New-generation fish oil and olive oil lipid for prevention of oxidative damage in preterm infants: Single center clinical trial at university hospital in Turkey.

BACKGROUND: Parenteral nutrition (PN) has been widely used in preterm infants. The lipid solutions used for PN, however, are associated with oxidative stress and morbidity. The aim of this study was to compare the effectiveness of a new-generation lipid emulsion (SMOFLipid) and olive-oil based lipid emulsion for prevention of PN-associated oxidative damage. METHODS: Preterm infants < 32 weeks of gestational age were included in this prospective randomized study. All infants were randomized to SMOFlipid or olive-oil based lipid emulsion (ClinOleic). Lipid peroxidation products were evaluated in all infants. In addition, total antioxidant capacity (TAC), and both pro- and anti-inflammatory cytokines were studied at days 0, 7 and 14. RESULTS: A total of 89 infants (SMOFlipid, n = 42; ClinOleic, n = 47) were enrolled. TAC was higher in the SMOFlipid group compared with the ClinOleic group at all time points, and the difference on day 7 was statistically significant. Although the anti-inflammatory cytokine interleukin-10 was higher in the SMOFlipid group, this difference was not significant. Bronchopulmonary dysplasia (BPD) was lower in the SMOFlipid group (14.1%) than in the ClinOleic group (31.2%), but this finding was non-significant p > 0.05. The rate of severe BPD was significantly lower in the SMOFlipid group. CONCLUSION: To our best of knowledge, this is the first study to suggest that SMOFlipid might decrease oxidative damage and oxidative-stress-associated morbidity compared with olive oil-based emulsion in preterm infants.

Distinguishing reference intervals and clinical decision limits - A review by the IFCC Committee on Reference Intervals and Decision Limits.

Reference Intervals (RIs) and clinical decision limits (CDLs) are a vital part of the information supplied by laboratories to support the interpretation of numerical clinical pathology results. RIs describe the typical distribution of results seen in a healthy reference population while CDLs are associated with a significantly higher risk of adverse clinical outcomes or are diagnostic for the presence of a specific disease. However, as the two concepts are sometimes confused, there is a need to clarify the differences between these terms and to ensure they are easily distinguished, especially because CDLs have a clinical association with specific diseases and risks, thereby implying that effective clinical interventions are available. It is important to note that, because population-based RIs are derived from the range of values expected in a typical community population, laboratory results that fall outside a RI do not necessarily indicate a disease but rather that additional medical follow-up and/or treatment may be warranted. In contrast, CDLs are associated with a risk of specific adverse outcomes, and are commonly used to interpret laboratory test results, including lipid parameters, glucose, hemoglobin A1c (HbA1c), and tumor markers, to determine risk of disease, to diagnose or to treat. In recent years, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) has focused primarily on RIs and has performed multicenter studies to obtain common RIs. However, the broader responsibility of the Committee, from its name, includes "decision limits". C-RIDL now aims to emphasize the importance of the correct use of both RIs and CDLs and to encourage laboratories to specify the appropriate information to clinicians as needed. This review discusses RIs and CDLs in detail, describes the similarities and the differences between these two important tools in laboratory medicine, and clearly explains the processes used to define them. C-RIDL encourages the involvement of laboratory professionals in the establishment of both RIs and CDLs.

Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations.

Reference intervals (RIs) are fundamental tools used by healthcare and laboratory professionals to interpret patient laboratory test results, ideally enabling differentiation of healthy and unhealthy individuals. Under optimal conditions, a laboratory should perform its own RI study to establish RIs specific for its method and local population. However, the process of developing RIs is often beyond the capabilities of an individual laboratory due to the complex, expensive and time-consuming process to develop them. Therefore, a laboratory can alternatively verify RIs established by an external source. Common RIs can be established by large, multicenter studies and can subsequently be received by local laboratories using various verification procedures. The standard approach to verify RIs recommended by the Clinical Laboratory Standards Institute (CLSI) EP28-A3c guideline for routine clinical laboratories is to collect and analyze a minimum of 20 samples from healthy subjects from the local population. Alternatively, "data mining" techniques using large amounts of patient test results can be used to verify RIs, considering both the laboratory method and local population. Although procedures for verifying RIs in the literature and guidelines are clear in theory, gaps remain for the implementation of these procedures in routine clinical laboratories. Pediatric and geriatric age-groups also continue to pose additional challenges in respect of acquiring and verifying RIs. In this article, we review the current guidelines/approaches and challenges to RI verification and provide a practical guide for routine implementation in clinical laboratories.

Indirect methods for reference interval determination - review and recommendations.

Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these 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.

Thromboelastographic evaluation of the effectiveness of choline or CDP-choline treatment on endotoxin-induced hemostatic alterations in dogs.

Sepsis/endotoxemia associates with coagulation abnormalities. We showed previously that exogenous choline treatment reversed the changes in platelet count and function as well as prevented disseminated intravascular coagulation (DIC) in endotoxemic dogs. The aim of this follow-up study was to evaluate the effect of treatment with choline or cytidine-5'-diphosphocholine (CDP-choline), a choline donor, on endotoxin-induced hemostatic alterations using thromboelastography (TEG). Dogs were randomized to six groups and received intravenously (iv) saline, choline (20 mg/kg) or CDP-choline (70 mg/kg) in the control groups, whereas endotoxin (0.1 mg/kg, iv) was used alone or in combination with choline or CDP-choline at the same doses in the treatment groups. TEG variables including R- and K-time (clot formation), maximum amplitude (MA) and α-angle (clot stability), G value (clot elasticity), and EPL, A, and LY30 (fibrinolysis), as well as overall assessment of coagulation (coagulation index - CI), were measured before and at 0.5-48 h after the treatments. TEG parameters did not change significantly in the control groups, except for CI parameter after choline administration. Endotoxemia resulted in increased R-time and A value (P < 0.05), decreased K-time (P < 0.05), α-angle (P < 0.001) and CI values (P < 0.01) at different time points. Treatment with either choline or CDP-choline attenuated or prevented completely the alterations in TEG parameters in endotoxemic dogs with CDP-choline being more effective. These results confirm and extend the effectiveness of choline or CDP-choline in endotoxemia by further demonstrating their efficacy in attenuating or preventing the altered viscoelastic properties of blood clot measured by TEG.

Protocol and standard operating procedures for common use in a worldwide multicenter study on reference values.

The reference intervals (RIs) given in laboratory reports have an important role in aiding clinicians in interpreting test results in reference to values of healthy populations. In this report, we present a proposed protocol and standard operating procedures (SOPs) for common use in conducting multicenter RI studies on a national or international scale. The protocols and consensus on their contents were refined through discussions in recent C-RIDL meetings. The protocol describes in detail (1) the scheme and organization of the study, (2) the target population, inclusion/exclusion criteria, ethnicity, and sample size, (3) health status questionnaire, (4) target analytes, (5) blood collection, (6) sample processing and storage, (7) assays, (8) cross-check testing, (9) ethics, (10) data analyses, and (11) reporting of results. In addition, the protocol proposes the common measurement of a panel of sera when no standard materials exist for harmonization of test results. It also describes the requirements of the central laboratory, including the method of cross-check testing between the central laboratory of each country and local laboratories. This protocol and the SOPs remain largely exploratory and may require a reevaluation from the practical point of view after their implementation in the ongoing worldwide study. The paper is mainly intended to be a basis for discussion in the scientific community.

Utility of a panel of sera for the alignment of test results in the worldwide multicenter study on reference values.

BACKGROUND: In a planned International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) worldwide study on reference intervals (RIs), a common panel of serum samples is to be measured by laboratories from different countries, and test results are to be compared through conversion using linear regression analysis. This report presents a validation study that was conducted in collaboration with four laboratories. METHODS: A panel composed of 80 sera was prepared from healthy individuals, and 45 commonly tested analytes (general chemistry, tumor markers, and hormones) were measured on two occasions 1 week apart in each laboratory. Reduced major-axis linear regression was used to convert reference limits (LL and UL). Precision was expressed as a ratio of the standard error of converted LL or UL to the standard deviation (SD) comprising RI (approx. 1/4 of the RI width corresponding to between-individual SD). The allowable and optimal levels of error for the SD ratio (SDR) were set as ≤0.250 and ≤0.125, respectively, in analogy to the common method of setting limits for analytical bias based on between-individual SD. RESULTS: The values for the calculated SDRs depended upon the distribution patterns of test results: skewness toward higher values makes SDRLL lower and SDRUL higher. However, the CV of the regression line slope, CV(b), is less affected by skewness. The average of SDRLL and SDRUL (aveSDR) correlates closely with CV(b) (r=0.995). The aveSDRs of ≤0.25 and ≤0.125 corresponds approximately to CV(b) values of ≤11% and ≤5.5%, respectively. For all results (i.e., n=80), conversion was allowable (optimal) in 98% (89%) of the analytes, as judged by CV(b). Resampling studies using random subsets of data with a data size (n) of 70 to 20 revealed that SDRs and CV(b) gradually increase with reduction of n, especially with n ≤30. CONCLUSIONS: CV(b) is a robust estimator for judging the convertibility of reference values among laboratories, even with a skewed distribution. Assuming 40 sera to be a practical size for the panel, reference values of 89% (80%) of analytes examined were made comparable by regression analysis with the allowable (optimal) level of precision.

The concentration of adiponectin in breast milk is related to maternal hormonal and inflammatory status during 6 months of lactation.

BACKGROUND: Varying concentrations of adiponectin are present in human breast milk. This study aimed to determine the relationship between milk adiponectin concentration and the hormonal and inflammatory status of breast-feeding women. METHODS: Blood and breast milk samples were collected from 157 breast-feeding women enrolled at 1-180 post-partum lactation days. The milk and serum adiponectin concentrations were measured by radioimmunoassays. The serum oestradiol, prolactin, thyroxine, triiodothyronine, cortisol and insulin concentrations were measured by the chemiluminescent immunometric method. The leptin, resistin and ghrelin concentrations were measured by the immunometric methods. RESULTS: The milk, but not serum, adiponectin concentration increased during the 180-day lactation period and displayed a positive correlation (r=0.748; p<0.001) to the lactation day. The milk adiponectin concentration was positively correlated to the maternal serum ghrelin concentration (r=0.299; p<0.001) and inversely to the maternal serum oestradiol (r=-0.366; p<0.001), prolactin (r=-0.444; p<0.001), thyroxine (r=-0.355; p<0.001), triiodothyronine (r=-0.291; p<0.001), cortisol (r=-0.537; p<0.001), and C-reactive protein (r=-0.483; p<0.001) concentrations. The milk adiponectin concentration was positively correlated to the milk leptin (r=0.344; p<0.001) and ghrelin (r=0.458; p<0.001) concentrations, and inversely to milk resistin concentration (r=-0.518; p<0.001). The serum adiponectin concentration in breastfed infants was positively correlated (r=0.711; p<0.001) to the adiponectin concentration in the consumed breast milk. CONCLUSIONS: The adiponectin concentration in breast milk increases over time during lactation and is affected by the maternal hormonal and inflammatory status.

Comparison of lipid emulsions on antioxidant capacity in preterm infants receiving parenteral nutrition.

BACKGROUND: Although a variety of different lipid emulsions with varying fatty acid contents have been developed, there are some concerns about the administration of these lipid emulsions because of potential adverse effects, including oxidative stress-related morbidity. The aim of the present study was to evaluate and compare the effects of the standard soybean oil-based and olive oil-based i.v. lipid emulsions (ILE) on oxidative stress, determined by total antioxidant capacity (TAC), and to investigate the safety of the use of these two emulsions in terms of biochemical indices. METHODS: In this prospective study, premature infants were randomly assigned to two groups, each group consisting of 32 patients who received parenteral ILE of either 20% olive oil or 20% soybean oil. They were given ILE for 7 days and then were evaluated with regard to TAC. RESULTS: No statistically significant difference was observed between the groups in terms of routine biochemical parameters. TAC for both groups on day 7 was significantly lower compared with that on day 0. Although the decrease in TAC within 7 days of ILE administration was greater in the soybean group compared with that in the olive oil group, it was not statistically significant. CONCLUSIONS: Olive oil-based ILE exhibit similar antioxidant activity and can be used as an alternative to soybean oil-based ILE. TAC significantly decreased in infants following administration of either lipid emulsion, and premature infants tolerated either ILE well, both biochemically and clinically.

Stability of hematological analytes during 48 hours storage at three temperatures using Cell-Dyn hematology analyzer.

BACKGROUND: The complete blood count (CBC) with differential leukocyte count (DLC) is one of the most common tests requested by physicians. The results of this test are affected by storage temperature and time of incubation. This study was designed to evaluate the stability of hematologic parameters in blood specimens stored for 48 h at three temperatures. METHODS: K2-EDTA - blood was collected from 22 healthy adults. The CBC was performed using a hematology analyser immediately; 0 time point and at 4, 8, 12, 16, 20, 24, and 48 h after storage at 4 °C, 10 °C or 23 °C. Changes in values of CBC parameters from the 0 time point were determined and reported as % of the initial value. RESULTS: Red blood cells, platelet, hemoglobin, and mean corpuscular hemoglobin were found stable during 48 h storage at 4 °C, 10 °C or 23 °C. Hematocrite and mean corpuscular volume increased, while white blood cells decreased at 48 h when stored at 23 °C. Lymphocytes, neutrophils, eosinophils, and basophils showed significant differences after 12 h of storage at 23 °C. CONCLUSIONS: Red blood cells, platelet, hemoglobin, and mean corpuscular hemoglobin are the only suitable parameters without refrigeration during 24 h storage. When CBC and DLC are performed, 4 °C can be recommended as the most suitable storage temperature for 12 h storage.

Comparison of reference intervals derived by direct and indirect methods based on compatible datasets obtained in Turkey.

BACKGROUND: Indirect derivation of reference intervals (RIs) from the laboratory information system (LIS) has been recently pursued. We aimed at evaluating the accuracy of indirectly predicted RIs compared to the RIs established directly from healthy subjects in the nationwide RI study in Turkey, targeting 25 major chemistry analytes. METHODS: LIS data were retrieved from the laboratory that performed measurements for the direct study. They were cleaned by limiting to outpatients with age 18-65 years, and by allowing only one record per year per patient. Evaluated were four indirect methods of univariate approach: Hoffmann, Bhattacharya, Arzideh, and Wosniok methods. Power transformation of the LIS dataset was performed either using the power (λ) reported by the IFCC global RI study (the first two methods) or using a λ predicted (the last two). RESULTS: Compared to the direct study dataset, the LIS dataset showed a variable degree of alterations in peak location and shape. Consequently, lower-side peak-shifts observed in sodium, albumin, etc. led to lowered RI limits, whereas higher-side peak-shift observed in triglyceride, low-density lipoprotein cholesterol, etc. led to raised RI limits. Overall, 72% (62-81) of the RI limits predicted by indirect methods showed significant biases from direct RIs. However, the biases observed in total cholesterol, lactic dehydrogenase, etc. were attributed to a higher-side age-bias in LIS dataset. After excluding them, the overall proportion of biased RIs was reduced to 47% (38-54). CONCLUSION: To reduce prediction biases that remained after age adjustment, it is necessary to apply more rigorous data-cleaning before applying indirect methods.

Choline or CDP-choline restores hypotension and improves myocardial and respiratory functions in dogs with experimentally - Induced endotoxic shock.

Endotoxin shock is associated with severe impairments in cardiovascular and respiratory functions. We showed previously that choline or cytidine-5'-diphosphocholine (CDP-choline) provides beneficial effects in experimental endotoxin shock in dogs. The objective of the present study was to determine the effects of choline or CDP-choline on endotoxin-induced cardiovascular and respiratory dysfunctions. Dogs were treated intravenously (i.v.) with saline or endotoxin (LPS, 0.1 mg/kg) 5 min before i.v. infusion of saline, choline (20 mg/kg) or CDP-choline (70 mg/kg). Blood pressure, cardiac rate, myocardial and left ventricular functions, respiratory rate, blood gases, serum electrolytes and cardiac injury markers were determined before and at 0.5-48 h after endotoxin. Plasma tumor necrosis factor alpha (TNF-α), high mobility group box-1 (HMGB1), catecholamine and nitric oxide (NO) levels were measured 2 h and 24 h after the treatments. Endotoxin caused immediate and sustained reductions in blood pressure, cardiac output, pO2 and pH; changes in left ventricular functions, structure and volume parameters; and elevations in heart rate, respiratory rate, pCO2 and serum electrolytes (Na, K, Cl, Ca and P). Endotoxin also resulted in elevations in blood levels of cardiac injury markers, TNF-α, HMGB1, catecholamine and NO. In choline- or CDP-choline-treated dogs, all endotoxin effects were much smaller in magnitude and shorter in duration than observed values in controls. These data show that treatment with choline or CDP-choline improves functions of cardiovascular and respiratory systems in experimental endotoxemia and suggest that they may be useful in treatment of endotoxin shock in clinical setting.

Big data and reference intervals: rationale, current practices, harmonization and standardization prerequisites and future perspectives of indirect determination of reference intervals using routine data.

Reference intervals are commonly used as a decision-making tool. In this review, we provide an overview on "big data" and reference intervals, describing the rationale, current practices including statistical methods, essential prerequisites concerning data quality, including harmonization and standardization, and future perspectives of the indirect determination of reference intervals using routine laboratory data.

Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study.

BACKGROUND: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) measurements are important for the assessment of liver damage. The aim of this study was to define the reference intervals (RIs) for these enzymes in adults, paying attention to standardization of the methods used and careful selection of the reference population. METHODS: AST, ALT and GGT were measured with commercial analytical systems standardized to the IFCC-recommended reference measurement systems. Three centers (two in Italy and one in China) measured their own freshly collected samples; one of these centers also measured frozen samples from the Nordic Countries RI Project and from a Turkish center. RIs were generated using non-parametric techniques from the results of 765 individuals (411 females and 354 males, 18-85 years old) selected on the basis of the results of other laboratory tests and a specific questionnaire. RESULTS: AST results from the four regions (Milan, Beijing, Bursa and Nordic Countries) were statistically different, but these differences were too small to be clinically relevant. Likewise, differences between the upper reference limits for genders was only 1.7 U/L (0.03 µkat/L), allowing a single RI of 11-34 U/L (0.18-0.57 µkat/L) to be defined. Interregional differences were not statistically significant for ALT, but partitioning was required due to significant gender differences. RIs for ALT were 8-41 U/L (0.13-0.68 µkat/L) for females and 9-59 U/L (0.15-0.99 µkat/L) for males, respectively. The upper reference limits for GGT from the Nordic Country population were higher than those from the other three regions and results from this group were excluded from final calculations. The GGT RIs were 6-40 U/L (0.11-0.66 µkat/L) for females and 12-68 U/L (0.20- 1.13 µkat/L) for males, respectively. CONCLUSIONS: For AST and ALT, the implementation of common RIs appears to be possible, because no differences between regions were observed. However, a common RI for GGT that is applicable worldwide appears unlikely due to differences among populations.

Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals.

BACKGROUND: There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. METHODS: Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis. RESULTS: Our study revealed significant uptrend in AM to PM FT4 (p < 0.0001) samples, downtrend in AM to PM TT3 (p = 0.0004) and FT3 samples (p < 0.0001), and AM to PM uptrend in rT3 samples (p < 0.0001). No difference was observed for TT4 between AM and PM. No significant sex differences were seen for any of the five thyroid hormones. CONCLUSION: When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement.

Rate of T alleles and TT genotype at MTHFR 677C->T locus or C alleles and CC genotype at MTHFR 1298A->C locus among healthy subjects in Turkey: impact on homocysteine and folic acid status and reference intervals.

Methylenetetrahydrofolate reductase (MTHFR) is important for folate and homocysteine (Hcy) metabolism. MTHFR 677C->T and 1298A->C MTHFR are two most common mutations which can affect folate and total homocysteine (tHcy) status. This study was designed to determine the rate of MTHFR 677C->T and 1298A->C mutations, and their influence on serum folate, Hcy and vitamin B12 status and the reference intervals in 402 healthy Turkish adults. The rate of MTHFR 677C->T or 1298A->C mutations was 50.7% or 54.7%, respectively. The MTHFR 677C->T mutation-specific reference intervals for serum folate and tHcy were characterized by marked shifts in their upper limits. In homozygote subjects for MTHFR 677C->T serum folate concentration was lower and serum tHcy concentration was higher than those in the wild genotype; all subjects had lower serum folate and 54% of the subjects had higher tHcy concentrations than the cutoff values of or=12 micromol/L, respectively. Serum vitamin B12 status was similar in all genotypes. Serum tHcy concentrations were inversely correlated with serum folate and vitamin B12 concentrations in all genotypes. These data show that the rate of MTHFR 677C->T and 1298A->C mutations is very high in Turks and serum folate and tHcy status are impaired by these mutations.

Difference in the magnitude of muscle damage between elbow flexors and knee extensors eccentric exercises.

The aim of this study was to investigate the difference in the magnitude of muscle damage between maximal eccentric exercises of the elbow flexors (EF) and knee extensors (KE). Twelve sedentary male volunteers participated in the study. Range of motion (ROM), isometric peak torque (IPT), delayed onset of muscle soreness (DOMS), creatine kinase activity (CK), and myoglobin concentration (Mb) were evaluated before, immediately after, and on the 1(st) , 2(nd), 3(rd) , and 7(th) days following exercise. Total work (TW) during exercises was recorded and corrected by muscle volume (TWc). TWc was greater (p < 0.01) for EF [24 (2) joule·cm-3] than for KE [7 (0.4) joule·cm(-3)]. Increases in CK on the 2(nd) , 3(rd) , and 7(th) days (p < 0.01) and increases in Mb on the 1(st) , 2(nd) , 3(rd) , and 7(th) days were significantly (p<0.01) larger for EF than for KE. The decline in IPT was greater (p < 0.05- 0.01) for EF at all test occasions compared with KE. The results of this study demonstrate that the magnitude of muscle damage is greater and the recovery is slower following maximal eccentric exercise of the EF than of the KE for sedentary males. Key pointsThe magnitude of muscle damage is greater and the recovery is slower following maximal eccentric exercise of the EF than of the KE for sedentary males.This may be because of the higher total eccentric work per muscle unit in elbow flexors.

Reference Intervals: Comparison of Calculation Methods and Evaluation of Procedures for Merging Reference Measurements From Two US Medical Centers.

OBJECTIVES: To analyze consistency of reference limits and widths of reference intervals (RIs) calculated by six procedures and evaluate a protocol for merging intrainstitutional reference data. METHODS: The differences between reference limits were compared with "optimal" bias goals. Also, widths of the RIs were compared. RIs were calculated using Mayo-SAS quantile, EP Evaluator, and four International Federation of Clinical Chemistry and Laboratory Medicine methods: parametric and nonparametric (NP) with and without latent abnormal values exclusion (LAVE). Regression parameters from cotested samples were evaluated for harmonizing intrainstitutional reference data. RESULTS: Mayo-SAS quintile, LAVE(-)NP, and EP Evaluator generated similar RIs, but these RIs often were wider than RIs from parametric procedures. LAVE procedures generated narrower RIs for nutritional and inflammatory markers. Transformation with regression parameters did not ensure homogeneity of merged data. CONCLUSIONS: Parametric methods are recommended when inappropriate values cannot be excluded. The nonparametric procedures may generate wider RIs. Data sets larger than 200 are recommended for robust estimates. Caution should be exercised when merging intrainstitutional data.

A global multicenter study on reference values: 2. Exploration of sources of variation across the countries.

OBJECTIVES: The intent of this study, based on a global multicenter study of reference values (RVs) for serum analytes was to explore biological sources of variation (SVs) of the RVs among 12 countries around the world. METHODS: As described in the first part of this paper, RVs of 50 major serum analytes from 13,396 healthy individuals living in 12 countries were obtained. Analyzed in this study were 23 clinical chemistry analytes and 8 analytes measured by immunoturbidimetry. Multiple regression analysis was performed for each gender, country by country, analyte by analyte, by setting four major SVs (age, BMI, and levels of drinking and smoking) as a fixed set of explanatory variables. For analytes with skewed distributions, log-transformation was applied. The association of each source of variation with RVs was expressed as the partial correlation coefficient (rp). RESULTS: Obvious gender and age-related changes in the RVs were observed in many analytes, almost consistently between countries. Compilation of age-related variations of RVs after adjusting for between-country differences revealed peculiar patterns specific to each analyte. Judged fromthe rp, BMI related changes were observed for many nutritional and inflammatory markers in almost all countries. However, the slope of linear regression of BMI vs. RV differed greatly among countries for some analytes. Alcohol and smoking-related changes were observed less conspicuously in a limited number of analytes. CONCLUSION: The features of sex, age, alcohol, and smoking-related changes in RVs of the analytes were largely comparable worldwide. The finding of differences in BMI-related changes among countries in some analytes is quite relevant to understanding ethnic differences in susceptibility to nutritionally related diseases.