Lower Z-scores Research Articles

Factors associated with statural growth in pediatric kidney transplant recipients with focus on metabolic acidosis.

We investigated factors associated with post-transplant growth in pediatric kidney transplant (KTx) recipients with a focus on plasma bicarbonate (HCO3-) and estimated the effect of alkali treatment on growth. In this study of the CERTAIN Registry, data were collected up to 5years post-transplant. Generalized Additive Mixed Models were applied to assess the association between post-transplant growth and covariates. A trial-emulation analysis was performed to estimate the causal effect of alkali supplementation on growth. We report on 2147 primary KTx recipients with a median age at KTx of 10.2 (IQR 5.1;14.3) years. No statistically significant association was found between growth and HCO3- (p = 0.21), but the shape of the estimated conditional association showed a decreasing estimated growth with increasing HCO3-. Glucocorticoid treatment and allograft rejection showed an inverse association with growth. Living donor KTx, glomerulopathy, recombinant growth hormone use, low height z-score at KTx, younger age, and higher eGFR were positively associated with growth. The trial-emulation analysis included patients at 30days and 3, 6, and 9months post-transplant with HCO3- < 22mmol/L and no prior alkaline treatment. Alkaline treatment was initiated in 194, 93, 47, and 25 patients, respectively. After adjustment for confounders, there was no significant difference in growth at 1-year post-transplant in treated and untreated patients. We found no association between HCO3- and growth nor evidence of improved growth after treatment of metabolic acidosis. Living donor KTx was positively associated with post-transplant growth, while there was an inverse association with allograft rejection.

The Effect of Being Born Moderate-to-Late Preterm on Lung Function and Respiratory Morbidity at 9 to 10 Years of Age.

Rationale: The effect of moderate-late preterm (MLP; 32 to 36 completed weeks' gestation) birth on childhood respiratory health is unclear. Objectives: To assess the effect of being born MLP, compared with being born at term (≥37 completed weeks' gestation), on lung function and respiratory morbidity at 9-10 years of age. Methods: Prospective cohort of children born MLP or at term at the Royal Women's Hospital, Victoria, Australia. Participants completed pre- and post-bronchodilator spirometry, DLCO, plethysmography, and multiple breath washout at 9-10 years of age. Parents completed the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Mean differences in z-scores of lung function outcomes and risk ratio (RR) for ISAAC outcomes between those born moderate-late preterm and those born at term were estimated using regression models with adjustment for potential confounding. Multiple imputation was used to handle missing data. Measurements and Main Results: 148 of 201 children born MLP and 120 of 201 term-born controls were assessed at 9-10 years. Compared with controls, children born moderate-late preterm had lower mean z-scores (mean difference, 95% confidence interval) for FEV1: -0.35, (-0.61, -0.08), FEV1/FVC: -0.29, (-0.58, -0.01), FEF25-75%: -0.33, (-0.62, -0.04) and DLCO: -0.24, (-0.45, -0.03). Participants born MLP had higher risk of experiencing asthma symptoms (RR, 95% CI: 1.52 [1.08, 2.14]). Conclusions: Children born MLP have lower lung function and increased risk of exhibiting asthma symptoms compared with term-born peers at 9-10 years. Such findings at the end of the first decade of life may portend adverse consequences for respiratory health in adulthood.

Evaluation of Bone Mineral Metabolism in Pre-Dialysis Chronic Kidney Disease: Quantitative Computed Tomography vs. Dual-Energy Absorptiometry and Correlation with Bone Turnover Markers.

Background and Objectives: Bone and mineral disease (BMD) is a prevalent complication of advanced chronic kidney disease (CKD). The risk of fractures can be assessed via dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). This study aims to evaluate the effectiveness of two imaging modalities in identifying bone mineral status in individuals with pre-dialysis chronic renal disease and to assess their correlation with bone turnover markers. Materials and Methods: This controlled cross-sectional study, conducted at a single center from 2019 to 2022, assessed two groups of individuals aged 18 to 50. The patient cohort consisted of individuals with stage 4-5 chronic kidney disease, whereas the control cohort consisted of healthy participants. The participants' bone and mineral status was evaluated using both QCT and DXA methods. Diagnostic measurements of the lumbar spine and femoral neck, obtained using DXA and QCT, were compared. Z-scores were utilized to evaluate low bone mineral density, with low Z-scores identified in either lumbar spine or femoral neck measures being seen as indicative of low bone mineral density. Results: Data from 38 participants (patient group: 18; control group: 20) who underwent QCT and/or DXA were evaluated. Thirty-three subjects were assessed using both QCT and DXA (patient group: 14; control group: 19). The median age of the patient cohort was 44 (range: 22-50), whereas the median age of the control cohort was 42 (range: 27-48) (p = 0.72). Women constituted 33% of the patient cohort and 50% of the control cohort (p = 0.23). In the patient cohort, low bone mineral density was detected in four individuals (28%) through QCT, and in just two patients (14%) through DXA. Compared to DXA, QCT identified a higher number of cases of low bone mineral density in the CKD cohort; however, no statistically significant difference was observed (p = 0.06). In addition, our study found that TRACP5b had a strong negative correlation with the DXA L1-L4 Z-score. Conclusions: This study revealed that QCT may be more sensitive than DXA for detecting low bone density in pre-dialysis CKD patients. Additionally, DXA may overestimate lumbar spine BMD in this population, and the strong negative correlation between TRACP5b levels and the DXA L1-L4 Z-score highlights the potential role of biochemical markers in assessing bone status in CKD.

Plant-based dietary patterns, nutrient intake, growth, and body composition in childhood: Results from a prospective population-based study.

Transitioning to more plant-based diets promotes environmental sustainability and has health benefits for adults. However, associations with nutrient intake adequacy and growth in children remain unknown. This study aimed to examine associations of plant-based diets with nutrient intake levels among children, and with longitudinal growth and body composition up to adolescence. We included 3340 children in the Generation R Study, a population-based cohort. Food and nutrient intake were assessed at the age of 8 years, and anthropometrics and body composition (using dual-energy X-ray absorptiometry) were measured at the ages of 10 and 13 years. Plant-based diets were quantified using three plant-based diet indices (PDIs): overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). Modified Poisson regression and linear mixed models were used to estimate the associations of PDIs with nutrient intake levels, and with sex- and age-standardized measures of anthropometrics and body composition. Higher scores on each of the three PDIs were associated with lower intake of vitamin B2, B12, and calcium, while higher hPDI score was associated with higher intake levels of fiber, vitamin C, magnesium, and copper. Higher hPDI score was also associated with higher fat-free mass index (FFMI) z-score (0.05 per 10-hPDI score increment, 95% CI: 0.01, 0.10), and with lower body fat percentage z-score (-0.05, 95% CI:-0.09,-0.01), while higher uPDI score was associated with lower height, weight, and FFMI z-score (FFMI:-0.08, 95% CI:-0.12,-0.03) up to age of 13 years. In this cohort study, higher adherence to healthful plant-based diets, rather than unhealthful ones, was associated with better nutrient intakes, and subsequent healthy body composition throughout childhood to adolescence. Our findings suggest that consuming healthful plant-based foods may contribute to children's diets' nutrient quality and subsequent body composition. Still, attention should be given to ensuring balanced and adequate nutrient intake for optimal plant-based eating.

Could cleaved embryo morphology and morphokinetics be associated with prenatal and neonatal outcomes?

To evaluate if morphology and morphokinetics of cleaved embryos affect prenatal and perinatal outcomes. This retrospective cohort study included 734 single fresh embryo transfer (SET) from ICSI from January 2014 to December 2020 at the Dijon University Hospital. Using time-lapse technology, embryos were defined as TOP or non-TOP according to morphological/morphokinetic criteria. Linear regression, adjusted for maternal factors, explored the association between cleaved-embryo quality and implantation rate, miscarriage rate, live birth rate, term, birthweight, and birthweight Z-score. Multivariate analyses showed that non-implanted embryos were significantly more often out of the interquartile range than implanted embryos for cell events t2 (p = 0.019), t3 (p = 0.038), t4 (p = 0.013), ECC1 (p = 0.047), and ECC2 (p = 0.001). After implantation, the morphokinetics was significantly different for non-TOP embryos ending in miscarriage or live birth. A significant high risk of miscarriage was found for embryos with a short or long ECC1 (3.27 [95% CI: 1.44;8.37]. There was no significant difference in birthweight, birthweight Z-score, or term between TOP and non-TOP embryos. An association with increased birthweight was observed in multivariate analysis for pronuclei appearance (tPNa) (p = 0.001out of the range. Late tPNa was associated with a higher birthweight Z-score (p < 0.0001) while late pronuclei disappearance (tPNf) was associated with a lower Z-score (p = 0.006). Morphological and morphokinetic parameters significantly influence implantation rates and the likelihood of a live birth from embryos with non-optimal morphological features. Birthweight Z-scores were significantly higher with late tPNa and lower with late tPNf.

Lower Bone Mineral Density in Female Elite Athletes With Menstrual Dysfunction From Mixed Sports.

Menstrual dysfunction (MD) in female athletes might be indicative of the syndrome of relative energy deficiency in sports (REDs), associated with, e.g., impaired bone health, an increased risk of injury, and decreased performance. In the present study, we investigated differences in objective indicators of REDs, bone mineral density (BMD), and blood-based biomarkers in female elite athletes with self-reported MD or eumenorrhoea (CON) from mixed sport disciplines. Athletes reporting < 9 menstrual bleedings within the last year were recruited in the MD group, whereas eumenorrheic athletes with no symptoms of eating disorders were recruited for CON. Of the 24 athletes included, 19 completed the examinations (9 MD; 10 CON, mean age ± SD: 24.8 ± 5.5 years). Dual-energy x-ray absorptiometry (DXA) was used to assess body composition and BMD. Fasted rested blood sampling was performed to assess blood-based biomarkers of bone and endocrine status. Two MD athletes were excluded from the analysis due to suspected polycystic ovary syndrome. Results showed that MD was associated with lower BMD Z-scores across several sites compared to CON (between-group differences ± SE); whole-body Z-score: -1.4 ± 0.5, p=0.03; lumbar spine Z-score: -1.4 ± 0.6, p=0.03; proximal femur: -1.6 ± 0.6, p=0.02). However, no between-group differences in biomarkers of bone turnover were observed. MD was associated with lower plasma concentrations of luteinizing hormone (p=0.02), prolactin (p < 0.001), and free T 3 (p=0.01). In conclusion, the present data indicate impairment in bone health and endocrine homeostasis in female elite athletes with current MD and underline the importance of MD as a potential indicator of REDs in female elite athletes. Furthermore, these findings call for regular screening of symptoms for early identification of athletes at risk in all sport disciplines and more education of athletes, coaches, and medical staff regarding this issue.

Designing a multi-epitope subunit vaccine against Orf virus using molecular docking and molecular dynamics

ABSTRACT Orf virus (ORFV) is an acute contact, epitheliotropic, zoonotic, and double-stranded DNA virus that causes significant economic losses in the livestock industry. The objective of this study is to design an immunoinformatics-based multi-epitope subunit vaccine against ORFV. Various immunodominant cytotoxic T lymphocytes (CTL), helper T lymphocytes (HTL), and B-cell epitopes from the B2L, F1L, and 080 protein of ORFV were selected and linked by short connectors to construct a multi-epitope subunit vaccine. Immunogenicity was enhanced by adding an adjuvant β-defensin to the N-terminal of the vaccine using the EAAAK linker. The vaccine exhibited a significant degree of antigenicity and solubility, without allergenicity or toxicity. The 3D formation of the vaccine was subsequently anticipated, improved, and verified. The optimized model exhibited a lower Z-score of −4.33, indicating higher quality. Molecular docking results demonstrated that the vaccine strongly binds to TLR2 and TLR4. Molecular dynamics results indicated that the docked vaccine-TLR complexes were stable. Immune simulation analyses further confirmed that the vaccine can induce a marked increase in IgG and IgM antibody titers, and elevated levels of IFN-γ and IL-2. Finally, the optimized DNA sequence of the vaccine was cloned into the vector pET28a (+) for high expression in the E.coli expression system. Overall, the designed multi-epitope subunit vaccine is highly stable and can induce robust humoral and cellular immunity, making it a promising vaccine candidate against ORFV

Clusters of diet, physical activity, screen-time and sleep among adolescents and associations with 3-year change in indicators of adiposity

Background Clusters of health behaviours could impact changes in adiposity among adolescents over time. This study examines the clustering of screen time, physical activity, dietary behaviours and sleep, and the associations with 3-year changes in indicators of adiposity. Methods Data from the UK’s Millennium Cohort Study were utilised when participants were aged 14 and 17 years respectively. At age 14, demographics, screen time, dietary behaviours and sleep duration were measured via self-report, and physical activity using wrist worn accelerometers. Height, weight, and percent body fat were measured at age 14 and 17 years. Behavioural clusters were determined using k-means clustering analysis, and associations with change in indicators of adiposity between age 14 and 17 years were examined using multivariate regression models. Results Three clusters were identified at age 14, a ‘healthy cluster’, a ‘mixed cluster’, and an ‘unhealthy cluster’ in the analytical sample of 3,065 participants (52.5% girls). The ‘unhealthy’ cluster was the most prevalent cluster among boys (53%), while the ‘healthy cluster’ was most prevalent among girls (55.9%). Adolescents in healthy clusters had a lower BMI z-score and percent body fat at age 14 compared to those in the unhealthy and mixed clusters, and maintained lower scores at age 17. Boys in the mixed and unhealthy clusters at 14 years had a lower change in BMI z-score between 14 and 17 compared to boys in the healthy cluster. Conclusion Adolescents in the healthy cluster had lower BMI z-scores and percent body fat at age 14 years than those in the unhealthy cluster, and they maintained this lower level at age 17. Given the upward trend in BMI during this period, this maintenance could be interpreted as a positive outcome. Further prospective research is needed to better understand these associations as well as research examining the stability of cluster membership over time.

Analysis of risk factors for post-prematurity respiratory disease in very preterm infants

Objective: To investigate the risk factors associated with post-prematurity respiratory disease (PPRD) in very preterm infants. Methods: A prospective cohort study was conducted, enrolling 369 very preterm infants who were admitted to the neonatal intensive care unit of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, within one week of birth from January 2019 to June 2023. Data on maternal and infant clinical characteristics, neonatal morbidities, and treatments during hospitalization were collected. The very preterm infants were divided into 2 groups based on whether they developed PPRD. Continuous variables were compared using Mann-Whitney U test, while categorical variables were compared using χ² tests or continuity correction χ2 test. Multivariate Logistic regression analysis was used to identify the independent risk factors for PPRD in very preterm infants. Results: Among the 369 very preterm infants, 217 cases(58.8%) were male, with a gestational age of 30 (28, 31) weeks at birth and a birth weight of 1 320 (1 085, 1 590) g. Of these, 116 cases (31.4%) developed PPRD, while 253 cases (68.6%) did not. The very preterm infants in the PPRD group had a lower gestational age and lower birth weight (both, P<0.001). The PPRD group also had a higher proportion of males, lower Apgar scores at the 1th minute after birth and the 5th minutes after birth, a higher rate of born via cesarean delivery, and a higher incidence of bronchopulmonary dysplasia, more pulmonary surfactant treatment, longer durations of mechanical ventilation, longer total oxygen therapy, and lower Z-score for weight at discharge (all P<0.05). Multivariate Logistic regression analysis showed that gestational age (OR=0.85, 95%CI 0.73-0.99, P=0.037), born via cesarean delivery (OR=2.23, 95%CI 1.21-4.10, P=0.010), a duration of mechanical ventilation ≥7 days (OR=2.51, 95%CI 1.43-4.39, P=0.001), and a Z-score for weight at discharge (OR=0.82, 95%CI 0.67-0.99, P=0.040) were all independent risk factors for PPRD in very preterm infants. Conclusion: Very preterm infants with a small gestational age, born via cesarean section, mechanical ventilation ≥7 days, and a low Z-score for weight at discharge should be closely monitored for PPRD, and provided with standardized respiratory management after discharge.

Awake rodent fMRI: gradient-echo echo planar imaging versus compressed-sensing fast low angle shot

Abstract Awake rodent fMRI is increasingly becoming a reliable neuroimaging technique to study neuronal activity at both the whole brain and high-resolution laminar scales. Prior studies have focused on developing acclimation protocols, experimental paradigms, and hardware to optimize outcomes. However, little effort has been made to address the impact of pulse sequence selection on detecting brain activation in awake fMRI experiments. In the current study, we compare gradient-echo echo planar imaging (GE-EPI) and compressed-sensing fast low angle shot (CS-FLASH) sequences with cerebral blood volume-weighted (CBVw) contrast enhancement to investigate their sensitivity to hemodynamic activity in the olfactory bulb of awake rodents. Compared to GE-EPI, CS-FLASH had comparable motion parameters but was more sensitive to large motions, often resulting in corruption of the image quality. The use of framewise displacement as a motion censoring technique may over censor the data, requiring alternative approaches, such as spatial correlation censoring. CS-FLASH images were qualitatively sharper than GE-EPI; however, the contrast-to-noise ratio for odor activation was consistently greater for GE-EPI compared to CS-FLASH that cannot be explained by olfactory adaptation alone. The activation maps of CS-FLASH to four different odors showed spatially unique patterns consistent with GE-EPI, but with lower z-scores or detection sensitivity. Activation maps were consistent with previously established histological findings. Additionally, odor-evoked laminar activation was greatest in the superficial layers that decreased with laminar depth, consistent with prior findings. We conclude that CS-FLASH produces sharper images with equivalent spatial activation maps to GE-EPI, albeit with lower statistical strength and CNR; and without being prohibited by motion-related image distortion.

Comparison of Race-neutral Versus Race-specific Spirometry Equations for Evaluation of Child Asthma.

Race-based estimates of pulmonary function in children could influence the evaluation of asthma in children from racial and ethnic minoritized backgrounds. To determine if race-neutral (GLI-Global) versus race-specific (GLI-Race-Specific) reference equations differentially impact spirometry evaluation of childhood asthma. The analysis included 8,719 children aged 5 to <12 years from 27 cohorts across the United States grouped by parent-reported race and ethnicity. We analyzed how the equations affected forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC z-scores. We used multivariable logistic models to evaluate associations between z-scores calculated with different equations and asthma diagnosis, emergency department (ED) visits, and hospitalization. For Black children, the GLI-Global vs. Race-Specific equations estimated significantly lower z-scores for FEV1 and FVC but similar values for FEV1/FVC, thus increasing the proportion of children classified with low FEV1 by 14%. While both equations yielded strong inverse relationships between FEV1 and FEV1/FVC z-scores and asthma outcomes, these relationships varied across racial and ethnic groups (p<0.05). For any given FEV1 or FEV1/FVC z-score, asthma diagnosis and ED visits were higher among Black and Hispanic versus White children (p<0.05). For FEV1, GLI-Global equations estimated asthma outcomes that were more uniform across racial and ethnic groups. Parent-reported race and ethnicity influenced relationships between lung function and asthma outcomes. Our data show no advantage to race-specific equations for evaluating childhood asthma, and the potential for race-specific equations to obscure lung impairment in disadvantaged children strongly supports using race-neutral equations.

Abstract 4126358: Fetal cardiac physiology but not cerebrovascular resistance predicts neurodevelopmental outcomes in congenital heart disease

Introduction: Fetal “brain sparing” autoregulatory mechanisms respond to reduced cardiac output or substrate delivery by decreasing cerebrovascular resistance to maintain cerebral blood flow. In patients with congenital heart disease (CHD), data are conflicting on the association between fetal cerebral Doppler measures and postnatal neurodevelopment, possibly due to the heterogeneity of fetal cardiac physiology. Aim: To evaluate whether fetal cerebrovascular resistance estimated by middle cerebral artery pulsatility index (MCA PI) and cerebroplacental ratio (CPR; MCA PI divided by umbilical artery PI) predict neurodevelopment in patients with CHD. Methods: This retrospective analysis of a prospectively-enrolled cohort included cases with isolated CHD and healthy controls with a family history of CHD. Cases were classified by fetal cardiac physiology: single vs. biventricular circulation, outflow obstruction (none, systemic, pulmonary), and cerebral substrate delivery (normal, mixed, abnormal). Subjects underwent fetal echocardiography with cerebral and umbilical doppler measures (normalized for gestational age) as well as neurodevelopmental evaluation at two years of age with the Bayley Scales of Infant and Toddler Development III and IV. Results: Fetal echocardiograms and neurodevelopmental testing were obtained in 82 cases and 48 controls. There was no difference in MCA PI or CPR between cases and controls; however cases with mixed vs. normal substrate delivery had lower z-scores for MCA PI (-1.08 + 1.16 vs. -0.43 + 1.38, p=0.05) and CPR (-0.74 + 0.62 vs. -0.37 + 0.59, p=0.02). Cases had lower Bayley scores across all composite domains: cognitive (97.8 + 11.8 vs. 103.4 + 14.7, p=0.03), language (97.6 + 15.6 vs. 105.6 + 21.3, p=0.03), and motor (94.0 + 10.7 vs. 100.4 + 10.9, p=0.003). MCA PI and CPR were not associated with Bayley scores in cases or in sub-group analysis by fetal cardiac physiology. In multivariable analyses of Bayley scores adjusting for medical and demographic data, lower motor composite score was predicted by mixed vs. normal substrate delivery (partial R2=12.4%, p&lt;0.001) and single ventricle physiology (partial R2=6.5%, p=0.008). Conclusions: In patients with CHD, fetal single ventricle physiology with mixed substrate delivery was associated with worse motor development. The lack of association of fetal cerebral dopplers with neurodevelopment may suggest that decreased cerebrovascular resistance is not necessarily an effective compensatory mechanism in CHD.

Biomarkers to Differentiate Acute Chest Syndrome From Vaso-Occlusive Crisis in Children With Sickle Cell Disease.

Acute Chest Syndrome (ACS) is the leading cause of death in children with sickle cell disease (SCD) in the US-about half of the children who develop ACS present initially with pain. Here, we studied biomarkers to differentiate ACS from vaso-occlusive crises (VOC) in children with SCD who presented with pain to the emergency department (ED). We conducted a prospective cohort study of consecutive patients who presented to the ED with pain and were discharged with ACS or VOC between March, 2017 and February, 2020. We identified 7 patients with ACS and 19 patients with VOC. The two groups were comparable in age and sex. All patients with ACS had asthma versus 42% of the VOC group. The ACS group had lower weight and BMI z-scores. Patients with ACS compared to VOC had significantly higher respiratory rates, lower O2 saturation, and longer hospital stays. They also had higher white blood cell count, glucose level (> 99 mg/dL), anion gap (> 9 mEq/L), sPLA2 (> 7 pg/mL), IFN-γ (> 17.8 pg/mL), IL-10 (1.54 pg/mL), and IL-12 (> 0.5 pg/mL) levels. We identified biomarkers associated with ACS development in children with SCD presenting with pain that allow for earlier ACS interventions to reduce mortality and morbidity.

Dementia risk factors and cognitive function in a nationwide population-based sample aged 65+

Abstract Background Cognitive function is fundamental to healthy aging and independent living. As there is no cure for dementia, prevention of risk factors (e. g. physical inactivity, obesity, hypertension, diabetes, social isolation, depression) is crucial. The aim of our study was to analyze selected dementia risk factors and their association with cognitive function in people aged 65 years and older. Methods Cross-sectional data from the nationally representative examination Study on Health of Older People in Germany (Gesundheit 65+) conducted between 2022-2023 by the Robert Koch Institute (n = 1.493; 48% women; mean age 78.8 years). Cognitive function was assessed by the Letter Digit Substitution Test (LDST), a measure of general speed of information processing, and of the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) 10-word list delayed recall (WLR), a measure of memory. Weighted associations between age, sex, education, dementia risk scores and z-standardized test scores were examined using linear regression analysis. Results Higher age, male sex and lower level of education were significantly associated with lower z-scores in both tests (all p &amp;lt; 0.001). In separate models, all adjusted for age, sex and education, social isolation was associated with lower performance on both LDST (ß=-0.22; 95% confidence interval -0.42, -0.01) and CERAD WLR (ß=-0.21; -0.41, -0.01); depressive symptoms were associated with lower LDST z-scores (ß=-0.40; -0.67, -0.13), and physical inactivity with lower CERAD WLR z-scores (ß=-0.12; -0.24, -0.01). Obesity, hypertension, and diabetes were not significantly associated with any test. Conclusions Our findings from this nationwide general population study of old and very old adults show a clustering of reduced cognitive function with social isolation, symptoms of mental health impairments, and physical inactivity in old age which call for coordinated intersectoral health promotion and prevention activities. Key messages • The clustering of reduced cognition with dementia risk factors calls for intersectoral health actions. • Limitations in cognition should only be defined by age-, sex-, and education-specific norms.

Unlocking Health Literacy: investigating Parental Health Literacy and Child Weight Outcomes

Abstract Background While parental health literacy (HL) is widely recognized as crucial for child health, research on its impact on children’s weight-related outcomes remains limited. This study aims to fill this gap by investigating the associations between parental HL and children’s anthropometric measurements, with a focus on child BMI Z-score and waist-to-height ratio (WHtR). Methods As part of a cluster randomized trial in primary schools serving vulnerable populations, 735 children (51.7% boys, mean age 7.7 years) participated. Parental HL was assessed using the HLS-Q12 questionnaire, comprising 12 items. Health literacy levels, standardized from 0 to 100, were categorized into ‘inadequate,’ ‘problematic,’ ‘sufficient,’ and ‘excellent’ HL. General HL and three specific domains-health promotion, disease prevention, and healthcare-were computed. Children’s weight, height, and BMI were measured following standardized procedures. Regression analyses examined HL’s impact on BMI Z-scores and WHtR. Results Parents with higher HL in disease prevention and health promotion had children with significantly lower BMI Z-scores, even after adjusting for parental education and children’s sex sex [-0.010 (-0.18; -0.0001) and -0.10 (-0.019; 0.01). Similar associations were found for WHtR [-0.0004 (-0.001; -0.0001)]. Parents with excellent HL in general and health promotion had significantly lower WHtR [-0.027 (-0.046; -0.008)] and BMI Z-score [-0.74 (-1.2; -0.28)]. Conclusions This study highlights the significant role of parental health literacy in shaping children’s weight-related outcomes. Higher levels of parental HL in disease prevention and health promotion were linked to lower BMI Z-scores and WHtR in children, independent of parental education and children’s sex. Enhancing parental HL, alongside promoting healthy behaviors and environments for children, could lead to more effective approaches for addressing this public health issue. Key messages • Parental health literacy is associated with children’s weight outcomes, emphasizing the need for HL-focused interventions. • Higher parental HL is associated with lower child BMI Z-scores and waist-to-height ratios, highlighting potential HL’s role in combating childhood obesity.

Efficacy of native T1 mapping for patients with non-ischemic cardiomyopathy and ventricular functional mitral regurgitation undergoing transcatheter edge-to-edge repair

Abstract Background The objectives of this study were to investigate the efficacy of LV myocardial damage assessment by native T1 mapping obtained with cardiac magnetic resonance (CMR) for symptomatic heart failure (HF) patients with non-ischemic cardiomyopathy (NICM) and ventricular functional mitral regurgitation (VFMR) undergoing transcatheter edge-to-edge repair (TEER). Methods We studied 40 symptomatic HF patients with NICM and VFMR undergoing TEER. LV myocardial damage was defined as the native T1 Z-score which was converted from native T1 value obtained with CMR before TEER. The primary endpoint was defined as first re-hospitalization for HF or cardiovascular death over a median follow-up period of 12 months after TEER. Results Multivariable Cox-proportional hazards analysis showed that a native T1 Z-score was the only independent parameter associated with cardiovascular events (hazard ratio: 3.40, 95% confidential interval: 1.51-7.67), and patients with native T1 Z-score &amp;lt; 2.41 experienced significantly fewer cardiovascular events than those with a native T1 Z-score ≥ 2.41 (log-rank P = 0.001). Moreover, such a low native T1 Z-score and more severe VFMR in an effective regurgitant orifice area (EROA) ≥ 0.30 cm2 was associated with fewer cardiovascular events than for a high native T1 Z-score of ≥ 2.41 and less severe VFMR of EROA &amp;lt; 0.30 cm2 (log-rank P = 0.002). Conclusion Assessment of baseline LV myocardial damage by means of native T1 Z-score obtained with CMR without the use of gadolinium-based contrast media is a valuable additional parameter for better management of symptomatic NICM patients with reduced LVEF and VFMR following TEER.

A Normal Forced Vital Capacity Does Not Reliably or Equitably Exclude Restriction.

European Respiratory Society and American Thoracic Society (ERS/ATS) guidelines for pulmonary function test (PFT) interpretation recommend the use of a normal forced vital capacity (FVC) to exclude restriction. However, this recommendation is based upon a single study from 1999, which was limited to White patients, and used race-specific reference equations that are no longer recommended by ERS/ATS. We sought to reassess the support for this recommendation by calculating the negative predictive value (NPV) of a normal FVC in a diverse, multicenter cohort using race-neutral reference equations. We interpreted PFTs performed between 2000 and 2023 in two academic medical systems and in a national electronic health record (EHR) database. We calculated the NPV of a normal FVC to exclude restriction overall and among pre-specified racial and ethnic groups. We included PFTs from 85 990 patients. The prevalence of restriction was 35.1%. The overall NPV of a normal FVC to exclude restriction was 80.5% (95% CI 80.1% to 80.8%), compared to an NPV of 97.6% cited in support of ERS/ATS guidelines. The NPV ranged from 65.2% (95% CI 64.4% to 66.0%) among non-Hispanic Black patients to 85.9% (95% CI 85.6% to 86.3%) among non-Hispanic White patients. This difference was largely attributable to lower FVC z-scores among non-Hispanic Black patients. The NPV of a normal FVC is lower than has been previously reported and varies by race and ethnicity. The approach to PFT interpretation recommended by ERS/ATS guidelines results in the under-recognition of restriction, particularly among non-Hispanic Black patients.

Gestational organophosphate pesticide exposure and childhood cardiovascular outcomes

IntroductionThe general population is chronically exposed to organophosphate pesticides through various routes including ingestion, hand-to-mouth contact, inhalation, and dermal contact. Exposure to organophosphate pesticides during pregnancy impairs fetal development, but the potential long-term effects of gestational organophosphate pesticide exposure are less well understood. MethodsWe investigated associations between gestational organophosphate pesticide exposure and cardiovascular outcomes in 643 children in the Generation R Study, a prospective pregnancy cohort based in Rotterdam, The Netherlands. Urinary organophosphate pesticide metabolites (dimethyl [∑DMAP], diethyl [∑DEAP], and total dialkyl phosphate [∑DAP] metabolites) were quantified in three urine samples collected from pregnant participants, and their children were followed until age 10 years at which time cardiac magnetic resonance imaging, ultrasonography, blood pressure, and serum biomarkers assessed cardiovascular health. Linear regression models estimated associations (β and 95 % confidence interval [CI]) between a one-interquartile range (IQR) increase in averaged gestational exposure biomarker concentrations and z-scored pediatric cardiovascular outcomes. We investigated effect modification of associations by PON1 genotype. ResultsCarotid intima-media thickness z-score was lower (β: -0.14 [95 % CI: −0.25, −0.02]) and HDL cholesterol z-score was higher (β: 0.14 [95 % CI: 0.02, 0.25]) for increases in ∑DEAP concentrations. Carotid intima-media distensibility z-score was lower (β: -0.08 [95 % CI: −0.19, 0.03]) for increases in ∑DMAP concentrations, and systolic blood pressure z-score was higher (β: 0.10 [95 % CI: −0.01, 0.21]) for increases in ∑DMAP and ∑DAP. Among those with PON1-161CC and PON1-L55MTT genotypes, higher organophosphate pesticide concentrations conferred an excess risk of adverse vascular and glycemic outcomes, respectively. ConclusionsWe observed heterogenous associations between gestational organophosphate pesticide exposure and pediatric cardiovascular health: an anti-atherogenic profile was observed for increases in ∑DEAP concentrations, and impairments in multiple aspects of cardiovascular health was observed for increases in ∑DMAP concentrations. PON1-161 and PON1-L55M single nucleotide polymorphisms modified associations for vascular and glycemic outcomes, respectively.

Endocrine Complications in Hepatic Glycogen Storage Diseases: A Long-term Perspective.

Patients with hepatic type of glycogen storage diseases (GSDs) can manifest endocrine features such as hypoglycemia, dyslipidemia, or osteoporosis. This study aimed to investigate the long-term endocrine consequences in patients with hepatic GSDs. This study included 64 patients from 52 families with hepatic GSDs including GSD type Ia (41 patients from 37 families), Ib (3 unrelated), III (8 from 6 families), IV (one patient), and IX (11 from 5 families). All patients were genetically confirmed. Clinical and endocrine findings were retrospectively analyzed. The median age at diagnosis and current age were 2.4 years (range, 0.1-42.4 years) and 17.6 years (range, 1.0-47.8 years), respectively. The mean height SDS at diagnosis was -3.5 ± 1.4, and short stature was observed in 35.6% of patients. Patients diagnosed after the age of 3.4 years exhibited a high risk of short stature (OR = 36.1; P-value < 0.001). Among 33 patients who reached final height, 23 (69.7%) showed delayed puberty. Hypertriglyceridemia was observed in 46 patients (71.9%), whereas 25 patients (39%) had elevated low-density lipoprotein cholesterol levels during the follow-up period. Among 24 patients who underwent dual energy X-ray absorptiometry, 22 showed a low bone mineral density Z-score of -3.0 ± 1.3 at the L-spine. This study described the long-term endocrine consequences in patients with hepatic GSDs. Pediatric endocrinologists should be aware of the presenting features and long-term endocrine sequelae of GSDs to provide proper management and decrease its morbidities.

Body composition and muscle composition phenotypes in patients on waitlist and shortly after liver transplant – results from a pilot study

BackgroundSarcopenia is common in end-stage liver disease and negatively impacts patients awaiting or undergoing liver transplantation (LT). Magnetic resonance imaging (MRI) may be used to measure body composition and sarcopenia. We aimed to evaluate the feasibility of MRI-based LT body composition profiling, describe waitlist body composition, and assess the natural rate of change in body composition while on the waitlist and post-LT.MethodsThis prospective pilot study recruited adults listed for LT at an urban, tertiary care facility. Eighteen participants were scanned at time of waitlisting and 15 had follow-up MRIs (waitlist and/or post-LT). An 8-min MRI was used to measure body composition (AMRA® Researcher) including thigh fat-free muscle volume (FFMV) and fat infiltration (MFI), visceral (VAT) and abdominal subcutaneous (ASAT) adipose tissue volumes, and liver fat. A sex- and BMI invariant FFMV z-score (z-FFMV) was calculated, and muscle composition (MC) phenotypes were defined using the muscle assessment score (consisting of the FFMV z-score and sex-adjusted MFI). Rate of body composition change was calculated using mixed-effect modelling and is presented as rate per 30 days.ResultsAt time of waitlisting, 73% of the 18 participants had high MFI and 39% had the adverse MC (low FFMV z-score and high MFI) phenotype. Seven participants received an LT. Post-LT serial MRIs, at a median of 147 days apart within the first 200 days post-LT, demonstrated increased z-FFMV 0.22 SDs/(30 days) (p = 0.002), VAT 0.23 (p < 0.001), and ASAT 0.52 (p = 0.001) L/(30 days), but no change in MFI (p = 0.200) nor liver fat (p = 0.232).ConclusionMRI-based body composition profiling is feasible in LT patients and shortly after LT. This can be amended to routine clinical scans and may help in early identification of patients who may benefit from interventions to improve body composition. In addition, body composition changes significantly over time after LT.