Identifying reference values for serum lipids in Chinese children and adolescents aged 6-17 years old: A national multicenter study.

BACKGROUND: Current reference values for pediatric dyslipidemia used in China were not developed based on local population studies and did not consider age and sex differences. OBJECTIVE: In this study, we aimed to determine suitable reference values for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and non-high-density lipoprotein cholesterol (nonHDL-C) for Chinese children and adolescents using a national multicenter school-based study. METHODS: A total of 15,830 students aged 6-17 years were recruited from seven provinces of China. Age- and sex-specific percentile values for each lipid indicator were derived based on levels measured in the fasting state, and percentile curves of each indicator were plotted using the LMS method. RESULTS: Serum lipid levels varied considerably with age in both sexes. Among boys, the cut-off value for high TC, nonHDL-C, LDL-C, and TG, based on the value of the 95th percentiles, ranged from 4.58 to 5.39, 3.34 to 3.99, 2.69 to 3.31, and 1.22 to 1.83 mmol/L, respectively; among girls, the cut-off value for high TC, nonHDL-C, LDL-C, and TC ranged from 5.01 to 5.39, 3.66 to 3.97, 2.97 to 3.32, and 1.41 to 1.93 mmol/L, respectively. The cut-point for low HDL-C ranged from 0.84 to 1.08 mmol/L in boys and from 0.89 to 1.04 mmol/L in girls. CONCLUSION: These findings may help to determine age- and sex-specific reference values for serum lipids among Chinese children and adolescents and provide valuable guidance for screening of dyslipidemia.

A Review of Efforts to Improve Lipid Stability during Sample Preparation and Standardization Efforts to Ensure Accuracy in the Reporting of Lipid Measurements.

Lipidomics is a rapidly growing field, fueled by developments in analytical instrumentation and bioinformatics. To date, most researchers and industries have employed their own lipidomics workflows without a consensus on best practices. Without a community-wide consensus on best practices for the prevention of lipid degradation and transformations through sample collection and analysis, it is difficult to assess the quality of lipidomics data and hence trust results. Clinical studies often rely on samples being stored for weeks or months until they are analyzed, but inappropriate sampling techniques, storage temperatures, and analytical protocols can result in the degradation of complex lipids and the generation of oxidized or hydrolyzed metabolite artifacts. While best practices for lipid stability are sample dependent, it is generally recommended that strategies during sample preparation capable of quenching enzymatic activity and preventing oxidation should be considered. In addition, after sample preparation, lipid extracts should be stored in organic solvents with antioxidants at -20 °C or lower in an airtight container without exposure to light or oxygen. This will reduce or eliminate sublimation, and chemically and physically induced molecular transformations such as oxidation, enzymatic transformation, and photon/heat-induced degradation. This review explores the available literature on lipid stability, with a particular focus on human health and/or clinical lipidomic applications. Specifically, this includes a description of known mechanisms of lipid degradation, strategies, and considerations for lipid storage, as well as current efforts for standardization and quality insurance of protocols.

Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP: A case study using protein-loaded liposomes.

Nanomedicines are well recognised for their ability to improve therapeutic outcomes. Yet, due to their complexity, nanomedicines are challenging and costly to produce using traditional manufacturing methods. For nanomedicines to be widely exploited, new manufacturing technologies must be adopted to reduce development costs and provide a consistent product. Within this study, we investigate microfluidic manufacture of nanomedicines. Using protein-loaded liposomes as a case study, we manufacture liposomes with tightly defined physico-chemical attributes (size, PDI, protein loading and release) from small-scale (1 mL) through to GMP volume production (200 mL/min). To achieve this, we investigate two different laminar flow microfluidic cartridge designs (based on a staggered herringbone design and a novel toroidal mixer design); for the first time we demonstrate the use of a new microfluidic cartridge design which delivers seamless scale-up production from bench-scale (12 mL/min) through GMP production requirements of over 20 L/h using the same standardised normal operating parameters. We also outline the application of tangential flow filtration for down-stream processing and high product yield. This work confirms that defined liposome products can be manufactured rapidly and reproducibly using a scale-independent production process, thereby de-risking the journey from bench to approved product.

The Impact of Alkyl-Chain Purity on Lipid-Based Nucleic Acid Delivery Systems - Is the Utilization of Lipid Components with Technical Grade Justified?

The physicochemical properties and transfection efficacies of two samples of a cationic lipid have been investigated and compared in 2D (monolayers at the air/liquid interface) and 3D (aqueous bulk dispersions) model systems using different techniques. The samples differ only in their chain composition due to the purity of the oleylamine (chain precursor). Lipid 8 (using the oleylamine of technical grade for cost-efficient synthesis) shows lateral phase separation in the Langmuir layers. However, the amount of attached DNA, determined by IRRAS, is for both samples the same. In 3D systems, lipid 8 p forms cubic phases, which disappear after addition of DNA. At physiological temperatures, both lipids (alone and in mixture with cholesterol) assemble to lamellar aggregates and exhibit comparable DNA delivery efficiency. This study demonstrates that non-lamellar structures are not compulsory for high transfection rates. The results legitimate the utilization of oleyl chains of technical grade in the synthesis of cationic transfection lipids.

A methodological approach for the simultaneous quantification of glycerol and fatty acids from cork suberin in a single GC run.

INTRODUCTION: Suberin, as part of plant protective barriers, is one of the most important natural polymers after cellulose and lignin. For a full elucidation of suberin structure the quantification of glycerol, fatty α,ω-diacids and ω-hydroxyacids, the major building blocks of suberin, is of primary importance. Glycerol is often lost in the most used analytical procedures or rarely determined by deficient or too laborious techniques. OBJECTIVES: Propose a simple, accessible and reliable methanolysis work-up procedure for an accurate and simultaneous quantification of glycerol and suberin fatty monomers in the same GC run. MATERIAL AND METHODS: Cork from Quercus suber L. was depolymerised by methanolysis. Glycerol was derivatised to an organic soluble form before the suberin monomers recovery in water/organic solvent partition. Gas chromatography flame ionisation detector (GC-FID) response factors were determined for glycerol, ferulic acid and one for each fatty monomer substructure. Additionally, 1,2,4-butanetriol and methyl nonadecanoate were used as internal standards. RESULTS: The proposed experimental approach allowed the glycerol and all the fatty suberin monomers in the same GC run to be quantified accurately. Glycerol represented 30.6 area%, 14.2 mass% and 38.4 molar% of suberin and the COOH/OH groups ratio was 0.6:1 in the proposed experimental approach in contrast with 0.10 area% and COOH/OH ratio of 3:1 in the most used protocol. Furthermore, ω-hydroxyacids/α,ω-diacids mass ratio was 1:1 as opposed to an area ratio of 1.5:1. CONCLUSION: The proposed work-up procedure revealed to be a reliable analytical tool for the complete analysis of suberin allowing the future knowledge to grow towards a better understanding of suberin structure throughout its range and variability.

Novel Lipid Thresholds for Screening Predict the Need for Pharmacotherapy.

OBJECTIVE: To identify non-high-density lipoprotein cholesterol (HDL-C) and HDL-C thresholds for pediatric nonfasting lipid screens that are more predictive of the need for lipid-lowering pharmacotherapy and estimate numbers of potentially avoidable fasting lipid panels. STUDY DESIGN: In this retrospective review of children and youths aged 8-21 years presenting for preventive cardiology care, initial lipid results, recommendations for pharmacotherapy, and presence of additional cardiovascular risk factors were noted. Receiver operating characteristic curve analysis calculated threshold lipid values predicting the need for pharmacotherapy and were applied to 2 screening populations. Rates of potentially unnecessary fasting lipid panels were calculated. RESULTS: A non-HDL-C value >156 mg/dL for children with ≥1 cardiovascular risk factors and >199 mg/dL for children without risk factors conferred 95% or greater sensitivity in predicting a recommendation for pharmacotherapy with higher specificity, positive predictive value, and negative predictive value compared with current guidelines. HDL-C was a poor predictor of pharmacotherapy. Application of the current thresholds to screening populations indicated that 38.5%-92.3% of follow-up fasting lipid panels would not result in pharmacotherapy. CONCLUSION: Using higher non-HDL-C and lower HDL-C thresholds could prevent unnecessary follow-up lipid panels and reduce patient anxiety, cost, and time. This could improve compliance with universal pediatric lipid screening for both health care providers and families.

Internal quality assurance of HIL indices on Roche Cobas c702.

Automatic assessment of hemoglobin (H), lipaemia (L) and icterus (I) in serum or plasma (HIL indices) is the mainstay for evaluating sample quality. We planned this study to verify whether in-house prepared internal quality control (IQC) materials may be suitable for quality assurance of HIL indices. Pools containing different values of each of the three HIL indices were prepared from routine plasma samples, divided in aliquots and frozen at -20°C. Stability of frozen materials was assessed by thawing one aliquot of each pool after different days of freezing (1, 4, 8, 15, 22 and 29), and by measuring HIL indices on baseline fresh samples and frozen-thawed aliquots with Roche Cobas c702. Five fresh liquid IQCs materials were also measured at the same time points. Intra-assay and inter-assay imprecision of HIL indices calculated with commercial IQC materials ranged between 1.1-2.0% and 1.6-3.3%, respectively. When target values of HIL indices were calculated using frozen-thawed aliquots, the inter-assay imprecision of in-house prepared materials was optimal, even better than that of commercial liquid IQCs (H-index, 0.8% versus 1.6%; L-index, 2.2% versus 2.5%; I-index, 0.8% versus 3.3%). In conclusion, in-house prepared IQC materials are cost-effective alternatives to commercial liquid IQCs for HIL quality assurance.

The EuBIVAS: Within- and Between-Subject Biological Variation Data for Electrolytes, Lipids, Urea, Uric Acid, Total Protein, Total Bilirubin, Direct Bilirubin, and Glucose.

BACKGROUND: The European Federation of Clinical Chemistry and Laboratory Medicine European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined data describing biological variation (BV) of clinically important measurands. Here, EuBIVAS-based BV estimates of serum electrolytes, lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and glucose, as well as their associated analytical performance specifications (APSs), are presented. METHOD: Samples were drawn from 91 healthy individuals (38 male, 53 female; age range, 21-69 years) for 10 consecutive weeks at 6 European laboratories. Samples were stored at -80 °C before duplicate analysis of all samples on an ADVIA 2400 (Siemens Healthineers). Outlier and homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data, when relevant, to determine BV estimates with CIs. RESULTS: The within-subject BV (CVI) estimates of all measurands, except for urea and LDL cholesterol, were lower than estimates available in an online BV database, with differences being most pronounced for HDL cholesterol, glucose, and direct bilirubin. Significant differences in CVI for men and women/women <50 years of age were evident for uric acid, triglycerides, and urea. The CVA obtained for sodium and magnesium exceeded the EuBIVAS-based APS for imprecision. CONCLUSIONS: The EuBIVAS, which is fully compliant with the recently published Biological Variation Data Critical Appraisal Checklist, has produced well-characterized, high-quality BV estimates utilizing a stringent experimental protocol. These new reference data deliver revised and more exacting APS and reference change values for commonly used clinically important measurands, thus having direct relevance to diagnostics manufacturers, service providers, clinical users, and ultimately patients.

Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs).

Safe and effective DNA delivery systems are required to enable or enhance clinical strategies and research involving gene therapy and DNA vaccinations. To address this delivery problem, a series of charge-altering releasable transporters (CARTs) with varied lipid content were prepared and evaluated for plasmid DNA (pDNA) delivery into cultured cells. These lipid-modified CART co-oligomers were synthesized in only two steps via sequential organocatalytic ring-opening polymerization of lipid-containing cyclic carbonate monomers and morpholinone monomers. Lipid variations of the CARTs substantially impacted the delivery efficiency of pDNA, with oleyl- and linoleyl-based CARTs showing enhanced performance relative to the commercial transfection agent Lipofectamine 2000 (L2000). The best-performing oleyl CART was carried forward to study stable luciferase transfection with a Sleeping Beauty ( SB) transposon system. The oleyl CART outperformed the L2000 positive control with respect to stable transfection efficiency. CART-pDNA complexes represent a new DNA delivery system for research and clinical applications.

NIST lipidomics workflow questionnaire: an assessment of community-wide methodologies and perspectives.

INTRODUCTION: Efforts to harmonize lipidomic methodologies have been limited within the community. Here, we aimed to capitalize on the recent National Institute of Standards and Technology lipidomics interlaboratory comparison exercise by implementing a questionnaire that assessed current methodologies, quantitation strategies, standard operating procedures (SOPs), and quality control activities employed by the lipidomics community. OBJECTIVES: Lipidomics is a rapidly developing field with diverse applications. At present, there are no community-vetted methods to assess measurement comparability or data quality. Thus, a major impetus of this questionnaire was to profile current efforts, highlight areas of need, and establish future objectives in an effort to harmonize lipidomics workflows. METHODS: The 54-question survey inquired about laboratory demographics, lipidomic methodologies and SOPs, analytical platforms, quantitation, reference materials, quality control procedures, and opinions regarding challenges existing within the community. RESULTS: A total of 125 laboratories participated in the questionnaire. A broad overview of results highlighted a wide methodological diversity within current lipidomic workflows. The impact of this diversity on lipid measurement and quantitation is currently unknown and needs to be explored further. While some laboratories do incorporate SOPs and quality control activities, these concepts have not been fully embraced by the community. The top five perceived challenges within the lipidomics community were a lack of standardization amongst methods/protocols, lack of lipid standards, software/data handling and quantification, and over-reporting/false positives. CONCLUSION: The questionnaire provided an overview of current lipidomics methodologies and further promoted the need for community-accepted guidelines and protocols. The questionnaire also served as a platform to help determine and prioritize metrological issues to be investigated.

Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using SRM 1950-Metabolites in Frozen Human Plasma.

As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950-Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each laboratory using a different lipidomics workflow. A total of 1,527 unique lipids were measured across all laboratories and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and interlaboratory quality control and method validation. These analyses were performed using nonstandardized laboratory-independent workflows. The consensus locations were also compared with a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement.

Selection of internal standards for accurate quantification of complex lipid species in biological extracts by electrospray ionization mass spectrometry-What, how and why?

Lipidomics is rapidly expanding because of the great facilitation of recent advances in, and novel applications of, electrospray ionization mass spectrometry techniques. The greatest demands have been for successful quantification of lipid classes, subclasses, and individual molecular species in biological samples at acceptable accuracy. This review addresses the selection of internal standards in different methods for accurate quantification of individual lipid species. The principles of quantification with electrospray ionization mass spectrometry are first discussed to recognize the essentials for quantification. The basics of different lipidomics approaches are overviewed to understand the variables that need to be considered for accurate quantification. The factors that affect accurate quantification are extensively discussed, and the solutions to resolve these factors are proposed-largely through addition of internal standards. Finally, selection of internal standards for different methods is discussed in detail to address the issues of what, how, and why related to internal standards. We believe that thorough discussion of the topics related to internal standards should aid in quantitative analysis of lipid classes, subclasses, and individual molecular species and should have big impacts on advances in lipidomics. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:693-714, 2017.

Impact of lipid markers and high-sensitivity C-reactive protein on the value of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I.

OBJECTIVES: i) To assess the relationship between lipid markers and high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin I (hs-cTnI) in the reference population, and ii) to evaluate the impact of lipid markers and hs-CRP on the 99th percentile upper reference limit (URL) for hs-cTnI. METHODS: 531 questionnaire-identified presumably healthy individuals were enrolled in a single-center, cross-sectional study. Surrogate biomarkers for diabetes, myocardial and renal dysfunction were used to refine the healthy cohort (n=408). Lipid profile, total cholesterol:high-density lipoprotein cholesterol (HDL-C) ratio, non-HDL-C, apolipoprotein AI (apoAI), apolipoprotein B (apoB), apoB:apoAI ratio, lipoprotein(a), small dense low-density lipoprotein cholesterol (LDL-C) and hs-CRP were determined. RESULTS: Individuals with detectable vs. non-detectable hs-cTnI concentrations more often showed elevated LDL-C (60% vs. 46%; p=0.002), apoB (73% vs. 61%; p=0.008), apoB:apoAI ratio (53% vs. 40%; p=0.005) and lipoprotein(a) (15% vs. 7%; p=0.015). The apoB:apoAI ratio and to a lesser extent other lipid markers, but not hs-CRP, were positively associated with hs-cTnI concentration in univariate and multivariate analyses. Exclusion of individuals with elevated apoB:apoAI ratio or apoB, but not hs-CRP, lowered the 99th percentile URL in the healthy cohort respectively by 12.9% (6.2 vs. 5.4ng/L) and 14.5% (6.2 vs. 5.3ng/L). The corresponding reduction for both lipid biomarkers in the presumably healthy population was 24.0% (7.5 vs. 5.7ng/L). CONCLUSION: Our study demonstrates that atherogenic lipid markers, particularly apoB:apoAI ratio or apoB, influence the 99th percentile URL for hs-cTnI.

Age and Sex Distributions of Age-Related Biomarker Values in Healthy Older Adults from the Long Life Family Study.

OBJECTIVES: To determine reference values for laboratory tests in individuals aged 85 and older. DESIGN: Cross-sectional cohort study. SETTING: International. PARTICIPANTS: Long Life Family Study (LLFS) participants (N~5,000, age: range 25-110, median 67, 45% male). MEASUREMENTS: Serum biomarkers were selected based on association with aging-related diseases and included complete blood count, lipids (triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol), 25-hydroxyvitamin D2 and D3, vitamin D epi-isomer, diabetes mellitus-related biomarkers (adiponectin, insulin, insulin-like growth factor 1, glucose, glycosylated hemoglobin, soluble receptor for advanced glycation endproduct), kidney disease-related biomarkers (albumin, creatinine, cystatin), endocrine biomarkers (dehydroepiandrosterone, sex-hormone binding globulin, testosterone), markers of inflammation (interleukin 6, high-sensitivity C-reactive protein, N-terminal pro b-type natriuretic peptide), ferritin, and transferrin. RESULTS: Of 38 measured biomarkers, 34 were significantly correlated with age. Summary statistics were generated for all biomarkers according to sex and 5-year age increments from 50 and up after excluding participants with diseases and treatments that were associated with biomarkers. A biomarker data set was also generated that will be useful for other investigators seeking to compare biomarker levels between studies. CONCLUSION: Levels of several biomarkers change with older age in healthy individuals. The descriptive statistics identified herein will be useful in future studies and, if replicated in additional studies, might also become useful in clinical practice. The availability of the reference data set will facilitate appropriate calibration of biomarkers measured in different laboratories.

Impact of Peroderma cylindricum (Copepoda: Pennellidae) Infection on Fatty Acid Composition and Lipid Quality of Sardine (Sardina pilchardus).

The parasite Peroderma cylindricum uses its host Sardina pilchardus to meet its own needs. The parasite can have many harmful effects on its host. The present study aims at investigating the impact of the parasite on the composition of fatty acids and the quality of the lipids of the sardine. Peroderma cylindricum reduces the total lipid content of its host by about 25% and decreases the content of saturated fatty acid and polyunsaturated acid. However, it increases the amount of monounsaturated fatty acids. The parasite induced a selective diversion of some fatty acids, which are dominated by the docosahexaenoic acid. Consequently, lower n-3 fatty acid content and omega-3/omega-6 ratio were recorded in parasitized sardines. Furthermore, both atherogenic and thrombogenic indices were found to be higher than those of unparasitized specimens. Nevertheless, these alterations do not lead to an important reduction of the nutritional value of the fish.

Lipoprotein(a) mass: a massively misunderstood metric.

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.

Partial synthesis of ganglioside and lysoganglioside lipoforms as internal standards for MS quantification.

Within recent years, ganglioside patterns have been increasingly analyzed by MS. However, internal standards for calibration are only available for gangliosides GM1, GM2, and GM3. For this reason, we prepared homologous internal standards bearing nonnatural fatty acids of the major mammalian brain gangliosides GM1, GD1a, GD1b, GT1b, and GQ1b, and of the tumor-associated gangliosides GM2 and GD2. The fatty acid moieties were incorporated after selective chemical or enzymatic deacylation of bovine brain gangliosides. For modification of the sphingoid bases, we developed a new synthetic method based on olefin cross metathesis. This method was used for the preparation of a lyso-GM1 and a lyso-GM2 standard. The total yield of this method was 8.7% for the synthesis of d17:1-lyso-GM1 from d20:1/18:0-GM1 in four steps. The title compounds are currently used as calibration substances for MS quantification and are also suitable for functional studies.

A multicenter nationwide reference intervals study for common biochemical analytes in Turkey using Abbott analyzers.

BACKGROUND: A nationwide multicenter study was organized to establish reference intervals (RIs) in the Turkish population for 25 commonly tested biochemical analytes and to explore sources of variation in reference values, including regionality. METHODS: Blood samples were collected nationwide in 28 laboratories from the seven regions (≥400 samples/region, 3066 in all). The sera were collectively analyzed in Uludag University in Bursa using Abbott reagents and analyzer. Reference materials were used for standardization of test results. After secondary exclusion using the latent abnormal values exclusion method, RIs were derived by a parametric method employing the modified Box-Cox formula and compared with the RIs by the non-parametric method. Three-level nested ANOVA was used to evaluate variations among sexes, ages and regions. Associations between test results and age, body mass index (BMI) and region were determined by multiple regression analysis (MRA). RESULTS: By ANOVA, differences of reference values among seven regions were significant in none of the 25 analytes. Significant sex-related and age-related differences were observed for 10 and seven analytes, respectively. MRA revealed BMI-related changes in results for uric acid, glucose, triglycerides, high-density lipoprotein (HDL)-cholesterol, alanine aminotransferase, and γ-glutamyltransferase. Their RIs were thus derived by applying stricter criteria excluding individuals with BMI >28 kg/m2. Ranges of RIs by non-parametric method were wider than those by parametric method especially for those analytes affected by BMI. CONCLUSIONS: With the lack of regional differences and the well-standardized status of test results, the RIs derived from this nationwide study can be used for the entire Turkish population.

Argon cluster ion source evaluation on lipid standards and rat brain tissue samples.

Argon cluster ion sources for sputtering and secondary ion mass spectrometry use projectiles consisting of several hundreds of atoms, accelerated to 10-20 keV, and deposit their kinetic energy within the top few nanometers of the surface. For organic materials, the sputtering yield is high removing material to similar depth. Consequently, the exposed new surface is relatively damage free. It has thus been demonstrated on model samples that it is now really possible to perform dual beam depth profiling experiments in organic materials with this new kind of ion source. Here, this possibility has been tested directly on tissue samples, 14 µm thick rat brain sections, allowing primary ion doses much larger than the so-called static secondary ion mass spectrometry (SIMS) limit and demonstrating the possibility to enhance the sensitivity of time-of-flight (TOF)-SIMS biological imaging. However, the depth analyses have also shown some variations of the chemical composition as a function of depth, particularly for cholesterol, as well as some possible matrix effects due to the presence or absence of this compound.

Reference interval for lipid profile in North Indian population from Rajasthan according to various partitioning criteria.

OBJECTIVE: Lipid profile parameters are influenced by various factors like age, ethnicity, diet, genetic and gender differences hence it is essential to establish reference range of the values of serum lipids for a given population in India. We have planned this study to evaluate the reference values of lipid profile of a North Indian population according to the guidelines of the National Cholesterol Education Program (NCEP) of the USA. DESIGN AND METHODS: The present study was conducted on 2021 apparently healthy individuals of North Indian origin ranging in age from 15 to 60 years, who were selected randomly using defined criteria. Fasting samples were analyzed for total cholesterol, triglyceride, HDL-C and LDL-C. Data were analyzed for middle 95th percentile (2.5th-97.5th percentile), median and 95% confidence interval using SPSS software package version 10.0. RESULTS: No substantial difference could be observed between male and female and vegetarian and non-vegetarian, in cholesterol, triglyceride and LDL-C levels. However HDL-C reported higher limit in female as compared to male (33-64 vs 32-58 mg/dl). Similarly upper limit of HDL-C in vegetarians were higher than non-vegetarian (value 32.8-64.92 vs 30.72-58.10mg/dl). Median value for cholesterol, triglyceride, LDL-C progressively increased in different age groups (<20, 20-40 and 41-60 years). No marked difference was observed in reference interval of these parameters in rural and urban populations. CONCLUSION: It can be suggested that lipid values obtained in this study can be used as the reference value, based on which clinical correlation can be made.