Fluorescence shadow imaging of Hypsibius exemplaris reveals morphological differences between sucrose- and CaCl2-induced osmobiotes.

Tardigrades are renowned for their ability to survive a wide array of environmental stressors. In particular, tardigrades can curl in on themselves while losing a significant proportion of their internal water content to form a structure referred to as a tun. In surviving varying conditions, tardigrades undergo distinct morphological transformations that could indicate different mechanisms of stress sensing and tolerance specific to the stress condition. Methods to effectively distinguish between morphological transformations, including between tuns induced by different stress conditions, are lacking. Herein, an approach for discriminating between tardigrade morphological states is developed and utilized to compare sucrose- and CaCl2-induced tuns, using the model species Hypsibius exemplaris. A novel approach of shadow imaging with confocal laser scanning microscopy enabled production of three-dimensional renderings of Hys. exemplaris in various physiological states resulting in volume measurements. Combining these measurements with qualitative morphological analysis using scanning electron microscopy revealed that sucrose- and CaCl2-induced tuns have distinct morphologies, including differences in the amount of water expelled during tun formation. Further, varying the concentration of the applied stressor did not affect the amount of water lost, pointing towards water expulsion by Hys. exemplaris being a controlled process that is adapted to the specific stressors.

The importance of low-density lipoprotein cholesterol measurement and control as performance measures: A joint clinical perspective from the National Lipid Association and the American Society for Preventive Cardiology.

Despite the established role of low-density lipoprotein cholesterol (LDL-C) as a major risk factor for cardiovascular disease (CVD), and the persistence of CVD as the leading cause of morbidity and mortality in the United States, national quality assurance metrics no longer include LDL-C measurement as a required performance metric. This clinical perspective reviews the history of LDL-C as a quality and performance metric and the events that led to its replacement. It also presents patient, healthcare provider, and health system rationales for re-establishing LDL-C measurement as a performance measure to improve cholesterol control in high-risk groups and to stem the rising tide of CVD morbidity and mortality, cardiovascular care disparities, and related healthcare costs.

The importance of low-density lipoprotein cholesterol measurement and control as performance measures: A joint Clinical Perspective from the National Lipid Association and the American Society for Preventive Cardiology.

Despite the established role of low-density lipoprotein cholesterol (LDL-C) as a major risk factor for cardiovascular disease (CVD), and the persistence of CVD as the leading cause of morbidity and mortality in the United States, national quality assurance metrics no longer include LDL-C measurement as a required performance metric. This clinical perspective reviews the history of LDL-C as a quality and performance metric and the events that led to its replacement. It also presents patient, healthcare provider, and health system rationales for re-establishing LDL-C measurement as a performance measure to improve cholesterol control in high-risk groups and to stem the rising tide of CVD morbidity and mortality, cardiovascular care disparities, and related healthcare costs.

Bayesian network analysis of panomic biological big data identifies the importance of triglyceride-rich LDL in atherosclerosis development.

Introduction: We sought to explore biomarkers of coronary atherosclerosis in an unbiased fashion. Methods: We analyzed 665 patients (mean ± SD age, 56 ± 11 years; 47% male) from the GLOBAL clinical study (NCT01738828). Cases were defined by the presence of any discernable atherosclerotic plaque based on comprehensive cardiac computed tomography (CT). De novo Bayesian networks built out of 37,000 molecular measurements and 99 conventional biomarkers per patient examined the potential causality of specific biomarkers. Results: Most highly ranked biomarkers by gradient boosting were interleukin-6, symmetric dimethylarginine, LDL-triglycerides [LDL-TG], apolipoprotein B48, palmitoleic acid, small dense LDL, alkaline phosphatase, and asymmetric dimethylarginine. In Bayesian analysis, LDL-TG was directly linked to atherosclerosis in over 95% of the ensembles. Genetic variants in the genomic region encoding hepatic lipase (LIPC) were associated with LIPC gene expression, LDL-TG levels and with atherosclerosis. Discussion: Triglyceride-rich LDL particles, which can now be routinely measured with a direct homogenous assay, may play an important role in atherosclerosis development. Clinical trial registration: GLOBAL clinical study (Genetic Loci and the Burden of Atherosclerotic Lesions); [https://clinicaltrials.gov/ct2/show/NCT01738828?term=NCT01738828&rank=1], identifier [NCT01738828].

Operationalizing a Data to Care Strategy in Michigan Through Cross-Agency Collaborations.

BACKGROUND: For persons with HIV infection (PWH), viral load suppression is essential to maintaining health and reducing the likelihood of HIV transmission. Data to Care (D2C) is an important strategy for improving HIV outcomes but may be resource-intensive to execute. SETTING: In 2016, Michigan joined the HIV Health Improvement Affinity Group to strengthen D2C partnerships between its Medicaid and HIV program. Goals included establishing routine data sharing, matching data sources to understand health outcomes, and collaborating to turn data into action. METHODS: Michigan established data use agreements to assess gaps in care for PWH enrolled in Medicaid. The HIV Surveillance Program used Link Plus to match surveillance records on PWH to Medicaid's active beneficiary file to identify PWH who were beneficiaries as of December 31, 2015. RESULTS: Matching the 2,300,877 Michigan Medicaid beneficiaries with the 15,845 PWH in HIV surveillance yielded 4822 matched PWH enrolled in Medicaid in 2015. Of Medicaid beneficiaries with HIV, 597 had no evidence of receiving HIV care, representing 20% of all Michigan residents with HIV and not in care in 2015. CONCLUSION: D2C is an effective strategy for improving HIV care continuum outcomes but can be relatively inefficient if implementation models rely solely on public health infrastructure. Through the HIV Health Improvement Affinity Group, Michigan's Medicaid and HIV programs leveraged their combined data assets to evaluate and improve care quality and outcomes for PWH on Medicaid. Partnerships between Medicaid and public health offer attractive mechanisms for potentially increasing efficiency and effectiveness of D2C investments.

Mendelian Randomization Study of ACLY and Cardiovascular Disease.

BACKGROUND: ATP citrate lyase is an enzyme in the cholesterol-biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear. METHODS: We constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (ACLY) and HMGCR to create instruments that mimic the effect of ATP citrate lyase inhibitors and HMGCR inhibitors (statins), respectively. We then compared the associations of these genetic scores with plasma lipid levels, lipoprotein levels, and the risk of cardiovascular events and cancer. RESULTS: A total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The ACLY and HMGCR scores were associated with similar patterns of changes in plasma lipid and lipoprotein levels and with similar effects on the risk of cardiovascular events per decrease of 10 mg per deciliter in the LDL cholesterol level: odds ratio for cardiovascular events, 0.823 (95% confidence interval [CI], 0.78 to 0.87; P = 4.0×10-14) for the ACLY score and 0.836 (95% CI, 0.81 to 0.87; P = 3.9×10-19) for the HMGCR score. Neither lifelong genetic inhibition of ATP citrate lyase nor lifelong genetic inhibition of HMGCR was associated with an increased risk of cancer. CONCLUSIONS: Genetic variants that mimic the effect of ATP citrate lyase inhibitors and statins appeared to lower plasma LDL cholesterol levels by the same mechanism of action and were associated with similar effects on the risk of cardiovascular disease per unit decrease in the LDL cholesterol level. (Funded by Esperion Therapeutics and others.).

Aggregation Patterns of Sensory Sensillae in the Food Canal and Cibarium of Haematobia irritans (Diptera: Muscidae).

Although mean body lengths of females were significantly greater than males in individuals drawn from two Haematobia irritans (L.) sample populations (n = 20 females and n = 20 males from West Virginia; n = 20 females and n = 20 males from Georgia), there were no significant differences in food canal lengths for females versus males at either site. Variable numbers (21-37) of setiform sensillae occurred throughout the length of the food canal, but such sensillae were significantly aggregated in the distal-most canal region of both sexes at both sites. There was no significant difference in mean numbers of food canal setiform sensillae between females and males. Four basiconic (campaniform) sensillae were consistently observed in the food canal of every fly; always aggregated in the distal-most canal region. Setiform sensillae in the cibarium also varied in number (6-13), but were significantly aggregated in the median and proximal cibarial regions. Four (occasionally three) peg-like basiconic sensillae were also observed in the cibarium of sample individuals; always in the distal and distal median regions of both sexes. Sensory sensillae (both setiform and basiconic) in both the food canal and cibarium were similarly aggregated for both sexes at both sites. Aggregation of setiform and basiconic sensillae in the food canal suggests that the distal canal region is most critical for sensory input regarding monitoring blood flow, and stress forces brought to bear on the cuticle as the labrum tip penetrates the host's skin.

The Sapphire (0001) Surface: A Transparent and Ultraflat Substrate for DNA Nanostructure Imaging.

Mica is the current substrate of choice for DNA nanostructure imaging, mainly due to its atomically flat surface. However, these mica substrates are often not optically clear. In this work, sapphire has been evaluated as an alternative substrate, with potential to enable parallel optical and AFM studies. Well known for its thermal and chemical properties, sapphire is a hard ionic material with excellent optical properties. Because sapphire lacks the excellent basal cleavage properties of the sheet silicate mica, a process to anneal it at high temperature in water vapor was developed to achieve near atomically smooth (average roughness = 0.141 nm) terraces. AFM imaging was used to determine the dimensions of these terraces and to characterize the morphology of the DNA nanostructures, revealing that their structures were preserved, indicating that annealed c-plane cut (0001) sapphire is a promising substitute for mica as a flat and transparent substrate for DNA nanostructure studies.

Origami Arrays as Substrates for the Determination of Reaction Kinetics Using High-Speed Atomic Force Microscopy.

DNA nanostructures (DN) are powerful platforms for the programmable assembly of nanomaterials. As applications for DN both as a structural material and as a support for functional biomolecular sensing systems develop, methods enabling the determination of reaction kinetics in real time become increasingly important. In this report, we present a study of the kinetics of streptavidin binding onto biotinylated DN constructs enabled by these planar structures. High-speed AFM was employed at a 2.5 frame/s rate to evaluate the kinetics and indicates that the binding fully saturates in less than 60 s. When the the data was fitted with an adsorption-limited kinetic model, a forward rate constant of 5.03 × 105 s-1 was found.

Effects of force detecting sense organs on muscle synergies are correlated with their response properties.

Sense organs that monitor forces in legs can contribute to activation of muscles as synergist groups. Previous studies in cockroaches and stick insects showed that campaniform sensilla, receptors that encode forces via exoskeletal strains, enhance muscle synergies in substrate grip. However synergist activation was mediated by different groups of receptors in cockroaches (trochanteral sensilla) and stick insects (femoral sensilla). The factors underlying the differential effects are unclear as the responses of femoral campaniform sensilla have not previously been characterized. The present study characterized the structure and response properties (via extracellular recording) of the femoral sensilla in both insects. The cockroach trochantero-femoral (TrF) joint is mobile and the joint membrane acts as an elastic antagonist to the reductor muscle. Cockroach femoral campaniform sensilla show weak discharges to forces in the coxo-trochanteral (CTr) joint plane (in which forces are generated by coxal muscles) but instead encode forces directed posteriorly (TrF joint plane). In stick insects, the TrF joint is fused and femoral campaniform sensilla discharge both to forces directed posteriorly and forces in the CTr joint plane. These findings support the idea that receptors that enhance synergies encode forces in the plane of action of leg muscles used in support and propulsion.

Variation in PCSK9 and HMGCR and Risk of Cardiovascular Disease and Diabetes.

BACKGROUND: Pharmacologic inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) are being evaluated in clinical trials for the treatment of cardiovascular disease. The effect of lowering low-density lipoprotein (LDL) cholesterol levels by inhibiting PCSK9 on the risk of cardiovascular events or diabetes is unknown. METHODS: We used genetic scores consisting of independently inherited variants in the genes encoding PCSK9 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR; the target of statins) as instruments to randomly assign 112,772 participants from 14 studies, with 14,120 cardiovascular events and 10,635 cases of diabetes, to groups according to the number of LDL cholesterol-lowering alleles that they had inherited. We compared the effects of lower LDL cholesterol levels that were mediated by variants in PCSK9, HMGCR, or both on the risk of cardiovascular events and the risk of diabetes. RESULTS: Variants in PCSK9 and HMGCR were associated with nearly identical protective effects on the risk of cardiovascular events per decrease of 10 mg per deciliter (0.26 mmol per liter) in the LDL cholesterol level: odds ratio for cardiovascular events, 0.81 (95% confidence interval [CI], 0.74 to 0.89) for PCSK9 and 0.81 (95% CI, 0.72 to 0.90) for HMGCR. Variants in these two genes were also associated with very similar effects on the risk of diabetes: odds ratio for each 10 mg per deciliter decrease in LDL cholesterol, 1.11 (95% CI, 1.04 to 1.19) for PCSK9 and 1.13 (95% CI, 1.06 to 1.20) for HMGCR. The increased risk of diabetes was limited to persons with impaired fasting glucose levels for both scores and was lower in magnitude than the protective effect against cardiovascular events. When present together, PCSK9 and HMGCR variants had additive effects on the risk of both cardiovascular events and diabetes. CONCLUSIONS: In this study, variants in PCSK9 had approximately the same effect as variants in HMGCR on the risk of cardiovascular events and diabetes per unit decrease in the LDL cholesterol level. The effects of these variants were independent and additive. (Funded by the Medical Research Council and the National Heart, Lung, and Blood Institute.).

Time-related trends in variability of cIMT changes in statin trials.

This brief article provides complementary data supporting the results reported in "Changing Characteristics of Statin-related cIMT Trials from 1988 to 2006" [1]. That article described time-related trends in baseline factors and study characteristics that may have influenced the variability of carotid intima media thickness (cIMT) endpoints (mean of mean and maximum common carotid artery [CCA]/cIMT) in published statin trials. In this brief report, additional details for the studies included in the analysis, and further supporting data, including mean of the maximum CCA/cIMT changes and subgroup data (mean and maximum CCA/cIMT) are provided. For the analysis, study-level data was extracted from 17 statin cIMT trials conducted during 1988-2006, selected on the basis of having at least one statin monotherapy arm in the absence of mixed therapy, and baseline- and study-end values for mean mean and mean maximum CCA/cIMT endpoints. The baseline mean CCA/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Interestingly, all 8 studies conducted before 2000 were significant for cIMT change in which patients did not receive prior LLT; whereas after 2000, the results were more variable and in 4 of 6 trials that did not show a significant cIMT change, patients had received prior treatment. Baseline mean maximum cIMT and LDL-C levels, and annualized changes in studies conducted before 2000 were higher than those conducted after 2000, similar to the results reported in the original article for the mean mean cIMT endpoint. These findings were consistent across study populations of patients with CHD risk versus those without, and in studies with greater LDL-C reductions and with thickened baseline cIMT at study entry for both mean and maximum cIMT changes. Taken together, these results are consistent with trends in recent years toward greater use of lipid-lowering therapy and control of LDL-C that may have impacted the variability in the results of cIMT studies.

Changing characteristics of statin-related cIMT trials from 1988 to 2006.

OBJECTIVES: Changes in cIMT have not been consistently correlated with cardiovascular risk reduction in clinical studies. The variability of carotid intima media thickness (cIMT) changes in published statin LDL-C-lowering studies in relation to various baseline and study characteristics was assessed. METHODS: This was an exploratory analysis of study-level data pooled from statin-treatment arms of 13 studies conducted during 1988-2006. Baseline mean common carotid artery (CCA)/cIMT, maximum mean CCA/cIMT and LDL-C levels, and annualized cIMT changes were estimated for the overall studies, those conducted before/after 2000, and in risk-based subgroups. Potential relationships between prespecified covariates and cIMT changes were assessed. RESULTS: Baseline mean CCA/cIMT and LDL-C levels were higher in the combined studies conducted before year 2000 (0.8521 mm) than after 2000 (0.7458 mm), and somewhat higher in study populations of patients with coronary heart disease risk and those with greater LDL-C reductions. Mean CCA/cIMT changes were also larger for the studies conducted before 2000 (-0.0119 mm/year) than after 2000 (-0.0013 mm/year). Notably, studies conducted before 2000 were of longer duration (≥ 2 years) than after 2000 (<2 years). Heterogeneity in cIMT change was attributed to baseline and study-design characteristics. Longer study duration and greater LDL-C reductions were significantly related to larger annualized cIMT changes. Maximum cIMT results were similar. CONCLUSION: Baseline cIMT and LDL-C levels were lower, and cIMT changes were smaller in statin cIMT trials conducted after 2000 than those before 2000. These trends are consistent with increased treatment and control of high LDL-C levels over recent years in clinical practice, and may influence the results of cIMT studies.

DNA Origami Reorganizes upon Interaction with Graphite: Implications for High-Resolution DNA Directed Protein Patterning.

Although there is a long history of the study of the interaction of DNA with carbon surfaces, limited information exists regarding the interaction of complex DNA-based nanostructures with the important material graphite, which is closely related to graphene. In view of the capacity of DNA to direct the assembly of proteins and optical and electronic nanoparticles, the potential for combining DNA-based materials with graphite, which is an ultra-flat, conductive carbon substrate, requires evaluation. A series of imaging studies utilizing Atomic Force Microscopy has been applied in order to provide a unified picture of this important interaction of structured DNA and graphite. For the test structure examined, we observe a rapid destabilization of the complex DNA origami structure, consistent with a strong interaction of single-stranded DNA with the carbon surface. This destabilizing interaction can be obscured by an intentional or unintentional primary intervening layer of single-stranded DNA. Because the interaction of origami with graphite is not completely dissociative, and because the frustrated, expanded structure is relatively stable over time in solution, it is demonstrated that organized structures of pairs of the model protein streptavidin can be produced on carbon surfaces using DNA origami as the directing material.

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid-Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease.

BACKGROUND: Patients with diabetes mellitus and cardiovascular disease may not achieve adequate low-density lipoprotein cholesterol (LDL-C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL-C-lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL-C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose-doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low- and high-density lipoprotein particle number and lipoprotein-associated phospholipase A2 [Lp-PLA2]) was assessed. METHODS AND RESULTS: Treatment effects on low- and high-density lipoprotein particle number (by NMR) and Lp-PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low-density lipoprotein-particle number numerically more than did statin dose-doubling and was comparable with R10 (-133.3, -94.4, and -56.3 nmol/L, respectively; P>0.05). Increases in high-density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose-doubling (1.5 and -0.5 µmol/L; P<0.05) and comparable with R10 (0.7 µmol/L; P>0.05). Percentages of patients attaining low-density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose-doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp-PLA2 activity significantly more than did statin dose-doubling (-28.0 versus -3.8 nmol/min per mL, P<0.05) and was comparable with R10 (-28.0 versus -18.6 nmol/min per mL; P>0.05); effects on Lp-PLA2 concentration were modest. CONCLUSIONS: In diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp-PLA2 activity more than did statin dose-doubling and was comparable with R10, consistent with its lipid effects. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.

Limitations of real-world treatment with atorvastatin monotherapy for lowering LDL-C in high-risk cardiovascular patients in the US.

BACKGROUND: Guidelines endorse statin therapy for lowering low-density lipoprotein cholesterol (LDL-C) to recommended levels, in patients with cardiovascular disease (CVD) risk, if needed, after lifestyle changes. Atorvastatin is a common statin with greater LDL-C lowering efficacy than most other statins; its availability in generic form will likely increase its use. This study assessed attainment of guideline-recommended LDL-C levels in high-risk CVD patients treated with atorvastatin monotherapy. METHODS: Analyses of two retrospective US cohorts of patients who received a prescription for atorvastatin monotherapy between January 1, 2008 and December 31, 2010 (index date defined as first prescription date) in the GE Centricity Electronic Medical Record (EMR) (N=10,693) and Humana Medicare (N=16,798) databases. Eligible patients were ≥18 years, diagnosed with coronary heart disease or atherosclerotic vascular disease, with ≥1 LDL-C measurement between 3 months and 1 year postindex date, and continuously enrolled for 1 year prior to and following the index date. RESULTS: Of the eligible patients, 21.8%, 29.6%, 29.9%, and 18.7% (GE Centricity EMR) and 25.4%, 32.9%, 27.8%, and 14.0% (Humana Medicare) received 10, 20, 40, and 80 mg doses of atorvastatin, respectively. The mean ± standard deviation (SD) follow-up LDL-C levels were 2.1±0.8 mmol/L (83±30 mg/dL) and 2.3±0.8 mmol/L (88±31 mg/dL) for the GE Centricity EMR and Humana Medicare cohorts, respectively. Regardless of dose, only 28.3%-34.8% of patients had LDL-C levels <1.8 mmol/L (<70 mg/dL), and 72.0%-78.0% achieved LDL-C <2.6 mmol/L (<100 mg/dL) in both cohorts. As many as 41% and 13% of patients had LDL-C levels ≥0.5 mmol/L (≥20 mg/dL) above LDL-C 1.8 mmol/L (70 mg/dL) and 2.6 mmol/L (100 mg/dL), respectively, in both cohorts; these percentages were generally similar across atorvastatin doses. CONCLUSION: In this real-world US setting, a large number of high-risk CVD patients did not attain guideline-recommended LDL-C levels with atorvastatin monotherapy. More than 65% of the patients had LDL-C levels >1.8 mmol/L (>70 mg/dL), and of these, 30%-40% had LDL-C levels ≥0.5 mmol/L (≥20 mg/dL) above this, regardless of dose. This suggests that more effective lipid-lowering strategies, such as statin uptitration, switching to a higher efficacy statin, and/or combination therapy, may be required to achieve optimal LDL-C lowering in high-risk patients.

LDL-C levels in US patients at high cardiovascular risk receiving rosuvastatin monotherapy.

BACKGROUND: Statin therapy is recommended as the first-line pharmacotherapeutic approach for lowering LDL-C levels in patients at high cardiovascular risk. OBJECTIVE: To assess LDL-C levels among patients at high cardiovascular risk treated with rosuvastatin monotherapy. METHODS: This retrospective cohort study used patient records from the GE Centricity Electronic Medical Records (GE Centricity EMR) database and administrative claims data from Humana Medicare to identify patients at high cardiovascular risk with a first prescription for rosuvastatin monotherapy (index date) from January 1, 2008 through December 31, 2010. Eligible adult patients had an International Classification of Diseases, Ninth Revision (ICD-9) diagnosis or a Current Procedural Terminology (CPT) procedure code indicating coronary heart disease or atherosclerotic vascular disease, ≥1 LDL-C measurement 3 to 12 months after the index date, and continuous data during 1-year baseline and 1-year follow-up. Mean LDL-C levels and distribution of patients around <70 mg/dL and <100 mg/dL thresholds overall and by daily rosuvastatin dose were assessed. RESULTS: Among 6004 GE Centricity EMR patients (mean [SD] age, 66 [10] years; 56% men) and 11,320 Humana Medicare patients (mean [SD] age, 74 [8] years; 44% men) who met selection criteria, the most frequently prescribed rosuvastatin dose was 10 mg, and the mean (SD) follow-up LDL-C level was 89 (37) mg/dL for GE Centricity EMR patients and 92 (36) mg/dL for Humana Medicare patients. Overall, lower mean LDL-C levels were observed as rosuvastatin dose increased. However, less than one-third of GE Centricity EMR and Humana Medicare patients had an LDL-C level <70 mg/dL, and approximately two-thirds had an LDL-C level <100 mg/dL. CONCLUSION: More effective lipid-lowering strategies, such as statin up-titration or combination therapy, may be needed to achieve therapeutic goals in a substantial proportion of high-risk patients.

Therapeutic practice patterns related to statin potency and ezetimibe/simvastatin combination therapies in lowering LDL-C in patients with high-risk cardiovascular disease.

BACKGROUND: Statin combination therapy and statin uptitration have been shown to be efficacious in low-density lipoprotein cholesterol (LDL-C) lowering and are recommended for patients with high-risk coronary heart disease (CHD) who do not reach guideline-endorsed LDL-C goals on statin monotherapy. OBJECTIVE: This analysis evaluated treatment practice patterns and LDL-C lowering for patients with CHD/CHD risk equivalent on statin monotherapy in a real-world practice setting in the United States. METHODS: In this retrospective, observational study, patients with CHD/CHD risk equivalent on statin therapy were identified during 2004 to 2008 in a US managed care database. Prescribing patterns and effect of switching from statin monotherapy to combination ezetimibe/simvastatin therapy vs uptitration to higher statin dose/potency level and no change from initial statin potency on LDL-C lowering were assessed. Percentage of change from baseline in LDL-C levels and odds ratios for LDL-C goal attainment were estimated with analyses of covariance and logistic regression. RESULTS: Of 27,919 eligible patients on statin therapy, 2671 (9.6%) switched to ezetimibe/simvastatin therapy, 11,035 (39.5%) uptitrated statins, and 14,213 (50.9%) remained on the same statin monotherapy. LDL-C reduction from baseline and attainment of LDL-C <100 and <70 mg/dL were substantially greater for patients who switched to ezetimibe/simvastatin therapy (-24.0%, 81.2%, and 35.2%, respectively) than for patients who titrated (-9.6%, 68.0%, and 18.4%, respectively) or remained on initial statin therapy (4.9%, 72.2%, and 23.7%, respectively). The odds ratios for attainment of LDL-C <100 and <70 mg/dL were also higher for patients who switched than for patients who uptitrated and had no therapy change than for patients who titrated vs no therapy change. Similarly, among a subgroup of patients not at LDL-C <100 mg/dL on baseline therapy, attainment of LDL-C <100 and <70 mg/dL was greater for patients who switched than for statin uptitration vs no change, as well as for patients who uptritrated statins vs no therapy change. CONCLUSION: In this study, LDL-C lowering and goal attainment rates improved substantially for patients with high-risk CHD on statin monotherapy who switched to combination ezetimibe/statin or uptitrated their statin therapies; however, approximately one-third of these patients still did not attain the optional recommended LDL-C goal of <70 mg/dL. Moreover, these higher efficacy lipid-lowering therapies were infrequently prescribed, indicating the need for further assessment of barriers to LDL-C goal attainment in actual practice settings.

Rapid, high yield, directed addition of quantum dots onto surface bound linear DNA origami arrays.

We have developed an approach, which routinely generates ~10 micron long one dimensional (1D) arrays of DNA origami. Coupled with a sequential assembly method with a very short (~1 min) reaction time, this extended platform enables the production, in high yield, of 1D arrays of biomolecules or conjugates.

Potential effects of reclassifying CKD as a coronary heart disease risk equivalent in the US population.

BACKGROUND: Persons with chronic kidney disease (CKD) are at high risk for cardiovascular disease events, but are not classified as such in current US cholesterol treatment guidelines. We examined potential effects of modified guidelines in which CKD was considered a "coronary heart disease (CHD) risk equivalent" for risk stratification. STUDY DESIGN: Nationally representative cross-sectional study. SETTING & PARTICIPANTS: 4,823 adults 20 years or older from the 2007-2010 National Health and Nutrition Examination Survey. PREDICTORS: Cardiovascular risk stratification based on current US cholesterol treatment guidelines and 2 simulated scenarios in which CKD stages 3-5 or CKD stages 1-5 were considered a CHD risk equivalent. OUTCOMES & MEASUREMENTS: Proportion of persons with low-density lipoprotein (LDL) cholesterol at levels above treatment targets and above the threshold for lipid-lowering therapy initiation, based on current guidelines and the 2 simulated scenarios. RESULTS: Under current guidelines, 55.1 million adults in 2010 did not achieve the target LDL cholesterol goal. Of these, 25.2 million had sufficiently elevated levels to meet recommendations for initiating lipid-lowering therapy; 12.1 million were receiving this therapy but remained above goal. When CKD stages 3-5 were considered a CHD risk equivalent, 59.2 million persons were above target LDL cholesterol goals, with 28.5 million and 13.3 million meriting therapy initiation and intensification, respectively. When CKD stages 1-5 were considered a CHD risk equivalent, 65.2 million adults were above goal, with 33.9 million and 14.4 million meriting therapy initiation and intensification, respectively. LIMITATIONS: CKD and LDL cholesterol defined using a single laboratory value. CONCLUSIONS: Many adults in the United States currently do not meet recommended goals for LDL cholesterol levels. Modifying the current cholesterol guidelines to include CKD as a CHD risk equivalent would lead to a substantial increase in both the number of persons with levels above LDL cholesterol treatment targets and those recommended to initiate lipid-lowering therapy.