A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

INTRODUCTION: Nutritional psychiatry is an emerging field of study that investigates the role of diet and nutrition in mental health. Studies conducted in the general population have linked depressive symptoms with poor dietary patterns. The aim of this study was to characterise the dietary intake and analyse the dietary pattern using the Dietary Approach to Stop Hypertension (DASH) in a sample of psychiatric patients in a multiethnic Asian nation. METHODS: Participants were recruited from an outpatient clinic and an inpatient unit at the Institute of Mental Health in Singapore. Self-reported dietary habits of a sample of psychiatric patients (N=380) were analysed using DASH. To examine the variables associated with DASH scores, a linear regression was conducted with the full sample and sociodemographic variables. RESULTS: Persons with depressive disorders had a mean DASH score of 21.3 (±4.2), while persons with psychotic disorders had a mean DASH score of 21.2 (±4.9). Respondents who were older (B=1.94, 95% confidence interval [CI] 0.91-2.96, CONCLUSION Dietary patterns of persons with mental disorders were characterised. A host of sociodemographic factors, and not diagnosis of mental disorders, influenced the dietary quality of people with depressive and psychotic disorders. Clinicians treating psychiatric patients need to be aware of the nuanced reasons behind poor dietary choices and provide targeted psychoeducation to specific subgroups within the patient population.

BACKGROUND: Chronic kidney disease (CKD) is associated with fluid retention, which increases total body water (TBW) and leads to changes in intracellular water (ICW) and extracellular water (ECW). This complicates accurate assessments of body composition. Analysis of bioelectrical impedance may improve the accuracy of evaluation in CKD patients and multiple machines and technologies are available. We compared body composition by bioimpedance spectroscopy (BIS) against multi-frequency bioimpedance analysis (BIA) in a multi-ethnic Asian population of stable, non-dialysis CKD patients. METHODS: We recruited 98 stable CKD patients comprising 54.1% men and 70.4% Chinese, 9.2% Malay, 13.3% Indian, and 8.2% other ethnicities. Stability was defined as no variation in serum creatinine > 20% over three months. Patients underwent BIS analyses using a Fresenius body composition monitor, while BIA analyses employed a Bodystat Quadscan 4000. RESULTS: Mean TBW values by BIS and BIA were 33.6 ± 7.2 L and 38.3 ± 7.4 L; mean ECW values were 15.8 ± 3.2 L and 16.9 ± 2.7 L; and mean ICW values were 17.9 ± 4.3 L and 21.0 ± 4.9 L, respectively. Mean differences for TBW were 4.6 ± 1.9 L (P < 0.001), for ECW they were 1.2 ± 0.5 L (P < 0.001), and for ICW they were 3.2 ±1.8 L (P < 0.001). BIA and BIS measurements were highly correlated: TBW r = 0.970, ECW r = 0.994, and ICW r = 0.926. Compared with BIA, BIS assessments of fluid overload appeared to be more associated with biochemical and clinical indicators. CONCLUSION: Although both BIA and BIS can be used for body water assessment, clinicians should be aware of biases that exist between bioimpedance techniques. The values of body water assessments in our study were higher in BIA than in BIS. Ethnicity, sex, body mass index, and estimated glomerular filtration rate were associated with these biases.
Adult ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Body Composition ; Body Mass Index ; Body Water ; Creatinine ; Electric Impedance ; Glomerular Filtration Rate ; Humans ; Kidney Diseases ; Male ; Methods ; Nutrition Assessment ; Renal Insufficiency, Chronic ; Spectrum Analysis ; Water

INTRODUCTIONFunctioning and quality of life (QOL) are negatively impacted as a result of mental illness. This study aimed to determine the: i) socio-demographic and clinical correlates of functioning and; ii) associations between functioning and QOL in a multiethnic sample of psychiatric outpatients.

MATERIALS AND METHODSThis was a cross-sectional study of outpatients receiving treatment from a tertiary psychiatric hospital. Functioning was assessed using the Global Assessment of Functioning (GAF) scale, while QOL was measured using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) which comprises 4 domains: physical health, psychological health, social relationships and environment.

RESULTSVarious socio-demographic and clinical correlates were associated with functioning including employment and marital status, education and diagnosis. Depression was the only clinical characteristic which negatively correlated with functioning (= 0.035). Amongst the whole sample, multiple linear regressions revealed that functioning was positively associated with all 4 QOL domains (physical health [<0.001], psychological health [<0.001], social relationships [<0.001] and environment [<0.001]). Further analysis of each diagnostic group revealed that functioning was positively associated with all 4 QOL domains in the anxiety, depression and obsessive compulsive disorder subsamples, while in the schizophrenia subsample, functioning was only significantly associated with all environment domain.

CONCLUSIONFunctional impairments were associated with different socio-demographic and clinical characteristics, which should be addressed when planning tailored treatment and interventions. Given that functioning is significantly associated with QOL, it is crucial to regularly assess and monitor them (in addition to symptomatic outcomes and adopting a more holistic and biopsychosocial approach).

INTRODUCTIONThis study aimed to identify predictors of the outcome and clinical efficacy of emergency pelvic artery embolisation (PAE) for primary postpartum haemorrhage (PPH) and to assess the post-embolisation fertility of PAE patients in a regional hospital setting.

METHODSA 12-year retrospective study of patients undergoing emergency PAE was conducted at a regional acute general hospital. Clinical and procedural parameters, clinical outcomes and post-embolisation pregnancy success rates were analysed.

RESULTSThere were 47,221 deliveries at the hospital during the study period, of which 33 patients required urgent PAE for primary PPH. The technical success rate of embolisation was 97.0% (n = 32). Clinically adequate haemostasis was achieved by a single embolisation procedure in 24 (72.7%) patients; the remaining eight eventually required surgery to achieve cessation of bleeding. Among the parameters studied, multivariate logistic regression analysis showed that pre-embolisation platelet count (p = 0.036) and maternal age (p = 0.019) were the only significant independent predictors of embolisation failure. Only two patients successfully conceived after PAE, although one of them had an ectopic pregnancy.

CONCLUSIONEmergency PAE is an effective measure to arrest life-threatening bleeding in patients with primary PPH. As low pre-embolisation platelet count and advanced maternal age are associated with higher odds of embolisation failure, careful post-embolisation monitoring may be required for such patients. Embolisation also allows subsequent pregnancy. However, further studies are required to assess the outcomes of post-embolisation pregnancies.

OBJECTIVETo assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants.

METHODSCaffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period.

RESULTSAIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants.

CONCLUSIONAIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.

Animals ; Caffeine ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Drosophila melanogaster ; drug effects ; physiology ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Mutation ; genetics ; Potassium Channels ; genetics ; Sleep ; drug effects ; Sleep Initiation and Maintenance Disorders ; drug therapy ; Wakefulness ; drug effects

BACKGROUNDSingle incision laparoscopic colectomy has been performed in recent years, and has been shown to be feasible and safe. This study was to assess the feasibility of single incision laparoscopic right hemicolectomy and to compare the differences in different approaches.

METHODSThis retrospective study included eighteen patients with carcinoma of caecum and ascending colon, undergoing single incision laparoscopic right hemicolectomy. This study also compared single incision laparoscopic right hemicolectomy using different approaches: (1) single incision multiport, (2) single access port and (3) glove port.

RESULTSThere was no statistical difference in surgical outcomes. Concerning the surgeon's satisfaction toward three methods, overcrowding and durability were similar but the single incision multiport was associated with the highest gas-leak and the "glove" port was associated with poor durability. However, the method of single incision multiport has the lowest average cost of the special trocar or port in each operation. The operative time and blood loss of the operations in this study were comparable to previous publications.

CONCLUSIONThere was no significant difference between different approaches of single incision laparoscopic right hemicolectomy for colonic cancer in right side colon.

Aged ; Cecal Neoplasms ; surgery ; Colectomy ; methods ; Colonic Neoplasms ; surgery ; Female ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Retrospective Studies

PURPOSE: The objectives of this study were to identify the prevalence and rationales of traditional Chinese pregnancy restrictions and to investigate the relationship between pregnancy restriction, health-related quality of life, and perceived stress level at a two-stage design. METHODS: Stage I consisted of exploring the traditional Chinese pregnancy restrictions and their underlying beliefs based on extensive literature review followed by in-depth interviews with 30 pregnant women. Stage II investigated the relationship between pregnancy restrictions, health-related quality of life, and perceived stress among 1,151 women. Self-developed traditional Chinese pregnancy restrictions lists were measured on adherence towards the traditional Chinese pregnancy restriction. Perceived stress and health-related quality of life were measured by the Perceived Stress Scale and the Short Form-12 (SF-12) Health Survey, respectively. RESULTS: The majority of the women adhered to traditional Chinese pregnancy restrictions in order to protect the unborn child from danger and to avoid the problems associated pregnancy and birth, such as miscarriage, stillbirth, death of the mother, and imperfections in the newborn. Pregnant women who adhered to behavioral restrictions were more likely to associate with poor physical component of healthrelated quality of life. However, there was no significant difference between pregnancy restrictions and Perceived Stress Scale scores. CONCLUSION: The findings provided cultural rationales of pregnancy restrictions within a Macao context that may assist health professionals to better understand women from different cultures. It is essential in the development of culturally appropriate healthcare to support women in making a healthy transition to motherhood.
Abortion, Spontaneous ; Asian Continental Ancestry Group ; Child ; China ; Delivery of Health Care ; Female ; Health Occupations ; Health Surveys ; Humans ; Infant, Newborn ; Macau ; Mothers ; Parturition ; Pregnancy ; Pregnant Women ; Prevalence ; Quality of Life ; Stillbirth ; Stress, Psychological

BACKGROUNDThe rise of the production of CTX-M class extended spectrum β-lactamases (ESBLs) has been well documented in traveling countries but no data are found for Macao, an international travel city. The objectives of this study were to identify the antimicrobial resistance pattern, and determine the prevalence, genotype and clonal relationship of ESBLs in 209 clinical Escherichia coli strains from Macao, China.

METHODSAntimicrobial susceptibility test was performed to determine the resistance patterns of the isolates using the disk diffusion method with 17 antimicrobial agents. Phenotypic detection was screened and confirmed according to the Clinical and Laboratory Standards Institute. Genotypic characterization was detected by isoelectric focusing analysis, polymerase chain reaction and sequencing. The clonal relationship between the different ESBL isolates was studied by pulsed-field gel electrophoresis (PFGE).

RESULTSImipenem and meropenem exhibited 100% susceptible among 209 strains. Overall, 82.3%, 67.3%, 52.9%, 51.2% and 51.0% of the isolates displayed resistance to ampicillin, tetracycline, ciprofloxacin, sulfamethoxazole trimethoprim and gentamycin. The prevalence rate of ESBLs was 30.1%. Antibiotic resistances were found to be significantly higher among the ESBL producing group compared to non-ESBL producing group. We detected CTX-M-14 to be the major genotypic characterization of ESBLs (76.2%). Two strains showed indistinguishable patterns by PFGE.

CONCLUSIONSThe prevalence of antimicrobial resistance is alarming high in Macao. Antimicrobial resistance is significantly higher among the ESBL producing group. This study documented CTX-M-14 as the predominant ESBL type. Although indistinguishable pattern was found between two strains, it was too small to decide whether any of the investigated strains was epidemic. Our findings may be also pertinent for other geographic areas undergoing similar travel characteristics to understand the corresponding effects on bacterial populations.

Anti-Infective Agents ; pharmacology ; China ; Drug Resistance, Microbial ; genetics ; Electrophoresis, Gel, Pulsed-Field ; methods ; Escherichia coli ; drug effects ; enzymology ; genetics ; Genotype ; Isoelectric Focusing ; Macau ; beta-Lactamases ; genetics ; metabolism

BACKGROUNDCardiac resynchronization therapy (CRT) is an effective electrical therapy for patients with moderate to severe heart failure and cardiac dyssynchrony. This study aimed to investigate the degree of acute left ventricular (LV) resynchronization with biventricular pacing (BVP) at different LV sites and to examine the feasibility of performing transthoracic echocardiography (TTE) to quantify acute LV resynchronization during CRT procedure.

METHODSFourteen patients with NYHA Class III-IV heart failure, LV ejection fraction < or = 35%, QRS duration > or = 120 ms and septal-lateral delay (SLD) > or = 60 ms on tissue Doppler imaging (TDI), underwent CRT implant. TDI was obtained from three apical views during BVP at each accessible LV site and SLD during BVP was derived. Synchronicity gain index (Sg) by SLD was defined as (1 + (SLD at baseline--SLD at BVP)/SLD at baseline).

RESULTSSeventy-two sites were studied. Positive resynchronization (R+, Sg > 1) was found in 42 (58%) sites. R+ was more likely in posterior or lateral than anterior LV sites (66% vs. 36%, P < 0.001). Concordance of empirical LV lead implantation sites and sites with R+ was 50% (7/14).

CONCLUSIONSThe degree of acute LV resynchronization by BVP depends on LV lead location and empirical implantation of LV lead results in only 50% concordance with R+. Performing TTE during CRT implantation is feasible to identify LV sites with positive resynchronization.

Aged ; Cardiac Resynchronization Therapy ; methods ; Echocardiography ; methods ; Female ; Heart Failure ; therapy ; Humans ; Male ; Middle Aged ; Ventricular Dysfunction, Left ; therapy