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Mitochondrial 26-hydroxylation of exogenous cholesterol, endogenous cholesterol, and 5β-cholestane-3α,7α,12α-triol was studied. 26-Hydroxylation of endogenous cholesterol was measured by mass fragmentography. NADPH and isocitrate stimulated 26-hydroxylation of endogenous as well as exogenous cholesterol. 26-Hydroxylation of endogenous cholesterol was linear with time for 15 min, whereas that of exogenous cholesterol was linear with time for at least 40 min. This finding indicates that the fractions of exogenous and endogenous cholesterol that were 26-hydroxylated did not equilibrate. Mg2+ stimulated isocitrate- and NADPH-dependent 26-hydroxylation of exogenous cholesterol but inhibited in the case of endogenous cholesterol. Ca2+ stimulated NADPH-dependent and inhibited isocitrate-dependent 26-hydroxylation of both exogenous and endogenous cholesterol. It is suggested that the differing effect of Mg2+ on the 26-hydroxylation of exogenous and endogenous cholesterol is related to transfer of the steroid to the enzyme. Isocitrate- and NADPH-dependent 26-hydroxylation of exogenous 5β-cholestane-3α,7α,12α-triol differed from that of exogenous cholesterol in response to Mg2+ and Ca2+. 26-Hydroxylation of 5β-cholestane-3α,7α,12α-triol was stimulated by Mg2+ in low concentrations but inhibited by Mg2+ and Ca2+ in high concentrations. Mg2+ had the same influence on the 26-hydroxylation of three dioxygenated C27-steroids known to be intermediates in bile acid biosynthesis. The results are not only compatible with heterogeneity of the mitochondrial 26-hydroxylase system but also with differences in the transport of cholesterol and 5β-cholestane-3α,7α,12α-triol to the enzyme. The finding of a differing effect of Mg2+ on 26-hydroxylation of exogenous and endogenous cholesterol seems to favor differences in transport rather than heterogeneity of the 26-hydroxylase as an explanation of the results.

The effect of biliary obstruction on side chain hydroxylations in the biosynthesis and metabolism of bile acids was studied in the rat. For comparison, several other hydroxylation reactions in bile acid biosynthesis and metabolism were assayed. Biliary obstruction inhibited microsomal 26-hydroxylation of 5β-cholestane-3α,7α-diol and microsomal 25- and 26-hydroxylation of 5β-cholestane-3α,7α-12α-triol. Microsomal 7α-hydroxylation of cholesterol and 6β-hydroxylation of lithocholic acid acid increased significantly, whereas the increase in microsomal 12α-hydroxylation of 5β-cholestane-3α,7α-diol was less. Mitochondrial 26-hydroxylation of cholesterol, 5-cholestene-3β,7α-diol, and 7α-hydroxy-4-cholesten-3-one was stimulated, whereas 26-hydroxylation of 5β-cholestane-3α,7α-diol was not affected and that of 5β-cholestane-3α,7α,12α-triol was markedly inhibited. The results indicate that mitochondrial 26-hydroxylation, particularly of substrates that primarily are precursors of chenodeoxycholic acid, plays a more important role in bile acid biosynthesis under conditions of biliary obstruction than under normal conditions.

The metabolism of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid was studied in the bile fistula rats and in preparations from rat liver homogenates. In the bile fistula rats, the main products were chenodeoxycholic acid, alpha-muricholic acid, and beta-muricholic acid. Only small amounts of cholic acid were formed. Incubations of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid with microsomes and NADPH yielded as the main product 3 alpha, 6 beta, 7 alpha-trihydroxy-5 beta-cholestanoic acid. The formation of small amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5 beta-cholestanoic acid was shown. The major product in incubations of 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid with microsomes and the 100,000 g supernatant fluid fortified with ATP was identified as 3 alpha, 7 alpha, 24 xi-trihydroxy-5 beta-cholestanoic acid. This compound was converted into chenodeoxycholic acid and its metabolites in the bile fistula rat.

Several hydroxylase activities in bile acid biosynthesis were assayed in subcellular fractions of human fetal liver. The livers were obtained at legal abortions performed between gestational weeks 14 and 24. Microsomal 12 alpha-hydroxylase and mitochondrial 12 alpha- and 26-hydroxylase activities were detected from week 14. The microsomal fraction also had capacity for 25-hydroxylation, whereas 7 alpha- and 26-hydroxylase activities were hardly detectable. The variation of the hydroxylase activities between different experiments can be explained by inactivation during the abortion or workup procedure. The results are discussed with respect to earlier studies of bile acid biosynthesis during development and adult life.

Background: The aim was to compare bias and precision for 177 Lu-SPECT activity-concentration estimation using a dual-headed Anger SPECT system and a ring-configured CZT SPECT system. This was investigated for imaging at 208 keV and 113 keV, respectively., Methods: Phantom experiments were performed on a GE Discovery 670 system with 5/8'' NaI(Tl) crystal (dual-headed Anger system) and a GE StarGuide (ring-configured CZT system). Six spheres (1.2 mL to 113 mL) in a NEMA PET body phantom were filled with 99m Tc and 177 Lu, separately. Mean relative errors and coefficients of variation (CV) in estimated sphere activity concentration were studied over six timeframes of 10 min each for the two systems. For 177 Lu, similar acquisitions were also performed for an anthropomorphic phantom with two spheres (10 mL and 25 mL) in a liver with non-radioactive background and a sphere-to-background ratio of 15:1. Tomographic reconstruction was performed using OS-EM with 10 subsets with compensation for attenuation, scatter, and distance-dependent spatial resolution. For the Anger system, up to 40 iterations were used and for the ring-configured CZT system up to 30 iterations were used., Results: The two systems showed similar mean relative errors and CVs for 177 Lu when using an energy window around 208 keV, while the ring-configured system demonstrated a lower bias for a similar CV compared to the Anger system for 99m Tc and for 177 Lu when using an energy window around 113 keV. However, total activity in the phantom tended to be overestimated in both systems for these cases., Conclusions: The ring-configured CZT system is a viable alternative to the dual-headed Anger system equipped with medium-energy collimators for 177 Lu-SPECT and shows a potential advantage for activity-concentration estimation when operated at 113 keV. However, further consideration of the preservation of total activity is warranted., (© 2024. The Author(s).)

The genomic signature of an organism captures the characteristics of repeated oligonucleotide patterns in its genome 1 , such as oligomer frequencies, GC content, and differences in codon usage. Viruses, however, are obligate intracellular parasites that are dependent on their host cells for replication, and information about genomic signatures in viruses has hitherto been sparse.Here, we investigate the presence and specificity of genomic signatures in 2,768 eukaryotic viral species from 105 viral families, aiming to illuminate dependencies and selective pressures in viral genome evolution. We demonstrate that most viruses have highly specific genomic signatures that often also differ significantly between species within the same family. The species-specificity is most prominent among dsDNA viruses and viruses with large genomes. We also reveal consistent dissimilarities between viral genomic signatures and those of their host cells, although some viruses present slight similarities, which may be explained by genetic adaptation to their native hosts. Our results suggest that significant evolutionary selection pressures act upon viral genomes to shape and preserve their genomic signatures, which may have implications for the field of synthetic biology in the construction of live attenuated vaccines and viral vectors., (© 2024. The Author(s).)

The term 'RNA-seq' refers to a collection of assays based on sequencing experiments that involve quantifying RNA species from bulk tissue, single cells or single nuclei. The kallisto, bustools and kb-python programs are free, open-source software tools for performing this analysis that together can produce gene expression quantification from raw sequencing reads. The quantifications can be individualized for multiple cells, multiple samples or both. Additionally, these tools allow gene expression values to be classified as originating from nascent RNA species or mature RNA species, making this workflow amenable to both cell-based and nucleus-based assays. This protocol describes in detail how to use kallisto and bustools in conjunction with a wrapper, kb-python, to preprocess RNA-seq data. Execution of this protocol requires basic familiarity with a command line environment. With this protocol, quantification of a moderately sized RNA-seq dataset can be completed within minutes., (© 2024. Springer Nature Limited.)

Background: The aim was to investigate the noise and bias properties of quantitative 177 Lu-SPECT with respect to the number of projection angles, and the number of subsets and iterations in the OS-EM reconstruction, for different total acquisition times., Methods: Experimental SPECT acquisition of six spheres in a NEMA body phantom filled with 177 Lu was performed, using medium-energy collimators and 120 projections with 180 s per projection. Bootstrapping was applied to generate data sets representing acquisitions with 20 to 120 projections for 10 min, 20 min, and 40 min, with 32 noise realizations per setting. Monte Carlo simulations were performed of 177 Lu-DOTA-TATE in an anthropomorphic computer phantom with three tumours (2.8 mL to 40.0 mL). Projections representing 24 h and 168 h post administration were simulated, each with 32 noise realizations. Images were reconstructed using OS-EM with compensation for attenuation, scatter, and distance-dependent resolution. The number of subsets and iterations were varied within a constrained range of the product number of iterations × number of projections ≤ 2400 . Volumes-of-interest were defined following the physical size of the spheres and tumours, the mean activity-concentrations estimated, and the absolute mean relative error and coefficient of variation (CV) over noise realizations calculated. Pareto fronts were established by analysis of CV versus mean relative error., Results: Points at the Pareto fronts with low CV and high mean error resulted from using a low number of subsets, whilst points at the Pareto fronts associated with high CV but low mean error resulted from reconstructions with a high number of subsets. The number of projection angles had limited impact., Conclusions: For accurate estimation of the 177 Lu activity-concentration from SPECT images, the number of projection angles has limited importance, whilst the total acquisition time and the number of subsets and iterations are parameters of importance., (© 2024. The Author(s).)

Purpose: Gender differences have been found in the outcomes of vocational rehabilitation (VR) and in Supported Employment (SE), therefore, the purpose of this study was to explore employment specialists' (ES) social representations of gender in relation to work and VR and how these social representations influence the ES's work in the VR process according to SE., Methods: The qualitative method of focus group discussions was employed. Ten focus groups were held with 39 ESs from four categories of SE organizations in Sweden. Topic analysis was applied to the transcribed material from the focus groups., Results: Five themes with different social representations about gender and disability in relation to VR and working life formed in the analysis: (1) differences in personal and health factors among VR-participants, (2) gender norms in society influencing VR, (3) energy-intensive environmental issues influencing VR, (4) gender-specific interactions in VR, and (5) gendered paths in the welfare system., Conclusion: Social representations of higher strains on women with disabilities compared to men with disabilities both in private and working life, which reflect the lived experiences of the ESs, is a possible explanation for gender differences in VR and working life for persons with disabilities.IMPLICATIONS FOR REHABILITATIONGender differences in the outcomes of vocational rehabilitation (VR) interventions have been noticed worldwide. In this study, pervasive social representations about gender and disability in relation to VR were found, but also unconsciousness about gender among VR professionals. Therefore, awareness of gender is necessary in VR.Individualized and person-centered approaches to VR like Supported Employment, although considered best practice, might hide structures like gender, which could lead to reproducing discriminating processes and therefore not achieving gender equality in VR. Therefore, knowledge of discrimination is important in VR.Gender-sensitivity in vocational rehabilitation models with a person-centered and individualized approach is needed and there might also be a need to systematically tailor vocational rehabilitation models to reach gender equality in the outcomes of the interventions. Therefore, gender equality indicators are needed for VR models, to evaluate model effectiveness from a gender perspective.

Peptide receptor radionuclide therapy presents the possibility of tracing and quantifying the uptake of the drug in the body and performing dosimetry, potentially allowing individualization of treatment schemes. However, the details of how neuroendocrine tumors (NETs) respond to different absorbed doses are insufficiently known. Here, we investigated the relationship between tumor-absorbed dose and tumor response in a cohort of patients with NETs treated with [ 177 Lu]Lu-DOTATATE. Methods: This was a retrospective study based on 69 tumors in 32 patients treated within a clinical trial. Dosimetry was performed at each cycle of [ 177 Lu]Lu-DOTATATE, rendering 366 individual absorbed dose assessments. Hybrid planar-SPECT/CT imaging using [ 177 Lu]Lu-DOTATATE was used, including quantitative SPECT reconstruction, voxel-based absorbed dose rate calculation, semiautomatic image segmentation, and partial-volume correction. Changes in tumor volume were used to determine tumor response. The volume for each tumor was manually delineated on consecutive CT scans, giving a total of 712 individual tumor volume assessments. Tumors were stratified according to grade. The relationship between absorbed dose and response was investigated using mixed-effects models and logistic regression. Tumors smaller than 4 cm 3 were excluded. Results: In grade 2 NETs, a clear relationship between absorbed dose and volume reduction was observed. Our observations suggest a 90% probability of partial tumor response for an accumulated tumor-absorbed dose of at least 135 Gy. Conclusion: Our findings are in accordance with previous observations regarding the relationship between tumor shrinkage and absorbed dose. Moreover, our data suggest an absorbed dose threshold for partial response in grade 2 NETs. These observations provide valuable insights for the design of dosimetry-guided peptide receptor radionuclide therapy schemes., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Although the importance of quantitative SPECT has increased tremendously due to newly developed therapeutic radiopharmaceuticals, there are still no accreditation programs to harmonize SPECT imaging. Work is currently underway to develop an accreditation for quantitative 177 Lu SPECT/CT. The aim of this study is to verify whether the positioning of the spheres within the phantom has an influence on the recovery and thus needs to be considered in SPECT harmonization. In addition, the effects of these recovery coefficients on a potential partial volume correction as well as absorbed-dose estimates are investigated., Methods: Using a low-dose CT of a SPECT/CT acquisition, a computerized version of the NEMA body phantom was created using a semi-automatic threshold-based method. Based on the mass-density map, the detector orbit, and the sphere centers, realistic SPECT acquisitions of all possible 720 sphere configurations of both the PET and the SPECT versions of the NEMA Body Phantom were generated using Monte Carlo simulations. SPECT reconstructions with different numbers of updates were performed without (CASToR) and with resolution modeling (STIR). Recovery coefficients were calculated for all permutations, reconstruction methods, and phantoms, and their dependence on the sphere positioning was investigated. Finally, the simulation-based findings were validated using SPECT/CT acquisitions of six different sphere configurations., Results: Our analysis shows that sphere positioning has a significant impact on the recovery for both of the reconstruction methods and the phantom type. Although resolution modeling resulted in significantly higher recovery, the relative variation in recovery within the 720 permutations was even larger. When examining the extreme values of the recovery, reconstructions without resolution modeling were influenced primarily by the sphere position, while with resolution modeling the volume of the two adjacent spheres had a larger influence. The SPECT measurements confirmed these observations, and the recovery curves showed good overall agreement with the simulated data., Conclusion: Our study shows that sphere positioning has a significant impact on the recovery obtained in NEMA sphere phantom measurements and should therefore be considered in a future SPECT accreditation. Furthermore, the single-measurement method normally performed for PVC should be reconsidered to account for the position dependency., (© 2024. The Author(s).)

Purpose: The aim of the current study was to explore the construct validity and internal consistency reliability of the International Classification of Functioning, Disability and Health (ICF)-based original English version of the Hearing and Functioning in Everyday Life Questionnaire (HFEQ) and to revise the HFEQ based on the results., Method: This study used a cross-sectional survey design. The data were collected using an online survey. Adults with self-reported hearing disability ( n = 513) from the United States were included. The ICF components of body functions, activity and participation, and environmental factors were tested as the underlying structure of the HFEQ using confirmatory factor analysis and then adjusted by triangulation with previous content validation., Results: The results of the current study confirmed the ICF components of body functions, activity and participation, and environmental factors as underlying constructs of the HFEQ. However, after triangulation with previous content validation, fine adjustments were made. The revised version of the HFEQ includes two removed items and a fine-tuned factor structure., Conclusion: The results confirm that the structure of the HFEQ aligns with the ICF, and the overall results indicate that HFEQ has acceptable construct validity and internal consistency.

With the development of new radiopharmaceutical therapies, quantitative SPECT/CT has progressively emerged as a crucial tool for dosimetry. One major obstacle of SPECT is its poor resolution, which results in blurring of the activity distribution. Especially for small objects, this so-called partial-volume effect limits the accuracy of activity quantification. Numerous methods for partial-volume correction (PVC) have been proposed, but most methods have the disadvantage of assuming a spatially invariant resolution of the imaging system, which does not hold for SPECT. Furthermore, most methods require a segmentation based on anatomic information. Methods: We introduce DL-PVC, a methodology for PVC of 177 Lu SPECT/CT imaging using deep learning (DL). Training was based on a dataset of 10,000 random activity distributions placed in extended cardiac-torso body phantoms. Realistic SPECT acquisitions were created using the SIMIND Monte Carlo simulation program. SPECT reconstructions without and with resolution modeling were performed using the CASToR and STIR reconstruction software, respectively. The pairs of ground-truth activity distributions and simulated SPECT images were used for training various U-Nets. Quantitative analysis of the performance of these U-Nets was based on metrics such as the structural similarity index measure or normalized root-mean-square error, but also on volume activity accuracy, a new metric that describes the fraction of voxels in which the determined activity concentration deviates from the true activity concentration by less than a certain margin. On the basis of this analysis, the optimal parameters for normalization, input size, and network architecture were identified. Results: Our simulation-based analysis revealed that DL-PVC (0.95/7.8%/35.8% for structural similarity index measure/normalized root-mean-square error/volume activity accuracy) outperforms SPECT without PVC (0.89/10.4%/12.1%) and after iterative Yang PVC (0.94/8.6%/15.1%). Additionally, we validated DL-PVC on 177 Lu SPECT/CT measurements of 3-dimensionally printed phantoms of different geometries. Although DL-PVC showed activity recovery similar to that of the iterative Yang method, no segmentation was required. In addition, DL-PVC was able to correct other image artifacts such as Gibbs ringing, making it clearly superior at the voxel level. Conclusion: In this work, we demonstrate the added value of DL-PVC for quantitative 177 Lu SPECT/CT. Our analysis validates the functionality of DL-PVC and paves the way for future deployment on clinical image data., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Aim: We aimed to evaluate the occurrence of, and risk factors for precocious and early puberty in a retrospective cohort study of girls with shunted infantile hydrocephalus., Methods: The study population comprised 82 girls with infantile hydrocephalus, born between 1980 and 2002, and treated with a ventriculoperitoneal shunt. Data were available for 39 girls with myelomeningocele and 34 without. Medical records were analysed regarding clinical data and timing of puberty. Precocious and early puberty was defined as the appearance of pubertal signs before 8 years and 0 months and 8 years and 9 months, respectively., Results: Median age at last admission was 15.8 years (range 10.0-18.0). In total, 15 girls (21%) had precocious puberty, and another 21 (29%) had early puberty. Three or more shunt revisions had been performed in 26/36 girls with early or precocious puberty and in 3/37 girls without (p = 0.01). The number of shunt revisions correlated negatively with age at the start of puberty in the girls with myelomeningocele (Spearman's correlation coefficient = -0.512, p = 0.001)., Conclusion: Girls with shunted infantile hydrocephalus have a high risk of precocious or early puberty. Repeated shunt revisions seemed to be associated with early puberty., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Purpose: The aim was to investigate the use of multiple small VOIs for kidney dosimetry in [ 177 Lu]Lu-DOTA-TATE therapy., Method: The study was based on patient and simulated SPECT images in anthropomorphic geometries. Images were reconstructed using two reconstruction programs (local LundaDose and commercial Hermia) using OS-EM with and without resolution recovery (RR). Five small VOIs were placed to determine the average activity concentration (AC) in each kidney. The study consisted of three steps: (i) determination of the number of iterations for AC convergence based on simulated images; (ii) determination of recovery-coefficients (RCs) for 2 mL VOIs using a separate set of simulated images; (iii) assessment of operator variability in AC estimates for simulated and patient images. Five operators placed the VOIs, using for guidance: a) SPECT/CT with RR, b) SPECT/CT without RR, and c) CT only. For simulated images, time-integrated ACs (TIACs) were evaluated. For patient images, estimated ACs were compared with results of a previous method based on whole-kidney VOIs., Results: Eight iterations and ten subsets were sufficient for both programs and reconstruction settings. Mean RCs (mean ± SD) with RR were 1.03 ± 0.02 (LundaDose) and 1.10 ± 0.03 (Hermia), and without RR 0.91 ± 0.03 (LundaDose) and 0.94 ± 0.03 (Hermia). Most stable and accurate estimates of the AC were obtained using five 2-mL VOIs guided by SPECT/CT with RR, applying them to images without RR, and including an explicit RC for recovery correction., Conclusion: The small VOI method based on five 2-mL VOIs was found efficient and sufficiently accurate for kidney dosimetry in [ 177 Lu]Lu-DOTA-TATE therapy., 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 © 2024. Published by Elsevier Ltd.)

Single-cell technologies have been widely used in biological studies and generated a plethora of single-cell data to be interpreted. Due to the inclusion of the priori metabolic network knowledge as well as gene-protein-reaction associations, genome-scale metabolic models (GEMs) have been a powerful tool to integrate and thereby interpret various omics data mostly from bulk samples. Here, we first review two common ways to leverage bulk omics data with GEMs and then discuss advances on integrative analysis of single-cell omics data with GEMs. We end by presenting our views on current challenges and perspectives in this field., 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 © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Genome-scale metabolic models (GEMs) are computational representations that enable mathematical exploration of metabolic behaviors within cellular and environmental constraints. Despite their wide usage in biotechnology, biomedicine and fundamental studies, there are many phenotypes that GEMs are unable to correctly predict. GECKO is a method to improve the predictive power of a GEM by incorporating enzymatic constraints using kinetic and omics data. GECKO has enabled reconstruction of enzyme-constrained metabolic models (ecModels) for diverse organisms, which show better predictive performance than conventional GEMs. In this protocol, we describe how to use the latest version GECKO 3.0; the procedure has five stages: (1) expansion from a starting metabolic model to an ecModel structure, (2) integration of enzyme turnover numbers into the ecModel structure, (3) model tuning, (4) integration of proteomics data into the ecModel and (5) simulation and analysis of ecModels. GECKO 3.0 incorporates deep learning-predicted enzyme kinetics, paving the way for improved metabolic models for virtually any organism and cell line in the absence of experimental data. The time of running the whole protocol is organism dependent, e.g., ~5 h for yeast., (© 2024. Springer Nature Limited.)

Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [ 177 Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software., Methods: A combined PBPK model for [ 68 Ga]Ga-DOTA-TATE and [ 177 Lu]Lu-DOTA-TATE was developed and implemented in both SAAM II and SimBiology. A retrospective analysis of 12 patients with metastatic neuroendocrine tumours (NETs) was conducted. First, time-activity curves (TACs) and TIAs from the two software were calculated and compared for identical parameter values. Second, pharmacokinetic parameters were fitted to activity concentrations, analysed and compared., Results: The PBPK model implemented in SimBiology produced TIA results comparable to those generated by the model implemented in SAAM II, with a relative deviation of less than 0.5% when using the same input parameters. The relative deviation of the fitted TIAs was less than 5% when model parameter values were fitted to the measured activity concentrations., Conclusion: The proposed PBPK model implemented in SimBiology can be used for dosimetry in radioligand therapy and TIA prediction. Its outputs are similar to those generated by the PBPK model implemented in SAAM II, confirming the correctness of the model implementation in SimBiology., 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 © 2024 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease. This cross-sectional study included 165 children (91 males, median age 6.9 yr range 0.2-17.7 yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen. Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes -45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure. In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: The prevalence of teenage pregnancy in Colombia is higher than the worldwide average. The identification of socio-geographical disparities might help to prioritize public health interventions., Aim: To describe variation in the probability of teenage maternity across geopolitical departments and socio-geographical intersectional strata in Colombia., Methods: A cross-sectional study based on live birth certificates in Colombia. Teenage maternity was defined as a woman giving birth aged 19 or younger. Multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was applied using multilevel Poisson and logistic regression. Two different approaches were used: (1) intersectional: using strata defined by the combination of health insurance, region, area of residency, and ethnicity as the second level (2) geographical: using geopolitical departments as the second level. Null, partial, and full models were obtained. General contextual effect (GCE) based on the variance partition coefficient (VPC) was considered as the measure of disparity. Proportional change in variance (PCV) was used to identify the contribution of each variable to the between-strata variation and to identify whether this variation, if any, was due to additive or interaction effects. Residuals were used to identify strata with potential higher-order interactions., Results: The prevalence of teenage mothers in Colombia was 18.30% (95% CI 18.20-18.40). The highest prevalence was observed in Vichada, 25.65% (95% CI: 23.71-27.78), and in the stratum containing mothers with Subsidized/Unaffiliated healthcare insurance, Mestizo, Rural area in the Caribbean region, 29.08% (95% CI 28.55-29.61). The VPC from the null model was 1.70% and 9.16% using the geographical and socio-geographical intersectional approaches, respectively. The higher PCV for the intersectional model was attributed to health insurance. Positive and negative interactions of effects were observed., Conclusion: Disparities were observed between intersectional socio-geographical strata but not between geo-political departments. Our results indicate that if resources for prevention are limited, using an intersectional socio-geographical approach would be more effective than focusing on geopolitical departments especially when focusing resources on those groups which show the highest prevalence. MAIHDA could potentially be applied to many other health outcomes where resource decisions must be made., (© 2024. The Author(s).)