Next-generation sequencing (NGS) is getting routinely used in the diagnosis of hereditary diseases, such as human cardiomyopathies. Hence, it is of utter importance to secure high quality sequencing data, enabling the identification of disease-relevant mutations or the conclusion of neg-ative test results. During the process of sample preparation, each protocol for target enrichment library preparation has its own requirements for quality control (QC); however, there is little evi-dence on the actual impact of these guidelines on resulting data quality. In this study, we analyzed the impact of QC during the diverse library preparation steps of Agilent SureSelect XT target enrichment and Illumina sequencing. We quantified the parameters for a cohort of around 600 sam-ples, which include starting amount of DNA, amount of sheared DNA, smallest and largest frag-ment size of the starting DNA; amount of DNA after the pre-PCR, and smallest and largest fragment size of the resulting DNA;as well as the amount of the final library, the corresponding smallest and largest fragment size, and the number of detected variants. Intriguingly, there is a high tolerance for variations in all QC steps, meaning that within the boundaries proposed in the current study, a considerable variance at each step of QC can be well tolerated without compromising NGS quality.

BACKGROUND: There is increasing interest in the role of traffic-related air pollution (TRAP) in allergic airway diseases. Few studies investigate the relationship between TRAP exposure and acute exacerbations of asthma. OBJECTIVE: The 2016 Melbourne thunderstorm asthma epidemic provided an opportunity to investigate the relationship between proxies of TRAP exposure and asthma exacerbation requiring urgent healthcare in the previous 12 months. METHODS: Current asthmatics who presented to the 3 Emergency Departments of Melbourne's second-largest health service with epidemic thunderstorm asthma in November 2016 were identified and completed a standard questionnaire. Their residential addresses were geocoded and the annual average nitrogen dioxide (NO2) exposure for each patient was assigned using a validated satellite-based land use regression model. Residential distance to the nearest major road was calculated using ArcGIS. Multivariate logistic regression was used to investigate the relationship between each TRAP proxy and healthcare use, adjusting for potential confounders. RESULTS: From 263 thunderstorm asthma patients, 88 patients identified with current asthma were analysed. Those with higher mean annual residential NO2 exposure had greater odds of urgent healthcare use in the previous year (odds ratio [OR], 3.45 per one interquartile-range increase; 95% confidence interval [CI], 1.31–9.10; p = 0.01), however distance from major road (OR, 0.95 per 100-m increase; 95% CI, 0.80–1.13; p = 0.57) and living < 200 m from a major road (OR, 1.47; 95% CI, 0.29–7.45; p = 0.64) were not significantly associated. CONCLUSION: In current asthmatics who presented during an epidemic thunderstorm asthma event, greater exposure to residential NO2 was significantly associated with greater odds of asthma exacerbations requiring urgent healthcare in the previous 12 months.
Air Pollution ; Asthma ; Bronchial Spasm ; Cohort Studies ; Delivery of Health Care ; Emergency Service, Hospital ; Environmental Exposure ; Environmental Pollutants ; Health Services ; Humans ; Hypersensitivity ; Logistic Models ; Nitrogen Dioxide ; Proxy

The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure (HF) with preserved ejection fraction (HF-pEF) is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging (MRI), heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau (s). Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated signif-icantly across the patient population with s. This study shows that multi-modal cardiac models can successfully capture diastolic (dys) function, a prerequisite for future clinical trials on HF-pEF.

Objectives: The aim of these Clinical Practice Guidelines is to provide evidence-based recommendations to assist healthcare providers in the screening, diagnosis and management of patients with postmenopausal osteoporosis (OP). Methods: A list of key clinical questions on the assessment, diagnosis and treatment of OP was formulated. A literature search using the PubMed, Medline, Cochrane Databases of Systematic Reviews, and OVID electronic databases identified all relevant articles on OP based on the key clinical questions, from 2014 onwards, to update from the 2015 edition. The articles were graded using the SIGN50 format. For each statement, studies with the highest level of evidence were used to frame the recommendation. Results: This article summarizes the diagnostic and treatment pathways for postmenopausal OP. Risk stratification of patients with OP encompasses clinical risk factors, bone mineral density measurements and FRAX risk estimates. Non-pharmacological measures including adequate calcium and vitamin D, regular exercise and falls prevention are recommended. Pharmacological measures depend on patients’ fracture risk status. Very high-risk individuals are recommended for treatment with an anabolic agent, if available, followed by an anti-resorptive agent. Alternatively, parenteral anti-resorptive agents can be used. High-risk individuals should be treated with anti-resorptive agents. In low-risk individuals, menopausal hormone replacement or selective estrogen receptor modulators can be used, if indicated. Patients should be assessed regularly to monitor treatment response and treatment adjusted, as appropriate. Conclusions The pathways for the management of postmenopausal OP in Malaysia have been updated. Incorporation of fracture risk stratification can guide appropriate treatment.

Alternative mRNA splicing is a fundamental process to increase the versatility of the gen-ome.In humans,cardiac mRNA splicing is involved in the pathophysiology of heart failure.Mutations in the splicing factor RNA binding motif protein 20(RBM20)cause severe forms of cardiomyopathy.To identify novel cardiomyopathy-associated splicing factors,RNA-seq and tissue-enrichment anal-yses were performed,which identified up-regulated expression of Sam68-Like mammalian protein 2(SLM2)in the left ventricle of dilated cardiomyopathy(DCM)patients.In the human heart,SLM2 binds to important transcripts of sarcomere constituents,such as those encoding myosin light chain 2(MYL2),troponin I3(TNNI3),troponin T2(TNNT2),tropomyosin 1/2(TPM1/2),and titin(TTN).Mechanistically,SLM2 mediates intron retention,prevents exon exclusion,and thereby medi-ates alternative splicing of the mRNA regions encoding the variable proline-,glutamate-,valine-,and lysine-rich(PEVK)domain and another part of the I-band region of titin.In summary,SLM2 is a novel cardiac splicing regulator with essential functions for maintaining cardiomyocyte integrity by binding to and processing the mRNAs of essential cardiac constituents such as titin.

High-quality data are the foundation to monitor the progress and evaluate the effects of road traffic injury prevention measures. Unfortunately, official road traffic injury statistics delivered by governments worldwide, are often believed somewhat unreliable and invalid. We summarized the reported problems concerning the road traffic injury statistics through systematically searching and reviewing the literature. The problems include absence of regular data, under-reporting, low specificity, distorted cause spectrum of road traffic injury, inconsistency, inaccessibility, and delay of data release. We also explored the mechanisms behind the problematic data and proposed the solutions to the addressed challenges for road traffic statistics.
Accidental Injuries ; epidemiology ; prevention & control ; Accidents, Traffic ; prevention & control ; statistics & numerical data ; Global Health ; Humans

Objective: To explore the anti-cancer activity of maslinic acid against colorectal cancer (CRC) cell lines and its possible mechanism. Methods: The inhibitory effect of maslinic acid was screened against five CRC cell lines (HT-29, HCT 116, SW480, SW48, and LS 174T) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle analyses were carried out using annexin V-FITC/propidium iodide staining and propidium iodide staining, respectively and subjected to fluorescence-activated cell sorting analysis. Protein expression studies of inhibitor of κB kinase-β (IKK-β), checkpoint kinase 1 (Chk1) and cyclin D1 were conducted using the JESS system. Results: Maslinic acid exhibited growth inhibitory effect in a doseand time-dependent manner in HT-29 and HCT 116 cell lines. A more prominent apoptosis induced by maslinic acid was observed in HCT 116 cell line. However, in HT-29 cell line, maslinic acid induced cell cycle arrest by inhibiting the G1-S transition, which was accompanied by the downregulation of cyclin D1. The expression of unphosphorylated IKK-β protein was increased in both (HT-29 and HCT 116) cell lines after maslinic acid treatment. Conclusions: Maslinic acid inhibits the growth of HT-29 and HCT 116 cells in a different manner, induces cell cycle arrest in HT-29 cells and causes apoptosis in HCT 116 cells partially via NF-κB pathway inhibition.