Expanded Newborn Screening for Inborn Errors of Metabolism in Hong Kong: Results and Outcome of a 7 Year Journey.

Newborn screening (NBS) is an important public health program that aims to identify pre-symptomatic healthy babies that will develop significant disease if left undiagnosed and untreated. The number of conditions being screened globally is expanding rapidly in parallel with advances in technology, diagnosis, and treatment availability for these conditions. In Hong Kong, NBS for inborn errors of metabolism (NBSIEM) began as a pilot program in October 2015 and was implemented to all birthing hospitals within the public healthcare system in phases, with completion in October 2020. The number of conditions screened for increased from 21 to 24 in April 2016 and then to 26 in October 2019. The overall recruitment rate of the NBS program was 99.5%. In the period between October 2015 and December 2022, 125,688 newborns were screened and 295 were referred back for abnormal results. The recall rate was reduced from 0.26% to 0.12% after the implementation of second-tier testing. An inherited metabolic disorder (IMD) was eventually confirmed in 47 infants, making the prevalence of IMD in Hong Kong 1 in 2674. At the time of the NBS result, 78.7% of the newborns with IMD were asymptomatic. There were two deaths reported: one newborn with methylmalonic acidemia cobalamin B type (MMACblB) died after the initial crisis and another case of carnitine palmitoyltransferase II deficiency (CPTII) died at 18 months of age after metabolic decompensation. The most common IMD noted were disorders of fatty acid oxidation metabolism (40%, 19 cases), closely followed by disorders of amino acid metabolism (38%, 18 cases), with carnitine uptake defect (19.1%, 9 cases) and citrullinemia type II (17%, 8 cases) being the two most common IMD picked up by the NBSIEM in Hong Kong. Out of the all the IMDs identified, 19.1% belonged to diverse ethnic groups. False negative cases were reported for citrullinemia type II and congenital adrenal hyperplasia during this period.

Haemophilia care in Asia: Learning from clinical practice in some Asian countries.

BACKGROUND: The healthcare systems in Asia vary greatly due to the socio-economic and cultural diversities which impact haemophilia management. METHODS: An advisory board meeting was conducted with experts in haemophilia care from Asia to understand the heterogeneity in clinical practices and care provision in the region. FINDINGS: The overall prevalence of haemophilia in Asia ranges between 3 and 8.58/100,000 patients. Haemophilia A was more prevalent as compared to haemophilia B with a ratio of around 5:1. There is under-diagnosis in the region due to lack of diagnosis, registries and/or lack of appropriate facilities in suburban areas. Most patients are referred to the haematologists by their families or primary care physicians, while some are identified during bleeding episodes. Genetic testing faces obstacles like resource constraints, services available at limited centres and unwillingness of patients to participate. Prophylaxis is offered for people with haemophilia (PWH) with a severe bleeding phenotype. Recombinant factors are approved in most countries across the region and are the preferred therapy. The challenges highlighted for not receiving a high standard of care include patients' reluctance to use an intravenous treatment, poor patient compliance due to frequency of infusions, budget constraints and lack of funding, insurance, availability and accessibility of factor concentrates. Prevalence of neutralizing antibodies ranged from 5% to 20% in the region. Use of immune tolerance induction and bypassing agents to treat inhibitors depends on their cost and availability. CONCLUSION: Haemophilia care in Asia has evolved to a great extent. However, some challenges remain for which a strategic approach along with multi-stakeholder involvement are needed.

Epigenome-wide association study of short-term temperature fluctuations based on within-sibship analyses in Australian females.

BACKGROUND: Temperature fluctuations can affect human health independent of the effect of mean temperature. However, no study has evaluated whether short-term temperature fluctuations could affect DNA methylation. METHODS: Peripheral blood DNA methylation for 479 female siblings of 130 families were analysed. Gridded daily temperatures data were obtained, linked to each participant's home address, and used to calculate nine different metrics of short-term temperature fluctuations: temperature variabilities (TVs) within the day of blood draw and preceding one to seven days (TV 0-1 to TV 0-7), diurnal temperature range (DTR), and temperature change between neighbouring days (TCN). Within-sibship design was used to perform epigenome-wide association analyses, adjusting for daily mean temperatures, and other important covariates (e.g., smoking, alcohol use, cell-type proportions). Differentially methylated regions (DMRs) were further identified. Multiple-testing comparisons with a significant threshold of 0.01 for cytosine-guanine dinucleotides (CpGs) and 0.05 for DMRs were applied. RESULTS: Among 479 participants (mean age ± SD, 56.4 ± 7.9 years), we identified significant changes in methylation levels in 14 CpGs and 70 DMRs associated with temperature fluctuations. Almost all identified CpGs were associated with exposure to temperature fluctuations within three days. Differentially methylated signals were mapped to 68 genes that were linked to human diseases such as cancer (e.g., colorectal carcinoma, breast carcinoma, and metastatic neoplasms) and mental disorder (e.g., schizophrenia, mental depression, and bipolar disorder). The top three most significantly enriched gene ontology terms were Response to bacterium (TV 0-3), followed by Hydrolase activity, acting on ester bonds (TCN), and Oxidoreductase activity (TV 0-3). CONCLUSIONS: Short-term temperature fluctuations were associated with differentially methylated signals across the human genome, which provides evidence on the potential biological mechanisms underlying the health impact of temperature fluctuations. Future studies are needed to further clarify the roles of DNA methylation in diseases associated with temperature fluctuations.

Validating lactate dehydrogenase (LDH) as a component of the PLASMIC predictive tool (PLASMIC-LDH)

Background@#The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of ＜10%.Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. @*Methods@#Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. @*Results@#46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of ＜10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. @*Conclusion@#Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Radiation exposure to allied health personnel handling blood specimens from patients receiving radioactive iodine-131 and recombinant human TSH (thyrogen®) stimulation.

With increasing use of recombinant human TSH (rhTSH) stimulation protocol in radioactive iodine-131 treatment of thyroidectomised differentiated thyroid carcinoma (DTC), there is increasing concern regarding radiation safety during collection and processing of radioactive blood samples. Our study aims to quantify this radiation exposure in the context of current radiation guidelines to provide a practical safety framework. We analysed 45 patients prospectively referred to a tertiary centre in Singapore, who had histologically proven DTC, and who were thyroidectomised and planned for I-131 with rhTSH stimulation. Each patient received rhTSH for two consecutive days, with I-131 administered 24 h after, and a stimulated Thyroglobulin blood sample collected and processed 72 h after the last rhTSH dose. We measured radiation exposures with dosimeters. Based on the average and maximum exposure rates calculated, we extrapolated and derived the number of radioactive blood samples that could be safely collected and processed. Mean hand and body radiation exposures during venepuncture and blood processing were generally significantly higher than background radiation. Based on average exposure rates, the permissible number of blood samples that can be collected and processed is 9.09 × 103per year (24 per day) and 8.70 × 104per year (238 per day), respectively. This is the first study to date to extrapolate permissible thresholds that can serve as a practical guideline to the number of radioactive blood samples which can be safely collected and processed, following radioactive iodine therapy, within the limits of current radiation guidelines. Once validated, generalisations to other radioactive therapies may be considered.

Extended Whole‑body Ga‑68 DOTATATE PET‑CT in evaluating Tumour‑Induced Osteomalacia: Case report and review of literature / 대한핵의학회잡지

Tumour-induced osteomalacia is a rare paraneoplastic syndrome that manifests as chronic hypophosphataemia, non-specific bone pain and muscle weakness. It is generally caused by phosphaturic mesenchymal tumour (PMT), which is uncommonly associated with synchronous tumours. However, diagnosis is often delayed for several years due to the rarity, indolent growing nature and non-specific symptoms of the disease, often resulting in an overlook by clinicians during assessments. The patient initially presented with hypophosphataemia and generalised skeletal pain with multiple atraumatic fractures. Blood tests revealed serum calcium levels at the upper limit and extremely low inorganic phosphate levels. Herein, we report a case where two synchronous PMTs from two different sites were detected by ‘extended’ whole-body Ga-68 DOTATATE PET-CT, leading to remission of the disease after complete surgical removal. Early detection and diagnosis of PMT neoplasm is crucial, as complete surgical resection of this tumour is the only definitive treatment currently known. Upon excision, this curable disease will result in complete resolution of symptoms and blood parameters, leading to remission of the disease which significantly improves the patient’s quality of life. PMT often over-expresses somatostatin receptors (SSTR), predominantly subtype 2A, and Ga-68 DOTATATE PET-CT is a selective SSTR imaging that targets this characteristic over-expression in these tumours. The high diagnostic accuracy of Ga-68 DOTATATE PET-CT should be the primary imaging modality for full evaluation of this disease.

Immunomodulator use in paediatric severe sepsis and septic shock

INTRODUCTION@#The use of drugs that modulate the immune system during paediatric severe sepsis and septic shock may alter the course of disease and is poorly studied. This study aims to characterise these children who received immunomodulators and describe their clinical outcomes.@*METHODS@#This is a retrospective chart review of patients with severe sepsis and septic shock admitted into the paediatric intensive care unit (PICU). Clinical, haematological and outcome characteristics of patients with or without exposure to immune-modulating drugs were compared. Primary outcome was PICU mortality; secondary outcomes were 28-day ventilator-free days (VFD) and intensive care unit-free days (IFD). Univariate and multivariable analyses were performed for these outcomes.@*RESULTS@#A total of 109 patients with paediatric severe sepsis or septic shock were identified. Of this number, 47 (43.1%), 16 (14.7%) and 3 (2.8%) patients received systemic corticosteroids, intravenous immunoglobulins and granulocyte colony stimulating factor, respectively. Patients who received immune-modulating drugs were more likely to require invasive ventilation (38/54 [70.4%] versus 26/55 [47.3%], @*CONCLUSION@#Immune-modulating drugs were frequently used in paediatric severe sepsis and septic shock. Patients who received these drugs seemed to require more PICU support. Further studies are required to examine this association thoroughly.

A Comparative Study of Licochalcone A Moisturiser versus Topical Hydrocortisone in Treating Mild-to-Moderate Atopic Dermatitis

Background@#Topical corticosteroids are the mainstay of treatment for patients with atopic dermatitis. However, adverse effects associated with long-term steroid use often limit its use. This interventional study compared the efficacy of a proprietary moisturiser containing licochalcone A, omega-6 fatty acids, and ceramide 3 against 1% hydrocortisone cream in treating patients with mild-to-moderate atopic dermatitis.@*Methods@#Patients with mild-to-moderate atopic dermatitis affecting either the cubital fossa or popliteal fossa symmetrically were given twice-daily applications of the moisturiser and hydrocortisone on opposite sides of the body and monitored for a total of three weeks in a non-randomised half body, doubleblind study. Hydrocortisone was switched to aqueous cream after two weeks, whereas the application of the moisturiser continued until study completion. The assessment of SCORing Atopic Dermatitis (SCORAD) index and Dermatology Life Quality index was performed at baseline and every subsequent follow-up visit to measure patients’ response to treatment. @*Results@#The licochalcone A (LA) moisturiser and 1% hydrocortisone (HC) cream both demonstrated significant reduction in sign and symptom scores after only 1 week of treatment (percentage of reduction in sign and symptom scores: 52.8% [LA] vs 58.5% [HC]). Further reduction in mean sign and symptom scores for both treatments was observed at week 2 (61.3% [LA] vs 56.8% [HC]) and also at week 3 when HC was switched to aqueous cream (70.5% [LA] vs 63.5% [HC→aqueous cream]) (p<0.001 vs baseline within the same treatment arm at weeks 1, 2 and 3). When comparing the mean difference in SCORAD index for both individual as well as total skin signs and symptoms between LA and HC (i.e. inter-arm comparison), there was no significant difference between the two treatments for all the assessed parameters. Patients reported improvements in itching, sleeplessness, and overall quality of life over the course of treatment.@*Conclusion@#The licochalcone A moisturiser can be considered as an effective steroid-sparing alternative to topical corticosteroids in managing mild-to-moderate atopic dermatitis.

Acupuncture for Poststroke Dysphagia: A Pilot, Nonrandomized, Self-Controlled Trial.

OBJECTIVE: To evaluate the effectiveness and safety of acupuncture treatment for dysphagia as a complication of stroke. Methods and Design. This is a multicenter, pragmatic, nonrandomized, self-controlled clinical trial. A total of 39 patients were recruited from several Chinese medicine outpatient clinics and hospital-affiliated speech therapy outpatient clinics in Hong Kong. 26 patients completed all the 24 sessions of acupuncture treatment within two months, and only 12 of them were used as self-control. For the self-control group, the retrospective clinical data was taken from the electronic patient records with patient consent. The descriptive swallowing function data were converted into the quantitative Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS) scores by two registered speech therapists through a validation process. And the data were validated by reaching consensus between the two speech therapists. All subjects underwent a baseline assessment before commencement of treatment, and outcome assessments were conducted upon the completion of treatment. The primary outcome measure is the RBHOMS score, which is a swallowing disability rating scale for monitoring difficulties in daily swallowing function. Secondary outcome measures include the Chinese version of the Swallow Quality-of-Life Questionnaire and adverse events. All the primary and secondary outcomes were assessed at baseline as well as at the end of acupuncture treatment (month 2). RESULTS: A total of 39 participants aged 46 to 89 years were enrolled in the study, and the male-to-female ratio was 15 : 11. The mean baseline RBHOMS score of all 39 participants was 5.92 ± 2.23. The mean retrospective RBHOMS score of the 12 subjects who were used as self-control was 5.67 ± 1.72 before enrollment, while the mean RBHOMS score of the 26 participants who completed all the 24 sessions of treatment was 6.92 ± 2.07. There were statistically significant differences between the RBHOMS score at the completion of treatment and baseline (p=0.006), and retrospective data (p=0.042). Moreover, a significant difference was also found in terms of swallow quality-of-life score before and after acupuncture treatment (p < 0.01). CONCLUSIONS: This pilot study provides preliminary evidence for the effectiveness of acupuncture for poststroke dysphagia. The findings from this trial can be used as a foundation for future full-scale randomized controlled clinical trials to assess the efficacy and safety of acupuncture for poststroke dysphagia. Ethics and Dissemination. The ethical approval of the clinical research study was granted by the Research Ethics Committee of both New Territories East and West Cluster of Hong Kong. Written informed consent was obtained from all participants, and the study was undertaken according to the ICH-GCP Guidelines. Trial Registration. This trial is registered with ChiCTR-TRC-12002621 and the registration date is 2012-10-26.

Laparoscopic transgastric resection of gastroduodenal intussusception due to gastric leiomyoma

@#part of the duodenum is a rare complication. We report herean 80-year-old woman who presented at the SarawakGeneral Hospital, Kuching, Sarawak, Malaysia with earlysatiety and epigastric fullness for 3 months. She had noprior medical or surgical history other than an uneventfulopen cholecystectomy. Upper endoscopy showed a largesubmucosal mass in the first part of duodenum with pyloricconverging gastric folds. Computed tomography scan of theabdomen showed a gastroduodenal intussusception with a4x6cm mass at the junction between the first and secondpart of duodenum. Laparoscopic transgastric resection wasperformed. Histopathological examination of the resectedspecimen confirmed leiomyoma. She remained well at 43months follow-up.

Open versus Endovascular Repair of Descending Thoracic Aortic Aneurysm Disease: A Systematic Review and Meta-analysis.

BACKGROUND: The purpose of this study was to determine whether thoracic endovascular aortic repair reduces death and morbidity compared with open surgical repair for descending thoracic aortic disease. METHODS: A comprehensive search was undertaken among the 4 major databases (PubMed, Embase, Scopus, and Ovid) to identify all randomized and nonrandomized controlled trials comparing open versus endovascular repair in thoracic aortic aneurysm. Databases where evaluated and assessed to July 2017. Odds ratios, weighted mean differences, or standardized mean differences and their 95% confidence intervals were analyzed. RESULTS: A total of 14,580 patients were analyzed in total of 13 articles, which were included in the synthesis of the meta-analysis. A total of 10,672 patients had open repair, and 3,908 patients had endovascular repair. Patients undergoing open repair were younger (mean of 65.1 years vs. 70.0 years, P = 0.0009), and there was higher elective rate in open repair patient (83.4% vs. 81%, P = 0.36). Duration of intensive care and total hospital stay was much shorter in endovascular patients (4.5 vs. 8.5 days, P = 0.002 and 5.7 vs. 9.5 days, P = 0.0004). Postoperative stroke was similar in both groups (P = 0.58); however, higher rate of paraplegia noted in open repair group (P = 0.007). The rate of renal failure (P = 0.01) and cardiac complications (P < 0.0001) was higher in the open repair group. The rate of vascular complications was much higher in the endovascular group of patients (5.29% vs. 1.17%, P = 0.002). Operative mortality was higher in endovascular procedures (4.4% vs. 3.2%, P = 0.005); however, 1- and 5-year mortality showed no statistical difference between the endovascular and open repair groups (22.19%, vs. 24.04%, P = 0.59, and 44.26% vs. 37.37%, P = 0.49). CONCLUSIONS: The present meta-analysis shows that endovascular repair of thoracic aortic aneurysm gives better perioperative outcomes during inhospital stay although the 1- and 5-year mortality remains the same in both groups; but the long-term outcome is yet to be established. A long-term data and studies are required to give a better understanding of comparing these 2 techniques beyond 5 years of follow-up.

Characteristics and Outcomes of Long-Stay Patients in the Pediatric Intensive Care Unit.

Long-stay patients in the PICU have a higher risk of mortality as compared with non-long-stay patients. We aim to describe mortality and characteristics of long-stay patients and to determine the risk factors for mortality in these children. Total 241 (4.8%) long-stay admissions were identified. Mortality of long-stayers was 48/241 (20%). Higher severity-of-illness score at admission, need for organ support therapies, number of nosocomial infections, and bloodstream nosocomial infection were associated with a higher mortality in long-stay patients in the PICU. Based on multivariate analysis, oncologic diagnosis as a preexisting comorbidity is a strong independent predictor of mortality for long-stay patients.

DNA methylation-based biological aging and cancer risk and survival: Pooled analysis of seven prospective studies.

The association between aging and cancer is complex. Recent studies have developed measures of biological aging based on DNA methylation and called them "age acceleration." We aimed to assess the associations of age acceleration with risk of and survival from seven common cancers. Seven case-control studies of DNA methylation and colorectal, gastric, kidney, lung, prostate and urothelial cancer and B-cell lymphoma nested in the Melbourne Collaborative Cohort Study were conducted. Cancer cases, vital status and cause of death were ascertained through linkage with cancer and death registries. Conditional logistic regression and Cox models were used to estimate odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals (CI) for associations of five age acceleration measures derived from the Human Methylation 450 K Beadchip assay with cancer risk (N = 3,216 cases) and survival (N = 1,726 deaths), respectively. Epigenetic aging was associated with increased cancer risk, ranging from 4% to 9% per five-year age acceleration for the 5 measures considered. Heterogeneity by study was observed, with stronger associations for risk of kidney cancer and B-cell lymphoma. An associated increased risk of death following cancer diagnosis ranged from 2% to 6% per five-year age acceleration, with no evidence of heterogeneity by cancer site. Cancer risk and mortality were increased by 15-30% for the fourth versus first quartile of age acceleration. DNA methylation-based measures of biological aging are associated with increased cancer risk and shorter cancer survival, independently of major health risk factors.

Parental Oral Health Literacy of children with severe early childhood caries in Hong Kong.

AIM: To assess the parental oral health literacy of children with severe early childhood caries. MATERIALS AND METHODS: A total of 315 children diagnosed with severe early childhood caries, and their parents were recruited to participate in the study. A clinical examination was conducted to assess the children's oral health status. Their parents were asked to complete a Hong Kong Oral Health Literacy Assessment Task for Paediatric Dentistry (HKOHLAT-P) questionnaire. RESULTS: There were 311 complete responses (98.7% response rate). The mean age of children was 4.7 years (standard deviation (SD) =0.8). The mean decayed, missing filled teeth (dmft) score was 10.2 (SD = 4.5). Most of the children had unfilled dental caries (98.7%). About 72.7% of the parents had an education level of up to secondary school. More than half (61.7%) had a monthly family income of below HKD 20,000. Parents with a lower education level and income had a significantly lower HKOHLAT-P score (p<0.001). Multiple regression analyses showed that a higher family income (p<0.05) and education level (p<0.05) predicted higher HKOHLAT-P scores. CONCLUSION: The parental oral health literacy of children with severe early childhood caries was associated with their socio-economic background. Oral health education should be targeted towards the lower socio-economic groups.

An Epidemiological Study of Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) overlap in University Malaya Medical Centre

Introduction: Steven-Johnson syndrome and Toxic Epidermal Necrolysis are rare but life threatening severe cutaneous adverse reactions to drugs. To determine the epidemiology of SJS, TEN and SJS/TEN overlap in University Malaya Medical Centre (UMMC). Methods: All patients admitted to UMMC from year 2013-2015 for SJS, SJS/TEN, TEN were recruited. The classification of SJS, SJS/TEN overlap and TEN was made based on the criteria laid down by Bastuji et al.2 Results: A total of 32 patients were recorded to have SJS, SJS/TEN overlap and TEN from 2013 to 2015. Drugs (n=32, 86.49%) remained the most common aetiology of SJS and TEN. The top three commonest drugs are allopurinol (n=6), followed by carbamazepine (n=5) and bactrim (n=3). Conclusion: This study demonstrates that drugs were the most common cause of SJS/TEN. Antibiotics were the most common drug group that caused SJS/TEN. Awareness of the common etiology such as drug is important and high index of suspicion of SJS and TEN is needed if patients were on the above medications.

Sarcocystis nesbitti related autoimmune diffuse alopecia

Background & Objective: Symptomatic sarcocystosis has been said to be rare until recent years, when there were reports of outbreaks of febrile myositis for travellers returning from the Malaysian island resorts. In 2012, an outbreak of Sarcocystis nesbitti infection involving 92 college students and staff occurred after returning from Pangkor Island, Malaysia. A few months after recovering from the febrile illness, some patients complained of hair loss. This study aimed to determine the prevalence, clinical features and outcome of this disorder. Methods: All patients who became sick in the outbreak were asked whether they had the hair loss. For those who had, they were interviewed with standard questionnaires, examined and investigated. Patients were followed-up via an online survey 2 years later. Results: Out of 89 patients who were ill, 19 patients (21.4%) complained of alopecia. The mean peak onset was 4 months after the initial illness. Eleven patients (57.9%) reported the hair fall of more than 100 per day. The other symptoms were itch 10 (52.6%), scaling 10 (52.6%), erythema 4 (21.1%), none had scarring. Eleven patients (57.8%) had positive antinuclear factor with high titre (speckled or nucleolar pattern). Two years after the event, 10 had complete or near complete spontaneous recovery, 1 had partial response and 1 had no improvement. Conclusions: A delayed transient diffuse alopecia is seen in close to half of patients with Sarcocystis nesbittiinfection. This high frequency of positive ANF suggested an immune-mediated mechanism.

Transcriptome profiling shows gene regulation patterns in a flavonoid pathway in response to exogenous phenylalanine in Boesenbergia rotunda cell culture.

BACKGROUND: Panduratin A extracted from Boesenbergia rotunda is a flavonoid reported to possess a range of medicinal indications which include anti-dengue, anti-HIV, anti-cancer, antioxidant and anti-inflammatory properties. Boesenbergia rotunda is a plant from the Zingiberaceae family commonly used as a food ingredient and traditional medicine in Southeast Asia and China. Reports on the health benefits of secondary metabolites extracted from Boesenbergia rotunda over the last few years has resulted in rising demands for panduratin A. However large scale extraction has been hindered by the naturally low abundance of the compound and limited knowledge of its biosynthetic pathway. RESULTS: Transcriptome sequencing and digital gene expression (DGE) analysis of native and phenylalanine treated Boesenbergia rotunda cell suspension cultures were carried out to elucidate the key genes differentially expressed in the panduratin A biosynthetic pathway. Based on experiments that show increase in panduratin A production after 14 days post treatment with exogenous phenylalanine, an aromatic amino acid derived from the shikimic acid pathway, total RNA of untreated and 14 days post-phenylalanine treated cell suspension cultures were extracted and sequenced using next generation sequencing technology employing an Illumina-Solexa platform. The transcriptome data generated 101, 043 unigenes with 50, 932 (50.41%) successfully annotated in the public protein databases; including 49.93% (50, 447) in the non-redundant (NR) database, 34.63% (34, 989) in Swiss-Prot, 24,07% (24, 316) in Kyoto Encyclopedia of Genes and Genomes (KEGG) and 16.26% (16, 426) in Clusters of Orthologous Groups (COG). Through DGE analysis, we found that 14, 644 unigenes were up-regulated and 14, 379 unigenes down-regulated in response to exogenous phenylalanine treatment. In the phenylpropanoid pathway leading to the proposed panduratin A production, 2 up-regulated phenylalanine ammonia-lyase (PAL), 3 up-regulated 4-coumaroyl:coenzyme A ligase (4CL) and 1 up-regulated chalcone synthase (CHS) were found. CONCLUSIONS: This is the first report of Boesenbergia rotunda de novo transcriptome data that could serve as a reference for gene or enzyme functional studies in the Zingiberaceae family. Although enzymes that are directly involved in the panduratin A biosynthetic pathway were not completely elucidated, the data provides an overall picture of gene regulation patterns leading to panduratin A production.

Waist circumference and not body mass index as the outcome of a group weight intervention for patients with severe mental illness.

OBJECTIVE: Most weight interventions among patients with severe mental illness (SMI) used body mass index (BMI) as outcome measure but excluded waist circumference (WC) although the latter is a stronger predictor of obesity complications. This study aimed to assess a weight-management program consisting of education, exercise and behavioural techniques for patients with SMI using weight parameters including WC as the outcome measures. METHODS: A group intervention was carried out as part of psychiatric outpatient community service. It used structured modules on diet, exercise and related topics comprising of education and exercises sessions with a total of 12-week duration. The participants were outpatients with SMI recruited through referrals to the program by the treating doctor. The participants' body weight, BMI and WC were measured at the baseline, fortnightly and at the end of the program. RESULTS: A total of 27 patients participated in the program which was carried out in 6 cycles. The pre- and post-intervention comparisons analysis of the weight parameters found a significant reduction in the WC (mean=3.878 cm+5.165, p=0.001) while no significant changes were recorded in body weight and BMI. CONCLUSION: Small but significant loss in WC and possibly weight maintenance were achieved using this non-pharmacological intervention. Modest loss in WC may have an impact on reducing the risk of obesity-related health risks.

Relationship between rainfall and Aedes larval population at two insular sites in Pulau Ketam, Selangor, Malaysia.

Two insular settlements (Kampung Pulau Ketam and Kampung Sungai Lima) were selected to study the population dynamics of Aedes aegypti and Aedes albopictus mosquitoes, vectors of dengue and chikungunya infections. Ovitrap surveillance was conducted between October 2007 and October 2008. There was an inverse negative association between ovitrap index and rainfall at the time of collection, probably because rainfall increased the number of available oviposition sites. Rainfall and ovitrap index were positively associates the 25th day after rainfall occurred. A minor, second peak was observed from the 38th to the 42nd day. The first peak was consistent with the minimum 18-day period between the hatching of eggs to the first oviposition. The second minor peak could be due to the second gonotrophic cycle of the female mosquitoes. Rainfall is an important environmental factor associated with Aedes breeding at the study sites.