Cost-Effectiveness of Coronary Artery Calcium Testing for Coronary Heart and Cardiovascular Disease Risk Prediction to Guide Statin Allocation: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background

The Multi-Ethnic Study of Atherosclerosis (MESA) showed that the addition of coronary artery calcium (CAC) to traditional risk factors improves risk classification, particularly in intermediate risk asymptomatic patients with LDL cholesterol levels <160 mg/dL. However, the cost-effectiveness of incorporating CAC into treatment decision rules has yet to be clearly delineated.

Objective

To model the cost-effectiveness of CAC for cardiovascular risk stratification in asymptomatic, intermediate risk patients not taking a statin. Treatment based on CAC was compared to (1) treatment of all intermediate-risk patients, and (2) treatment on the basis of United States guidelines.

Methods

We developed a Markov model of first coronary heart disease (CHD) and cardiovascular disease (CVD) events. We modeled statin treatment in intermediate risk patients with CAC≥1 and CAC≥100, with different intensities of statins based on the CAC score. We compared these CAC-based treatment strategies to a “treat all” strategy and to treatment according to the Adult Treatment Panel III (ATP III) guidelines. Clinical and economic outcomes were modeled over both five- and ten-year time horizons. Outcomes consisted of CHD and CVD events and Quality-Adjusted Life Years (QALYs). Sensitivity analyses considered the effect of higher event rates, different CAC and statin costs, indirect costs, and re-scanning patients with incidentalomas.

Results

We project that it is both cost-saving and more effective to scan intermediate-risk patients for CAC and to treat those with CAC≥1, compared to treatment based on established risk-assessment guidelines. Treating patients with CAC≥100 is also preferred to existing guidelines when we account for statin side effects and the disutility of statin use.

Conclusion

Compared to the alternatives we assessed, CAC testing is both effective and cost saving as a risk-stratification tool, particularly if there are adverse effects of long-term statin use. CAC may enable providers to better tailor preventive therapy to patients'' risks of CVD.     

Automatic Detection of Diseased Tomato Plants Using Thermal and Stereo Visible Light Images

Accurate and timely detection of plant diseases can help mitigate the worldwide losses experienced by the horticulture and agriculture industries each year. Thermal imaging provides a fast and non-destructive way of scanning plants for diseased regions and has been used by various researchers to study the effect of disease on the thermal profile of a plant. However, thermal image of a plant affected by disease has been known to be affected by environmental conditions which include leaf angles and depth of the canopy areas accessible to the thermal imaging camera. In this paper, we combine thermal and visible light image data with depth information and develop a machine learning system to remotely detect plants infected with the tomato powdery mildew fungus Oidium neolycopersici. We extract a novel feature set from the image data using local and global statistics and show that by combining these with the depth information, we can considerably improve the accuracy of detection of the diseased plants. In addition, we show that our novel feature set is capable of identifying plants which were not originally inoculated with the fungus at the start of the experiment but which subsequently developed disease through natural transmission.     

A novel variant in DMXL2 gene is associated with autosomal dominant non-syndromic hearing impairment (DFNA71) in a Cameroonian family

Approximately half of congenital hearing impairment cases are inherited, with non-syndromic hearing impairment (NSHI) being the most frequent clinical entity of genetic hearing impairment cases. A family from Cameroon with NSHI was investigated by performing exome sequencing using DNA samples obtained from three family members, followed by direct Sanger sequencing in additional family members and controls participants. We identified an autosomal dominantly inherited novel missense variant [NM_001174116.2:c.918G>T; p.(Q306H)] in DMXL2 gene (MIM:612186) that co-segregates with mild to profound non-syndromic sensorineural hearing impairment . The p.(Q306H) variant which substitutes a highly conserved glutamine residue is predicted deleterious by various bioinformatics tools and is absent from several genome databases. This variant was also neither found in 121 apparently healthy controls without a family history of hearing impairment , nor 112 sporadic NSHI cases from Cameroon. There is one previous report of a large Han Chinese NSHI family that segregates a missense variant in DMXL2. The present study provides additional evidence that DMXL2 is involved in hearing impairment etiology, and we suggest DMXL2 should be considered in diagnostic hearing impairment panels.     

Calcium chloride and gibberellic acid protect linseed (Linum usitatissimum L.) from NaCl stress by inducing antioxidative defence system and osmoprotectant accumulation

Salinity stress affects many metabolic facets of plants and induces anatomical and morphological changes resulting in reduced growth and productivity. To overcome the damaging effects of salinity, different strategies of the application of nutrients with plant hormones are being adopted. The present study was carried out with an aim to find out whether application of calcium chloride (CaCl₂) and gibberellic acid (GA₃) could alleviate the detrimental effects of salinity stress on plant metabolism. Fifteen days old plants were supplied with (1) 0 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 0 M GA₃ (control, T0); (2) 0 mM NaCl + 10 mg CaCl₂ kg^?1 sand + 0 M GA₃ (T1); (3) 0 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 10^?6 M GA₃ (T2); (4) 150 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 0 M GA₃ (T3); (5) 150 mM NaCl + 10 mg CaCl₂ kg^?1 sand + 0 M GA₃ (T4); (6) 150 mM NaCl + 0 mg CaCl₂ kg^?1 sand + 10^?6 M GA₃ (T5); (7) 150 mM NaCl + 10 mg CaCl₂ kg^?1 sand + 10^?6 M GA₃ (T6). To assess the response of the crop to NaCl, CaCl₂ and GA₃, plants were uprooted randomly at 60 days after sowing. The presence of NaCl in the growth medium decreased all the growth and physio-biochemical parameters, except electrolyte leakage, proline (Pro) and glycine betaine (GB) content, thiobarbituric acid reactive substances (TBARS), H₂O₂ content, activities of superoxide dismutase (SOD) and catalase (CAT) and leaf Na content, which exhibited an increase of 37.6, 29.3, 366.9, 107.5, 59.1, 17.1, 28.4 and 255.2%, respectively, compared to the control plants. However, application of CaCl₂ in combination with GA₃ appears to confer greater osmoprotection by the additive role with NaCl in Pro and GB accumulation. Although the activities of antioxidant enzymes (SOD, CAT and POX) were increased by salt stress, the combined application of CaCl₂ and GA₃ to salt-stressed plants further enhanced the activities of these enzymes by 25.1, 6.7 and 47.8%, respectively, compared to plants grown with NaCl alone. The present study showed that application of CaCl₂ and GA₃ alone as well as in combination mitigated the adverse effect of salinity, but combined application of these treatments proved more effective in alleviating the adverse effects of NaCl stress.     

A Mutation in SLC24A1 Implicated in Autosomal-Recessive Congenital Stationary Night Blindness

Congenital stationary night blindness (CSNB) is a nonprogressive retinal disorder that can be associated with impaired night vision. The last decade has witnessed huge progress in ophthalmic genetics, including the identification of three genes implicated in the pathogenicity of autosomal-recessive CSNB. However, not all patients studied could be associated with mutations in these genes and thus other genes certainly underlie this disorder. Here, we report a large multigeneration family with five affected individuals manifesting symptoms of night blindness. A genome-wide scan localized the disease interval to chromosome 15q, and recombination events in affected individuals refined the critical interval to a 10.41 cM (6.53 Mb) region that harbors SLC24A1, a member of the solute carrier protein superfamily. Sequencing of all the coding exons identified a 2 bp deletion in exon 2: c.1613_1614del, which is predicted to result in a frame shift that leads to premature termination of SLC24A1 (p.F538CfsX23) and segregates with the disorder under an autosomal-recessive model. Expression analysis using mouse ocular tissues shows that Slc24a1 is expressed in the retina around postnatal day 7. In situ and immunohistological studies localized both SLC24A1 and Slc24a1 to the inner segment, outer and inner nuclear layers, and ganglion cells of the retina, respectively. Our data expand the genetic basis of CSNB and highlight the indispensible function of SLC24A1 in retinal function and/or maintenance in humans.     

An unusual case of left ventricular aneurysm in duchenne muscular dystrophy

Various structural anomalies of the left ventricular papillary muscles have been observed in recent years. Many of these have been linked to electrocardiographic aberrations. Recently two reports have appeared where the base of the posterior papillary muscle was identified as the source of frequent premature ventricular complexes. In some of these patients these frequent premature ventricular complexes have led to left ventricular dysfunction. In this report a newly discovered structural variant of the anterior papillary muscle is described--the bifid papillary muscle. Furthermore, it is proposed that this bifid papillary muscle is the source of frequent ventricular premature complexes, presenting as bigeminy in a patient with normal left ventricular function.     

SHANK3 genetic polymorphism and susceptibility to ASD: evidence from molecular,in silico,and meta-analysis approaches

Molecular Biology Reports - The SHANK3 gene encodes a master synaptic scaffolding protein at the excitatory synapse’s postsynaptic density, which is predominantly responsible for constructing...     

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.     

Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and characterisation of its blend with oil palm empty fruit bunch fibers

Poly(3-hydroxybutyrate-co-38 mol%-3-hydroxyvalerate) [P(3HB-co-38mol%-3HV)] was produced by Cupriavidus sp. USMAA2-4 in the presence of oleic acid and 1-pentanol. Due to enormous production of empty fruit bunch (EFB) in the oil palm plantation and high production cost of P(3HB-co-3HV), oil palm EFB fibers were used for biocomposites preparation. In this study, maleic anhydride (MA) and benzoyl peroxide (DBPO) were used to improve the miscibility between P(3HB-co-3HV) and EFB fibers. Introduction of MA into P(3HB-co-3HV) backbone reduced the molecular weight and improved the thermal stability of P(3HB-co-3HV). Thermal stability of P(3HB-co-3HV)/EFB composites was shown to be comparable to that of commercial packaging product. Composites with 35% EFB fibers content have the highest tensile strength compared to 30% and 40%. P(3HB-co-3HV)/EFB blends showed less chemicals leached compared to commercial packaging.