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Background: Androgen could impact cervical remodeling during pregnancy, and a higher level is associated with adverse pregnancy outcomes. A population-based gestation age-specific reference interval of total testosterone (TT), androstenedione (A4), and 17-hydroxyprogesterone (17-OHP) can help to diagnose maternal hyperandrogenism., Methods: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation. The serum androgen profile was measured by liquid chromatography-tandem mass spectrometry. The equations for medians of TT, A4, and 17-OHP were generated by MedCal, and the variances adjusted for 2-level modeling were generated by MLwiN, a system for the specification and analysis of a range of multilevel models., Results: A4 and TT levels increased across the gestation, and they closely correlated with each other (R = .90, P = <.001), whereas the 17-OHP level decreased from the 5th gestational week to the 16th gestational week and then increased afterward toward the end of pregnancy. Women diagnosed with preeclampsia (PE) were found to have a significantly higher level of A4, TT, and 17-OHP when compared with non-PE cases with P≤ .01, whereas mothers carrying male vs female fetuses have comparable levels of A4, TT, and 17-OHP., Conclusion: The study highlights a methodology for constructing gestational age-specific TT, A4, and 17-OHP levels to provide a better interpretation of results in a cohort of healthy Chinese women. The observation in PE supports previous findings, and the higher levels of TT, A4, and 17-OHP were observed before the onset of PE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

In this computer simulation study, we examine four different statistical approaches of linearity assessment, including two variants of deviation from linearity (individual (IDL) and averaged (AD)), along with detection capabilities of residuals of linear regression (individual and averaged). From the results of the simulation, the following broad suggestions are provided to laboratory practitioners when performing linearity assessment. A high imprecision can challenge linearity investigations by producing a high false positive rate or low power of detection. Therefore, the imprecision of the measurement procedure should be considered when interpreting linearity assessment results. In the presence of high imprecision, the results of linearity assessment should be interpreted with caution. Different linearity assessment approaches examined in this study performed well under different analytical scenarios. For optimal outcomes, a considered and tailored study design should be implemented. With the exception of specific scenarios, both ADL and IDL methods were suboptimal for the assessment of linearity compared. When imprecision is low (3 %), averaged residual of linear regression with triplicate measurements and a non-linearity acceptance limit of 5 % produces <5 % false positive rates and a high power for detection of non-linearity of >70 % across different types and degrees of non-linearity. Detection of departures from linearity are difficult to identify in practice and enhanced methods of detection need development., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the Laboratory Evaluation and Analytical Performance Characteristics (LEAP) checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners.

Reporting a measurement procedure and its analytical performance following method evaluation in a peer-reviewed journal is an important means for clinical laboratory practitioners to share their findings. It also represents an important source of evidence base to help others make informed decisions about their practice. At present, there are significant variations in the information reported in laboratory medicine journal publications describing the analytical performance of measurement procedures. These variations also challenge authors, readers, reviewers, and editors in deciding the quality of a submitted manuscript. The International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Method Evaluation Protocols (IFCC WG-MEP) developed a checklist and recommends its adoption to enable a consistent approach to reporting method evaluation and analytical performance characteristics of measurement procedures in laboratory medicine journals. It is envisioned that the LEAP checklist will improve the standardisation of journal publications describing method evaluation and analytical performance characteristics, improving the quality of the evidence base that is relied upon by practitioners., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children's LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life., Methods: This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children's glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction., Results: Sex- and age-adjusted children's LTL was found to be associated with children's HOMA-IR (β=-0.046 ± 0.016, p=0.005). Interestingly, both children's and maternal post-load glucose levels were positively associated with children's LTL. However, negative associations were observed between children's LTL and children's OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels., Conclusions: Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response., (© 2022. The Author(s).)

Background: Circadian dysregulation has long been thought to be a key component in the pathophysiology of bipolar disorder (BD). However, it remains unclear whether this dysregulation constitutes a risk factor, manifestation, or consequence of BD. This study aimed to compare dim light melatonin secretion patterns between unaffected offspring of parents with BD (OBD) and offspring of control parents (OCP)., Methods: This case-control study included unaffected OBD (mean age 14.0 years; male 50.0 %) and age- and sex-matched OCP (mean age 13.0 years; male: 43.5 %). Seventeen saliva samples were collected in dim light conditions. Dim light melatonin onset (DLMO), phase angles, and area under the curve (AUC) were calculated., Results: 185 saliva samples from 12 OBD (n = 12) and 741 from OCP (n = 46) were collected. Unaffected OBD had a significant lower nocturnal melatonin level (14.8 ± 4.6 vs. 20.3 ± 11.7 pg/mL) and a smaller melatonin AUC within two hours after DLMO (35.5 ± 11.3 vs. 44.6 ± 18.1 pg/mL) but a significant larger phase angle between DLMO and sleep onset (2.2 ± 1.0 vs. 1.4 ± 1.2 h) than OCP. There was no significant between-group difference in DLMO. The graphic illustrations showed a considerably flattened melatonin secretion in unaffected OBD., Limitations: The main limitations include lack of 24-h dim melatonin secretion measurement, large age range of participants, and small sample size., Conclusions: These findings suggest that unaffected OBD already presented with circadian rhythm dysregulations. Future investigations are needed to clarify the role of abnormal melatonin secretion in the onset of BD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chronotype, referred to as an individual's diurnal preference of timing for rest and activity, can be subjectively measured using the Munich Chronotype Questionnaire (MCTQ). However, the validity of MCTQ has yet to be tested in the youth population. In addition, it remains uncertain if MCTQ is a good measure of chronotype in individuals with insomnia. The current study aimed to validate the Chinese version of MCTQ (MCTQ HK ) in the youth population and to explore the utility of MCTQ HK in individuals with insomnia. The original MCTQ was translated into Chinese language using the translation-back-translation method. Part one of this study included 988 youths who completed a battery of self-report questionnaires online consisting of the MCTQ HK and the morningness-eveningness questionnaire (MEQ) for the measures of circadian preference, Insomnia Severity Index (ISI) to assess insomnia symptoms, and Patient Health Questionnaire (PHQ-9) to measure depressive symptoms. Test-retest reliability was examined in 442 participants at one-month follow-up. Of the overall sample, 69 participants were randomly drawn to complete the second part of the study, which included prospective 7-day actigraphy monitoring and a further subset (n = 40) additionally completed a laboratory-based assessment of dim-light melatonin onset (DLMO) as a circadian phase marker. A total of 659 participants with valid responses were finally included in the analyses of the data collected from part one of the study (female = 67.7%; mean age: 20.7 ± 2.02). Results showed that MCTQ parameters, namely the midpoint of sleep on free days (MSF), midpoint of sleep on workdays (MSW), and midpoint of sleep adjusted for sleep debt (MSFsc), were significantly correlated with MEQ score (r = -.514 to -.650, p < .01). Test-retest reliability for MCTQ HK was good (intraclass correlation = 0.75 to 0.84). Later MSFsc was significantly associated with greater insomnia and depressive symptoms after controlling for age and sex. All MCTQ parameters showed significant correlations with actigraphy-based midpoint of sleep and circadian rhythm parameters, i.e., acrophase and L5 onset (r = .362 to .619, p < .01), as well as DLMO (r = .393 to .517, p < .05). The associations remained significant after controlling for age. MSFsc derived from MCTQ was significantly correlated with MEQ score in both the healthy sleepers and participants with insomnia (as defined by ISI > 14), r = -.600, p < .001 and r = -.543, p < .001, respectively. The present study demonstrated that MCTQ HK is suitable for assessing chronotype with good reliability and validity in Chinese youths and supported the utility of MCTQ HK in individuals with insomnia.

Liquid chromatography mass spectrometry (LC-MS) is a widely used technique in the clinical laboratory, especially for small molecule quantitation in biological specimens, for example, steroid hormones and therapeutic drugs. Analysis of circulating macromolecules, including proteins and peptides, is largely dominated by traditional enzymatic, spectrophotometric, or immunological assays in clinical laboratories. However, these methodologies are known to be subjected to interfering substances, for example heterophilic antibodies, as well as subjected to non-specificity issues. In recent years, there has been a growing interest in using LC-MS platforms for protein analysis in the clinical setting, due to the superior specificity compared to immunoassay, and the possibility of simultaneous quantitation of multiple proteins. Different analytical approaches are possible using LC-MS-based methodology, including accurate mass measurement of intact molecules, protein digestion followed by detection of proteolytic peptides, and in combination with immunoaffinity purification. Proteins with different complexity, isoforms, variants, or chemical alteration can be simultaneously analysed by LC-MS, either by targeted or non-targeted approaches. While the LC-MS platform offers a more specific determination of proteins, there remain issues of LC-MS assay harmonization, correlation with current existing platforms, and the potential impact in making clinical decision. In this review, the clinical utility, historical aspect, and challenges in using LC-MS for protein analysis in the clinical setting will be discussed, using insulin-like growth factor (IGF) as an example.