Lower Z-scores Research Articles

The impact of age, disease severity, and BMI on bone health and growth in children and young people with Crohn'sdisease.

The objective of this study was to explore the correlation between paediatric Crohn's disease (CD)characteristics, bone health and growth parameters at diagnosis and follow-up. Retrospective data was collected for 47 children aged 4-16 who were newly diagnosed with CD between January 2018 and December 2019. Mean follow-up time was 2.5 years. Eleven (24%) children had growth delay at diagnosis, which persisted in 4 (44%) of 9 recorded children at follow-up. Of the 35 children tested, 20 (57%) had inadequate Vitamin D levels (<50 mmol/L) at diagnosis. Thirty-seven (79%) children had a dual-energy X-ray absorptiometry scan at diagnosis, with 20 of them having at least 1 low Z-score. Children with poorer bone mineral density and bone mineral concentration Z-scores for age had a younger age at diagnosis (p = .042 and p = .021), more severe disease (p = .04 and p = .029) and a lower BMI (p < .001) at diagnosis. Children diagnosed with CD ≥11 years had a lower-than-expected height velocity (p < .0001 and p < .001). Multivariate regression analysis demonstrated an older age of diagnosis was a significant predictor of a lower height velocity at follow-up. Disease severity and age of diagnosis are important CD-related factors that influence bone health and growth. Vitamin D is an accessible component that if optimised can improve all three factors. Monitoring and optimising each aspect systematically has the potential to enable children to achieve their bone health and growth potentials.

Genetic susceptibility and late bone outcomes in childhood acute lymphoblastic leukemia survivors.

Childhood acute lymphoblastic leukemia (cALL) survivors are at increased risk for bone comorbidities, but accurate screening tools for such comorbidities are limited. Polygenic scores (PGS) could stratify cALL survivors for risk of long-term adverse bone outcomes. We evaluated 214 (51% female) cALL survivors from the Prévenir les Effets TArdifs de la LEucémie study (median age 21yr). Bone mineral density (BMD) measurements were obtained using dual X-ray absorptiometry at the lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and vertebral fractures (VF) were documented using the vertebral deformity criterion. We computed a PGS for adult heel quantitative ultrasound speed of sound (gSOS), known to be associated with the risk of osteoporotic fracture, using imputed genotype data of the participants, and tested it for association with BMD Z-scores and VF risk, adjusting for clinical risk factors, and in sex and prognostic risk-stratified analyses. We found that a gSOS below the mean was associated with lower BMD in all three sites in univariate and multivariate models. In univariate analyses, 1 SD increase in gSOS conferred a 0.16 SD increase in LS-BMD (95% CI 0.005-0.31), whereas a gSOS above the mean was associated with a 0.31 SD higher LS-BMD (95% CI 0.008-0.61), a 0.36 SD higher TB-BMD (95% CI 0.06-0.67), and a 0.43 SD higher FN-BMD (95% CI 0.13-0.72). Models combining gSOS with clinical risk factors explained up to 16% of the variance of BMD phenotypes and obtained an area under the receiver operating characteristic curve for VF of 0.77 in subgroup analyses. Cranial radiation, high cumulative glucocorticoid doses, high risk group, and male sex were significant risk factors for lower BMD Z-scores. In conclusion, a PGS, in combination with clinical risk factors, could be used as a tool to risk stratify cALL survivors for treatment-related bone morbidity.

Bone mineral density in young adults 5 to 11 years after adolescent metabolic and bariatric surgery for severe obesity compared to peers.

Metabolic and bariatric surgery (MBS) is associated with decreased bone mineral density (BMD) in adults. The long-term impact of MBS during adolescence on BMD is unknown. We report bone health status 5 to 11 years after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) from the Teen-LABS study cohort. Between 2016 and 2022, BMD was measured by dual energy x-ray absorptiometry (DXA) in 106 young adults who had undergone MBS as adolescents. Volumetric BMD by peripheral quantitative computed tomography was measured on a subset. Ninety-one controls who had not undergone MBS were recruited for comparison. In cases (RYGB: mean age 26.8 ± 1.9 years, mean BMI 42.1 ± 9.9 kg/m2, VSG: mean age 25.1 ± 2.1 years, mean BMI 37.1 ± 8.4 kg/m2), compared to controls (mean age 26.5 ± 2.7 years, mean BMI 40.2 ± 8.7 kg/m2) (age p < 0.001, BMI p = 0.02), adjusted mean DXA-BMD (g/cm2) of the RYGB (n = 58) and VSG (n = 48) groups were lower at the hip (-10.0% and -6.3%), femoral neck (-9.6% and -5.7%) and ultra-distal radius (-7.9% and -7.0%; all p < 0.001), respectively. DXA-BMD did not differ between RYGB and VSG groups. Trabecular volumetric BMD at the radius and tibia were lower in the RYGB (-30% and -26%) and VSG (-15% and -14%) groups compared to the control group (p < 0.001). Greater time since MBS was associated with lower BMD Z-scores at the hip (p = 0.05) and femoral neck (p = 0.045). Percent change in body mass index (BMI) from baseline or in the first year after MBS were not associated with bone measures at a median of 9.3 years post MBS. BMD, especially of the hip and femoral neck, was lower in young adults who underwent MBS during adolescence compared to matched peers who had not undergone MBS. BMD Z-scores of the femoral neck were inversely associated with time since MBS but were not associated with BMI change.

Association of Anatomical Location of Neuroarthropathic (Charcot's) Destruction with Age-and Sex-Matched Bone Mineral Density Reduction.

It is well documented that diabetes has a systemic impact on bone mineral density. Recent literature has evaluated the relationship between the development of Charcot neuroarthropathy and reduced local bone mineral density; however, it is not clear if there is an association between osteoporosis/osteopenia and Charcot onset, or, even further, location of neuroarthropathic breakdown. We retrospectively identified and assessed 39 patients with 41 feet (4 bilateral) with a history of Charcot breakdown who underwent a bone mineral density scan over a 15-year period. Demographic, radiographic, and bone mineral density information was analyzed. The average patient age at the time of bone mineral density scan was 53.44 ± 8.09 years, and 52.77 ± 8.19 years at the time of Charcot diagnosis. Four feet were considered Sanders-Frykberg I (9.3%), 17 were Sanders-Frykberg II (39.5%), ten were Sanders-Frykberg III (23.3%), and 12 were Sanders-Frkyberg IV/V (27.9%). Neuroarthropathic breakdown of the rearfoot region (Sanders-Frykberg IV/V) was found to be associated and preceded by osteoporosis and osteopenia at the hip as demonstrated by a lower Z-score (P = 0.05). Charcot neuroarthropathy was not associated with poor bone health or loss of bone mineral density at the femoral neck, forearm, or lumbar spine. We believe that the present findings suggest a possible relationship between osteoporosis/osteopenia and the location of CN development. With these findings in mind, we conclude that patients with diabetic skeletal fragility may benefit from treatment of underlying poor bone mineral density to prevent the onset of Charcot neuroarthropathy.

Inpatient Growth in Infants Requiring Pharmacologic Treatment for Neonatal Opioid Withdrawal Syndrome.

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short-acting opioids (SAOs), long-acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed-effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z-score of -0.19 at birth and decreased to a median of -0.72 at discharge. Exposure to SAO was associated with an increase in Z-scores nearing discharge across all growth parameters (Z-score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z-scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z-score for weight trends. Male infants had a decrease in Z-scores for weight (male -0.96, female -0.59, interaction p = 0.06) and length (male -1.17, female -0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z-scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z-scores for length and occipital frontal circumference (OFC).

Parents' Knowledge and Skills in Feeding, Children's Response to Feeding on the Nutritional Status of Toddlers with Malnutrition Problems

Malnutrition, notably stunting, significantly impacts children's health and development, particularly during the first 1000 days of life. The prevalence of stunting in Indonesia is notably high, affecting approximately 30% of children under five in 2019, with Kediri Regency reporting a prevalence rate of 10.23% in 2022. The aim of this research is to analyze the influence of parental knowledge and skills in improving nutritional status as well as children's responses to feeding on the nutritional status of children with malnutrition problems. The research design used in this research is a pre-experimental one group pre-test post-test design. The sampling technique was total sampling with respondents in this study being 22 underprivileged families with toddlers who had nutritional problems and stunting in the Gempolan Village area. The problem of malnutrition in toddlers is quite high with an average Z Score of -2.42 (BB/U), -2.46 (TB/U), and -1.53 (BB/TB). Pre-test data on parents' knowledge and ability to fulfill children's nutrition shows that 68% have fairly good knowledge and skills and only 9% have good knowledge and skills. In this study, 50% of respondents had a fairly good response to feeding. The data highlights a significant problem of malnutrition in toddlers, characterized by low Z-Scores indicating undernutrition and growth stunting. These low Z-Scores pose substantial health risks, including compromised growth, weakened immunity, and potential long-term health issues. Parental knowledge and skills in nutrition are crucial, with most parents having reasonable knowledge levels. However, feeding problems persist, contributing to food rejection by children, exacerbating malnutrition.

SERUM SOLUBLE ALPHA-KLOTHO AND COGNITIVE FUNCTIONING IN OLDER ADULTS AGED 60 AND 79

Abstract Objectives We aimed to examine the association of serum soluble alpha-klotho with cognitive functioning among older adults using a nationally representative sample of U.S. older adults. Method: A total of 2,173 U.S. older adults aged 60-79 years in the National Health and Nutrition Examination Survey 2011 to 2014 were included. Serum soluble alpha-klotho was measured in the laboratory. Cognitive function was measured using the Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest (CERAD-WL) immediate and delayed memory, the Animal fluency test (AFT), and the Digit Symbol Substitution Test (DSST). Test-specific and global cognition z-scores were calculated based on sample means and standard deviations. Multivariable linear regression models were applied to examine the association of quartiles of serum soluble alpha-klotho with test-specific and global cognition z-scores. Subgroup analysis was conducted by sex. The following covariates were included in the analysis- age, sex, race/ethnicity, education, depressive symptoms, smoking status, body mass index (BMI), physical activity, stroke, prevalent coronary heart disease, total cholesterol, and systolic blood pressure. Results Serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (beta [β] =-0.13, 95% confidence interval [CI]: -0.25, -0.01). For subgroup analysis, serum soluble alpha-klotho level in the lowest quartile was associated with lower z-scores for DSST (β=-0.16, 95% CI: -0.32, -0.003) and global cognition (β=-0.14, 95% CI: -0.28, -0.01) among female participants. No significant association was found among male participants. Conclusions Lower serum soluble alpha-klotho level was associated with poorer cognitive functioning among older women.

Influence of efavirenz and 8-hydroxy-efavirenz plasma levels on cognition and central nervous system side effects.

To investigate whether efavirenz (EFV) or 8-hydroxy-EFV (8-OH-EFV) plasma levels are associated with neurocognitive impairment and central nervous system (CNS) side effects. We conducted a cross-sectional analysis to explore the potential links between EFV/8-OH-EFV levels and cognitive performance or CNS-related side effects in patients screened within a randomized trial involving a switch from EFV to rilpivirine. The Mann-Whitney test was employed to compare drug levels in patients with or without cognitive impairment, depression, anxiety, sleep disorder or CNS symptoms. Additionally, Spearman's test was used to assess correlations between drug levels and test scores. Among 104 patients, neither EFV nor 8-OH-EFV levels were linked to cognitive impairment, although trends towards higher EFV levels were observed in those with impaired executive function (p = 0.055) and language performances (p = 0.021). On the other hand, elevated 8-OH-EFV levels, but not EFV levels, were associated with more CNS side effects (222 vs. 151 ng/mL, p = 0.027), depressive symptoms (247 vs. 164 ng/mL, p = 0.067) and sleep impairment (247 vs. 164 ng/mL, p = 0.078). Consistently, a trend towards a correlation between EFV levels and lower z-scores in executive function and motor function was observed, while 8-OH-EFV levels, but not EFV levels, were directly correlated with symptom scores. Higher levels of 8-OH-EFV were associated with CNS side effects, while EFV levels were only marginally associated with cognitive performance, thus suggesting that EFV and its metabolite may act differently in determining detrimental neurological effects.

The Relationship Between Anthropometric Z-Score Measurements and Ocular Structures in Turkish Children.

Objective (Aim): This study explores the contact between anthropometric Z-score values and ocular parameters in children. Recent studies investigated the relationship, and contact between anthropometric measurements and ocular parameters in children, and height, weight, body mass index, and percentile curves are mostly used as anthropometric data. However, today, different scoring systems such as "Z-score" classify anthropometric values. Methods: Height and body mass index Z-scores were calculated for 725 children. Biometric and refractive measurements of all children were noted. For different reference values, those with a Z-score below the negative value of the reference were defined as a low Z-score, those between the negative and positive value of the reference were defined as a normal Z-score, those with a Z-score greater than the positive value of the reference were defined as a high Z-score. The mean ocular measurement results in the low, normal, and high Z-score groups were compared, and they were pointed to reach the reference value in both negative and positive sides which created the foremost critical contrast between the groups. Results: For a value of "-1" and "+1.5" in the height Z-score, from low to normal and from there to high Z-score group, axial length, and average corneal radius increased, and average corneal power decreased significantly. Anterior chamber depth increased from normal to high Z-score group, but no critical distinction was made between low and normal Z-score groups. Moreover, no critical distinction was observed in spherical equivalent refraction, central corneal thickness for height, and all values of body mass index. Conclusion: Considering a Z-score value of "-1" and "+1.5" as a reference value in children and anticipating the changes that may happen in the ocular structures of children at both ends of the Z-score, it may be useful to understand the effect of body development on ocular development more. Abbreviations: AL = Axial Length, ACD = Anterior Chamber Depth, BMI = Body Mass Index, NCHS = The United States National Center for Health Statistics, WHO = World Health Organization, NFHS 2 = National Family Health Survey 2, SER = Spherical Equivalent Refraction, CR = Average Corneal Radius, CP = Average Corneal Power, CCT = Central Corneal Thickness, HFAsZ = Height for Age Z-Score, BMIsZ = BMI for Age Z-Score, L = Low Z-score, N = Normal Z-score, H = High Z-score.

Association between gut microbiota at 3.5 years of age and body mass index at 5 years: results from two French nationwide birth cohorts.

The relationship between gut microbiota and changes in body mass index (BMI) or pediatric overweight in early life remains unclear, and information regarding the preterm population is scarce. This study aimed to investigate how the gut microbiota at 3.5 years of age is associated with (1) later BMI at 5 years, and (2) BMI z-score variations between 2 and 5 years in children from two French nationwide birth cohorts. Bacterial 16S rRNA gene sequencing was performed to profile the gut microbiota at 3.5 years of age in preterm children (n = 143, EPIPAGE 2 cohort) and late preterm/full-term children (n = 369, ELFE cohort). The predicted abundances of metabolic functions were computed using PICRUSt2. Anthropometric measurements were collected at 2 and 5 years of age during medical examinations or retrieved from children's health records. Statistical analyses included multivariable linear and logistic regressions, random forest variable selection, and MiRKAT. The Firmicutes to Bacteroidetes (F/B) ratio at 3.5 years was positively associated with the BMI z-score at 5 years. Several genera were positively ([Eubacterium] hallii group, Fusicatenibacter, and [Eubacterium] ventriosum group) or negatively (Eggerthella, Colidextribacter, and Ruminococcaceae CAG-352) associated with the BMI z-scores at 5 years. Some genera were also associated with variations in the BMI z-scores between 2 and 5 years of age. Predicted metabolic functions, including steroid hormone biosynthesis, biotin metabolism, glycosaminoglycan degradation, and amino sugar and nucleotide sugar metabolism, were associated with lower BMI z-scores at 5 years. The unsaturated fatty acids biosynthesis pathway was associated with higher BMI z-scores. These findings indicate that the gut microbiota at 3.5 years is associated with later BMI during childhood, independent of preterm or term birth, suggesting that changes in the gut microbiota that may predispose to adult obesity begin in early childhood.

Changes in dietary habits and BMI z-score after a 6-month non-randomized cluster-controlled trial among 6-12 years old overweight and obese Norwegian children.

Effective prevention programs to address the high prevalence of childhood overweight and obesity and the concomitant health consequences have been warranted. To improve dietary habits and weight status among Norwegian children with overweight/obesity in the primary care setting. A 6-month non-randomized cluster-controlled intervention among 137 children, aged 6-12 years, with overweight/obesity and their parents. Intervention and control groups were recruited by public health nurses and followed-up by 12 Healthy Life Centers across Norway. The intervention group received individual family counseling and participated in nutrition courses and physical activity groups. A frequency questionnaire assessing sociodemographic characteristics and dietary habits was completed by the parents. Trained public health nurses measured height and weight using standardized methods to calculate body mass index (BMI) and BMI z-scores. The intervention resulted in an increased odds of consuming evening meals (OR: 3.42), a decreased availability of salty snacks (β = -0.17), a decreased intake of salty snacks (-0.18), an increased consumption of water (β = 0.20), and a decreased estimated total intake of energy (β = -0.17), carbohydrates (β = -0.17), mono- and disaccharides (β = -0.21), sucrose (β = -0.24), and saturated fatty acids (β = -0.17). The intervention directly predicted lower BMI z-score (β = -0.17), and post-treatment levels of energy (β = -0.65), saturated fat (β = 0.43), and total carbohydrates (β = 0.41) were directly linked to BMI z-score after intervention. Age and sex were indirectly associated with BMI after intervention through energy and saturated fat intake. The intervention had a beneficial impact on nutrient intake and weight status among children with overweight/obesity. These findings provide support for implementing complex intervention programs tailored to local primary care settings. Clinicaltrials.gov, NCT02290171. Registered 13. November 2014, https://clinicaltrials.gov/ct2/show/NCT02290171.

Risk Factors of Low Bone Mineral Density in Newly Diagnosed Pediatric Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with an increasing worldwide incidence. IBD is frequently diagnosed during childhood in the adolescent period of ongoing growth and development, and it can affect patients' linear growth, puberty, nutrition, and bone health. Therefore, its treatment and monitoring are critical to prevent secondary outcomes. However, few studies have highlighted the association between pediatric IBD and skeletal outcomes in Asian populations. We aimed to identify the prevalence and risk factors for low bone mineral density (BMD) in Korean children and adolescents with newly diagnosed IBD. Patients aged 10-18 years diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) who underwent lumbar spine bone mineral density (LSBMD) and femoral bone mineral density (FBMD) analyses via dual-energy X-ray absorptiometry at the time of IBD diagnosis were included. Low BMD was considered when the age- and sex-matched BMD Z-score was <-1.0. The LSBMD and FBMD Z-scores were correlated with clinical parameters, including general characteristics, anthropometry, and IBD-associated laboratory markers. Regression analyses were performed to identify the risk factors for low BMD. Although the general characteristics between CD (n = 42) and UC (n = 9) groups did not differ, the mean Z-scores of LSBMD and FBMD of the 51 subjects were -0.11 ± 1.24 and -0.58 ± 1.38, respectively. Furthermore, 7.8% and 18% of the study subjects had LSBMD and FBMD Z-scores < -2.0, whereas more than 50% had scores of 0--1.0. Among the clinical factors, body mass index (BMI) Z-score, duration of clinical manifestations, and serum alanine aminotransferase and selenium levels were associated with LSBMD Z-scores in the final multivariate regression analyses. Odds ratios of BMI < -2.0 standard deviation for low LSBMD and FBMD Z-scores were 31.97 and 41.45, respectively. A BMI Z-score < -0.93 was determined as the best cut-off for predicting low BMD. In newly diagnosed pediatric IBD, a substantial number of children are likely to have low BMD in prior to initial treatment while lower BMI, longer duration of clinical manifestation, and higher selenium concentration could affect initial BMD status. Routine bone health surveillance from initial IBD diagnosis throughout the treatment's completion is recommended for preventing the early development of secondary osteoporosis.

Assessment of risk factors for osteopenia development in premature babies

Neonatal osteopenia (KB 61.3 (ICD-11)) – violation of mineral exchange of bone tissue (BT) of premature babies (PB). Predicting and detection of osteopenia is the key to its successful control.&#x0D; Aim. The aim of the article was to determine risk factors influencing the formation of neonatal osteopenia of PB and during the term of intensive care / postintensive nursing.&#x0D; Materials and methods. Ultrasound densitometer Sunlight Omnisense 9000 was used to measure the ultrasound speed in BT (SOS, m/s) with estimation Z-score (SD) according to gestational age of 56 PB and 20 mature babies (control group) in the early neonatal age. Verification of osteopenia was carried out under the WHO guidelines for radiation methods by Z-score indicator less than SD by -1.0. Estimation of Z-score -2.0 SD and less was attributed to ultra-low indicators. The characteristics of obstetric and gynecological, somatic anamnesis and pregnancy course of premature babies’ mothers, factors of PB postnatal development that influence the formation of BT were studied.&#x0D; Results. Children born at 33 weeks or earlier are 3.23 times more likely (OR = 3.23; CI 95 % [1.08; 9.70]) to develop BT demineralization by the corresponding term of birth than other PB. The chances of ultra-low SOS by Z-score are 14.22 times higher (OR = 14.22; CI 95 % [3.29; 61.57]) in PB born at 32 weeks of gestation and earlier. Extragenital diseases, clinical signs of calcium deficiency in mothers, and women’s intake of calcium and vitamin D3 during pregnancy did not have a statistically significant difference (p &gt; 0.05) in the studied PB and control group. The mother’s preeclampsia increases the chances of insufficient BT mineralization by 5.47 times (OR = 5.47; CI 95 % [1.07; 27.93]), second parity pregnancy (and subsequent ones) – by 4.51 times (OR = 4.51, CI 95 % [1.38; 14.80]). The factors of the ratio of the duration of mechanical ventilation relative to the total time of PB treatment, the duration of parenteral feeding have an inverse correlation (moderate (r = -0.42, р &lt; 0.05) and significant (r = -0.51, р &lt; 0.05) respectively) with a decrease in SOS to low Z-score.&#x0D; Conclusions. In PB born at 32 weeks of gestation and earlier, the chances of ultra-low SOS indicators by Z-score are 14.22 times higher (OR = 14.22; CI 95 % [3.29; 61.57]). The following factors predicts insufficient mineralization of BT according to SOS indicators according to the Z-score: mother’s second parity pregnancy (and subsequent ones), preeclampsia, parenteral feeding of PB for more than 8 days (Se = 75.00 %, Sp = 71.87 %, p &lt; 0.0001), duration of mechanical ventilation, which is more than 6.48 % of the total time of PB treatment (Se = 86.67 %, Sp = 59.38 %, p &lt; 0.046).

Extreme deviations from the normative model reveal cortical heterogeneity and associations with negative symptom severity in first-episode psychosis from the OPTiMiSE and GAP studies

There is currently no quantifiable method to predict long-term clinical outcomes in patients presenting with a first episode of psychosis. A major barrier to developing useful markers for this is biological heterogeneity, where many different pathological mechanisms may underly the same set of symptoms in different individuals. Normative modelling has been used to quantify this heterogeneity in established psychotic disorders by identifying regions of the cortex which are thinner than expected based on a normative healthy population range. These brain atypicalities are measured at the individual level and therefore potentially useful in a clinical setting. However, it is still unclear whether alterations in individual brain structure can be detected at the time of the first psychotic episode, and whether they are associated with subsequent clinical outcomes. We applied normative modelling of cortical thickness to a sample of first-episode psychosis patients, with the aim of quantifying heterogeneity and to use any pattern of cortical atypicality to predict symptoms and response to antipsychotic medication at timepoints from baseline up to 95 weeks (median follow-ups = 4). T1-weighted brain magnetic resonance images from the GAP and OPTiMiSE samples were processed with Freesurfer V6.0.0 yielding 148 cortical thickness features. An existing normative model of cortical thickness (n = 37,126) was adapted to integrate data from each clinical site and account for effects of gender and site. Our test sample consisted of control participants (n = 149, mean age = 26, SD = 6.7) and patient data (n = 295, mean age = 26, SD = 6.7), this sample was used for estimating deviations from the normative model and subsequent statistical analysis. For each individual, the 148 cortical thickness features were mapped to centiles of the normative distribution and converted to z-scores reflecting the distance from the population mean. Individual cortical thickness metrics of +/– 2.6 standard deviations from the mean were considered extreme deviations from the norm. We found that no more than 6.4% of psychosis patients had extreme deviations in a single brain region (regional overlap) demonstrating a high degree of heterogeneity. Mann-Whitney U tests were run on z-scores for each region and significantly lower z-scores were observed in FEP patients in the frontal, temporal, parietal and occipital lobes. Finally, linear mixed-effects modelling showed that negative deviations in cortical thickness in parietal and temporal regions at baseline are related to more severe negative symptoms over the medium-term. This study shows that even at the early stage of symptom onset normative modelling provides a framework to identify individualised cortical markers which can be used for early personalised intervention and stratification.

Association between Low Bone Mineral Density and Pain in a Prospective Cohort of Adults with Sickle Cell Disease: Preliminary Results from the SCD Bone Pain Study

Background: Osteonecrosis (ON), a prevalent skeletal complication of sickle cell disease (SCD), typically associates with severe chronic pain, frequent acute care utilization, and permanent disability. We previously showed that low bone mineral density (BMD) independently associates with hip ON and chronic pain in a pediatric SCD cohort. We now present preliminary data on the association between low BMD and pain in a prospective cohort of adults enrolled in the SCD Bone Pain Study (NCT05283148). Methods: Written informed consent was obtained from all participants, who were recruited from ambulatory adults with SCD seen at the University of California Davis Comprehensive Cancer Center. All participants underwent dual-energy X-ray absorptiometry (DXA) scans of their lumbar spine, left hip, and left forearm. Vertebral fractures were assessed by thoracolumbar morphometry in the DXA scanner. All participants also completed the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact questionnaire. We used linear regression to evaluate the association between ASCQ-Me pain scores and low BMD (categorically defined as BMD Z-score ≤ -2 at any DXA site). We also used linear regression to determine the association between ASCQ-Me pain scores and continuous total hip and lumbar spine BMD Z-scores. Lastly, we evaluated the impact of other covariates on pain scores, with low BMD or BMD Z-scores included in the least absolute shrinkage and selection operator (LASSO, no shrinkage). Results: Thirty adults (median age 34.5 years [20-67 years]) completed the study between Nov 2022-Jul 2023. Baseline characteristics are summarized in Table 1. There was a borderline significant association between low BMD and lower (worse) pain scores (p=0.077). Continuous BMD Z-scores of the total hip (p=0.081) and lumbar spine (p=0.024) were independently associated with higher (better) pain scores. In addition to low BMD, only white blood cell count (WBC), indirect bilirubin, and vitamin D were identified as possible covariates (all had non-zero coefficients in LASSO analysis). Low BMD was significantly associated with pain (p=0.024), even after adjusting for WBC, indirect bilirubin, and vitamin D (Table 2). Similarly, we found that higher hip (p=0.059) and lumbar (p=0.027) BMD Z-scores were associated with higher (better) pain scores, despite adjusting for the same confounders. Discussion: We found low BMD in 12 of 30 (40%) adults enrolled in the SCD Bone Pain Study. Like other chronic hemolytic anemias, compensatory increased erythropoiesis leads to trabeculae degradation, cortical bone thinning, and eventual low bone mass. Lumbar vertebrae comprises mostly of trabecular bone, while the hip joint has mostly cortical bone. This might explain why mean lumbar BMD Z-scores were lower than hip BMD Z-scores (Table 1), and why lumbar spine BMD Z-scores directly and significantly correlated with pain scores (Table 2). These preliminary data suggest that pain is more prevalent in SCD adults with low BMD than those with normal BMD as we previously reported in a pediatric SCD cohort. Pain scores decrease (worsen) with increasing WBC, which suggests an inflammatory component to chronic SCD pain. Contrary to expectation, higher indirect bilirubin (a marker of increased hemolysis) significantly correlated with higher (better) pain scores. Similarly, higher vitamin D (a proxy for bone health) correlated with lower (worse) pain scores, though this association was non-significant. The reason(s) for these counterintuitive associations between pain scores, indirect bilirubin, and vitamin D levels is currently unknown. Limitations include a small sample size, though using the LASSO method for multivariate regression adjusted for this. Further, low BMD causality could not be determined at this time. Recruitment is ongoing with an enrollment target of 50 adults with SCD by Nov 2023. Analysis are ongoing to determine if SCD-modifying therapies will impact the association between low BMD and pain. Bone biomarker studies are also pending. Further, the thoracolumbar morphometry is still undergoing radiologic review, so we can further assess how vertebral compression fractures (i) correlate with pain scores, and/or (ii) attenuate the association between low BMD and pain. Identifying and treating risk factors for low BMD may alleviate bone pain and potentially improve quality of life for all people with SCD.

Using the altman’s Z-score formula to assess the financial situation of military construction enterprises in Vietnam

Military construction enterprises are classified as defense economic enterprises and are subject to regulation by two legal systems: the State’s legal system for regulating enterprises in general and provisions of law on national defense. As a result, military construction enterprises have unique characteristics that distinguish them from other enterprises. These characteristics include the organizational form, capital mobilization form, depreciation management, receivable management, and profits distribution of military construction enterprises. This study uses data from financial statements of 22 military construction enterprises from 2015 to 2019 including both joint stock companies and 100% state-owned enterprises to calculate the Altman Z-score formula. The Altman Z-score is a linear combination of four or five common business ratios, weighted by coefficients. Z-scores are used to predict corporate defaults and an easy-to-calculate control measure for the financial distress status of enterprises with high reliability. Due to the difference between military construction enterprises and conventional enterprises, the Altman model is applied in the article to evaluate the financial status of military construction enterprises. The research results show that the decrease in business efficiency causes the ratio of revenue and profit to total assets of military construction enterprises to decrease sharply, the proportion of working capital in total assets is low. Furthermore, the ratio of equity to total debt is the most important reason to make low Z-score that means prediction of a high risk of bankruptcy in military construction enterprises. An evidence base from the research results is used for making a number of proposals to reduce the risk of bankruptcy and improving the efficiency of financial management of enterprises.

Demographic, Clinical, and Laboratory Characteristics of Children with Renal Tubular Acidosis

This study included patients followed up for primary renal tubular acidosis (RTA) between 1991 and 2012. Clinical characteristics at presentation, physical examination findings, laboratory test results, and treatments were recorded. The patients’ laboratory results, drug doses, height, and weight were recorded every 3 months for the first year of follow-up. Standard deviation scores (Z-scores) of height and weight for age were determined and the patients’ growth rates were evaluated. Of 50 patients followed up for primary RTA, 31 (62%) had distal RTA and 19 (38%) had proximal RTA. The median age at diagnosis was 3 months (range, 1-174 months) for patients with distal RTA and 10 months (range, 2-33 months) for patients with proximal RTA. The median follow-up times in these two groups were 96 months (range, 6-204 months) and 89 months (range, 6-180 months), respectively. Family history of RTA was more common among patients with distal RTA than those with proximal RTA (p=0.013). Nephrocalcinosis and deafness were detected more frequently in the distal RTA group (p=0.001), while ocular pathologies were more common in the proximal RTA group (p&lt;0.001). In patients with distal RTA, older age at diagnosis was associated with lower weight and height Z-scores (p&lt;0.05). Early diagnosis had a positive effect on the growth of patients with primary RTA.

Differential sex-association between PCSK1 polymorphisms and obesity risk in Portuguese children.

The proprotein convertase subtilisin/Kexin type 1 gene (PCSK1) is implicated in hypothalamic appetite control. Several studies have addressed the relationship between PCSK1 polymorphisms and obesity, although conflicting results were observed. We tested the potential association of four PCSK1 variants with the risk of overweight/obesity and related variables in Portuguese children. This is a case-control study, where four PCSK1 variants, rs6230 (c.-101T>C), rs6232 (p.N221D), rs6235 (p.S690T), and rs3811942 (c.*265T>C), were analyzed in Portuguese children (aged 5-13 years-old). Anthropometric measures were objectively collected and used to provide weight-for-age, height-for-age, and body mass index (BMI) for age. The indices generated were compared to standard reference values of WHO to obtain the corresponding Z-scores. Logistic regression, in the dominant model, revealed no significant associations between the four individual PCSK1 variants and the risk of overweight/obesity in the total population. However, stratifying the sample by sex, a marginally significant association was found between the rs6235 minor C-allele and increased overweight/obesity in boys (n = 345) (OR 1.55 [1.01-2.38] p = .044), but not in girls (n = 340) (OR 0.73 [0.46-1.14] p = .169). Consistently, boys with genotype GG presented lower BMI Z-score (0.62) when compared to those with the genotypes GC + CC (1.04). Testing for different effects in males versus females, a significant interaction was found between the rs6235 polymorphism and sex for BMI Z-score (p = .025). Results of this study suggest for a sex-differentiated association between PCSK1 rs6235 and overweight/ obesity in Portuguese children.

Association between endometrial thickness and birthweight of singletons from vitrified-warmed cycles: a retrospective cohort study

Research questionWhat is the association between endometrial thickness (EMT) and the birthweight of singleton infants born from frozen-thawed embryo transfer cycles? DesignThis retrospective cohort study was conducted from January 2016 to December 2019. Participants were categorized into a natural cycle (NC, n = 8132) group and hormone replacement therapy (HRT, n = 4975) group. Only singleton deliveries were included. The primary outcomes were measures of birthweight and relevant indexes. Multivariable logistic regression and multivariable-adjusted linear regression models that incorporated restricted cubic splines were used. ResultsIn the HRT group, the risk of delivering a small for gestational age (SGA) infant was increased in women with an EMT <8.0 mm (adjusted odds ratio [aOR] 1.85, 95% confidence interval [CI] 1.17–2.91) compared with women with an EMT of 8.0 to <12.0 mm, and increased with an EMT ≥12.0 mm (aOR 1.85, 95% CI 1.03–3.33). An inverted U-shaped relationship was found between EMT and birthweight in women with HRT. No significant differences were shown in birthweight z-score, or being SGA or large for gestational age, in singletons among the three EMT groups in the natural cycles. ConclusionsA thinner endometrium seen in women undergoing HRT cycles was associated with a lower birthweight z-score, as well as a higher risk of SGA. However, no significant association was observed between EMT and birthweight z-score or SGA in the NC group. It is noteworthy that a thicker endometrium was not associated with a higher birthweight in frozen-thawed embryo transfer (FET) cycles. Women with a thin endometrium who achieve pregnancy require specialized attention, particularly if they are undergoing FET with HRT cycles.

Особенности продольного роста у скотоводческого населения Южного Урала и земледельцев Средней Азии эпохи бронзы: анализ стандартизированных оценок

Introduction. In this paper, we compared patterns of longitudinal long bone growths of the Late Bronze Age population from Southern Urals, representing pastoral communities, predominantly cattle breeders, and the relatively synchronous agricultural population from Central Asia using standardized z-scores. Materials and methods. The analyzed sample comes from two cemeteries of the Srubnaya culture in Pre-Urals (Karanayevsky and Chumarovo-1), and two cemeteries of the Srubnaya-Alakul cultural type in Trans-Urals (Nepluyevsky and Yulaly-8). The comparative sample represents data from Gonur Depe, a Bronze Age proto-urban center in Southeastern Turkmenistan. The sample sizes were 32 and 56 individuals respectively, aged between 2 and 12 years old. The measurements of all six long bones and updated reference Maresh standards (mid-20th century, USA) were used to calculate z-scores. The obtained z-scores were analyzed using both parametric methods and nonparametric statistics. Results. Z-scores for the diaphyseal lengths differed significantly between the two analyzed samples. The distribution of z-scores for the Gonur Depe sample was more noticeably shifted towards lower values. In the Southern Ural sample, 6.7% of children had z-scores no lower than those in the reference group, while in the Gonur Depe sample this value constituted only 0.6%. Z-scores for the upper limb bones in both groups were significantly higher than those for the lower limb bones. In the Southern Ural sample, children under 6 years of age had significantly higher z-scores compared to 9–12-year old children. No such differences were found in the Gonur Depe sample. Discussion. The pooled Bronze Age sample from Southern Urals showed overall less stunting from the reference group compared to the Gonur Depe sample. This is consistent with the hypothesis of a smaller long bone lengths and shorter stature in agricultural compared to pastoral populations. In both groups, the lower limb bones had lower z-scores compared to the upper limb bones, indicating that growth stunting relative to the reference values is more expressed for the lower limbs.@ 2023. This work is licensed under a CC BY 4.0 license