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Background Appropriate age- and sex-specific reference intervals for alkaline phosphatase (ALP) are essential to identify patients with hypophosphatasia (low ALP) and to avoid unnecessary ALP isoenzymes analysis (elevated ALP). This study used patient ALP historical data to statistically derive sex- and age-specific reference intervals. Methods The ALP values reported as part of clinical management during an 18 month period (from July 2021 to March 2023) were obtained. Following logarithmic transformation of ALP data and repeated removal of outliers, cumulative frequency plots were generated using a modified Hoffmann approach to derive age- and sex-specific reference intervals. Results Age-specific ALP reference intervals ranged from 110 to 250 and 120 to 295 U/L for males and females <15 days old, 80 to 400 and 90 to 380 U/L for males and females 15 days to 1 year old, 105 to 280 and 90 to 290 U/L for males and females 1 to 10 years old, 75 to 300 and 90 to 300 U/L for males and females 10 to 13 years old, 80 to 300 and 60 to 175 U/L for males and females 13 to 15 years old, 55 to 150 and 60 to 180 U/L for males and females 15 to 18 years old, and 55 to 140 and 60 to 147 U/L for male and female adults, respectively (>18 years old). Conclusion By applying derived ranges, a retrospective review of ALP isoenzymes would eliminate 24.5% of requests. Additionally, 9 neonates would have required investigation for possible hypophosphatasia. [ABSTRACT FROM AUTHOR]

Reference ranges are invaluable in laboratory medicine, as these are indispensable tools for the interpretation of laboratory test results. When assessing measurements on a single analyte, univariate reference intervals are required. In many cases, however, measurements on several analytes are needed by medical practitioners to diagnose more complicated conditions such as kidney function or liver function. For such cases, it is recommended to use multivariate reference regions, which account for the cross-correlations among the analytes. Traditionally, multivariate reference regions (MRRs) have been constructed as ellipsoidal regions. The disadvantage of such regions is that they are unable to detect component-wise outlying measurements. Because of this, rectangular reference regions have recently been put forward in the literature. In this study, we develop methodologies to compute rectangular MRRs that incorporate covariate information, which are often necessary in evaluating laboratory test results. We construct the reference region using tolerance-based criteria so that the resulting region possesses the multiple use property. Results show that the proposed regions yield coverage probabilities that are accurate and are robust to the sample size. Finally, we apply the proposed procedures to a real-life example on the computation of an MRR for three components of the insulin-like growth factor system. [ABSTRACT FROM AUTHOR]

To establish age- and sex-specific reference intervals (RIs) for serum tumor markers (AFP, CEA, CA125, CA199, CA153, HE4, CA724, CYFRA21-1, PSA, and NSE) among a cohort of healthy individuals in South China, a retrospective analysis was conducted on 51,353 samples collected from 2015 to 2020, during health assessments at Guangdong Provincial People's Hospital. The influence of age and gender on serum tumor markers was investigated. New RIs were determined using non-parametric rank-based methods per CLSI EP28-A3C guidelines. Significant differences were detected across age groups for AFP, CEA, CA125, CA199, HE4, CYFRA21-1, PSA, and NSE (p < 0.05). The upper reference limits (URLs) for CA153 and HE4 are significantly lower compared to our current laboratory standards. The URL for CA125 exceeds these limits in individuals under 50 but decreases in those aged 50 and above. For CA199, CEA, and PSA, the URLs are below current standards in individuals younger than 60 but exceed them in those aged 60 and older. Noteworthy elevations were observed in CA724, CYFRA21-1, and NSE levels. Our study establishes age- and sex-specific RIs for ten serum tumor markers among healthy individuals from South China, providing a fundamental resource for the prevention, early detection, and management of tumor-related disorders. [ABSTRACT FROM AUTHOR]

Reference intervals (RI) play a decisive role in the interpretation of medical laboratory results. An important step in the determination of RI is age- and sex specific partitioning, which is usually based on an empirical approach by graphical representation. In this study, we evaluate an automated machine learning approach. This study uses pediatric data from the CALIPER RI (Canadian Laboratory Initiative on Pediatric Reference Intervals) study. The calculation of potential partitions is carried out using a regression tree model included in the rpart package of the statistical programming language R. The Harris & Boyd method is used to compare the corresponding partitions suggested by rpart and CALIPER. For better comparability, the reference ranges of the partitions of both approaches are then calculated using reflimR. Most of the partitions suggested by rpart or CALIPER show sufficient heterogeneity among themselves to justify age- and/or sex-specific RI partitioning. With only few individual exceptions, both methods yield comparable results. The partitions of both approaches for albumin and γ-glutamyltransferase are very similar to each other. For creatinine rpart suggests a slightly earlier distinction between the sexes. Alkaline phosphatase shows the most pronounced differences. In addition to a considerable earlier sex split, rpart suggests different age intervals for both sexes, resulting in three partitions for females and four partitions for males. Our findings indicate that the automated analysis provided by rpart yields results that comparable to traditional methods. Nevertheless, the medical plausibility of the automatic suggestions needs to be validated by human experts. [ABSTRACT FROM AUTHOR]

Mucosal barriers are gatekeepers of health and exhibit homeostatic variation in relation to habitat and disease. Mucosal Mapping technology provides an in‐depth examination of the dynamic mucous cells (MCs) in fish mucosal barriers on tangential sections, about 90° from the view of traditional histology. The method was originally developed and standardized in academia prior to the establishment of QuantiDoc AS to apply mucosal mapping, now trademarked as Veribarr™ for the analysis of skin, gills and gastrointestinal tracts. Veribarr™ uses design‐based stereology for the selection and measurement of cell area (size) (μm2), the volumetric density of MCs in the epithelium (MCD, amount of the epithelia occupied by MCs, in %) and the calculated abundance of the MCs (barrier status or defence activity). MC production was mapped across the skin and gill epithelia in 12 species, discovering that gills consistently have two distinct groups of MCs, one on the lamellae where MCs are few and small and one on the filament where MCs are larger and more abundant. MCs were usually much larger in the skin than in the gills, with the latter requiring fewer and smaller cells for adequate respiration. The difference observed between MCs in gill lamella and gill filament is likely a result of functional demands. In addition, our findings also highlight a variation in the mucosal parameters between the species skin, which cannot be explained by the weight differences, and a potential link between MC distribution and species‐specific lifestyles in the gill lamella. This diversity necessitates the development of species and tissue site‐specific reference intervals for mucosal health evaluation. Mucosal bivariate reference intervals were developed for MC production, including size (trophy) and calculated defence activity (plasia) in the skin and gills of Atlantic salmon, to contrast new measurements against historical data patterns. The application of mucosal reference intervals demonstrates that stress from parasites and treatments can manifest as changes in mucosal architecture, as evidenced by MC hypertrophy and hyperplasia within the gill lamellae. These reference intervals also facilitate comparisons with wild Atlantic salmon, revealing a somewhat higher MC level in farmed salmon gill lamellae. These findings suggest that MC hyperplasia and hypertrophy in the gills are stress/environmental responses in aquaculture. They also advocate for developing specific mucosal bivariate homeostatic reference intervals in aquaculture to improve fish health and welfare across all farmed species. [ABSTRACT FROM AUTHOR]

With the increasing demand and application of lymphocyte subsets detection in clinical laboratories, different single-platform flow cytometer (FCM) systems have been developed. There is an urgent need to establish the reference intervals (RIs) for different single-platform FCMs and transferring them from one FCM system to another provides a much more feasible and convenient approach. This study aimed to explore the transferability of RIs for lymphocyte subsets across different flow cytometry platforms.We first conducted the pairwise method comparison across four FCM platforms, including NovoCyte, BriCyteE6, DxFLEX, and FACSCantoII systems. Next, the transferability of RIs of lymphocyte subsets was evaluated. Furthermore, we conducted the RIs transference based on the FACSCantoII system, BriCyteE6 system and DxFLEX system, except for NK cells. The transferred RIs were further verified by calculating the bias (CV) between the established ones.The results of lymphocyte subsets detection based on the NovoCyte, BriCyteE6, DxFLEX, and FACSCantoII systems were comparable and it was feasible to transfer the RIs of lymphocyte subsets detected by the four FCM systems. The RIs of lymphocyte subsets detection using FACSCantoII, DxFLEX, and BriCyteE6 systems were established. Upon transferring the RIs of lymphocyte subsets from the FACSCantoII system to the BriCyteE6 system, and DxFLEX system except for NK cells, the CV between the transferred RIs and the established ones was below 20 % for all parameters.The present study illustrated that the RIs of lymphocyte subsets could be transferred across different flow cytometry systems except for NK cells with different definition strategies. [ABSTRACT FROM AUTHOR]

Background: There is a lack of standardization of reference intervals (RIs) for ferritin across laboratories, particularly for postmenopausal women. Depending on the RI used, there can be more than a 4-fold difference in the upper limit of normal between laboratories, resulting in potential misinterpretation. Methods: This retrospective study used a large dataset of blood test results from 25,425 healthy participants aged 18 to 97 over a 7-year period. Exclusion criteria were used to screen out individuals with conditions known to affect iron metabolism or raise ferritin as part of the acute phase response. Distributions were assessed using density and Q-Q plots, and age-banded cut-offs were determined. The non-parametric method was used to establish RIs for sex and age bands. Results: For females, 4 age bands were established (18–39, 40–49, 50–59 and 60+). For males, 2 bands were identified (18–39 and 40+). Performance against a validation dataset, followed by an expansive validation against an inclusive dataset, demonstrated the robustness of the derived RIs. Conclusion: This study addresses the inconsistency in serum ferritin RIs by presenting intervals based on demographic parameters. This approach can potentially enhance the accuracy of interpreting serum ferritin levels, assisting clinicians in identifying patients requiring further evaluation. [ABSTRACT FROM AUTHOR]

Harmonization of the laboratory total testing process (TTP) is critical to improving patient outcome. In 2016, an EFLM survey on the harmonization of TTP underlined the serious shortcomings pertaining to the post-analytical phase. In 2023, the WG-H conducted a new survey aiming to update information in the 2016 harmonization report in order to ascertain whether countries that had declared they were keen to adopt SI units had continued with this program, the aim being to verify the state-of art in harmonization units in areas of laboratory medicine not included in the previous survey. Questionnaires were distributed to the Presidents and National Representatives of EFLM Full Member Societies and EFLM affiliate Members. The survey questions were grouped into three categories: measurement units, reference intervals, and nomenclature/terminology, and results were evaluated using Survey Monkey software and Excel. A total of 123 questionnaires from 31 countries were analyzed. A trend (+19.3 %) was observed toward a wider use of SI units for general clinical biochemistry parameters. The results for tests not included in the 2016 survey (i.e., endocrinology diagnostics and coagulation panels), demonstrated that for reports on hormones, responses were satisfactory, 70–90 % of the responders adopting the recommended units, whereas for coagulation test panels, a serious lack of harmonization was found, "seconds", which are inaccurate and not recommended, being widely used units (91 %). The findings made in the 2023 survey demonstrated a progressive, albeit slow, improvement in harmonization reports. However, further efforts at improvement are mandatory. [ABSTRACT FROM AUTHOR]

The aims of this study were to verify the bile acids (BA) method and to establish reference intervals (RIs) for bile acids (BA) and biochemical and haematological parameters in Croatian pregnant women. BA spectrophotometric method verification was performed on Siemens Atellica Solution CH 930 automated analyser using Sentinel reagent. Stability, precision, trueness, linearity, and RIs, as well as lipemia interference were tested according to CLSI guidelines. BA, biochemical, and haematological parameters were measured in serum (BA, biochemical) and whole blood (haematological) samples of fasting healthy third-trimester pregnant women from Croatia (n=121). The establishment of the RIs was done a priori according to the CLSI EP28-A3C:2010 guideline. Selected reference individuals' data were analysed using parametric, non-parametric, and robust methods. Stability study showed that BA are stable in serum samples for 2 days at 20 °C, 14 days at 4–8 °C, and 22 days at −20 °C. The precision study and adult RIs verification met the criteria. Linearity was verified for the concentration range of 3.5–172.1 μmol/L whereas the lipemia interference test showed a positive bias (%) in BA concentration. The determined reference limits generally exhibited better precision for haematological parameters, being lower than the upper recommended value 0.2, unlike biochemical parameters. Haematological parameters showed notable differences between pregnant and non-pregnant women, while many biochemical parameters' RIs remained similar. Only ALT and GGT showed lower non-comparable RI upper limits in the population pregnant women. Spectrophotometric BA method showed satisfactory performance and all examined parameters were within the set criteria. Moreover, RIs for key biochemical and haematological parameters, including BAs, have been established for the first time in the population of Croatian pregnant women. [ABSTRACT FROM AUTHOR]

Abdifatah Abdullahi Jalei,1 Abdifetah Ibrahim Omar,1,2 Shafie Abdulkadir Hassan,1 Yahye Sheikh Abdulle Hassan,1 Nur Rashid Ahmed1,2 1Faculty of Medicine and Health Sciences, Jamhuriya University of Science and Technology, Mogadishu, Somalia; 2Jamhuriya Research Center, Jamhuriya University of Science and Technology, Mogadishu, SomaliaCorrespondence: Abdifatah Abdullahi Jalei, Faculty of Medicine and Health Sciences, Jamhuriya University of Science and Technology, Mogadishu, Somalia, Tel +252617000684, Email Jeele301@gmail.comIntroduction: Reference intervals (RIs) are crucial for the accurate interpretating of laboratory test results in clinical settings, serving as benchmarks for evaluating individual health status. This study investigates the influence of sex and age on common liver function tests (LFTs) and renal function tests (RFTs) in healthy adults in Mogadishu, Somalia.Methods: A community-based cross-sectional study was carried out from October 2022 to January 2023 on a randomly selected sample of 255 healthy participants from Mogadishu, Somalia. Approximately 5 mL of whole blood was collected from each participant and processed screening of hepatitis B and C, and human immunodeficiency virus, and then biochemical analyses were conducted for common liver and kidney parameters.Results: The study found significant sex and age-related differences in the measured LFTs and RFTs parameters. For LFTs, males had higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to females (ALT: 11.5 vs 7.5 U/L; AST: 25.5 vs 19.1 U/L; both p < 0.001). Age-related differences were also observed, with individuals aged 30 and above had higher levels of ALT and AST compared to those aged 18– 29 (ALT: 10.9 vs 8.5 U/L; AST: 24.3 U/L vs 21.0 U/L, both p < 0.001). For RFTs, males had higher levels of creatinine (0.9 vs 0.7 mg/dL), urea (23.1 vs 16.1 mg/dL), and uric acid (5.2 vs 4.2 mg/dL) than females, all with p < 0.001.Conclusion: The study established population specific RIs for common liver and renal function parameters and revealed significant variations across sex and age groups. These findings underscore the importance of developing and using local RIs to ensure accurate clinical interpretation and effective patient management. Further research with larger sample sizes and in diverse regions of Somalia is highly recommended.Keywords: reference intervals, liver function tests, renal function tests, Mogadishu, Somalia

The reference intervals (RIs) for clinical parameters of fish are crucial to identify abnormal test results. The well-established RIs for hemato-biochemical analytes are lacking for Pangas (Pangasianodon hypophthalmus) reared in different culture systems. The present study aimed to analyze the condition factor and generate RIs for hemato-biochemical parameters in diverse culture systems, which are very critical to improve fish welfare and production. Briefly, the fish sampling was conducted from three different fish farms practicing extensive (no supplemented food with a relatively low stocking density of 10–15 fish/m3), semi-intensive (supplementary feed provided with a stocking density of 80 fish/m3), and intensive culture systems (feed-based culture with a high stocking density of 100–150 fish/m3). Results showed that Fulton's condition factor for fish reared in an intensive culture system was significantly higher (0.98 ± 0.18), followed by semi-intensive (0.85 ± 0.30) and extensive (0.72 ± 0.16) systems. Hematological parameters such as hemoglobin, total erythrocyte count, and packed cell volume were significantly (P < 0.05) higher in the semi-intensive system. Total leucocyte count and mean corpuscular hemoglobin were significantly (P < 0.05) higher in the intensive system. Serum biochemical parameters, including glucose, cortisol, protein profile, and lipid profile, were significantly (P < 0.05) high in the intensive and semi-intensive systems. The study indicated that the condition factor and haemato-biochemical parameters could serve as indicators of the health status of P. hypophthalmus. The intensive and semi-intensive culture systems of P. hypophthalmus demonstrated better health indicators compared to the extensive system. The established normative database can ensure the correct assessment of health and the growth of P. hypophthalmus in diverse culture systems. The reference intervals established for hemato-biochemical parameters in the current study can provide valuable benchmarks for monitoring the fish in different culture systems, enabling effective management and reducing economic losses associated with stress-related issues. [ABSTRACT FROM AUTHOR]

With about 60%-70% of medical decisions based on laboratory investigations, modern medicine is increasingly more reliant on laboratory medicine. Pediatric healthcare particularly depends on laboratory testing, with reference intervals (RIs) serving as critical tools for accurate result interpretation. However, establishing pediatric RIs poses distinctive challenges due to developmental, growth, nutritional, and disease-related variations across age groups, along with technical, ethical, and logistical challenges. Despite these limitations, there are several ongoing initiatives for developing pediatric RIs globally, underscoring the importance of developing accurate pediatric RIs. This review outlines the particularities of pediatric laboratory medicine and the specific challenges in establishing pediatric RIs, highlighting the recent initiatives in this area. It also addresses biological and analytical variability issues and explores future perspectives aimed at enhancing diagnostic accuracy and elevating patient care standards.

Objective To establish reference intervals for serum soluble transferrin receptor (sTfR) and sTfR/log serum ferritin index (sTfR/lgSF) in apparently healthy adults in the Wuhan area, so as to provide reference for clinical diagnosis and treatment of iron deficiency and iron-deficiency anemia. Methods A total of 273 individuals from the Wuhan Aisa General Hospital, including health examination participants and blood donors, were selected to measure sTfR, other iron metabolism indicators and high sensitivity C-reactive protein(hsCRP). The sTfR/lgSF values were calculated and reference intervals for sTfR and sTfR /lgSF were established using the percentile method (P2.5 to P97.5). Spearman correlation analysis was used to evaluate the relationships between sTfR, sTfR/lgSF, and other iron metabolism indicators, as well as hsCRP. Results The sTfR levels (M, mg/L) between males and females (1.01 vs 1.07) were not statistically significant (P>0.05), but the sTfR/lgSF levels if males were significantly lower than those in females (0.45 vs 0.62)(P0.05). The reference interval for STfR was (0.72-1.68) mg/L, the sTfR/lgSF reference interval was (0.31-0.88) for males, and (0.37-1.19) for females. Correlation analysis showed no correlation between sTfR, sTfR/lgSF and hsCRP (r=0.043, P>0.05; r=-0.064, P>0.05), while serum ferritin(SF), serum iron(SI), transferrin saturation(TSAT)were correlated with hsCRP (r=0.128, P0.05), while sTfR/lgSF was significantly correlated with and SF (r=-0.685, P

Abstract Objectives Although recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age. Design and methods The NBS data of 199,693 preterm newborns (

Background: Elevated oxidized low-density lipoprotein (Ox-LDL) was significantly associated with the atherosclerotic cardiovascular disease as well as retinal vascular diseases but there were no studies to show the reference range of Ox-LDL levels in any Indian population. Aims and Objectives: The aim of this study was to formulate the reference intervals of Ox-LDL cholesterol in a population of West Bengal. Materials and Methods: Ox-LDL levels of 434 apparently healthy individuals were estimated based on the history, clinical examination, and laboratory investigations. Statistical analysis was performed using the statistical package for the social sciences software. Results: The reference range of Ox-LDL levels for all ages was 34.1±4.9 mol/L in healthy male and 34.5±4.5 mol/L in healthy female. The 2.5th and 97.5th percentile values of Ox-LDL level in the reference population were 27 (0.90 CI = 26.4–27.6) and 42 (0.90 CI = 41.4–42.6), respectively. Conclusions: Reference intervals for Ox-LDL may help clinicians to predict the future risk for coronary heart disease and retinal vascular disease by taking medical decision limits and also open up the scope for further research for other laboratories to formulate their own reference interval of Ox-LDL.

Introduction: Thyroid function during pregnancy fluctuates with gestational weeks, seasons and other factors. However, it is currently unknown whether there is a fetal sex-specific thyroid function in pregnant women. The purpose of this study was to investigate the fetal sex differences of maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in pregnant women. Methods: This single-center retrospective real-world study was performed by reviewing the medical records of pregnant women who received regular antenatal health care and delivered liveborn infants in Shanghai First Maternity and Infant Hospital (Pudong branch), from Aug. 18, 2013 to Jul. 18, 2020. Quantile regression was used to evaluate the relationship between various variables and TSH and FT4 concentrations. The quantile regression also evaluated the sex impact of different gestational weeks on the median of TSH and FT4. Results: A total of 69,243 pregnant women with a mean age of 30.36 years were included. 36197 (52.28%) deliveries were boys. In the three different trimesters, the median levels (interquartile range) of TSH were 1.18 (0.66, 1.82) mIU/L and 1.39 (0.85, 2.05) mIU/L, 1.70 (1.19, 2.40) mIU/L; and the median levels (interquartile range) of FT4 were 16.63 (15.16, 18.31) pmol/L, 14.09 (12.30, 16.20) pmol/L and 13.40 (11.52, 14.71) pmol/L, respectively. The maternal TSH upper limit of reference ranges was decreased more in mothers with female fetuses during gestational weeks 7 to 12, while their FT4 upper limit of the reference ranges was increased more than those with male fetuses. After model adjustment, the median TSH level was 0.11 mIU/L lower (P <0.001), and FT4 level was 0.14 pmol/L higher (P <0.001) for mothers with female fetuses than those with male fetuses during gestational weeks 9 to 12. Discussion: We identified sexual dimorphism in maternal thyroid function parameters, especially during 9-12 weeks of pregnancy. Based on previous research, we speculated that it may be related to the higher HCG levels of mothers who were pregnant with girls during this period. However, longitudinal studies are needed to determine if fetal sex differences impact the maternal thyroid function across pregnancy. [ABSTRACT FROM AUTHOR]

Personalized reference intervals (prRI) have been proposed as a diagnostic tool for assessing measurands with high individuality. Here, we evaluate clinical performance of prRI using carcinoembryonic antigen (CEA) for cancer detection and compare it with that of reference change values (RCV) and other criteria recommended by clinical guidelines (e.g. 25 % of change between consecutive CEA results (RV25) and the cut-off point of 5 μg/L (CP5)).Clinical and analytical data from 2,638 patients collected over 19 years were retrospectively evaluated. A total 15,485 CEA results were studied. For each patient, we calculated prRI and RCV using computer algorithms based on the combination of different strategies to assess the number of CEA results needed, consideration of one or two limits of reference interval and the intraindividual biological variation estimate (CVI) used: (a) publicly available (CVI-EU), (b) CVI calculated using an indirect method (CVI-NOO) and (c) within-person BV (CVP). For each new result identified falling outside the prRI, exceeding the RCV interval, RV25 or CP5, we searched for records identifying the presence of tumour at 3 and 12 months after the test. The sensitivity, specificity and predictive power of each strategy were calculated.PrRI approaches derived using CVI-EU, and both limits of reference interval achieve the best sensitivity (87.5 %) and NPV (99.3 %) at 3 and 12 months of all evaluated criteria. Only 3 results per patients are enough to calculate prRIs that reach this diagnostic performance.PrRI approaches could be an effective tool to rule out new oncological findings during the active surveillance of patients. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 1 (IGF-1), primarily synthesized in the liver, was initially discovered due to its capacity to replicate the metabolic effects of insulin. Subsequently, it emerged as a key regulator of the actions of growth hormone (GH), managing critical processes like cell proliferation, differentiation, and apoptosis. Notably, IGF-1 displays a longer half-life compared to GH, making it less susceptible to factors that may affect GH concentrations. Consequently, the measurement of IGF-1 proves to be more specific and sensitive when diagnosing conditions such as acromegaly or GH deficiency. The recognition of the existence of IGFBPs and their potential to interfere with IGF-1 immunoassays urged the implementation of various techniques to moderate this issue and provide accurate IGF-1 results. Additionally, in response to the limitations associated with IGF-1 immunoassays and the occurrence of discordant IGF-1 results, modern mass spectrometric methods were developed to facilitate the quantification of IGF-1 levels. Taking advantage of their ability to minimize the interference caused by IGF-1 variants, mass spectrometric methods offer the capacity to deliver robust, reliable, and accurate IGF-1 results, relying on the precision of mass measurements. This also enables the potential detection of pathogenic mutations through protein sequence analysis. However, despite the analytical challenges, the discordance in IGF-1 reference intervals can be attributed to a multitude of factors, potentially leading to distinct interpretations of results. The establishment of reference intervals for each assay is a demanding task, and it requires nationwide multicenter collaboration among laboratorians, clinicians, and assay manufacturers to achieve this common goal in a cost-effective and resource-efficient manner. In this comprehensive review, we examine the challenges associated with the standardization of IGF-1 measurement methods, the minimization of pre-analytical factors, and the harmonization of reference intervals. Particular emphasis will be placed on the development of IGF-1 measurement techniques using "top-down" or "bottom-up" mass spectrometric methods. [ABSTRACT FROM AUTHOR]

This article discusses the importance and complexity of reference intervals for thyroid-stimulating hormone (TSH) levels. Reference intervals are established based on a sample of healthy individuals and are used to determine whether an individual's TSH levels are within the normal range. However, factors such as age, ethnicity, sex, iodine status, and pregnancy can affect the reference intervals for TSH. The article also highlights the impact of genetic factors on TSH reference intervals and suggests that personalized treatment based on more accurate reference intervals may improve patient outcomes. However, further research is needed to explore these possibilities. [Extracted from the article]

Purpose: This study aims to analyze the distribution of plasma aldosterone, renin activity, deoxycorticosterone (DOC), cortisol, cortisone, and 24 h urinary aldosterone (24 h-uAld) levels based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Materials and methods: Plasma and 24 h urine were collected from 129 healthy volunteers in Northeast China. The effect of sodium intake, age, gender, blood sampling time on plasma aldosterone concentration (PAC), plasma renin activity (PRA), PAC to PRA ratio (ARR), DOC, cortisol, cortisone, cortisol to cortisone ratio, and 24 h-uAld were investigated by nonparametric test, multiple linear regression and Harris–Boyd's standard deviate test. Results: There was no significant difference observed in 24 h-uAld, PAC (AM), PRA(AM), ARR (AM), DOC (AM), cortisol (AM), cortisone (AM), and cortisol to cortisone (AM) between high and low sodium intake group. Significant differences were observed between morning and afternoon sampling groups in terms of PAC, ARR, DOC, cortisol, and cortisone. Reference intervals (RIs) of 24 h-uAld, PAC (AM) were recommended to be partitioned by gender. RI of PRA was recommended age stratification. Conclusion: We recommend that the same reference interval could be used regardless of sodium intake. Gender is the main influence factor for 24 h-uAld, PAC, and ARR. Age is key influence factor for PRA. [ABSTRACT FROM AUTHOR]

Simple Summary: Miranda's donkey is an autochthonous Portuguese breed that is important for the culture and economy of the country's northern region. Knowledge of the physiological characteristics of the breed is crucial for its preservation, and even if studies have been conducted, none have focused on its coagulation profile. The aim of this study was to establish reference intervals for coagulation and assess the influence of sex and age. For this, seven parameters involved in coagulation were analyzed in blood samples from 75 clinically healthy animals. Statistical differences were only found between ages in two parameters, platelet count and plateletcrit, both of which were higher in young animals. The reference intervals described here can help monitor health and guide the diagnosis and treatment of sick Miranda's donkey, contributing to its preservation. Miranda's donkey, originating in northern Portugal, is an autochthonous breed that is deeply intertwined with the region's culture and economy. Knowledge of the physiological characteristics of the breed is important for its preservation, and several studies have been carried out, but none have focused on its coagulation profile. The aim of this study was to establish reference intervals (RIs) for coagulation in healthy Miranda's donkey and to assess the influence of sex and age. Blood samples from 75 clinically healthy animals were analyzed for seven coagulation parameters: four using IDEXX ProCyte Dx and three using Start® 4-Diagnostica-Stago. The RI values were calculated following the ASVCP guidelines and with the Reference Advisor V.2.1 software. To analyze the influence of sex and age, SPSS version 29 was used. No significant differences were found between sexes (p > 0.05), but statistically significant differences were found between ages (p < 0.05) for platelet count and plateletcrit (both higher in young animals). The RIs described here can help monitor health and guide the diagnosis and treatment of diseased Miranda's donkeys, contributing to their preservation. Our study encourages further research on coagulation in donkeys and the use of different methodologies to obtain information for veterinarians working with this species. [ABSTRACT FROM AUTHOR]

Objective: Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non‐pregnant and pregnant adults. Design: Cross‐sectional study. Participants: Serum samples were obtained from 192 blood donors (non‐pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease. Measurements: Each sample was used for measurement of thyroid‐stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI). Results: In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30–1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48–1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61–1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37–2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69–3.62 mIU/L)). Conclusion: Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non‐pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease. [ABSTRACT FROM AUTHOR]

The cardiac biomarkers high sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are utilised in paediatric healthcare for the diagnosis and prognostic assessment of many conditions including myocarditis, congenital heart disease, multisystem inflammatory syndrome in children (MIS-C) and heart failure. However, the standardised age-related reference intervals, 99th percentile cut-offs and clinical guidelines are not available, making the interpretation of these biomarkers challenging. This study aimed to generate normative data in a paediatric cohort for the Siemens Atellica® IM 1300 analyser. Residual plasma samples were collected from children aged up to 17 years attending primary care and out-patient settings and with no apparent evidence of cardiac dysfunction, renal dysfunction or other confounders. Reference intervals were generated using the 2.5th–97.5th percentiles, and 99th percentile cut-offs determined according to CLSI EP28-A3c. Statistical analysis revealed that partitioning was not required for gender for either biomarker. The reference interval for hs-cTnI for children aged one month to 16 years (n=292, 146 females and 146 males) was <14 ng/L with a 99th percentile cut-off of 19 ng/L. The reference interval for NT-proBNP for children aged one month up to one year was <714 ng/L (n=14) and for children aged 1–16 years (n=339) was <295 ng/L. This is the first paediatric reference interval data generated on the Siemens Atellica® solution. These reference intervals and 99th percentiles will inform clinical decisions in the paediatric cardiology setting. [ABSTRACT FROM AUTHOR]

Objective To investigate the trends of major thyroid function indices in Chinese adolescent females at different ages and the differences from adult reference intervals. Methods A total of 791 female students from 4 junior high schools were enrolled in the study by selecting one junior high school in each of the following locations: Minhang District of Shanghai, Haimen City of Jiangsu Province, Yuhuan City of Zhejiang Province, and Deqing County of Zhejiang Province from Oct to Nov 2017 and from Jan to Mar 2019. The subjects were subjected to physical examination as well as thyroid hormone levels; and the Pubertal Developmental Events Self-Assessment Scale (PDS) was used to evaluate the staging of pubertal development. Follow-ups were conducted after 2 years, with the same survey content. Thyroid function levels were assessed in 5 age groups between 11 to 15 years old, 95% CI were calculated, and mixed linear models were used to analyze the effects of age and pubertal developmental stage on hormone levels. Results The reference intervals for thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) in adolescent females differed significantly from those of adults, with misclassification rates ranging from 2.98% to 5.17%. Statistically significant differences were found for age, pubertal development staging, and the interaction of age and pubertal staging after correcting for BMI, waist circumference (all P<0.05). TSH levels were more affected by age before the completion of pubertal development, the level of the 12-year-old group was higher than that of the 11-year-old group (P=0.001 2) and the 13-year-old group (P<0.000 1); FT3 levels showed greater variability with age during late pubertal stage, with levels significantly higher at 13 years of age than at 11 and 12 years of age (P<0.0001), and gradually decreasing after 13 years of age (P<0.000 1). In contrast, FT4 levels were generally less affected by age between 11 and 15 years of age, with levels slightly higher at 13-15 years of age than at 11-12 years of age (P<0.000 1). Conclusion The levels of TSH, FT3, and FT4, as indicators of thyroid function in adolescent females, differ significantly from those of adults, and are differently affected by age and the stages of pubertal development; further refinement of the reference intervals for age- and pubertal-development-specific thyroid indicators is necessary. [ABSTRACT FROM AUTHOR]

Background: Elevated oxidized low-density lipoprotein (Ox-LDL) was significantly associated with the atherosclerotic cardiovascular disease as well as retinal vascular diseases but there were no studies to show the reference range of Ox-LDL levels in any Indian population. Aims and Objectives: The aim of this study was to formulate the reference intervals of OxLDL cholesterol in a population of West Bengal. Materials and Methods: Ox-LDL levels of 434 apparently healthy individuals were estimated based on the history, clinical examination, and laboratory investigations. Statistical analysis was performed using the statistical package for the social sciences software. Results: The reference range of Ox-LDL levels for all ages was 34.1±4.9 mol/L in healthy male and 34.5±4.5 mol/L in healthy female. The 2.5th and 97.5th percentile values of Ox-LDL level in the reference population were 27 (0.90 CI = 26.4–27.6) and 42 (0.90 CI = 41.4–42.6), respectively. Conclusions: Reference intervals for Ox-LDL may help clinicians to predict the future risk for coronary heart disease and retinal vascular disease by taking medical decision limits and also open up the scope for further research for other laboratories to formulate their own reference interval of Ox-LDL. [ABSTRACT FROM AUTHOR]

Objectives: Although recent discoveries regarding the biomarkers of newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) highlight the critical need to establish reference intervals (RIs) specifically for preterm infants, no such RIs has been formally published yet. This study addressed the gap by offering a comprehensive set of reference intervals (RIs) for preterm neonates, and illustrating the dynamic changes of each biomarker with age. Design and methods: The NBS data of 199,693 preterm newborns (< 37 weeks of gestation) who met the inclusion and exclusion criteria from the NNSCP database were included in study analysis. The birth weight stratified dynamic trend of each biomarker were captured by their concentrations over age. Reference partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated using a non-parametric rank approach. Results: Increasing birth weight is associated with an elevation in the levels of arginine, citrulline, glycine, leucine and isobarics, methionine, ornithine, phenylalanine, and valine, whereas the levels of alanine, proline and tyrosine decrease. Additionally, two short-chain acylcarnitines (butyrylcarnitine + isobutyrylcarnitine and isovalerylcarnitine + methylbutyrylcarnitine) and a median-chain acylcarnitine (octenoylcarnitine) decrease, while four long-chain acylcarnitines (tetradecanoylcarnitine, palmitoylcarnitine, palmitoleylcarnitine and oleoylcarnitine) increase with increasing birth weight. Age impacts the levels of all MS/MS NBS biomarkers, while sex only affects the level of malonylcarnitine + 3-hydroxybutyrylcarnitine (C3-DC + C4-OH) in very low birth weight preterm neonates. Conclusion: The current study developed reference intervals (RIs) specific to birth weight, age, and/or sex for 35 MS/MS biomarkers, which can help in the timely evaluation of the health and disease of preterm neonates. [ABSTRACT FROM AUTHOR]

Background: Clinical laboratory tests are being evaluated with reference intervals (RI). Therefore, it is important that each laboratory determines and classifies its own reliable RI for each test to ensure an accurate and effective interpretation. The proposed method for determining RI is the "direct" approach, but it is a difficult, troublesome, time-consuming, and expensive method. An alternative approach is the “indirect” approach. In this study, we aimed to compare the RI values determined by the indirect method from the Calcium (Ca), Magnesium (Mg), Phosphate (P), 25-Hydroxy Vitamin D (25(OH)D), and Parathyroid hormone (PTH) test results with the RI provided by the manufacturer. Methods: A total of 1,520,314 Ca, Mg, P, 25(OH)D, and PTH test results, which were studied in our laboratory between January and November 2022, were included in the study. Data cleaning was done for individuals between the ages of 18 - 89, and only one record was allowed. The Tukey method was used to determine and exclude extreme values. Ca and Mg tests were divided into age groups (18 - 59 and 60 - 89 years), P, 25(OH)D, and PTH tests were divided into female - male groups. RI was calculated by using the Bhattacharya and Hoffmann methods. CLIA 19 acceptable limits were used to evaluate the compliance with the manufacturer's RI. Results: The RI results obtained by applying the Bhattacharya and Hoffmann methods were found to be significantly consistent and compatible with each other. According to the manufacturer's RI, Ca and Mg were compatible with RI in both methods, P was considered compatible with PTH and 25(OH)D upper reference limit in the Bhattacharya method, P was considered compatible with 25(OH)D lower reference limit and PTH upper reference limit in the Hoffmann method, while 25(OH)D lower reference limit was found to be different in the Bhattacharya method, and 25(OH)D upper reference limit and PTH lower reference limit were found to be different in the P male group in the Hoffmann method. Conclusions: We believe that it is of great importance for each laboratory to determine the RI specific for the population they serve and to choose the analytical method they use according to age and gender while periodically updating them to interpret the test results correctly. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) and Doppler echocardiography is considered the most practical diagnostic tool for antemortem evaluation of reptilian heart disease but has only been described in a limited number of chelonian species. Cardiac morphology and function were evaluated by ultrasonography in 35 clinically healthy, captive non-sedated European pond turtles (Emys orbicularis) using 2D mode, M mode, and pulsed-wave spectral Doppler. Turtles were placed in a temperature-controlled water tank (24–26°C, 75.2–78.8°F) for cardiac examination through the right cervicobrachial window using water as coupling agent. Each echocardiogram included the evaluation of 19 variables—including six in 2D mode, seven in M mode, and six in Doppler mode—and was performed in 5.64 min on average. Morphological and functional abnormalities were identified in eight turtles, including atrioventricular insufficiencies (n = 5), pericardial effusions (n = 4), increased velocity of the ventricular outflow tract (n = 1), and bradyarrhythmia (n = 2). Reference intervals could be established for the 19 parameters in the remaining individuals after excluding outliers (n = 25). Statistically significant positive correlations between weight and diastolic (0.61, P = 0.001) and systolic (0.46, P = 0.018) ventricular volumes, and diastolic ventricular diameter (0.35, P = 0.03) were identified. This study establishes an initial database for the evaluation of captive European pond turtle cardiovascular system by a simple and clinically applicable echocardiographic technique. [ABSTRACT FROM AUTHOR]

Correct interpretation of thyroid function tests relies on correct reference intervals (RIs) for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). ISO15189 mandates periodic verification of RIs, but laboratories struggle with cost-effective approaches. We investigated whether indirect methods (utilizing historical laboratory data) could replace the direct approach (utilizing healthy reference individuals) and compared results with manufacturer-provided RIs for TSH and FT4. We collected historical data (2008–2022) from 13 Dutch laboratories to re-establish RIs by employing indirect methods, TMC (for TSH) and refineR (for FT4). Laboratories used common automated platforms (Roche, Abbott, Beckman or Siemens). Indirect RIs (IRIs) were determined per laboratory per year and clustered per manufacturer (>1.000.000 data points per manufacturer). Direct RIs (DRIs) were established in 125 healthy individuals per platform. TSH IRIs remained robust over the years for all manufacturers. FT4 IRIs proved robust for three manufacturers (Roche, Beckman and Siemens), but the IRI upper reference limit (URL) of Abbott showed a decrease of 2 pmol/L from 2015. Comparison of the IRIs and DRIs for TSH and FT4 showed close agreement using adequate age-stratification. Manufacturer-provided RIs, notably Abbott, Roche and Beckman exhibited inappropriate URLs (overall difference of 0.5–1.0 µIU/mL) for TSH. For FT4, the URLs provided by Roche, Abbott and Siemens were overestimated by 1.5–3.5 pmol/L. These results underscore the importance of RI verification as manufacturer-provided RIs are often incorrect and RIs may not be robust. Indirect methods offer cost-effective alternatives for laboratory-specific or platform-specific verification of RIs. [ABSTRACT FROM AUTHOR]

To echocardiographically evaluate a large number of apparently healthy Czechoslovakian wolfdogs (CWDs) to identify possible subclinical cardiac abnormalities and to generate reference intervals. One-hundred and seventeen apparently healthy client-owned CWDs. Standard two-dimensional, M-mode, and Doppler echocardiographic measurements were obtained on non-sedated, manually restrained standing dogs. Animals with no relevant echocardiographic abnormalities were used to generate reference intervals. Echocardiographic variables were compared between males and females and between dogs with and without mitral regurgitation (MR). Among the 117 CWDs, 103 dogs were used to generate reference intervals. The 14 dogs with abnormalities had more than trivial MR (12 dogs), subaortic stenosis (one dog), and equivocal subaortic stenosis (one dog). The 44 males were heavier than 59 females (P<0.001) and had a larger maximum left atrial dimension (P=0.015), left ventricular internal dimension at end-diastole (P<0.001) and systole (P<0.001), and thicker interventricular septum thickness at end-diastole (P=0.016). A positive linear correlation was identified between bodyweight and aortic root and left atrial diameters and left ventricular dimensions and between age and aortic root and left atrial diameter and peak late transmitral flow velocity. A negative linear correlation was identified between age and peak early transmitral flow velocity and the ratio between peak early and late transmitral flow velocities. No differences in echocardiographic-derived cardiac dimensions were detected between healthy dogs and dogs with more than trivial MR. In this population of CWDs, subclinical cardiac abnormalities were uncommon, and they were mainly classified as MR. [ABSTRACT FROM AUTHOR]

Background: The current bone marrow (BM) reference intervals (RI) are based on a limited number of cats. Age-related changes in BM variables might be important, possibly affecting the interpretation of the results. Objectives: Establish BM cytologic reference intervals (RIs) and association of age and sex on these findings, in healthy juvenile and young adult cats. Methods: BM aspirates of cats deemed healthy based on history and clinical, CBC, serum chemistry findings, and negative retrovirus serology were obtained and examined cytologically. The examination included a 1000-nucleated differential cell count and cell morphologic assessment. RIs were calculated using parametric, robust, and nonparametric methods. The cytologic findings were examined for associations with sex and age. Results: The study included 40 cats (females, 22 [55%]; males, 18 [45%]) with a median age of 1.5 years (range 0.5–5). Most calculated RIs were similar to those previously reported. BM plasma cell and monocyte counts were weakly and positively correlated with age (rs, .312 and .373, respectively; P< .05). Metarubricytes were higher in females (mean, 25.1%; SD, 6.0%) than males (mean, 21.2%; SD, 6.0%; P< .05). Conclusions: The BM differential cell counts determined in this study can serve as RIs for cats aged 0.5–5 years. [ABSTRACT FROM AUTHOR]

The study aims to establish trimester-specific reference ranges for serum iodine (SI) in Chinese pregnant women and explore its associations with maternal and infantile thyroid function. Apparently healthy pregnant women were enrolled during their first antenatal visit. Fasting venous and spot urine samples were collected for determining serum and urinary iodine (UI) levels by a validated inductively coupled plasma mass spectrometry. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), and neonatal TSH levels were tested by electro-chemiluminescent assay. The reference ranges of SI were established by percentile method and reported as 2.5–97.5%. ROC analysis was applied to compare the discriminative ability of SI, UI, and UI to urinary creatine ratio (UI /UCr) in early pregnancy for various thyroid conditions. The trimester-specific reference ranges of SI for Chinese pregnant women were 60.91–114.53 μg/L for the first trimester (T1, n = 1029), 54.57–103.42 μg/L for the second trimester (T2, n = 379), and 52.03–110.40 μg/L for the third trimester (T3, n = 455). Maternal SI at T1 but not UI and UI/UCr was significantly correlated with FT3 (r = 0.393, P < 0.001), FT4 (r = 0.637, P < 0.001), and TSH (r = −0.299, P<0.001). Maternal SI change% from T1 to T2 (but not SI change% from T1 to T3) had marginal correlation with neonatal TSH (r=−0.106, P=0.046). ROC analysis showed that maternal SI at T1 had better predictability for several thyroid conditions than UIC and UI/UCr. [ABSTRACT FROM AUTHOR]

Background: Reference intervals are essential for the interpretation of clinical laboratory tests and patient management. This study aims to determine age and gender reference intervals of complete blood count (CBC) in the Moroccan population by using the indirect approach. Methods: The study used data of ostensibly healthy adults collected retrospectively using the laboratory information system (LIS) of the Laboratory for Research and Medical Analysis of the Fraternal Royal Gendarmerie in Rabat (Morocco), between January 2018 and February 2020. The study included 5,898 men and 10,172 women ranging in age from 18 to 90 years. The lower and upper reference limits of CBC parameters were calculated using the nonparametric technique, as suggested by the Clinical and Laboratory Standards Institute (CLSI). Results: All hematological parameters showed no clinically significant gender-related differences, except small differences in the values of hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). There were also no clinically significant agerelated differences for median values of all hematology analytes in both genders, except for platelet count (PLT) that continued to decline with increasing age in men and women, and Red blood cell count (RBC), Hematocrit (HCT), and hemoglobin (HB) that tended to increase with age but decrease in older age groups in men while they tended to increase with age in women. Conclusions: The indirect method can be used to establish reference intervals for CBC, with appropriate selection criteria and statistical tools. Our findings differed from the reference ranges provided in the textbook and also in other countries' reports. [ABSTRACT FROM AUTHOR]

Introduction: To derive the reference intervals of serum soluble FMS like tyrosine kinase -1/Placental growth factor ratio in pregnant and non-pregnant females. Aims & Objectives: To derive the reference intervals of serum soluble FMS like tyrosine kinase -1/Placental growth factor ratio in pregnant and non-pregnant females. Place and Duration of Study: A comparative Cross-sectional study conducted in department of Chemical Pathology and Immunology, Chughtai Institute of Pathology, Lahore from February 2024 till May 2024 Material & Method: Blood samples from 120 pregnant and 120 non-pregnant females from 14±1 to 27±1 weeks were taken. All participants were of reproductive age group, disease free, non-hypertensive, non-diabetic, without any inherited or autoimmune disorders and not any significant drug history. Levels of placental growth factor (PGF) and soluble FMS like tyrosine kinase -1(sFlt-1) were estimated by Elecsys cobas e601. Data was analysed by SPSS 21. Shapiro-Wilk test and Kolmogorov Smirnov test were applied. p value

Objective: To determine the reference intervals (RI) for serum levels of IgG, IgM, and IgE in healthy children aged 1–10 years living in central Brazil. Method: A sample of 1743 healthy children was randomly selected from kindergartens and public schools. Reference intervals were defined by non-parametric rank (Clinical Laboratory Standards Institute, USA), bootstrapping, and Horn's robust methods. Results: By the rank method, the IgG RI was 792–1771 mg/dL for children of both sexes aged 1–10 years. IgM RI were different for gender and age groups, being 45–196 mg/dL and 34–190 mg/dL for boys aged 1–2 years and 3–10 years, respectively. For girls, the IgM RI were 50–212 mg/dL and 39–212 mg/dL, for ages 1–4 and 5–10 years, respectively. The IgE RI for both sexes and ages 1–10 years was 6–1005 mg/dL. The bootstrap method showed RI similar to the rank method but with slightly different confidence intervals. Horn's robust method determined RI different from those obtained by previous methods. Conclusion: RI for serum concentrations of IgG, IgM, and IgE were established for Brazilian children aged 1–10 years. This definition will be useful for Brazilian physicians, who will have more adequate parameters for their clinical decision-making.

Background: Studies have shown that there are racial and age-group differences in Reference Intervals (RI) of total Prostate-Specific Antigen (tPSA), its isoform [-2] pro PSA(p2PSA) and % p2PSA, Free PSA(fPSA) and %f PSA, and Prostate Health Index (PHI), all of which have been used for screening and diagnosis of prostate cancer. Aim and Objectives: To establish age-specific Reference Interval (RI) for these markers in Indian males. Materials and Methods: Four hundred and six subjects with tPSA£4ng/ml and negative transabdominal prostate ultrasound findings formed the study group in whom the markers tPSA, p2PSA, fPSA were estimated and %p2PSA, %fPSA and PHI were calculated. Results: About 98 (24.1%) were £50 years, 182 (44.8%) were between 50 -59 years and 126 (31%) were 60 years. The mean of tPSA, fPSA, p2PSAand PHI in 60 years age group were significantly more than £50 years age group across all percentiles. The overall RI (2.5 - 97.5 percentiles) for p2PSA, % p2PSA and PHI were 1.29 - 12.52 pg/mL, 0.65 - 3.82 and 8.08 - 66.42 respectively. Though there were some changes in the RI as the age increased, the 90% confidence intervals of the groups overlapped with one another. Conclusion: There is need for establishing and validating the age specific RI in healthy subjects belonging to a particular race and ethnicity for any biomarker.

Abstract Background A complete blood count (CBC) analysis is one of the most common conventional blood tests that physicians frequently prescribe. The objective of this study was to determine the reference intervals (RIs) of CBC parameters in the population of healthy adults living in the western Sudan region. Methods A cross-sectional study of healthy people residing in the western area of Sudan was carried out. We assessed the CBC RIs in samples taken from 153 individuals using an automated haematology analyser (Sysmex KX-21) and a modified Box–Cox transformation procedure to transform the data into a Gaussian distribution after eliminating outliers using the Dixon method. IBM SPSS Statistics version 25 was used to analyse the data, and t tests were employed to examine variations in the mean CBC parameters according to sex and age. P was considered significant at ≤ 0.05. Results Beyond all the other measured values, the only CBC parameters that significantly differed between the sexes were haemoglobin (HGB) and white blood cell (WBC) counts. Women were found to experience more WBC counts than men did. However, they have less HGB RIs.The male participants in our study exhibited lower WBC count RIs, a significantly lower limit, and a greater upper limit of platelet RIs than did the individuals from other nations. Conclusions Compared with males, females had higher platelet and WBC counts and lower HGB.

Abstract Background Circulating ceramide (Cer) drives various pathological processes associated with cardiovascular diseases, liver illness, and diabetes mellitus. Although recognized as predictors of cardiometabolic diseases (CMD) in research and clinical settings, their potential for predicting CMD risk in individuals under 18 remains unexplored. Objectives This study was designed to utilize Liquid Chromatography-Mass Spectrometry (LC-MS/MS) methodology to determine the biological reference ranges for Cer in plasma samples of Emirati children and develop a risk assessment score (CERT-1) based on Cer concentrations. Methods Using LC-MS/MS, we developed a method to measure five Cer species in plasma samples of 582 Emirati participants aged 5–17. We used the circulating concentrations of these Cer to determine their reference intervals in this population. We employed traditional statistical analyses to develop a risk score (CERT-1) and assess the association between Cer levels and conventional biomarkers of CMD. Results We validated a high-throughput methodology using LC–MS/MS to quantify five Cer species in human plasma. Reference values for this population (n = 582) were quantified: CerC16:0 (0.12–0.29 µmol/L), CerC18:0 (0.019–0.067 µmol/L), CerC22:0 (0.102–0.525 µmol/L), CerC24:0 (0.65–1.54 µmol/L) and CerC24:1 (0.212–0.945 µmol/L). We devised a risk assessment score (CERT-1) based on plasma Cer content in the study participants, showing that 72.5% have low to moderate risk and 9.3% are at a higher risk of developing CMD. Our analyses also revealed a significant correlation (P

A reference interval represents the normative range for measurements from a healthy population. It plays an important role in laboratory testing, as well as in differentiating healthy from diseased patients. The reference interval based on a single study might not be applicable to a broader population. Meta‐analysis can provide a more generalizable reference interval based on the combined population by synthesizing results from multiple studies. However, the assumptions of normally distributed underlying study‐specific means and equal within‐study variances, which are commonly used in existing methods, are strong and may not hold in practice. We propose a Bayesian nonparametric model with more flexible assumptions to extend random effects meta‐analysis for estimating reference intervals. We illustrate through simulation studies and two real data examples the performance of our proposed approach when the assumptions of normally distributed study means and equal within‐study variances do not hold. [ABSTRACT FROM AUTHOR]

Objective: To determine the reference intervals (RI) for serum levels of IgG, IgM, and IgE in healthy children aged 1-10 years living in central Brazil. Method: A sample of 1743 healthy children was randomly selected from kindergartens and public schools. Reference intervals were defined by non-parametric rank (Clinical Laboratory Standards Institute, USA), bootstrapping, and Horn-s robust methods. Results: By the rank method, the IgG RI was 792-1771 mg/dL for children of both sexes aged 1-10 years. IgM RI were different for gender and age groups, being 45-196 mg/dL and 34-190 mg/dL for boys aged 1-2 years and 3-10 years, respectively. For girls, the IgM RI were 50-212 mg/dL and 39-212 mg/dL, for ages 1-4 and 5-10 years, respectively. The IgE RI for both sexes and ages 1-10 years was 6-1005 mg/dL. The bootstrap method showed RI similar to the rank method but with slightly different confidence intervals. Horn-s robust method determined RI different from those obtained by previous methods. Conclusion: RI for serum concentrations of IgG, IgM, and IgE were established for Brazilian children aged 1-10 years. This definition will be useful for Brazilian physicians, who will have more adequate parameters for their clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that there are racial and age-group differences in Reference Intervals (RI) of total Prostate-Specific Antigen (tPSA), its isoform [-2] pro PSA(p2PSA) and % p2PSA, Free PSA(fPSA) and %f PSA, and Prostate Health Index (PHI), all of which have been used for screening and diagnosis of prostate cancer. Aim and Objectives: To establish age-specific RI) for these markers in Indian males. Materials and Methods: Four hundred and six subjects with tPSA£4ng/ml and negative transabdominal prostate ultrasound findings formed the study group in whom the markers tPSA, p2PSA, fPSAwere estimated and %p2PSA, %fPSAand PHI were calculated. Results: About 98 (24.1%) were £50 years, 182 (44.8%) were between 50 -59 years and 126 (31%) were ³ 60 years. The mean of tPSA, fPSA, p2PSAand PHI in ³ 60 years age group were significantly more than £50 years age th th group across all percentiles. The overall RI (2.5th - 97.5th percentiles) for p2PSA, % p2PSA and PHI were 1.29 - 12.52 pg/mL, 0.65 - 3.82 and 8.08 - 66.42 respectively. Though there were some changes in the RI as the age increased, the 90% confidence intervals of the groups overlapped with one another. Conclusion: There is need for establishing and validating the age specific RI in healthy subjects belonging to a particular race and ethnicity for any biomarker. [ABSTRACT FROM AUTHOR]

The Chinese sturgeon (Acipenser sinensis) is a critically endangered aquatic fish. Health monitoring and welfare assessments are critical for the conservation of Chinese sturgeon. In this study, biochemical parameters of serum and skin mucus in Chinese sturgeon were examined to evaluate the potential biomarkers. Serum and mucous samples were obtained from Chinese sturgeon, and the levels of total protein (TP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), lactic acid (LD), acid phosphatase (ACP), lysozyme (LYZ), glucose (GLU), and cortisol were determined. The concentrations of ALT, AST, cortisol, and LYZ were significantly higher in the mucous group than those in the serum group (p < 0.05). In addition, the concentrations of ALP, ACP, LD, LDH, CK, and TP were significantly higher level in the serum group than those in the mucous group (p < 0.05). Moreover, the correlations between serum and mucous biochemical parameters were established. Statistical analysis showed a positive correlation between serum and skin mucous markers (ACP, cortisol, and LYZ). AST versus ALT in serum and mucus showed a significant positive correlation (p < 0.01). A significant positive correlation was found between cortisol and CK in mucus (p < 0.01). Moreover, LD versus LDH in serum showed a significant but weak positive correlation (p < 0.01). Principal component analysis revealed a complete separation between the serum and mucous groups, with the biomarkers that contributed the most being ALP, TP, ALT, and AST. This study provides baseline data and reference intervals for serum and mucous biochemical parameters in presumably healthy Chinese sturgeons. The current study has important implications for the development of conservation strategies and the conservation status of critically endangered species. [ABSTRACT FROM AUTHOR]

Background: A complete blood count (CBC) analysis is one of the most common conventional blood tests that physicians frequently prescribe. The objective: of this study was to determine the reference intervals (RIs) of CBC parameters in the population of healthy adults living in the western Sudan region. Methods: A cross-sectional study of healthy people residing in the western area of Sudan was carried out. We assessed the CBC RIs in samples taken from 153 individuals using an automated haematology analyser (Sysmex KX-21) and a modified Box–Cox transformation procedure to transform the data into a Gaussian distribution after eliminating outliers using the Dixon method. IBM SPSS Statistics version 25 was used to analyse the data, and t tests were employed to examine variations in the mean CBC parameters according to sex and age. P was considered significant at ≤ 0.05. Results: Beyond all the other measured values, the only CBC parameters that significantly differed between the sexes were haemoglobin (HGB) and white blood cell (WBC) counts. Women were found to experience more WBC counts than men did. However, they have less HGB RIs.The male participants in our study exhibited lower WBC count RIs, a significantly lower limit, and a greater upper limit of platelet RIs than did the individuals from other nations. Conclusions: Compared with males, females had higher platelet and WBC counts and lower HGB. [ABSTRACT FROM AUTHOR]

Free light chain (FLC) assays and the ratio of κ/λ are recommended for diagnosis, prognosis and monitoring of plasma cell dyscrasias (PCD). Limited data exists on FLC clinical specificity in patients diagnosed with other conditions. We assessed the κ, λ, and κ/λ FLC ratio using the FreeLite assay and the Sebia FLC ELISA assay in 176 patients with clinical presentations of fatigue, anemia, polyclonal hypergammaglobulinemia, joint disorders, kidney disease and non PCD-cancers with no monoclonal protein observed on serum protein electrophoresis or MASS-FIX immunoglobulin isotyping. Manufacturer defined reference intervals (RI) and glomerular filtration rate (GFR) specific RI (renal RI) were utilized. For the κ/λ ratio, 68.7 % (121/176) of specimens on the FreeLite and 87.5 % (154/176) of specimens on the Sebia assay were within RI. For κ, 68.2 % (120/176) and 72.2 % (127/176) of results were outside RI for FreeLite and Sebia respectively. For λ, 37.5 % (66/176) and 84.1 % (148/176) of FreeLite and Sebia results were outside RI. With FreeLite and Sebia, patients with kidney disease (n=25) had the highest κ/λ ratios. 44 patients (25.0 %) had GFR <60 mL/min/BSA. When renal RI were applied, 13.6 % had a FLCr outside the renal RI with FreeLite, and 4.5 % with Sebia. In a cohort of patients with signs and symptoms suggestive of PCDs, but ultimately diagnosed with other conditions, Sebia FLC had improved clinical specificity relative to FreeLite, if one was using an abnormal κ/λ ratio as a surrogate for monoclonality. [ABSTRACT FROM AUTHOR]

Background: Circulating ceramide (Cer) drives various pathological processes associated with cardiovascular diseases, liver illness, and diabetes mellitus. Although recognized as predictors of cardiometabolic diseases (CMD) in research and clinical settings, their potential for predicting CMD risk in individuals under 18 remains unexplored. Objectives: This study was designed to utilize Liquid Chromatography-Mass Spectrometry (LC-MS/MS) methodology to determine the biological reference ranges for Cer in plasma samples of Emirati children and develop a risk assessment score (CERT-1) based on Cer concentrations. Methods: Using LC-MS/MS, we developed a method to measure five Cer species in plasma samples of 582 Emirati participants aged 5–17. We used the circulating concentrations of these Cer to determine their reference intervals in this population. We employed traditional statistical analyses to develop a risk score (CERT-1) and assess the association between Cer levels and conventional biomarkers of CMD. Results: We validated a high-throughput methodology using LC–MS/MS to quantify five Cer species in human plasma. Reference values for this population (n = 582) were quantified: CerC16:0 (0.12–0.29 µmol/L), CerC18:0 (0.019–0.067 µmol/L), CerC22:0 (0.102–0.525 µmol/L), CerC24:0 (0.65–1.54 µmol/L) and CerC24:1 (0.212–0.945 µmol/L). We devised a risk assessment score (CERT-1) based on plasma Cer content in the study participants, showing that 72.5% have low to moderate risk and 9.3% are at a higher risk of developing CMD. Our analyses also revealed a significant correlation (P < 0.05) between this score and the conventional risk factors linked to CMD, indicating its potential clinical implication. Conclusion: This study presents a clinical-scaled LC–MS/MS methodology for assessing clinically relevant Cer, setting reference ranges, and developing a risk score (CERT-1) for young Emirati individuals. Our findings can enhance primary risk prediction and inform the management and follow-up of CMD from an early age. [ABSTRACT FROM AUTHOR]

Simple Summary: This review addresses the health challenges of western-European hedgehogs in human environments, emphasizing their exposure to contaminants and diseases. As vital contributors to One Health studies, hedgehogs serve as indicators of environmental health. This study underscores the importance of comprehending their well-being via blood value exploration, which is crucial for identifying threats and ensuring their conservation. By analyzing the existing literature on hedgehog blood reference values, this review emphasizes the ongoing necessity for research to create a valuable tool for the assessment of species health. The western-European hedgehog (Erinaceus europaeus), in expanding its range towards human habitats, faces exposure to contaminants and biological agents, potentially leading to diseases associated with hematological and biochemical changes. As bioindicators of environmental pollution and carriers of zoonotic agents, hedgehogs play a crucial role in One Health studies, emphasizing the need for a comprehensive understanding of their clinical-pathological aspects. Exploring the blood reference values in healthy animals of this species is crucial for understanding and improving their well-being, and identifying possible diseases/pathogens that may affect its conservation and/or impact human health. This review is focused on analyzing the data available in the literature for Erinaceus europaeus blood reference intervals. A comprehensive literature review of the studies published in Europe is performed, highlighting their specificities, and emphasizing the need for continuous research in this field. Our final goal is to provide a crucial tool for assessing the health status of the species, and underscoring the significance of research in this specific domain. [ABSTRACT FROM AUTHOR]

Simple Summary: Miranda's donkey is a breed from the north of Portugal, considered endangered. Knowledge of its physiological and pathological conditions is essential to assist in the conservation of this breed. The objective of our study was to determine reference intervals for twenty-one blood biochemistry parameters and to evaluate the influence of gender and age on these parameters. Several parameters were influenced by gender and age, emphasizing the importance of taking these factors into account during the interpretation of clinical results by veterinarians. The RIs described here can be used to evaluate and monitor the health status of animals and herds, thus contributing to the preservation of this breed. Miranda's donkey is an endangered, autochthone breed from Northern Portugal. Understanding the physiological and pathological conditions of Miranda's donkey is crucial for the conservation of the breed. Our study aimed to establish reference intervals (RIs) for blood biochemistry parameters and to evaluate the influence of gender and age on these parameters. Blood samples from 75 clinically healthy animals were analyzed for 21 blood biochemistry parameters using Respons® 920 and Start® 4-Diagnostica-Stago. RIs were calculated according to the ASVCP guidelines, utilizing Reference Advisor software V. 2.1 and the statistical program SPSS version 29 to analyze the effects of gender and age. Significant gender-related differences (p < 0.05) were observed in cholesterol, chlorine, creatinine (CREA), glucose (GLU), sodium, and triglycerides (with higher values in females) and in aspartate aminotransferase, creatine phosphokinase (CK), gamma-glutamyl transferase, potassium, magnesium (Mg), and urea (with higher values in males). Age-related differences (p < 0.05) were noted for alkaline phosphatase, CK, fibrinogen, GLU, and phosphorus (higher in young animals) and for globulin, Mg, and total protein (higher in adults). The RIs described here are invaluable for assessing and monitoring the health status of individual animals and herds. Our study highlights the importance of considering gender and age in the interpretation of biochemical parameters, providing critical insights for the conservation and management of this endangered breed. [ABSTRACT FROM AUTHOR]