Lower Z-scores Research Articles

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 < 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 < 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 < 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.

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.

12566 Adult Growth Hormone Deficiency, Replacement Therapy Use, and IGF1 Levels in Association with Physical, Psychosocial, and Neurocognitive Outcomes Among Childhood Cancer Survivors

Abstract Disclosure: T. Yoshida: None. J.L. Baedke: None. H. Wang: None. C.H. Yu: None. C.L. Wilson: None. D.A. Mulrooney: None. S.B. Dixon: None. I. Huang: None. T.M. Brinkman: None. K.R. Krull: None. S. Mostoufi-Moab: None. J. Miguel Martínez: None. K.K. Ness: None. M.M. Hudson: None. Y. Yasui: None. A. Delaney: None. Background: Adult growth hormone deficiency (aGHD) is a common and often untreated late effect among childhood cancer survivors. Untreated aGHD likely adds to the burden of health outcomes in survivors already experiencing cancer treatment related late toxicities. As comprehensive data on the consequences of untreated aGHD in survivors are scarce, we assessed the clinical impact of untreated aGHD among survivors, together with socioeconomic factors as potential contributing factors, utilizing a large, clinically characterized cohort of childhood cancer survivors. Methods: 3902 five-year survivors ≥ 18 years old [median (25th-75th percentile) age, 31.7y (25.2-40.0); age at cancer diagnosis 8.1y (3.5-13.6); 47.5% female] were examined. We assessed the: 1) proportion of survivors with aGHD on GH therapy (GHT); 2) association between GHT and socioeconomic factors (e.g., household income, area deprivation index) by multivariable logistic regression; and 3) associations between age- and sex-adjusted insulin-like growth factor 1 (IGF1) z-score and prevalence of clinically-assessed (i.e., body composition, metabolic/cardiovascular factors, neurocognitive function) and self-reported [i.e., quality of life (QoL), emotional symptom] outcomes by multivariable logistic regression with trend test, adjusting for potential confounders (e.g., radiation to the hypothalamic-pituitary region). Results: aGHD was observed in 9.1% (354/3902) of survivors; among them, 9.0% (32/354) were on GHT. Survivors on GHT were more likely to have higher household income, hold health insurance, and reside in less socioeconomically disadvantaged neighborhoods, compared to survivors with untreated aGHD. Socioeconomic factors had significant independent associations with GHT use in multivariable analysis [e.g., annual household income &amp;lt;$40,000 vs. ≥$80,000, adjusted odds ratio (aOR) of GHT use, 0.28; 95% confidence interval (CI), 0.08-0.86]. Lower IGF1 z-score (IGF1 z-score ≤ -2, vs. IGF1 z-score &amp;gt;0) was associated with a higher prevalence of various outcomes (aOR, 95% CI), such as abdominal obesity (2.56, 1.98-5.26), weak handgrip strength (2.49, 1.65-3.73), hypertension (1.47, 1.06-2.04), abnormal glucose metabolism (2.07, 1.49-2.86), impaired health-related QoL (e.g., physical functioning, 1.97, 1.35-2.86), depression (1.58, 1.06-2.33), and impairment in multiple neurocognitive functions (e.g., verbal reasoning, a global measure of intelligence, 2.22, 1.49-3.30) with a dose-response relationship. Conclusions: Our data support a negative impact of untreated aGHD on physical, psychosocial, and neurocognitive outcomes among survivors and suggest the potential of GHT to improve QoL of survivors with aGHD. As lower socioeconomic status may affect survivors’ access to GHT, this disparity should be considered in interventions evaluating GHT for survivors with aGHD. Presentation: 6/3/2024

6805 Impact of Feeding Types on Catch-Up Growth in Early Infancy Among Small-for-Gestational-Age Infants: A Nationwide Korean Study

Abstract Disclosure: J. Choi: None. Y. Choe: None. S. Yang: None. Purpose: The study aimed to compare growth patterns and catch-up growth (CUG) in small-for-gestational-age (SGA) infants up to age four, based on feeding type during the first 4-6 months, using nationwide data. Methods: A total of 42,295 children born SGA (21,917 boys, 52.%) who underwent the first (4-6 month), 2nd (9-12 month), 3rd (18-24 month) and 5th (42-48 month) National Health Screening Program for Infants and Children (NHSPIC) under the National Health Insurance Service from 2007 to 2014 were included. The study population was categorized into two groups based on the primary milk feeding type recorded in the self-reported questionnaire during the first round of NHSPIC: the ”Breastfed”group, and the "Formula-fed" group. Catch-up growth (CUG) was defined as a Height Standard Deviation Score (Ht SDS) of 3rd percentile or above at the 5th NHSPIC visits. We used propensity scores to 1:1 match breastfed and formula-fed group based on sex, birth weight, cesarean section, socioeconomic status, residance. Multivariate logistic regression analysis was performed to evaluate the effect of milk feeding type on CUG at 4 years of age. Results: 49.1% of infants (n = 20,774) were breastfed and 50.9% (n = 21,521) were formula-fed. The median birth weight was 2.7 kg (interquartile range: 2.5-2.9 kg), and 98.7% of the children (n = 41,752) achieved CUG by the 5th NHSPIC round. Following propensity score matching, both groups included 19,308 infants. At four years of age, the breastfed group showed a lower likelihood of achieving CUG compared to the formula-fed group (aOR 0.794, 95% CI 0.665-0.948). During the 1st NHSPIC round, the breastfed group had a significantly lower weight Z-score (mean: -0.05, range: -0.64 to 0.41) than the formula-fed group (mean: 0.14, range: -0.42 to 0.78, p &amp;lt; 0.001). This trend was more pronounced from the 1st to 2nd round, with greater decreases in both weight and height Z-scores for the breastfed group (weight difference: -0.36, range: -0.74 to 0.02; height difference: -0.21, range: -0.62 to 0.20) compared to the formula-fed group (weight difference: -0.17, range: -0.53 to 0.20; height difference: -0.13, range: -0.53 to 0.28, p &amp;lt; 0.001). However, from the 2nd round, the breastfed group demonstrated faster gains in both weight and height (p &amp;lt; 0.001). Conclusion : In a study of Korean SGA infants, those breastfed during the first 4-6 months post-birth had lower CUG rates at four years compared to formula-fed infants. The breastfed group exhibited less weight and height gain, especially between the 1st and 2nd NHSPIC rounds, aligning with the initial phase of solid food introduction. These findings may suggest the need for enhanced nutritional supplementation for breastfed SGA infants. Further research is necessary to explore other factors that may impact growth during this critical developmental period. Presentation: 6/3/2024

Long-term respiratory consequences of prematurity.

Approximately 10% of all children worldwide are born preterm and respiratory consequences are amongst the most common sequelae of preterm birth. Except for a higher prevalence of respiratory symptoms and hospital admissions, preterm birth is associated with lower lung function that may track into adulthood. Lung function impairment is not restricted to extreme or very preterm-born subjects as also children born moderate-late preterm have lower Z-scores for lung function. Given the heterogeneity of prematurity-associated lung disease, phenotype-based, multidisciplinary management is needed to improve respiratory health in preterm-born subjects.

Fixed Airflow Obstruction in Asthma Can Be Identified Early by Low FEF25-75% and is Associated with Environmental Exposure.

This study aimed to identify environmental risk factors associated with asthmatic fixed airflow obstruction (FAO) and assess the relationship between small airway abnormalities defined by forced expiratory flow at 25-75% (FEF25-75%) and FAO. We analyzed data from 312han Chinese patients with stable asthma on standard treatment. Low FEF25-75% was defined as post-bronchodilator FEF25-75% z-score <-0.8435, and FAO as post-bronchodilator FEV1/FVC z-score <-1.645. Exposure levels were retrospectively analyzed in relation to FAO risk in asthmatics. Asthmatics were grouped by low FEF25-75% and FAO, and lung function, environmental exposure, daily symptoms, and exacerbations in the previous year were compared cross-sectionally across groups. In retrospective analyses, pack-years of smoking in male patients (adjusted odd ratio [95% confidence interval] 1.05 [1.03-1.07], P<0.001), biomass exposure for >20 years (2.65 [1.13-6.43], P=0.027), occupational exposure for >10 years (2.01 [1.06-3.86], P=0.035) and occupational exposure for >20 years (2.67 [1.24-5.91], P=0.013) were associated with asthmatic FAO. In cross-sectional analyses, compared with the normal FEF25-75%/ asthmatics without FAO (NON-FAO) group, the low FEF25-75%/ asthmatics with FAO (FAO) group had lower FEV1 z-scores and FEV1/FVC z-scores, more pack-years and years of biomass and occupational exposure, higher Asthma Control Questionnaire-5 and Chronic Obstructive Pulmonary Disease Assessment Test scores, and more frequent exacerbations. The low FEF25-75%/NON-FAO group showed the same trend, but to a lesser extent. Chronic airway inflammation is not the only driver of asthmatic FAO, and management and treatment targeting environmental risk factors (smoking and biomass and occupational exposures) may slow FAO progression in asthmatics. The FEF25-75% determined by the z-score is a reliable marker of small airway abnormalities, and patients with low FEF25-75% are at greater risk for FAO, requiring more frequent follow-up.

Potential effects of attention deficit hyperactivity disorder medication on body height and body weight in a longitudinal pediatric cohort study, the LIFE Child study.

Purpose: To investigate the potential impact of drugs for the treatment of attention deficit hyperactivity disorder (ADHD) on body weight and height in children and adolescents from the LIFE ('Leipzig Research Centre for Civilization Diseases', Leipzig, Germany) Child cohort. Methods: We included 2,115 participants aged ≥6 to <18.25 years who attended the LIFE study center between 2011 and 2020 in our analysis, of whom 48 used ADHD drugs. Anthropometric and medication data from baseline to the third follow-up visit were available for 659 participants. Body height and body weight measurements were subsequently converted to z-scores. A repeated measures analysis of variance (ANOVA) was performed on the z-scores of both ADHD drug users and non-users to determine potential trends in body weight and body height from baseline to the 3 rd annual follow-up. Results: At the last visit with ADHD drug use of the 48 ADHD drug users, 40% (19/48) of the children and adolescents were below the 25 th reference percentile for weight. Z-scores for body height declined from baseline to the 3rd annual follow-up in individuals who used ADHD drugs (n=10; Differencemeans =-0.310; p=0.002) compared to non-users (n=649; Differencemeans =0.102; p<0.001). Body weight also decreased from baseline to 3rd follow-up in the ADHD drug group (n=10; Differencemeans =-0.473; p<0.001) compared to the non-user group (n=649; Differencemeans =0.015; p=0.161). Conclusion: We observed a potential tendency towards lower Z-scores for body height and body weight in individuals taking ADHD medication for an extended period compared to the corresponding age- and sex-matched populations.

Characterization and Z-score Calculation of Cardiac MRI parameters in patients after the Fontan operation. A Fontan Outcome Registry using CMR Examinations (FORCE) study

BackgroundCardiac magnetic resonance (CMR) offers valuable hemodynamic insights post-Fontan, but is limited by the absence of normative single ventricle data. The Fontan Outcomes Registry using CMR Examinations (FORCE) is a large international Fontan-specific CMR registry. This study used FORCE registry data to evaluate expected CMR ventricular size/function and create Fontan-specific z-scores adjusting for ventricular morphology (VM) in healthier Fontan patients. Methods“Healthier” Fontan patients were defined as patients free of adverse outcomes, who are New York Heart Association Class I, have mild or less valve disease, and <30% aortopulmonary collateral burden. General linear modeling was performed on 70% of the dataset to create z-scores for volumes and function. Models were tested using the remainder (30%) of the data. The z-scores were compared between children and adults. The z-scores were also compared between “healthier” Fontan and patients with adverse outcomes (death, listing for transplantation or multiorgan disease). ResultsThe “healthier” Fontan population included 885 patients (15.0 ± 7.6 years) from 18 institutions with 1,156 CMR examinations. Patients with left ventricle morphology had lower volume, mass and higher ejection fraction (EF) compared to right or mixed (two-ventricles) morphology (p<0.001 for all pairwise comparisons). Gender, BSA and VM were used in z-scores. Of the “healthier” Fontan patients, 647 were children <18 years and 238 were adults. Adults had lower ascending aorta flow (2.9 ± 0.7 vs 3.3 ± 0.8L/min/m2, p<0.001) and ascending aorta flow z-scores (-0.16 ± 1.23 vs 0.05 ± 0.95, 0.02) compared to children. Additionally, there were 1595 patients with adverse outcomes who were older (16.1 ± 9.3 vs 15.0 ± 7.6, p<0.001) and less likely to have LV morphology (35 vs 47%, p<0.001). Patients with adverse outcomes had higher z-scores for ventricular volume and mass and lower z-scores for EF and ascending aorta flow compared to the “healthier” Fontan cohort. ConclusionThis is the first study to generate CMR z-scores post-Fontan. Importantly the z-scores were generated and tested in “healthier” Fontan patients and both pediatric and adult Fontan patients. These equations may improve CMR-based risk stratification after the Fontan operation.

Efficacy and mechanism of Schisandra chinensis active component Gomisin A on diabetic skin wound healing: network pharmacology and in vivo experimental validation

Ethnopharmacological relevanceSchisandra chinensis (Turcz.) Baill., a common traditional Chinese herbal medicine, has been used for the treatment of diabetes mellitus and its complications. However, the major active component for treating diabetic foot ulcers, a serious complication of diabetes mellitus, was unclear. This study aimed to predict the treatment effect of the active components in Schisandra chinensis against diabetic skin wound using network pharmacology and to confirm the underlying mechanism using a diabetic skin wound model in vivo. Aim of the studyTo study the effects and underlying mechanisms of Schisandra chinensis and its main component Gomisin A on diabetic skin wound healing by network pharmacology and high-fat diet (HFD)-induced obese mice model in vivo. Materials and methodsTo determine the effectiveness of Schisandra chinensis on diabetic skin wound, network pharmacology was first used. Components of Schisandra chinensis were obtained from the Traditional Chinese Medicine Systems Pharmacology database. The active components were further verified through absorption, distribution, metabolism and excretion. The potential targets of the active components were identified from the Traditional Chinese Medicine Systems Pharmacology, SwissTargetPrediction, TargetNet, and the Comparative Toxicogenomics Database. Targets related to diabetic skin wound were collected from the GeneCards, OMIM, DisGeNET, and PharmGKB databases. The interaction network formed by the intersection of the two datasets was analyzed using Gephi. Network-based proximity was used to predict the network distance between the active components of Schisandra chinensis and diabetic skin wound. Gomisin A was found to have the lowest Z-score and was administered either orally or via topical injection to HFD-induced obese mice daily until the wounds healed, and its effects on skin wound healing were evaluated. ResultsOnly five active ingredients of Schisandra chinensis were screened in our system: Gomisin A, Longikaurin A, Deoxyharringtonine, Wuweizisu C, and Interiotherin B, which can regulate biological processes related to diabetic skin wound, including positive regulation of phosphorous metabolic process, positive regulation of cell migration, and response to wounding. Network proximity analysis found that Gomisin A has the closest distance-based Z-score among the diabetic skin wound modules and drug targets in the human protein-protein interaction network. The HFD-induced obese mice model further revealed that Gomisin A accelerated skin wound healing by increasing insulin sensitivity and decreasing the advanced glycation end-products mediated toll-like receptor 4 (TLR4)-p38 MAPK-IL6 inflammation signaling pathway. ConclusionsThe network pharmacology and in vivo studies indicated that Gomisin A from Schisandra chinensis played a crucial role in improving diabetic skin wound healing.

Meta-analysis of bone mineral density in adults with phenylketonuria

BackgroundLifelong management of phenylketonuria (PKU) centers on medical nutrition therapy, including dietary phenylalanine (Phe) restriction in addition to Phe-free or low-Phe medical foods/protein substitutes. Studies have reported low bone mineral density (BMD) in mixed-age PKU populations, possibly related to long-term Phe restriction. Therefore, a meta-analysis investigating BMD specifically in adults with PKU was conducted.MethodsStudies reporting BMD-related outcomes were identified from a systematic literature review evaluating somatic comorbidities experienced by adults with PKU on a Phe-restricted diet (searched February 1, 2022, updated November 1, 2023). Risk of study bias was assessed (Scottish Intercollegiate Guidelines Network checklists). The primary outcome of the meta-analysis was pooled mean BMD Z-scores of different bones. Secondary outcomes were the prevalence of low BMD Z-scores at pre-specified thresholds. Subgroup analyses of mean BMD Z-scores (decade of study publication, controlled versus uncontrolled blood Phe levels, gender) were conducted.ResultsBMD-related data from 4097 individuals across 10 studies rated as at least acceptable quality were included. Mean BMD Z-scores were statistically significantly lower compared with an age-matched control or reference (non-PKU) population, across bones, but still within the expected range for age (> -2.0): lumbar spine (seven studies, n = 304), -0.63 (95% confidence interval (CI): -0.74, -0.52); femoral neck (four studies, n = 170), -0.74 (95% CI: -1.25, -0.22); radius (three studies, n = 114), -0.77 (95% CI: -1.21, -0.32); total body (four studies, n = 157), -0.61 (95% CI: -0.77, -0.45). The small number of observations in the subgroup analyses resulted in a high degree of uncertainty, limiting interpretation. Estimated prevalence of BMD Z-scores ≤ -2.0 was 8% (95% CI: 5%, 13%; four studies, n = 221) and < -1.0 was 42% (95% CI: 35%, 51%; five studies, n = 144).ConclusionsAdults with PKU had lower BMD Z-scores than the reference (non-PKU) population but < 1 in 10 were below the expected range for age. The low number of studies prevents identification of which population characteristics are most impacting BMD.This meta-analysis was supported by BioMarin Pharmaceutical Inc., Novato, CA and is registered with the Research Registry (reviewregistry1476).

Using the Altman’s Z-score formula to assess the bankruptcy risk of state - owned construction enterprises in Vietnam

In the current economic situation affected by epidemics, wars, recessions, etc., construction enterprises in Vietnam in general and state – owned construction enterprises in particular face many difficulties to maintain performance efficiency. On the other hand, the policies of restructuring and equitization of state-owned enterprises also have a strong impact on the financial management of construction enterprises in Vietnam. This study uses data from financial statements of 22 state-owned construction enterprises in Hanoi from 2017 to 2021 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. The research results show that a few enterprises are in the "safe" zone and "grey" one while most are in "distress" zone. The cause of inefficient business performance is that the revenue and profit ratio to total assets of state-owned construction enterprises to decrease sharply, the ratio of working capital to total assets is low. Moreover, the ratio of equity to total debt is the most important reason for the low Z-score, which means predicting a high risk of bankruptcy in state-owned construction enterprises. The evidence base from the research results is used to propose 5 solutions to reduce the risk of bankruptcy and improve the efficiency of financial management of enterprises.

Nutritional status and extended metabolic screening in Egyptian children with uncomplicated type 1 diabetes

Nutritional status assessment, including amino acids, carnitine, and acylcarnitine profile, is an important component of diabetes care management, influencing growth and metabolic regulation. A designed case–control research included 100 Egyptian participants (50 T1DM and 50 healthy controls) aged 6 to 18 years old. The participants' nutritional status was assessed using the Body Mass Index (BMI) Z-score. Extended metabolic screening (EMS) was performed using a high-performance liquid chromatography-electrospray ionization-mass spectroscopy system to evaluate the levels of 14 amino acids, free carnitine, and 27 carnitine esters. T1DM children had considerably lower anthropometric Z-scores than the control group, with 16% undernutrition and 32% short stature. Total aromatic amino acids, phenylalanine, phenylalanine/tyrosine ratio, proline, arginine, leucine, isoleucine, free carnitine, and carnitine esters levels were considerably lower in the diabetic group, suggesting an altered amino acid and carnitine metabolism in type 1 diabetes. BMI Z-score showed a significant positive correlation with Leucine, Isoleucine, Phenylalanine, Citrulline, Tyrosine, Arginine, Proline, free carnitine, and some carnitine esters (Acetylcarnitine, Hydroxy-Isovalerylcarnitine, Hexanoylcarnitine, Methylglutarylcarnitine, Dodecanoylcarnitine, Tetradecanoylcarnitine, and Hexadecanoylcarnitine). HbA1c% had a significant negative correlation with Total aromatic amino acids, Branched-chain amino acid/Total aromatic amino acids ratio, Glutamic Acid, Citrulline, Tyrosine, Arginine, Proline, and certain carnitine esters (Propionylcarnitine, Methylglutarylcarnitine, Decanoylcarnitine, Octadecanoylcarnitine and Octadecenoylcarnitine), suggest that dysregulated amino acid and carnitine metabolism may be negatively affect the glycaemic control in children with TIDM. In conclusion, regular nutritional assessments including EMS of T1DM patients are critical in terms of diet quality and protein content for improved growth and glycemic management.

Social determinants of health and somatic growth in preterm infants and children with chronic lung disease.

Bronchopulmonary dysplasia (BPD), a common complication of prematurity, is associated with impaired lung function and increased morbidity in childhood. These children display heterogeneous somatic growth patterns which may ultimately impact their risk for later respiratory disease. We aim to understand the relationship between socioenvironmental exposures and growth in this population. A retrospective longitudinal cohort study was conducted using participants (n = 616) enrolled in the Johns Hopkins Outpatient BPD Registry. Growth measurements between 0 and 36 months of age were obtained. Somatic growth measurements, both corrected and uncorrected for gestational age, were converted to z-scores using Center for Disease Control and Prevention normative data. Using a participant's residential zip code, we utilized the 2019 Area Deprivation Index (ADI), the Childhood Opportunity Index (COI) 2.0, and neighborhood food insecurity data from the Maryland Food Bank. Linear regression analysis was performed employing individual socioenvironmental measures as independent variables and growth z-scores as dependent variables in univariate analysis. Univariate analysis was repeated adjusting for gestational age, BPD severity, and the presence of a gastrostomy tube (GT). Of the three measures analyzed, national COI (nCOI) showed a significant association with mean weight z-scores, mean ADI showed some association with mean weight z-scores, and the percentage of a community experiencing food insecurity showed no association with mean weight z-scores. After adjusting for gestational age, BPD severity, and presence of a GT, children living in areas of greater opportunity (higher nCOI values), had significantly lower weight z-scores at 12 months corrected and at 24 and 36 months uncorrected CONCLUSIONS: Our findings suggest that the COI 2.0, a multidimensional measure, captures more facets of an individual's social environment, as compared to the singular nature of a measure of food insecurity. There are several potential explanations for the phenomenon seen, and further understanding of this dynamic is crucial for designing effective interventions and policies to better address inequities in outcomes.

Association between HIV and cytomegalovirus and neurocognitive outcomes among children with HIV.

Children with HIV may experience adverse neurocognitive outcomes despite antiretroviral therapy (ART). Cytomegalovirus (CMV) is common in children with HIV. Among children on ART, we examined the influences of early HIV viral load (VL) and CMV DNA on neurocognition. We determined the association between pre-ART VL, cumulative VL, and CMV viremia and neurocognition using data from a cohort study. Children who initiated ART before 12 months of age were enrolled from 2007-2010 in Nairobi, Kenya. Blood was collected at enrollment and every 6 months thereafter. Four neurocognitive assessments with 12 domains were conducted when children were a median age of 7 years. Primary outcomes included cognitive ability, executive function, attention, and motor. Generalized linear models were used to determine associations between HIV VL (pre-ART and cumulative; N = 38) and peak CMV DNA (by 24 months of age; N = 20) and neurocognitive outcomes. In adjusted models, higher peak CMV viremia by 24 months of age was associated with lower cognitive ability and motor z-scores. Higher pre-ART HIV VL was associated with lower executive function z-scores. Among secondary outcomes, higher pre-ART VL was associated with lower mean nonverbal and metacognition z-scores. Higher pre-ART VL and CMV DNA in infancy were associated with lower executive function, nonverbal and metacognition scores and cognitive ability scores in childhood, respectively. These findings suggest long-term benefits of early HIV viral suppression and CMV control on neurocognition.

Accurate prenatal diagnosis of coarctation of the aorta by 3-step echocardiographic diagnostic protocol

BackgroundCoarctation of the aorta (CoA) is the most common undiagnosed congenital heart defect during prenatal screening. High false positive and false negative rates seriously affect prenatal consultation and postnatal management. The objective of the study was to assess the utility of various measurements to predict prenatal CoA and to derive a diagnostic algorithm.MethodsOne hundred and fifty-four fetuses with suspected CoA who presented at Fuwai Hospital between December 2017 and August 2021 were enrolled and divided into confirmed CoA cases (n = 47) and false positive cases (n = 107), according to their postnatal outcomes. The transverse aortic arch, isthmus, and descending aorta were measured in the long-axis view of the aortic arch. The angle between the transverse aortic arch (TAO) and the descending aortic arch (DAO) was defined as the TAO-DAO angle and measured in the long axis or sagittal view. Based on the database in GE Voluson E10 and the formula (Z = \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\frac{\ ext{x}-{\\mu }}{\\alpha }$$\\end{document}), the standard score (Z-score) of the dimensions of the aorta were calculated in relation to the gestational age. The main echocardiographic indices were combined to design a 3-step diagnostic protocol. The TAO-DAO angle was used as the first step in the diagnostic model. The diameter of the transverse arch and the Z-score of the isthmus were the second step. The third-step indices included a Z-score of the transverse arch, diameter of the isthmus, distance from the left subclavian artery (LSA) to left common carotid artery (LCCA), the ratio of isthmus diameter and LSA diameter and ratio of the distances (the distance between the LSA and LCCA to the distance between the right innominate artery and LCCA). The receiver operating characteristic (ROC) curve determined the predictive capability of each diagnostic parameter, and the kappa test determined the diagnostic accuracy of the proposed model.ResultsThe cases with confirmed CoA had thinner transverse arches (1.92 ± 0.32 mm vs. 3.06 ± 0.67 mm, P = 0.0001), lower Z-scores of the isthmus (-8.97 ± 1.45 vs. -5.65 ± 1.60, P = 0.0001), smaller TAO-DAO angles (105.54 ± 11.51° vs. 125.29 ± 8.97°, P = 0.0001) and larger distance between the LSA and LCCA (4.45 ± 1.75 mm vs. 2.74 ± 1.07 mm, P = 0.0001) than the false positive cases. The area under the curve (AUC) was 0.947 (95% CI 0.91–0.98) for the TAO-DAO angle ≤ 115.75°, 0.942 (95% CI 0.91–0.98) for the transverse arch diameter ≤ 2.31 mm, 0.937 (95% CI 0.90–0.98) for the Z-score of the isthmus ≤ -7.5, and 0.975 (95% CI 0.95–1.00) for the 3-step diagnostic protocol with 97.8% sensitivity and 97.2% specificity. The kappa test showed that the model’s diagnostic accuracy was consistent with postnatal outcomes (kappa value 0.936, P = 0.0001).ConclusionsThe 3-step diagnostic protocol included the three most useful measurements and the additional indices with appropriate cut-off values. The algorithm is useful for the detection of aortic coarctation in fetuses with a high degree of accuracy.Trial registrationRetrospectively registered.

Exploring the relationship between Total Athleticism score and CrossFit® Open Performance in amateur athletes: single measure involving body fat percentage, aerobic capacity, muscle power and local muscle endurance.

There has been an increasing interest among CrossFit® coaches and practitioners in identifying indicators of sport performance. This study aimed to examine the correlation between anthropometric measures, cardiorespiratory capacity, power, local muscle endurance, and total athleticism score, with performance in the CrossFit® Open 2021. Fourteen male volunteers (aged 30.3 ± 5.8 years) participated in the study and underwent a series of tests on separate weeks. These tests included assessments of body fat percentage (subcutaneous adipose thickness measured at seven sites), maximal oxygen consumption (2 km test in rowing ergometer), muscle power (one repetition maximum in power clean), and muscle endurance (Tibana test, which included the conclusion of four distinct rounds of work). These results were used to calculate the total score of athleticism, which was then compared to the participants performance during the CrossFit® Open 2021. The athletes presented an average of body fat (8.6 ± 2.0%), maximal oxygen consumption (53.3 ± 2.4 mL. (kg.min)-1), 2km row time (07:00 ± 00:21 mm:ss), 1-Repetition maximum in power clean (125.2 ± 21.2 kg) and Tibana test performance (281.0 ± 35.9 repetitions). Interestingly, the top five athletes with the highest scores also achieved the highest z-scores in the CrossFit® Open 2021. Conversely, the four athletes with the lowest TSA score had the lowest z-scores in the CrossFit® Open. Moreover, almost perfect correlation (r = 0.91; p<0.01) was found between the total athleticism score and z-scores in the CrossFit® Open 2021. The total score may be a single measure and holistic indication of athleticism level in CrossFit®. Furthermore, coaches can potentially apply this useful tool for monitoring athletic performance and designing training sessions that address specific areas of CrossFit® performance.