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This study assesses the impacts of the Science program at Piedmont Virginia Community College and its flagship capstone research experience, Supervised Study, through psychosocial perceptions associated with persistence in science and through a comparative analysis of subsequent science bachelor's degree attainment. Supervised Study involves authentic, independent projects, a research methods course and learning community, and one-on-one faculty mentoring. The Persistence in the Sciences survey was used as a repeated-measures instrument in four semesters of Supervised Study. Positive trends were observed for self-efficacy, science identity, community values, and networking, while responses related to project ownership were mixed ( n = 13). To contextualize these observations, transfer and bachelor's degree completion rates were analyzed. Students who earn an associate's degree in Science ( n = 113 between 2012 and 2019) complete bachelor's degrees at high rates (66.4%). Moreover, they are two to four times more likely to major in physical and natural sciences than their science-oriented peers, who take many of the same courses, with the exception of Supervised Study. Notably, these comparison rates remain consistent between different demographic groups. These findings further describe a model for research at the community college level that supports persistence in undergraduate science for a broad group of students.

Background: Clinical laboratory patient databases are an untapped source of valuable diagnostic and prognostic information. However, the lack of associated clinical and/or demographic information and questionable generalizability to nonpatient populations often limit utility of these data., Objectives: This study compared levels of cardiometabolic biomarkers between a national clinical laboratory patient cohort (Health Diagnostic Laboratory [HD Lab]) and the US population as inferred from the National Health and Nutrition Examination Survey (NHANES, 2011-2012)., Methods: Sample sizes for HD Lab ranged from 199,000 to 739,000 and for NHANES from 2200 to 5300. The latter were weighted to represent the adult US population (∼220 million). Descriptive statistics were compared for body mass index, 5 lipid biomarkers, and 3 glycemic biomarkers., Results: Using age- and sex-matched data, mean biomarker values (mg/dL unless noted) and percent differences (%) for HD Lab vs NHANES were body mass index (kg/m(2)), 29.1 vs 28.6 (1.7%); total cholesterol, 185 vs 193 (-4.1%); apolipoprotein B, 92 vs 90 (2.2%); low-density lipoprotein cholesterol, 107 vs 115 (-7%); high-density lipoprotein cholesterol, 53 vs 53 (0%); triglycerides, 128 vs 127 (0.8%); glucose, 99 vs 108 (-8.3%); insulin (uU/mL), 13.7 vs 13.4 (2.2%); and hemoglobin A1c (%), 5.6 vs 5.8 (-3.4%). Although all differences were statistically significant, only low-density lipoprotein cholesterol and glucose differed by more than 5%. These may reflect a greater use of medications among HD Lab patients and/or preanalytical factors., Conclusions: Cardiometabolic risk markers from a national clinical laboratory were broadly similar to those of the US population; thus, with certain caveats, data from the former may be generalizable to the latter., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

A 52-year-old man with a longstanding history of hypertriglyceridaemia (approximately 7 mmol/L (600 mg/dL)), unresponsive to treatment, presented to a lipid-specialty clinic. Additional triglyceride-lowering therapies were added with no effect. It was then noted that despite the apparent hypertriglyceridaemia, his serum sample was clear. A 'glycerol blank' was then requested from an advanced lipid laboratory, which reported a triglyceride value of 0.7 mmol/L (62 mg/dL). These findings suggest isolated asymptomatic glycerol kinase deficiency (GKD) or 'pseudohypertriglyceridaemia'. The falsely elevated triglyceride values in such individuals are a result of excess serum glycerol and clinical laboratories measuring glycerol to report triglyceride concentrations. After discontinuation or modification of the patient's primary triglyceride-lowering agents, the lipid panels and triglyceride values remained comparable to previous readings. Recognition of asymptomatic GKD is important to prevent unnecessary treatment and overestimated cardiovascular risk., (2015 BMJ Publishing Group Ltd.)

Objective: We aimed to examine associations of lipoprotein(a) (Lp(a)) concentrations with coronary heart disease (CHD) and determine whether current Lp(a) clinical laboratory cut points identify risk of disease incidence in 4 races/ethnicities of the Multi-Ethnic Study of Atherosclerosis (MESA)., Approach and Results: A subcohort of 1323 black, 1677 white, 548 Chinese American, and 1044 Hispanic MESA participants were followed up during a mean 8.5-year period in which 235 incident CHD events were recorded. Lp(a) mass concentrations were measured using a turbidimetric immunoassay. Cox regression analysis determined associations of Lp(a) with CHD risk with adjustments for lipid and nonlipid variables. Lp(a) concentrations were continuously associated with risk of CHD incidence in black (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.09-2.04] and white participants (HR, 1.22; 95% CI, 1.02-1.45). Examining Lp(a) risk by the 50 mg/dL cut point revealed higher risks of incident CHD in all races except Chinese Americans: blacks (HR, 1.69; 95% CI, 1.03-2.76), whites (HR, 1.82; 95% CI, 1.15-2.88); Hispanics (HR, 2.37; 95% CI, 1.17-4.78). The lower Lp(a) cut point of 30 mg/dL identified higher risk of CHD in black participants alone (HR, 1.87; 95% CI, 1.08-3.21)., Conclusions: Our findings suggest that the 30 mg/dL cutoff for Lp(a) is not appropriate in white and Hispanic individuals, and the higher 50 mg/dL cutoff should be considered. In contrast, the 30 mg/dL cutoff remains suitable in black individuals. Further research is necessary to develop the most clinically useful Lp(a) cutoff values in individual races/ethnicities., (© 2015 American Heart Association, Inc.)

Background: Low-density lipoprotein (LDL) particle (P, or molar) concentration has been shown to be a more sensitive marker of cardiovascular disease (CVD) risk than LDL cholesterol. Although elevated circulating lipoprotein(a) [Lp(a)] cholesterol and mass have been associated with CV risk, no practicable method exists to measure Lp(a)-P. We have developed a method of determining Lp(a)-P suitable for routine clinical use., Methods: Lipoprotein immunofixation electrophoresis (Lipo-IFE) involves rigidly controlled electrophoretic separation of serum lipoproteins, probing with polyclonal apolipoprotein B antibodies, then visualization after staining with a nonspecific protein stain (Acid Violet). Lipo-IFE was compared to the Lp(a) mass assay for 1086 randomly selected patient samples, and for 254 samples stratified by apo(a) isoform size., Results: The Lipo-IFE method was shown to be precise (CV <10% above the 50 nmol/l limit of quantitation) and linear across a 16-fold range. Lipo-IFE compared well with the mass-based Lp(a) assay (r=0.95), but was not affected by variations in apo(a) isoform size. With a throughput of 100 samples in 90 min, the assay is suitable for use in the clinical laboratory., Conclusions: The Lipo-IFE method will allow Lp(a)-P to be readily tested as a CVD risk factor in large-scale clinical trials., (Copyright © 2014. Published by Elsevier B.V.)

The importance of lipoprotein (a)-Lp(a)-as a cardiovascular (CV) risk marker has been underscored by recent findings that CV risk is directly related to baseline Lp(a) levels, even in well-treated patients. Although there is currently little that can be done pharmacologically to lower Lp(a) levels, knowledge of its serum concentration is important in overall risk assessment. This review focuses on 1 aspect of Lp(a) that is rarely discussed directly: how to express its levels in serum. There is considerable confusion on this point, and a fuller understanding of what the concentration units mean will help improve study-to-study comparisons and thereby advance our understanding of the pathobiology of this lipoprotein particle. As discussed here, the term Lp(a) mass refers to the entire mass of the particle: lipids, proteins, and carbohydrates combined. At present, there are no commercially available assays that are completely insensitive to the variability in particle mass, which arises not only from differences in apo(a) isoform mass but also from variations in lipid mass. Because lipoprotein "particle number" (molar concentration) has been found to be superior to component-based metrics (ie, low-density lipoprotein particle vs cholesterol concentrations) for CV disease risk prediction, the development of a mass-insensitive Lp(a) assay should be a high priority., (Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Objective: Coronary heart disease (CHD) is the leading cause of death in the United States, yet assessing risk of its development remains challenging. The present study evaluates a new automated assay of small dense low-density lipoprotein cholesterol content (sdLDL-C) and whether sdLDL-C is a risk factor for CHD compared with LDL-C or small LDL particle concentrations derived from nuclear magnetic resonance spectroscopy., Approach and Results: sdLDL-C was measured using a new automated enzymatic method, and small LDL concentrations were obtained by nuclear magnetic resonance in 4387 Multi-Ethnic Study of Atherosclerosis participants. Cox regression analysis estimated hazard ratios for developing CHD for 8.5 years after adjustments for age, race, sex, systolic blood pressure, hypertension medication use, high-density lipoprotein cholesterol, and triglycerides. Elevated sdLDL-C was a risk factor for CHD in normoglycemic individuals. Those in the top sdLDL-C quartile showed higher risk of incident CHD (hazard ratio, 2.41; P=0.0037) compared with those in the bottom quartile and indicated greater CHD risk than the corresponding quartile of LDL-C (hazard ratio, 1.75; P=0.019). The association of sdLDL-C with CHD risk remained significant when LDL-C (<2.57 mmol/L) was included in a multivariate model (hazard ratio, 2.37; P=0.012). Nuclear magnetic resonance-derived small LDL concentrations did not convey a significant risk of CHD. Those with impaired fasting glucose or diabetes mellitus showed higher sdLDL-C and small LDL concentrations but neither was associated with higher CHD risk in these individuals., Conclusions: This new automated method for sdLDL-C identifies risk for CHD that would remain undetected using standard lipid measures, but only in normoglycemic, nondiabetic individuals.

Background: Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue-level markers within the myocardium that precede organ-level alterations have not been described., Methods and Results: We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m(2), including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years; BMI, 20.1±3.5 kg/m(2)) using biomarkers of cardiometabolic risk and cardiac magnetic resonance imaging (CMR) to phenotype cardiac structure, function, and interstitial matrix remodeling by standard techniques. Although left ventricular ejection fraction and left atrial volumes were similar in healthy volunteers and obese patients (and within normal body size-adjusted limits), interstitial matrix expansion by CMR extracellular volume fraction (ECV) was significantly different between healthy volunteers (median, 0.264; interquartile range [IQR], 0.253 to 0.271), obese adolescents without T2D (median, 0.328; IQR, 0.278 to 0.345), and obese adolescents with T2D (median, 0.376; IQR, 0.336 to 0.407; P=0.0001). ECV was associated with BMI for the entire population (r=0.58, P<0.001) and with high-sensitivity C-reactive protein (r=0.47, P<0.05), serum triglycerides (r=0.51, P<0.05), and hemoglobin A1c (r=0.76, P<0.0001) in the obese stratum., Conclusions: Obese adolescents (particularly those with T2D) have subclinical alterations in myocardial tissue architecture associated with inflammation and insulin resistance. These alterations precede significant left ventricular hypertrophy or decreased cardiac function.

Background: The number of circulating LDL particles is a strong indicator of future cardiovascular disease (CVD) events, even superior to the concentration of LDL cholesterol. Atherogenic (primarily LDL) particle number is typically determined either directly by the serum concentration of apolipoprotein B (apo B) or indirectly by nuclear magnetic resonance (NMR) spectroscopy of serum to obtain NMR-derived LDL particle number (LDL-P)., Content: To assess the comparability of apo B and LDL-P, we reviewed 25 clinical studies containing 85 outcomes for which both biomarkers were determined. In 21 of 25 (84.0%) studies, both apo B and LDL-P were significant for at least 1 outcome. Neither was significant for any outcome in only 1 study (4.0%). In 50 of 85 comparisons (58.8%), both apo B and LDL-P had statistically significant associations with the clinical outcome, whereas in 17 comparisons (20.0%) neither was significantly associated with the outcome. In 18 comparisons (21.1%) there was discordance between apo B and LDL-P., Conclusions: In most studies, both apo B and LDL-P were comparable in association with clinical outcomes. The biomarkers were nearly equivalent in their ability to assess risk for CVD and both have consistently been shown to be stronger risk factors than LDL-C. We support the adoption of apo B and/or LDL-P as indicators of atherogenic particle numbers into CVD risk screening and treatment guidelines. Currently, in the opinion of this Working Group on Best Practices, apo B appears to be the preferable biomarker for guideline adoption because of its availability, scalability, standardization, and relatively low cost., (© 2013 American Association for Clinical Chemistry.)

Background: Low-density lipoprotein cholesterol (LDL-C) has been the cornerstone measurement for assessing cardiovascular risk for nearly 20 years., Content: Recent data demonstrate that apolipoprotein B (apo B) is a better measure of circulating LDL particle number (LDL-P) concentration and is a more reliable indicator of risk than LDL-C, and there is growing support for the idea that addition of apo B measurement to the routine lipid panel for assessing and monitoring patients at risk for cardiovascular disease (CVD) would enhance patient management. In this report, we review the studies of apo B and LDL-P reported to date, discuss potential advantages of their measurement over that of LDL-C, and present information related to standardization., Conclusions: In line with recently adopted Canadian guidelines, the addition of apo B represents a logical next step to National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) and other guidelines in the US. Considering that it has taken years to educate physicians and patients regarding the use of LDL-C, changing perceptions and practices will not be easy. Thus, it appears prudent to consider using apo B along with LDL-C to assess LDL-related risk for an interim period until the superiority of apo B is generally recognized.

Lipoprotein-associated phospholipase A2 (LP-PLA2) is an emerging inflammatory marker that is used to assess the risk for cardiovascular disease (CVD) and associated events. Several epidemiologic studies have demonstrated an independent association between plasma Lp-PLA2 concentration and risk for cardiovascular events. HMG-CoA reductase inhibitors (statins) and fenofibrates can reduce Lp-PLA2 concentrations in plasma, and orally active, specific Lp-PLA2 inhibitors have been developed and are in clinical trials to evaluate the potential of Lp-PLA2 as a therapeutic target. This article reviews recent studies of Lp-PLA2 in the setting of CVD, discusses the proposed mechanisms of action of Lp-PLA2, and describes methods for measurement and their clinical application. Recent evidence that suggests Lp-PLA2's potential usefulness as a therapeutic target also is reviewed.

Most tumor markers in current use are glycoproteins that are measured by routine immunoassay techniques. The primary utility of serum tumor markers is for evaluating the effectiveness of therapy in advanced stages of cancer; in addition, they are used for monitoring "cured" patients for cancer recurrence. Regrettably, this latter use has not led to a significant improvement in patient outcomes when a recurrence is detected early. Sensitivity and/or specificity is frequently lacking for most tumor marker tests and their utility as screening tools to detect early cancer is extremely limited. For the most part, decisions based on the concentration of these cancer-associated molecules should always be made in light of the entire clinical picture. A monumental goal in cancer research is to find markers that are significantly more sensitive and specific for early cancer detection, as well as the other uses described herein. In Part II of this series, practical considerations and limitations regarding laboratory testing of tumor markers will be addressed.

Background: Recent evidence suggests that the presence of small, dense LDL is independently associated with increased risk of developing coronary artery disease. Current methods to subfractionate LDL are time-consuming and/or technically demanding. Therefore, we have sought the development of a less complex LDL subfractionation procedure., Methods: LDL subfractions were separated using the Quantimetrix Lipoprint(TM) LDL System. High-resolution 3% polyacrylamide gel tubes were scanned densitometrically (610 nm) with a Helena EDC system. A computerized method to identify and quantitatively score the resolved LDL subfractions was developed. Results from the Quantimetrix method were compared using 51 plasma samples with values obtained by nondenaturing gradient gel electrophoresis (NDGGE) and nuclear magnetic resonance (NMR) spectroscopy., Results: LDL subfractionation scores correlated significantly (P <0.05) with triglyceride, HDL-cholesterol, apolipoprotein B100, and LDL-cholesterol/apolipoprotein B100 (r = 0.591, -0.392, 0.454, and -0.411, respectively). For 51 samples, the Quantimetrix method classified 21 with small, 14 with intermediate, and 16 with large LDL. Of the 21 samples classified as small by Quantimetrix, 20 (95%) were classified as small (n = 18) or intermediate (n = 2) by NDGGE. All of the 16 specimens classified as large by Quantimetrix were either large (n = 14) or intermediate (n = 2) by NDGGE. LDL score was inversely correlated (r = -0.674; P <0.0001) with LDL particle size determined by NMR spectroscopy., Conclusions: A quantitative method for the assessment of LDL particle size phenotype was developed using the Quantimetrix Lipoprint LDL System. The method can be performed in less than 3 h in batch mode and is suitable for routine use in clinical laboratories.

Tritiated p-azidobenzylphlorizin (p-AzBPhz) was photoactivated in the presence of red blood cells under conditions previously found to alter morphology, flexibility and volume. When less than 0.25 million molecules were added per cell, only a 28 kDa peptide was photolabeled: at 1-2 million molecules added, band 3 also incorporated significant radioactivity. When using leaky ghosts, other proteins became labeled, including those limited to the cytoplasm. Protein N-deglycosylation caused a shift of radiolabeled band 3 to higher Rf values on SDS-PAGE gels but not for the 28 kDa band; the latter was, however, susceptible to enzymatic digestion by NANase (N-acetylneuraminidase) III but not by NANase II. Inhibition of photoincorporation into both receptors by unlabeled p-AzBPhz was dose-dependent. Mercuric chloride and p-CMBS selectively blocked 28 kDa peptide labeling. DIDS partially blocked at band 3; after 15% inhibition, greater DIDS concentrations caused increased incorporation into the 28 kDa peptide. These results, and a temperature-dependent labeling pattern, suggest that: (i) cellular changes occur when p-AzBPhz binds to the exofacial sides of the anion transporter and 28 kDa peptide; (ii) these proteins may be physically associated in the native membrane; (iii) they mediate ligand-induced changes in morphology, flexibility, and volume.

Two nonpenetrating membrane probes, p-azidobenzylphlorizin (p-AzBPhz) and 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS), have been shown in earlier studies to induce dose-dependent changes in red blood cell (RBC) shape and volume at the same low concentrations that inhibit anion transport. In the present work, these ligand-induced morphology and rheology changes were studied using video digital image morphometry (VDIM) and microfiltration techniques. The results of these experiments corroborate our earlier investigation. RBCs were filmed using a Nomarski optics microscope with video camera attachment and cell size and shape changes were computer analyzed using VDIM. Low microM p-AzBPhz or DIDS levels caused collapse of the cell's biconcave structure and cell flattening occurred within 1-2 sec after drug exposure. Higher doses of either agent converted cells to a new steady-state in which a concurrent limited increase in erythrocyte volume and blunt membrane protrusions were produced. These changes were reversed in less than 2 sec by washing the drug from the membrane. Both ligands increased the deformability of RBCs in a dose-dependent manner as determined by filtration through Nuclepore polycarbonate filters (3 microns pore diameter). The improvement in deformability of drug-treated sickle cells was much more dramatic than for normal cells at low p-AzBPhz concentrations. These results support our earlier conclusions that the ligands, through a common interaction with band 3, induce volume-associated cytoskeletal alterations which lead to changes in morphology and flexibility.

p-Azidobenzylphlorizin (p-AzBPhz) is a potential photoaffinity labeling agent for the anion and glucose transporters in human RBCs. In the absence of light and at the same low concentrations which block these transport processes (only 1-2 million molecules bound/cell), this impermeable membrane probe produces rapid morphological and volume alterations. This high-affinity activity, called phase 1, can be rapidly and completely reversed by simply diluting the azide-treated cell suspension. Phase 2 effects, including formation of cells with multiple, long spicules (stage 3/4 echinocytes), followed by an influx of salt and water with eventual lysis, occur at two log units higher concentration by a different mechanism, probably by intercalating into and selectively expanding the outer lipid monolayer. Light scattering, electronic cell sizing, microhematocrit measurements and scanning electron microscopy have been employed to compare the effects of the azide and the anion transport inhibitor, DIDS (4,4'-diisothiocyano-2,2'-stilbene disulfonate), on red cells. DIDS produced only those changes analogous to the azide's low dose phase 1 action; cells swell, lose the ability to scatter 800 nm light and undergo a limited shape change (comparable to stage 1 echinocytosis). The mechanism by which the two ligands perturb the membrane is additive, suggesting that a Band 3-mediated transmembrane signaling is involved which leads to altered cytoskeleton dynamics.