Ratio Z-score Research Articles

Growth Parameters and Prevalence of Obesity in PKU Patients and Peers: Is This the Right Comparison?

One of the main objectives of Phenylketonuria (PKU) management is represented by optimising the growth trend under restricted protein diet regimen. The data on long-term growth in PKU children are limited and mostly based on earlier studies. The data for this twelve-year longitudinal study were collected from 34 PKU children and 37 healthy peers, whose auxological parameters were taken at 7 time-points over the follow-up. The weight-for-length ratio (WLR) z-score and body mass index (BMI) z-score were considered according to age. Prevalence of overweight/obesity was evaluated at last assessment. The median BMI z-score of PKU children was normal and not statistically different from that of controls on all the seven time-point assessments. Their distributions tended to be wider than those of peers, with the upper limit exceeding the normal range since 12 months old, with a peak specifically at 3 years of age. In controls, there was a tendency to approach the BMI z-score values of overweight in later childhood. The prevalence of overweight was comparable (29% vs. 25%, p: 0.78) between the two groups at last assessment, and obese subjects (3/37) were only detected in the control group. In this study, we report data from a long-term follow-up on growth, highlighting that the median BMI z-score of PKU children was normal and not statistically different from that of controls. Also, the prevalence of obesity at 12 years of age was overlapping. However, the high prevalence of overweight children in the general population may explain the lack of difference and does not reassure about patients' nutritional risk.

Salivary Physicochemical Parameters in Relation to Dental Caries and Adiposity Status.

The objective of this study was to investigate the correlations between salivary physicochemical parameters, adiposity, and caries indices in Hong Kong adolescents. A total of 921 adolescents aged 12-15 years from four randomly selected local secondary schools were invited to participate in this cross-sectional study. Dental examinations including the number of decayed, missing, and filled teeth (DMFT), salivary physicochemical parameters, and anthropometric measurements were performed. The Mann-Whitney U test was used to examine the differences in salivary parameters and adiposity indices between participants with different levels of caries experience. Correlations between adiposity indices, salivary parameters, and caries indices were examined using Spearman's correlation coefficients. The participation rate was 83.6%. After exclusion, data from 695 adolescents were analysed. Adolescents with high caries experience (DMFT ≥ Significant Caries Index [SiC Index]) had significantly higher weight-to-height ratio (W/H) and waist circumference (WC) z-scores and lower unstimulated and stimulated salivary flow rates and buffering capacity than those with DMFT < SiC Index. Except for body mass index z-score, the other adiposity indices were negatively correlated with at least one salivary physicochemical parameter (stimulated salivary flow rate or salivary buffering capacity) (rs ranged from -0.078 to -0.132). After adjusting for age and sex, decreased stimulated salivary flow rate was associated with higher body fat percentages, WC, and waist-to-height ratio z-scores, whereas low salivary buffering capacity was associated with higher W/H and WC z-scores. There is a potential link between adiposity indices and certain salivary physicochemical parameters that are implicated in the aetiology of dental caries.

Delay discounting and nucleus accumbens functional connectivity are related to weight status in adolescents from the ABCD study.

Despite the growing epidemic of paediatric obesity, questions remain regarding potential neural mechanisms for individual risk. Delay discounting is a cognitive process of comparison of valuation between immediate and delayed reward, which has been inconsistently linked to weight status. Moreover, central to the brain's reward system is the nucleus accumbens, a region structurally and functionally altered in obesity. This study aimed to examine the relationships between two continuous metrics of weight status, performance on a monetary delay-discounting task and nucleus accumbens functional connectivity in 10-12-year-olds from the Adolescent Brain and Cognitive Development (ABCD) Study. Using multilevel longitudinal linear modelling, we found greater discounting was associated with higher BMI Z-scores (BMIz) and waist-to-height ratio Z-scores (WHtRz) (N = 3819). Moreover, we observed functional connectivity of the nucleus accumbens to the cingulo-opercular, dorsal attention, fronto-parietal, salience and ventral attention networks were predictive of BMIz (N = 1817). Nucleus accumbens functional connectivity was not found to mediate the association between delay-discounting behaviour and BMIz. Delay discounting and nucleus accumbens functional connectivity are independently related to weight status in a large sample of early adolescents. A better understanding of the relationship between reward and overeating behaviours may better inform obesity interventions.

Respiratory, cardio-metabolic and neurodevelopmental long-term outcomes of moderate to late preterm birth: not just a near term-population. A follow-up study.

Moderate-to-late preterm infants constitute the majority within the preterm infant population. Most research on preterm infants has focused on very preterm children, often treating moderate-to-late preterm infants as similar to full-term infants. Our objective was to compare clinical, respiratory, cardio-metabolic and neurodevelopmental outcomes in adolescents aged 12-15 years born moderate and late preterm with a control group of the same age born full-term. Observational cross-sectional study, comparing moderate-to-late preterm (32-36+6 weeks' gestational age) with full-term adolescents (37-41+6 weeks' gestational age; 75 each group). Perinatal and neonatal history were collected as well as data on respiratory evolution (ISAAC questionnaire for asthma symptoms for adolescents 13-14 years), anthropometric values, learning difficulties, behavioral test (screening questionnaire for high-performance autism spectrum disorder and evaluation test for attention deficit hyperactivity disorder), skin prick test, pulmonary function test, echocardiogram and blood pressure. A blood test with metabolic profile was conducted. Moderate-to-late preterm adolescents had more current asthma [p = 0.008, OR3 (95% CI 1.26-7.14)] and longer duration of combined treatments to control asthma (inhaled corticosteroids and anti-leukotrienes; p = 0.048). Forced vital capacity <80% was detected more often in moderate-to-late preterm patients (p = 0.013). When assessing right ventricle, moderate-to-late preterm adolescents showed better tricuspid annular plane systolic excursion z-score (p = 0.003), shortening fraction (p < 0.001) and E/A ratio z-score (p = 0.002). Regarding left ventricular assessment, moderate-to-late preterm group had smaller ventricle diastolic diameter (p = 0.04) and lower posterior wall z-score values (p = 0.037). They also showed a better S'wave z-score (p = 0.027), E wave (p = 0.005), E/A ratio (p = 0.003) and a higher septal myocardial performance index z-score (p = 0.025). Moderate-to-late preterm adolescents presented lower weight z-score (p = 0.039), body mass index z-score (p = 0.013), Waterlow weight index (p = 0.006) and higher undernutrition index [p = 0.04; OR 1.4 (95% CI 1-1.9)]. Although there were no differences in neurodevelopmental survey or behavioral tests. Our findings underscore the importance of extended follow-up for this predominant group of premature infants to identify potential respiratory, cardiac and anthropometric issues that may emerge in the future.

Body composition, metabolic syndrome, and lifestyle in treatment-naïve gender-diverse youth in Israel.

There is a scarcity of published studies evaluating transgender/gender-diverse youth before initiating gender-affirming hormones. To study the body composition, metabolic syndrome (MetS) components and lifestyle habits in treatment-naïve transgender youth. Cross-sectional study evaluating 153 transgender youth [median age 15.7 years, 94 transgender males] who attended The Israeli Children and Adolescents Gender Clinic between 6/2021-12/2022. Clinical, metabolic data and lifestyle habits (diet, physical activity and sleep patterns) were retrieved from the medical files. Body composition was determined by bioelectrical impedance analysis. Body mass index and muscle-to-fat ratio z-scores were calculated by sex designated at birth. Weight categories differed between genders, with a greater proportion of subjects classified as underweight among transgender females, and a greater proportion affected by overweight/obese/severe obese among transgender males (p = 0.035). The odds for MetS components were increased by 2.2 for every 1 standard deviation decrease in the muscle-to-fat ratio z-score (95%CI: 1.45 to 3.26, p < 0.001). About one-third of the cohort did not meet any of the three lifestyle recommendations. Transgender males had increased odds for MetS components by 3.49 (95%CI: 1.63 to 7.44, p = 0.001). Treatment-naïve transgender-male adolescents have an imbalance between muscle and adipose tissue, which places them at increased susceptibility for MetS components even prior to hormonal treatment.

The role of IGF1 in determining body composition in children and adolescents with growth hormone deficiency and those with idiopathic short stature.

Treatment with recombinant human growth hormone (rhGH) increases insulin growth factor-1 (IGF1) levels, therefore, monitoring both IGF1 and growth constitutes an acceptable parameter of therapeutic safety and efficacy. We aimed to investigate the relationship between IGF1 level and body composition in children and adolescents undergoing rhGH therapy for growth hormone deficiency (GHD) and idiopathic short stature (ISS). This observational retrospective study included the bioimpedance analysis (BIA) reports (n = 305) of 135 pediatric patients (age 5-18 years), 64 with GHD and 71 with ISS, conducted as part of routine clinic visits. Sociodemographic and clinical data were extracted from medical records. Generalized estimating equations linear models were used to explore the contributing factors for body composition components of fat percentage (FATP), appendicular skeletal muscle mass (ASMM) z-score, and muscle-to-fat ratio (MFR) z-score while adjusting for cumulative doses of rhGH. Subjects with GHD exhibited higher body mass index z-scores (p < 0.001), higher FATP and truncal FATP scores, lower MFR z-score, and higher diastolic blood pressure percentiles than the ISS group (p = 0.010, p = 0.027, p = 0.050, and p = 0.050, respectively). Female sex (p < 0.001) and a GHD diagnosis (p < 0.001), were major contributors to higher FATP scores; female sex (p = 0.049) and ISS diagnosis (p = 0.005) were major contributors to higher MFR z-scores; and female sex (p < 0.001), older age (p < 0.001) and higher insulin-like growth factor 1 z-scores (p = 0.021) were major contributors to higher ASMM z-scores. Socioeconomic position and cumulative rhGH dose were not significant contributors to body composition parameters. Children with GHD, including those undergoing rhGH treatment, may be at risk for increased adiposity and associated metabolic implications. Sex- and age-adjusted IGF1 levels were related to muscle mass but not to adiposity. Hence, rhGH treatment aimed at increasing IGF1 levels may alleviate these effects by promoting muscle growth.

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence

To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. Project Viva is a prospective prebirth cohort (n=2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n=1107), early adolescence (n=1027), and mid-adolescence (n=693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n=27) had a higher BMI z-score (β; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Safety and feasibility pilot study of continuous low-dose maternal supplemental oxygen in fetal single ventricle heart disease.

Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low-dose MSO in the setting of SVP. This single-center, open-label, pilot phase-1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self-administered continuous MSO using medical-grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late-gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC). Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self-administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment-associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head-circumference-to-abdominal-circumference ratio Z-scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z-score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late-gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z-score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age. This pilot phase-1 clinical trial indicates that low-dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Body Composition and Metabolic Syndrome Components in Transgender/Gender Diverse Adolescents and Young Adults.

Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.

GENDER DIVERSITY AND FINANCIAL DISTRESS: EVIDENCE FROM NON-FINANCIAL COMPANIES IN INDONESIA

This research aims to empirically test the influence of board gender diversity on the likelihood of financial distress in non-financial companies in Indonesia. The percentage of women on the board of directors and board of commissioners is used as a proxy for the board gender diversity variable. Financial distress is measured using the Altman Z-score ratio. 2553 total observations were used from 2018-2022 to measure the effect of board gender diversity on the likelihood of distress. The results of logistic regression show that the presence of women on the board of directors and board of commissioners reduces the possibility of financial distress. The research results also show that the increase in supervision is directly proportional to the number of members of the board of directors and board of commissioners. The results of these findings can be input for decision makers regarding regulations on the number of women in company top management.

Clinical relevance of lung function trajectory clusters in middle-aged and older adults

BackgroundThe determinants and health outcomes of lung function trajectories in adults among the general population are poorly understood. We aimed to identify and characterise clusters of lung function trajectories in adults aged ≥45 years.MethodsGaussian finite-mixture modelling was applied to baseline and annualised change of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio z-scores in participants of the Rotterdam Study, a prospective population-based cohort study, with repeated spirometry (n=3884; mean±sdage 64.7±8.9 years). Longitudinal outcomes were all-cause mortality, respiratory outcomes (symptoms, COPD (FEV1/FVC &lt;0.7 in absence of asthma), preserved ratio impaired spirometry (PRISm; FEV1/FVC ≥0.7 and FEV1or FVC &lt;80%)), smoking cessation and weight changes. Independent risk factors, including genetics, were identified by multiple logistic regression.ResultsWe identified eight trajectory clusters, with the reference group having persistently normal spirometry (prevalence 42.8%). Three clusters showed higher mortality, adjusted for confounders: 1) the persistently low FEV1cluster (prevalence 6.8%, hazard ratio (HR) 1.71, 95% CI 1.37–2.13); 2) rapid FEV1decliners (prevalence 4.6%, HR 1.48, 95% CI 1.10–1.99); and 3) FVC decliners (prevalence 3.7%, HR 1.49, 95% CI 1.09–2.03). In contrast, FVC improvers (prevalence 6.7%, HR 0.61, 95% CI 0.41–0.90) and persistently high FEV1(prevalence 29.2%, HR 0.82, 95% CI 0.69–0.98) were protective trajectory clusters. Clusters were characterised by differences in genetic predisposition (polygenic scores of FEV1and FEV1/FVC), demographics, cigarette smoking, respiratory symptoms (chronic cough, wheezing and dyspnoea), cardiovascular factors (body mass index, hypertension and heart failure) and serum C-reactive protein levels. Frailty, weight changes and the development of respiratory symptoms, COPD and PRISm were significantly associated with trajectory clusters.ConclusionsThis study reveals clinically relevant lung function trajectory clusters in older adults of the general population.

Survivors of Pediatric Hematopoietic Stem Cell Transplantation Exhibit Progressive Diastolic Dysfunction Over Years of Follow-Up

Patients who have undergone hematopoietic stem cell transplantation (HSCT) in childhood have a higher risk of diastolic heart failure (HF). The rate of progression of diastolic dysfunction in aging pediatric patients is unknown and is more difficult to assess in young patients secondary to changes in diastolic indices as they grow. HSCT recipients at our center were previously found to have decline in diastolic function indices at 1 year after HSCT. This study provides follow-up of this cohort, using age-normalized z-scores to assess whether the decline in diastolic function noted at 1-year post-HSCT persists, worsens, or improves over time. Patients age <21 years who underwent HSCT at Boston Children's Hospital/Dana-Farber Cancer Center between 2005 and 2008 with ≥3 surveillance echocardiograms, including 1 performed pre-HSCT, were included. Diastolic measures included mitral inflow (E/A ratio) and Doppler tissue imaging of left ventricular lateral wall (LV lateral e'), LV septal wall (septal e') and right ventricular free wall (RV e'). Systolic function was measured by LV ejection fraction (LVEF). Normalization by age was done using z-scores, and >±2 SD was defined as abnormal in linear modeling of diastolic dysfunction and systolic dysfunction over time. In a subset of patients with adequate post-HSCT images of the entire left atrium (LA), LA volume and LA strain analyses also were performed. The study cohort comprised 61 patients (41% female; median age at HSCT, 10.7 years; median follow-up, 7.4 years). Diastolic index z-scores declined by -.045/year for LV lateral e', -.06/year for LV septal e', and -.14/year for RV e' (P < .01). The E/A ratio z-score increased by .034/year (P=.028). Linear modeling demonstrated that LV lateral e' and LV septal e' would become abnormal at 25 and 20 years post-HSCT, respectively, whereas RV e' would become abnormal sooner, at 12.6 years. LVEF z-score declined by -.04/year (P < .01) and was estimated to become abnormal at 40 years post-HSCT. Exposure to total body irradiation (TBI) was associated with worsening diastolic indices, lower LVEF (P ≤ .002), and decreased LA reservoir strain (42.0% versus 45.0%; P=.016) and conduit strain (-31.5% versus -35.1%; P=.029), although there was significant overlap between TBI and anthracycline exposure. Treatment with anthracyclines even at low doses (median, 150 mg/m2) was associated with declining LVEF but not with changes in diastolic indices. Long-term survivors of childhood HSCT exhibit declines in both LV and RV diastolic function indices. These results inform the rate of progression of LV and RV diastolic dysfunction indices over time in long-term survivors of pediatric HSCT. A significant association was observed between TBI and diastolic dysfunction and a decline in LVEF. Treatment with anthracyclines even at low doses was associated with a mild decline in LVEF. Our results can inform a lifespan perspective on disease management in this population, encourage clinicians and patients to be vigilant in following guideline-directed surveillance echocardiography, and inform anticipatory responses by clinicians as patients transition from pediatric care to adult care.

How to Broke the Dependence on Debt and Strengthen Firms: the DEBRA Proposal Against the Tax-induced Debt Bias

Objective: This article assesses the impact of the debt-equity bias reduction allowance (DEBRA) proposal on the tax-induced debt bias. The tax-induced debt bias is present in most fiscal systems around the world that “subsidize” debt. Debt is more interesting than equity because its cost, the interest, is tax-deductible. As a result, firms tend to have more debt, which then generates negative externalities. To break this trend, the European Commission published a directive proposal comprising a DEBRA. Methods: The proposal includes both a notional deduction on growth in equity and an additional limitation on interest deduction for corporate income tax purposes. To evaluate the impact of the DEBRA proposal, Polish firms’ data from the BACH database over six years, from 2015 to 2020, are analyzed. Two criteria are analyzed: the impact on the ratio of total financial debt to net equity and on an Altman’s Z-score to estimate their solidity. Results: We observe that firms tend to keep a higher level of net equity and to reduce the level of debt. A stronger solidity of firms is also noted by a reduction in their likelihood of bankruptcy. Conclusion: The DEBRA should be an interesting fiscal tool in building an anti-fragility fiscal system. The proposal appears to be promising as it reinforces the stability of the firm in reducing the global level of its financial debt. Moreover, in improving the Z-score ratio, the DEBRA proposal tends to reduce the probability of firms going bankrupt.

Cross-sectional associations between phthalates, phenols, and parabens with metabolic syndrome risk during early-to-mid adolescence among a cohort of Mexican youth

BackgroundEpidemiological studies on children and adults have linked toxicants from plastics and personal care products to metabolic disruption. Yet, the impact of endocrine-disrupting chemicals (EDCs) on adolescent metabolic syndrome (MetS) risk during early and mid-adolescence is unclear. MethodsTo examine the links between exposure to EDCs and MetS risk and its components, cross-sectional data from 344 Mexican youth in early-to-mid adolescence (10–17 years) were analyzed. Urinary biomarker concentrations of phthalates, phenol, and paraben analytes were measured from a single spot urine sample collected in 2015; study personnel obtained anthropometric and metabolic measures. We examined associations between summary phthalates and metabolites, phenol, and paraben analytes with MetS risk z-scores using linear regression, adjusted for specific gravity, sex, age, pubertal status, smoking, alcohol intake, physical activity level, and screen time. As a secondary aim, mediation analysis was conducted to evaluate the role of hormones in the association between summary phthalates with lipids and MetS risk z-scores. ResultsThe mean (SD) age was 13.2 (1.9) years, and 50.9% were female. Sex-stratified analyses revealed associations between summary phthalates and lipids ratio z-scores, including Σ DEHP [β = 0.21 (95% CI: 0.04, 0.37; p < 0.01)], phthalates from plastic sources (Σ Plastic) [β = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], anti-androgenic phthalates (Σ AA) [β = 0.22 (95% CI: 0.05, 0.39; p < 0.01)], and individual phthalate metabolites (MEHHP, MEOHP, and MECPP) among males. Among females, BPA [β = 0.24 (95% CI: 0.03, 0.44; p < 0.05)] was positively associated with lipids ratio z-score and one phenol (2,5 DCP) [β = 0.09 (95% CI: 0.01, 0.18); p < 0.05)] was associated with increased waist circumference z-score. Results showed no evidence of mediation by hormone concentrations in the association between summary phthalates with lipids ratio or MetS risk z-scores. ConclusionHigher EDC exposure was positively associated with serum lipids during adolescence, particularly among males.

Chest configuration in children and adolescents with infantile nephropathic cystinosis compared with other chronic kidney disease entities and its clinical determinants.

Infantile nephropathic cystinosis (INC) is a systemic lysosomal storage disease causing intracellular cystine accumulation, resulting in renal Fanconi syndrome, progressive kidney disease (CKD), rickets, malnutrition, and myopathy. An INC-specific disproportionately diminished trunk length compared to leg length poses questions regarding the functionality of the trunk. Thus, we prospectively investigated thoracic dimensions and proportions, as well as their clinical determinants in 44 pediatric patients with INC with CKD stages 1-5 and 97 age-matched patients with CKD of other etiology between the ages of 2-17years. A total of 92 and 221 annual measurements of patients with INC and CKD, respectively, were performed, and associations between anthropometric and clinical parameters were assessed using linear mixed-effects models. Patients with INC exhibited altered chest dimensions that were distinct from CKD controls, characterized by markedly increased chest depth to height and chest depth to chest width ratio z-scores (> 1.0), while those of patients with CKD were only mildly affected (z-score within ± 1.0). Ratio z-scores differed significantly between both patient groups from 2-6years of age onward. The degree of chest disproportion in INC patients was significantly associated with both the degree of CKD and tubular dysfunction (e.g., low serum phosphate and bicarbonate) across three different age groups (2-6, 7-12, and 13-17years). Our data show an INC-specific alteration in thoracic shape from early childhood onward, which is distinct from CKD of other etiologies, suggesting early childhood subclinical changes of the musculoskeletal unit of the thoracic cage, which are associated with kidney function. A higher resolution version of the Graphical abstract is available as Supplementary information.

Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy.

Implementing genetic analyses have unraveled rare alterations causing early-onset obesity and complications, in whom treatment is challenging. We aimed to report on the effects of adjuvant off-label therapy with liraglutide, glucagon-like peptide-1 analogue (GLP-1a), in rare genetic diagnoses. Case scenarios and review of the literature. Case 1: Nine-year-old boy with early-onset severe obesity and nonalcoholic fatty liver disease (NAFLD) due to a homozygous mutation in the MC4R gene deteriorated under lifestyle change and metformin therapy [at 10.5 years: body mass index (BMI) 51.2kg/m2, 226% of the 95th percentile, fat percentage (FP) 65% and muscle-to-fat ratio (MFR) z-score of -2.41]. One year of liraglutide treatment halted progressive weight gain [BMI 50.3kg/m2, 212% of the 95th percentile, 63.7% FP and MFR z-score of -2.34], with biochemical improvement. Case 2: Twelve-year-old boy with obesity presented with diabetes and progressive NAFLD. Exome analysis revealed two heterozygous mutations compatible with monogenic diabetes (HNF1A) and familial hypercholesterolemia (LDLR). Lifestyle modifications resulted in clinical and laboratory improvement (BMI 87th percentile, 32.8% FP, MFR z-score of -1.63, HbA1c 5.5%) without the expected recovery in liver transaminases. Liraglutide treatment augmented the improvement in weight status (BMI 68th percentile, 22.6% FP, MFR z-score of -1.13) with normalization of liver transaminases. Case 3: Nineteen-year-old male with spinal muscular atrophy type 3 presented with sarcopenic obesity and comorbidities. Treatment strategy included dietary counseling and multiple drug therapies (metformin, anti-hypertensive and statins). Liraglutide therapy led to a gradual recovery of metabolic complications allowing tapering-down other medications. Considering the pleiotropic effects of GLP1-a beyond BMI reduction, this treatment modality may serve as a game changer in challenging cases.

Analysis of Bankruptcy Prediction with Financial Ratios Altman Z-Score Model: Case Study of Oil and Gas Companies Listed on IDX in 2017-2021

Because Indonesia has abundant oil and natural gas, companies that manage oil and natural gas have established themselves there. The advent of these businesses will most likely result in rivalry. So, in this study, we will use the Altman Z-score ratio to assess the probability of bankruptcy in oil and gas companies listed on the IDX. The population targeted is individuals working in the mining sector, which produces oil and gas and is traded on the Indonesian Stock Exchange. A total of seven samples were collected. The data collection technique is a documentation technique that involves gathering secondary data with the requirements received from www.idx.co.id (IDX official website). The data analyst used panel data regression analysis with reviews. The data analyst employed is panel data regression analysis using reviews. The results of the study showed that the ratio used has a significant effect on bankruptcy prediction with the Altman Z-score model. They are evidenced by the value of f count (46.6564) &gt; f table (2.6896) with a significance of 0.000 &lt;0.05.

Symptomatology in 4-repeat tauopathies is associated with data-driven topology of [18F]-PI-2620 tau-PET signal

In recent years in vivo visualization of tau deposits has become possible with various PET radiotracers. The tau tracer [18F]PI-2620 proved high affinity both to 3-repeat/4-repeat tau in Alzheimer’s disease as well as to 4-repeat tau in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). However, to be clinically relevant, biomarkers should not only correlate with pathological changes but also with disease stage and progression. Therefore, we aimed to investigate the correlation between topology of [18F]PI-2620 uptake and symptomatology in 4-repeat tauopathies.72 patients with possible or probable 4-repeat tauopathy, i.e. 31 patients with PSP-Richardson’s syndrome (PSP-RS), 30 with amyloid-negative CBS and 11 with PSP-non-RS/CBS, underwent [18F]PI-2620-PET. Principal component analysis was performed to identify groups of similar brain regions based on 20–40 min p.i. regional standardized uptake value ratio z-scores. Correlations between component scores and the items of the PSP Rating Scale were explored.Motor signs like gait, arising from chair and postural instability showed a positive correlation with tracer uptake in mesial frontoparietal lobes and the medial superior frontal gyrus and adjacent anterior cingulate cortex. While the signs disorientation and bradyphrenia showed a positive correlation with tracer uptake in the parietooccipital junction, the signs disorientation and arising from chair were negatively correlated with tau-PET signal in the caudate nucleus and thalamus. Total PSP Rating Scale Score showed a trend towards a positive correlation with mesial frontoparietal lobes and a negative correlation with caudate nucleus and thalamus. While in CBS patients, the main finding was a negative correlation of tracer binding in the caudate nucleus and thalamus and a positive correlation of tracer binding in medial frontal cortex with gait and motor signs, in PSP-RS patients various correlations of clinical signs with tracer binding in specific cerebral regions could be detected.Our data reveal [18F]PI-2620 tau-PET topology to correlate with symptomatology in 4-repeat tauopathies. Longitudinal studies will be needed to address whether a deterioration of signs and symptoms over time can be monitored by [18F]PI-2620 in 4-repeat tauopathies and whether [18F]PI-2620 may serve as a marker of disease progression in future therapeutic trials. The detected negative correlation of tracer binding in the caudate nucleus and thalamus with the signs disorientation and arising from chair may be due to an increasing atrophy in these regions leading to partial volume effects and a relative decrease of tracer uptake in the disease course. As cerebral regions correlating with symptomatology differ depending on the clinical phenotype, a precise knowledge of clinical signs and symptoms is necessary when interpreting [18F]PI-2620 PET results.

Altered Fetal Cardiac Function in Smoking During Pregnancy

AbstractMaternal smoking during pregnancy remains a major public health issue and is associated with adverse perinatal outcomes. This study aimed to evaluate fetal cardiac functions in chronic maternal smoking during pregnancy and to compare them with non-smoker pregnant women. Forty-two smoker pregnant women between 24 and 34 weeks of gestation and gestational age-matched 44 non-smoker pregnant women were enrolled in this cross-sectional study. Fetal cardiac functions were measured using conventional Doppler echocardiography. The peak velocities of the mitral valve during early diastole (E) and atrial contraction (A) were measured, and the E/A ratio was calculated. The following time periods were also calculated; isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET). Then, the fetal left ventricle modified myocardial performance index (Mod-MPI) was calculated. No significant differences were noted between the groups in terms of E, A, and E/A ratio z-scores (p &gt; 0.05). The ICT and IRT z-scores were found to be significantly higher in the study group compared with those in the control group (p = 0.001 and p = 0.034). Mod-MPI z-score was also found significantly higher in the study group than in the control group (p = 0.034). There was no significant difference between the groups in terms of ET (p &gt; 0.05). The signs of systolic, diastolic, and global cardiac dysfunction were demonstrated in fetuses of pregnant women with chronic smoking. It, therefore, merits consideration that the fetal heart is also exposed to the detrimental effects of smoking.

Growth During Infancy After Extremely Preterm Birth: Associations with Later Neurodevelopmental and Health Outcomes

To evaluate associations between changes in weight, length, and weight/length ratio during infancy and outcomes later in life among individuals born extremely preterm. Among participants in the Extremely Low Gestational Age Newborn (ELGAN) study, we measured weight and length at discharge from the neonatal intensive care unit (NICU) and at age 2years and evaluated neurocognitive, psychiatric, and health outcomes at age 10years and 15years. Using multivariable logistic regression, we estimated associations between gains in weight, length, and weight/length ratio z-scores between discharge and 2years and outcomes at 10 and 15years. High gain was defined as the top quintile of change; low gain, as the bottom quintile of change. High gains in weight and weight/length were associated with greater odds of obesity at 10years, but not at 15years. These associations were found only for females. High gain in length z-score was associated with lower odds of obesity at 15years. The only association found between high gains in growth measures and more favorable neurocognitive or psychiatric outcomes was between high gain in weight/length and lower odds of cognitive impairment at age 10years. During the 2years after NICU discharge, females born extremely preterm with high gains in weight/length or weight have greater odds of obesity at 10years, but not at 15years. Infants with high growth gains in the 2years after NICU discharge have neurocognitive and psychiatric outcomes in middle childhood and adolescence similar to those of infants with lower gains in weight and weight/length.