Methods: First, studies of codon usage in monocots were reviewed. The current information was then extended regarding codon usage, as well as codon-pair context bias, using four completely sequenced non-grass monocot genomes (Musa acuminata, Musa balbisiana, Phoenix dactylifera and Spirodela polyrhiza) for which comparable transcriptome datasets are available. Measurements were taken regarding relative synonymous codon usage, effective number of codons, derived optimal codon and GC content and then the relationships investigated to infer the underlying evolutionary forces.
Key Results: The research identified optimal codons, rare codons and preferred codon-pair context in the non-grass monocot species studied. In contrast to the bimodal distribution of GC3 (GC content in third codon position) in grasses, non-grass monocots showed a unimodal distribution. Disproportionate use of G and C (and of A and T) in two- and four-codon amino acids detected in the analysis rules out the mutational bias hypothesis as an explanation of genomic variation in GC content. There was found to be a positive relationship between CAI (codon adaptation index; predicts the level of expression of a gene) and GC3. In addition, a strong correlation was observed between coding and genomic GC content and negative correlation of GC3 with gene length, indicating a strong impact of GC-biased gene conversion (gBGC) in shaping codon usage and nucleotide composition in non-grass monocots.
Conclusion: Optimal codons in these non-grass monocots show a preference for G/C in the third codon position. These results support the concept that codon usage and nucleotide composition in non-grass monocots are mainly driven by gBGC.
METHODS AND RESULTS: Using the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, 5276 patients with symptomatic HF and reduced ejection fraction (HFrEF) from 11 Asian regions and across 3 income regions (high: Hong Kong, Japan, Korea, Singapore, and Taiwan; middle: China, Malaysia, and Thailand; and low: India, Indonesia, and Philippines) were studied. ICD utilization, clinical characteristics, as well as device perception and knowledge, were assessed at baseline among ICD-eligible patients (EF ≤35% and New York Heart Association Class II-III). Patients were followed for the primary outcome of all-cause mortality. Among 3240 ICD-eligible patients (mean age 58.9±12.9 years, 79.1% men), 389 (12%) were ICD recipients. Utilization varied across Asia (from 1.5% in Indonesia to 52.5% in Japan) with a trend toward greater uptake in regions with government reimbursement for ICDs and lower out-of-pocket healthcare expenditure. ICD (versus non-ICD) recipients were more likely to be older (63±11 versus 58±13 year; P<0.001), have tertiary (versus ≤primary) education (34.9% versus 18.1%; P<0.001) and be residing in a high (versus low) income region (64.5% versus 36.5%; P<0.001). Among 2000 ICD nonrecipients surveyed, 55% were either unaware of the benefits of, or needed more information on, device therapy. ICD implantation reduced risks of all-cause mortality (hazard ratio, 0.71; 95% confidence interval, 0.52-0.97) and sudden cardiac deaths (hazard ratio, 0.33; 95% confidence interval, 0.14-0.79) over a median follow-up of 417 days.
CONCLUSIONS: ICDs reduce mortality risk, yet utilization in Asia is low; with disparity across geographic regions and socioeconomic status. Better patient education and targeted healthcare reforms in extending ICD reimbursement may improve access.
CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT01633398. Unique identifier: NCT01633398.
METHODS: A literature search was performed using MEDLINE, Embase and the Cochrane Collaboration Central Register of Clinical Trials from inception until December 2014, to identify randomized controlled trials of intravenous iron and ESA, in patients undergoing haemodialysis for end-stage kidney disease. Dosing of IV iron in concordance with the Kidney Disease Improving Global Outcomes guidelines was considered optimal iron therapy.
RESULTS: Of the 28 randomized controlled trials identified, seven met the criteria for inclusion in the meta-analysis. Results of random-effects meta-analysis show a statistically significant weighted mean (95% CI) difference of -1733 [-3073, -392] units/week in ESA dose for optimal iron versus suboptimal iron. The weighted average change in ESA dose was a reduction of 23% (range -7% to -55%) attributable to appropriate dosing of intravenous iron. A comparison of intravenous iron versus oral iron/no iron (five trials) showed a greater reduction in ESA dose, although this did not reach statistical significance (weighted mean difference, 95% CI: -2,433 [-5183, 318] units/week). The weighted average change in ESA dose across the five trials was a reduction of 31% (range -8% to -55%).
CONCLUSION: Significant reductions in ESA dosing may be achieved with optimal intravenous iron usage in the haemodialysis population, and suboptimal iron use may require higher ESA dosing to manage anaemia.
METHODS: The concepts and items were developed based on findings from our prior exploratory qualitative study on factors influencing individuals' intention to undergo CVD health checks. Content validity of the questionnaire was assessed by a panel of six experts and the item-level content validity index (I-CVI) was determined. After pretesting the questionnaire was pilot tested to check reliability of the items. Exploratory factor analysis was used to test for dimensionality using a sample of 240 participants.
RESULTS: The finalized questionnaire consists of 36 items, covering nine concepts. The I-CVI for all items was satisfactory with values ranging from 0.83 to 1.00. The exploratory factor analysis showed that the number of factors extracted was consistent with the theoretical concepts. Correlations values between items ranged from 0.30 to 0.85 and all the factor loadings were more than 0.40, indicating satisfactory structural validity. All concepts showed good internal consistency, Cronbach's alpha values ranged 0.66-0.85.
CONCLUSIONS: The determinants for CVD health check questionnaire has good content and structural validity, and its reliability was established. It can be used to assess determinants influencing individuals' intention to undergo CVD health checks.
METHODS: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry. Demographics, clinical data and laboratory test results were extracted from the medical records of the patients or electronic databases. The main outcome measure is the occurrence of a bleeding event. Bleeding events were classified into major bleeding, clinically relevant non-major bleeding, or minor bleeding, according to the International Society on Thrombosis and Haemostasis criteria. We consider clinically relevant non-major bleeding events or major bleeding events as clinically relevant bleeding events. An occurrence of any bleeding event was recorded from the initiation of NOAC therapy until the death of a patient, or the date of permanent discontinuation of NOAC use, or the last day of data collection. The predicted rate of dabigatran-induced bleeding events per 100 patient-years was estimated.
RESULTS: During a median follow-up period of 18 months, 73 patients experienced 90 bleeding events. Among these patients, 25 including 4 fatal cases, experienced major bleeding events. The predicted rate per 100 patient-years of follow-up of any bleeding events was 9.0 [95% CI 6.9 to 11.1]; clinically relevant bleeding events 6.0 [95% CI 4.8 to 8.3], and major bleeding events 3.0 [95% CI 1.9 to 4.2]. The independent risk factor for clinically relevant bleeding events is prior bleeding. While prior bleeding or congestive heart failure is linked with major bleeding events.
CONCLUSIONS: The predicted rate for dabigatran-induced major bleeding episodes is low but these adverse events carry a high fatality risk. Preventive measures should target older patients who have prior bleeding or congestive heart failure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
METHODS: A systematic literature search was performed using electronic databases, such as EMBASE, PubMed/Medline, CINAHL, NHS and CEA Registry from 2000 until 2017. The quality of each included study was assessed using Joanna Briggs Institute Critical Appraisal Checklist for Economic Evaluations and Consolidated Health Economic Evaluation Reporting Standards Statement checklist.
RESULTS: Of the 313 papers retrieved, five papers were included in this review after assessment for eligibility. The majority of the studies were cost-effectiveness studies, comparing ASP to standard care. Four included economic studies were conducted from the provider (hospital) perspective while the other study was from payer (National Health System) perspective. The cost included for economic analysis were as following: personnel costs, warded cost, medical costs, procedure costs and other costs.
CONCLUSIONS: All studies were generally well-conducted with relatively good quality of reporting. Implementing ASP in the hospital setting may be cost-effective. However, comprehensive cost-effectiveness data for ASP remain relatively scant, underlining the need for more prospective clinical and epidemiological studies to incorporate robust economic analyses into clinical decisions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
OBJECTIVE(S): The present study was aimed to investigate the mechanism of bone-forming capacity of EL using MC3T3-E1 as an in vitro osteoblastic model.
MATERIALS AND METHODS: The cell differentiation capacity of EL was investigated by evaluating cell growth, alkaline phosphatase (ALP) activity, collagen deposition and mineralization. Taken together, time-mannered expression of bone-related mediators which include bone morphogenic protein-2 (BMP-2), ALP, runt-related transcription factor-2 (Runx-2), osteocalcin (OCN), type I collagen, osteopontin (OPN), transforming growth factor-β1 (TGF-β1) and androgen receptor (AR) were measured to comprehend bone-forming mechanism of EL.
RESULTS: Results demonstrated a superior cell differentiation efficacy of EL (particularly at a dose of 25 μg/mL) that was evidenced by dramatically increased cell growth, higher ALP activity, collagen deposition and mineralization compared to the testosterone. Results analysis of the bone-related protein biomarkers indicated that the expression of these mediators was well-regulated in EL-treated cell cultures compared to the control groups. These findings revealed potential molecular mechanism of EL for the prevention and treatment of male osteoporosis.
CONCLUSION: The resulting data suggested that EL exhibited superior efficacy in stimulating bone formation via up-regulating the expression of various mitogenic proteins and thus can be considered as a potential natural alternative therapy for the treatment of osteoporosis.
DESIGN: Two cross-sectional studies using the WHO STEPS methodology.
SETTING: Both the urban and rural areas of the Yangon Region, Myanmar.
PARTICIPANTS: A total of 1370 men and women aged 25-74 years participated based on a multistage cluster sampling. Physically and mentally ill people, monks, nuns, soldiers and institutionalised people were excluded.
RESULTS: Compared with rural counterparts, urban dwellers had a significantly higher age-standardised prevalence of hypercholesterolaemia (50.7% vs 41.6%; p=0.042) and a low HDL level (60.6% vs 44.4%; p=0.001). No urban-rural differences were found in the prevalence of hypertriglyceridaemia and high LDL. Men had a higher age-standardised prevalence of hypertriglyceridaemia than women (25.1% vs 14.8%; p<0.001), while the opposite pattern was found in the prevalence of a high LDL (11.3% vs 16.3%; p=0.018) and low HDL level (35.3% vs 70.1%; p<0.001).Compared with rural inhabitants, urban dwellers had higher age-standardised mean levels of total cholesterol (5.31 mmol/L, SE: 0.044 vs 5.05 mmol/L, 0.068; p=0.009), triglyceride (1.65 mmol/L, 0.049 vs 1.38 mmol/L, 0.078; p=0.017), LDL (3.44 mmol/L, 0.019 vs 3.16 mmol/L, 0.058; p=0.001) and lower age-standardised mean levels of HDL (1.11 mmol/L, 0.010 vs 1.25 mmol/L, 0.012; p<0.001). In linear regression, the total cholesterol was significantly associated with an urban location among men, but not among women.
CONCLUSION: The mean level of total cholesterol and the prevalence of hypercholesterolaemia were alarmingly high in men and women in both the urban and rural areas of Yangon Region, Myanmar. Preventive measures to reduce cholesterol levels in the population are therefore needed.