. A questionnaire was administered to 364 randomly selected mothers to determine whether as consumers of the hearing screening service, mothers would find screening desirable. RESULTS: Results of the screening demonstrated an incidence of permanent bilateral hearing loss (>or=40 dB in the better ear) of 0.28%. The results also showed that 3.5% of the screened infants were referred for subsequent diagnostic audiological assessment, including those suspected with unilateral as well as bilateral hearing loss. Data obtained were comparable to other reported results obtained using multi-stage screening protocols. Taking both the false positive rate and the default rate into consideration, the most appropriate time for screening in this hospital setting appeared to be around day 5 to 14 when infants returned to the hospital's day centre as out-patients for routine medical follow-up. Since this day centre service is not generally provided by all maternity hospitals in Hong Kong, an alternative time for screening would be around day 21 to 30 when infants could return as out-patients solely for the hearing test. The results of the questionnaire suggested that most mothers thought a neonatal hearing screening would be desirable (91.35%). The majority (81.70%) indicated a preference for screening either within a few days of birth at the maternity ward prior to discharge from the hospital, or between 5 and 30 days when returning to the hospital as an out-patient. CONCLUSION: It was concluded that a universal neonatal hearing screening programme could be readily implemented in a maternity hospital setting in Hong Kong.published_or_final_versio

Clinical utility of exercise training in heart failure with reduced and preserved ejection fraction

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed

SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer

Purpose: To evaluate haptoglobin (Hp) in ovarian cyst fluid as a diagnostic biomarker for epithelial ovarian cancers (EOCs) using surface-enhanced Raman spectroscopy (SERS)-based in vitro diagnostic assay for use in an intraoperative setting. Methods: SERS-based method was used to detect and quantify Hp in archived ovarian cyst fluids collected from suspicious ovarian cysts and differentiate benign tumors from EOCs. The diagnostic performance of SERS-based assay was verified against the histopathology conclusions and compared with the results of CA125 test and frozen sections. Results: Hp concentration present in the clinical cyst fluid measured by SERS was normalized to 3.3 mg/mL of standard Hp. Normalized mean values for patients with benign cysts were 0.65 (n=57) and malignant cysts were 1.85 (n=54), demonstrating a significantly (P<0.01) higher Hp in malignant samples. Verified against histology, Hp measurements using SERS had a sensitivity of 94% and specificity of 91%. Receiver operating characteristic curve analysis of SERS-based Hp measurements resulted in area under the curve of 0.966±0.03, establishing the robustness of the method. CA125 test on the same set of patients had a sensitivity of 85% and specificity of 90%, while frozen section analysis on 65 samples had 100% sensitivity and specificity. Conclusion: With a total execution time of <10 minutes and consistent performance across different stages of cancer, the SERS-based Hp detection assay can serve as a promising intraoperative EOC diagnostic test.National Medical Research Council (NMRC), Singapore; Bio-Medical Research Council of Agency for Science, Technology and Research (A*STAR), and the NHIC Innovation to Develop (I2D

Effect of remote ischemic preConditioning on liver injury in patients undergoing liver resection: the ERIC-LIVER trial

OBJECTIVE: Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). METHODS: This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. RESULTS: 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5-419.5 versus 172.5 IU/L IQR 115-298 respectively, p = 0.61). Groups were similar in secondary endpoints. CONCLUSION: This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy

A computational approach to chemical etiologies of diabetes.

Computational meta-analysis can link environmental chemicals to genes and proteins involved in human diseases, thereby elucidating possible etiologies and pathogeneses of non-communicable diseases. We used an integrated computational systems biology approach to examine possible pathogenetic linkages in type 2 diabetes (T2D) through genome-wide associations, disease similarities, and published empirical evidence. Ten environmental chemicals were found to be potentially linked to T2D, the highest scores were observed for arsenic, 2,3,7,8-tetrachlorodibenzo-p-dioxin, hexachlorobenzene, and perfluorooctanoic acid. For these substances we integrated disease and pathway annotations on top of protein interactions to reveal possible pathogenetic pathways that deserve empirical testing. The approach is general and can address other public health concerns in addition to identifying diabetogenic chemicals, and offers thus promising guidance for future research in regard to the etiology and pathogenesis of complex diseases

A new class of pluripotent stem cell cytotoxic small molecules

10.1371/journal.pone.0085039PLoS ONE93-POLN

Persistent orocutaneous and anal fistulae induced by nicorandil: a case report

<p>Abstract</p> <p>Introduction</p> <p>Although nicorandil is prescribed widely, awareness of its potential to cause serious complications to the gastrointestinal tract mucosa is limited. Whilst nicorandil-induced oral and anal ulceration is well documented in the literature, nicorandil-induced fistulation is not. This is the first report in the literature of a single patient demonstrating simultaneous orocutaneous and anal fistulae during nicorandil therapy. Two separate cases of orocutaneous and anal fistulae associated nicorandil usage have previously been documented in specialist journals.</p> <p>Case presentation</p> <p>A 71-year-old Caucasian man presented with a 3-year history of concurrent orocutaneous and anal fistulae. He had been exposed to 30 mg twice-daily nicorandil therapy for 4 years. Both fistulae responded poorly to intensive and prolonged conventional treatment but healed promptly on reduction and eventual withdrawal of nicorandil therapy.</p> <p>Conclusion</p> <p>Management of resistant cases of orocutaneous and anal fistulae in patients on high-dose nicorandil therapy may be impossible without reduction or even withdrawal of nicorandil.</p

Host Cell Transcriptome Profile during Wild-Type and Attenuated Dengue Virus Infection

10.1371/journal.pntd.0002107PLoS Neglected Tropical Diseases73

Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study)

10.1186/1471-2407-12-529BMC Cancer12-BCMA

Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for Hepatocellular Carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across TNM stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types