Sum Of Z-scores Research Articles

The influence of access to care on radiation therapy utilization among older women with breast cancer.

1539 Background: In 2004, the Cancer and Leukemia Group B (CALGB) C9343 trial compared outcomes among women aged ≥ 70 who had stage I, estrogen-receptor positive (ER+) breast cancer (BC) who received a lumpectomy and hormonal therapy, treated with and without radiation therapy (RT). While the trial found that overall survival was not different between groups, RT use did not significantly decline after its publication. We investigated regional variation in RT utilization in the United States (US) and its association to access to healthcare among women aged ≥ 70 diagnosed with localized ER+ BC after partial mastectomy (PM) between 2004–2020. We hypothesize that women with greater access to health care will more often receive RT. Methods: To examine regional variation in the use of RT and its association with access to healthcare, we extracted data from the Surveillance, Epidemiology, and End Results 17 registry. From 2004 – 2020, 105,694 women aged ≥ 70 years who received a PM for localized ER+ BC across 199 US counties with a population > 50,000 were identified. Access to healthcare was measured using six socioeconomic (SES) variables: median household income, % with high school education, % of families above poverty line, % with bachelor’s degree, % speaking English, and % employed, measured from 2015-2019. A multivariable linear regression model tested for association between each variable and RT use. A composite SES score was calculated as the sum of z-scores across all six variables and we identified the top 20 and bottom 20 scoring counties. SES score was used as a surrogate for access to healthcare and was correlated to RT use using a linear regression model. Results: The percentage of women aged ≥ 70 receiving RT after PM for localized ER+ BC varied across counties from 19.0% to 84.6%. In 2004, receipt of RT was similar between the top 20 and bottom 20 counties (67.8% vs 65.2%, respectively). This decreased after publication of CALGB C9343; by 2020 receipt of RT was 58.7% for the top 20 and 49.2% for the bottom 20 SES counties (Table). In linear regression analysis, SES was significantly associated with RT use (p<0.0001). In multivariable linear regression analysis, only % above high school education was significantly associated with RT use (p=0.0205). Conclusions: Among women aged ≥ 70 with localized ER+ BC who underwent PM and who were candidates for omission of RT, those who lived in higher SES counties were more likely to receive RT from 2004 – 2020. Since the CALGB C9343 trial in 2004, RT use has declined; however, the decline was less among those with higher SES and therefore likely less among those with greater access to healthcare. These women may experience over treatment, which may result in personal or system wide harms. [Table: see text]

Cytokine and Mutation Profiling Reveal Patterns of Complete Remission Rates with Lenzilumab Combination Therapy in Chronic Myelomonocytic Leukemia

Introduction: Chronic myelomonocytic leukemia (CMML) is characterized by accumulation of classical CD14+CD16- inflammatory monocytes driven in part by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), a pro-inflammatory cytokine. Standard of care in CMML includes hypomethylating agents such as azacytidine (AZA), with complete response (CR) rates of 16-21% 1,2 and no reliable biomarkers that predict response. The complete pro-inflammatory profile of CMML is unknown and no treatment addresses the hematologic aberrations of CMML. Lenzilumab (LENZ; Humanigen, Inc., Short Hills, NJ) is a proprietary Humaneered ® first-in-class monoclonal antibody with best-in-class off-rate and affinity that neutralizes GM-CSF. The interim analysis of the PREcision Approach to CHronic Myelomonocytic Leukemia (PREACH-M; ACTRN12621000223831) trial showed LENZ/AZA treatment in 11 subjects with RAS-pathway ( NRAS/ KRAS/ CBL) mutations resulted in 8 subjects with complete response or optimal marrow response and improvements in hematological parameters. This report describes the cytokine profiles and systemic C-reactive protein levels of these subjects. Methods: PREACH-M is a Phase 2/3 non-randomized, open-label trial in 72 subjects, aged at least 18 years, with newly diagnosed CMML based on the WHO 2016 criteria; and RAS-pathway mutations at a variant allele frequency ≥3%. Subjects received 24 cycles (every 28 days) of AZA (SC; 75 mg/m 2 for 7 days) and LENZ (IV; 552 mg; d1 & d15 of cycle 1 and d1 only for all subsequent cycles). Subjects without RAS-pathway mutations received the same AZA regimen and sodium ascorbate (IV; 30g for 7 days (15g for 1st dose only; 30g thereafter if no evidence of tumor lysis syndrome); PO; 1.1g on all other days). Cytokine profiling from bone marrow plasma was performed after 4,7,12 and 24 months using Milliplex Human Cytokine/Chemokine Magnetic bead panel and compared with 24 age-matched healthy subjects. Unsupervised hierarchical clustering with Ward's method sought distinct CMML patterns based on cytokine expression. C-reactive protein (CRP) was determined from blood samples using a routine assay. Variant allele frequencies were determined from bone marrow mononuclear cells using a 41-myeloid panel using Illumina Hi-Seq with a depth of 1000x. Results: As of July 2023, 15 subjects were enrolled in the LENZ/AZA arm (8 females, 7 males with mean age 69; mean white cell count, 21x10 9/L; mean Hb, 121 g/L, mean platelet count; 74x10 9/L, mean blast count, 10.1%). CRP decreased from a median of 5.6 at baseline to 2.1 mg/L after 6 months of LENZ/AZA (P=0.02). GM-CSF and other pro-inflammatory cytokines were increased in CMML bone marrow plasma compared with healthy subjects. Hierarchical clustering of all subjects revealed 2 patterns of CMML, distinct from healthy subjects. Cluster “INNATE-1” was comprised of medium increases in inflammatory cytokines associated with innate immune response and M1 macrophage activation (IFN-g, IL-1b, TNFa, IL-12p70, IL-12p40, IL-17, Fractalkine, MCP-3). Cluster “INNATE-2” was associated with extreme increases of these cytokines. The mean pro-inflammatory innate immune score (sum of z-scores) was 20-fold greater in INNATE-2 compared with INNATE-1 ( P=0.055). Somatic mutations SRSF2, WT1, PHF6 were enriched in INNATE-2. All patients (5/5) in INNATE-1 showed 100% response (CR or optimal marrow response resulting in <5% blasts) to AZA/LENZ. Two subjects (2/6) in INNATE-2 demonstrated partial responses or haematological improvement thus far. Conclusion: CMML is a disorder of profound innate immune activation, driven by GM-CSF and other pro-inflammatory cytokines. Early treatment with LENZ/AZA, a precision immunotherapeutic approach, leads to a) efficacy in INNATE-1 that exceeds historical CR rates for hypomethylating agents 1,2; and b) evolving efficacy in INNATE-2, in which pro-inflammatory activity is more robust. 1. Xu Y, Guo R, Miao M, Zhang G, Lan J, Jin J. Real-world data on efficacy and safety of azacitidine therapy in chronic myelomonocytic leukemia in China: results from a multicenter, retrospective study. Invest New Drugs 2022;40(5):1117-1124. DOI: 10.1007/s10637-022-01283-x. 2. Zheng X, Lv L, Li X, Jiang E. Efficacy and Safety of Hypomethylating Agents in Chronic Myelomonocytic Leukemia: A Single-Arm Meta-analysis. Glob Med Genet 2022;9(2):141-151. DOI: 10.1055/s-0042-1744157.

Composite Score of Readiness (CSR) as a Data Reduction Technique for Monitoring the RTS Process in Footballers following ACL Reconstruction

In recent years, many studies on the safe return to sport (RTS) have been published, but there are still no clear and validated guidelines. After ACL reconstruction between limbs, asymmetry of muscle strength affects knee mechanics during walking and running, and asymmetrical joint kinematics and kinetics are considered as a strong risk factor of musculoskeletal injury. Therefore, proper diagnosis of any motor deficits remaining after ACL reconstruction seems particularly important. The aim of this study was to analyze how many tests should be included in the RTS test battery and which of them are most indicative for functional deficits related to anterior cruciate ligament (ACL) reconstruction. Sixty-five male football players (age 18–25 years) were divided into three groups: ACL group—after ACL rupture and reconstruction, mild injury group—post mild lower limb injuries, and the control group—without injuries. They performed five tests: Functional Movement Screen, Tuck Jump Assessment, Y-balance Test, Hop Test for Distance, and Isokinetic Test. The Composite Score of Readiness (CSR) index was calculated and expressed as the sum of z-scores. The multiple regression model for all tests was calculated, and then redundant variables were excluded. We observed that all tests significantly influenced the final CSR index. The Y-balance Test, Tuck Jump Assessment, and Isokinetic Test for knee flexion influenced the final CSR index the most, which means that these tests are greatly indicative of functional deficits related to ACL reconstruction. The strength of the extensor (quadriceps) muscle and the quadriceps/hamstring ratio appeared to be non-sensitive for testing functional deficits related to ACL reconstruction. If the test battery includes 4–5 tests, it better differentiates the athletes following ACL reconstruction from those after mild injuries, even if they all were cleared to play.

The Impact of Applying Egyptian Regulations on the Lessor Business Health (Panel Data Approach)

The aim of this study is to indicate the non-financial institutions financial health before and after the application of the Egyptian Financial Leasing and Factoring Act. Lessor firms applied the new Regulations for leasing on the year 2018. The study uses numerical data for 5 years during 2016-2020 from the financial reports of 10 lessors listed in the Egyptian Financial Regulatory Authority FRA. The sample of the study was equivalent to 43 firm year observations. The selected firms operate in cash, have annual reports that date from 1/1 to 31/12, have not been disqualified at any time during the study period, have complete data, and currency recorded in Egyptian pound. The test tool used to forecast financial health was the adjusted Altman Z-Score model (1995). In addition, the study applied the simple regression model and five step panel analyses. The dependent variable was the firm health represented by the sum of Z-Score. The independent variable was the Financial Leasing and Factoring Act represented by sales, financial liabilities, EBIT/operating profit or loss and financial leased fixed assets. The results indicate a strong significant impact of applying the Financial Leasing and Factoring Act on the lessor business health. The results of this study might increase the quality of predictability of lessor financial health. The length of the study period makes it possible to track progress of lessor firms to be able to predict their future business health. This is a modest contribution to the literature relating to lessors in Egypt.

Association between BMI and health-related physical fitness: A cross-sectional study in Chinese high school students.

Existing studies reporting on the levels of physical fitness among high school students use relatively few fitness tests for indicators of physical fitness, thus, incomprehensively evaluating the levels of physical fitness. Therefore, this study investigated the relationship between body mass index (BMI) and physical fitness index (PFI) by investigating five physical fitness indicators and calculating PHI. Anthropometric measurements and indicators from five measures of physical fitness (50-m sprint, sit and reach, standing long jump, 800/1,000-m run, pull-up/bent-leg sit-up) were assessed. BMI was calculated to classify individuals into underweight, normal weight, overweight, and obese categories. Z-scores based on sex-specific mean and standard deviation were calculated, and the sum of Z-scores from the six fitness tests indicated the PFI. The findings were fitted to a linear regression model to elucidate the potential relationship between BMI and PFI. In total, 176,655 high school students (male: 88,243, female: 88,412, age: 17.1 ± 1.05 years, height: 168.87 ± 11.1 cm, weight: 62.54 ± 15.15 kg) in Jinan, China, completed the physical fitness tests between 2020 and 2021. The one-way ANOVA models showed that PFI in the normal category was significantly higher as compared to all the other BMI categories within both male and female groups (p < 0.001), and PFI in the obese category was significantly lower as compared to all the other BMI categories for both male and female groups (p < 0.001). The association between PFI and BMI showed an inverted U-shape relationship. This study demonstrated that BMI affects the PFI in both males and females. As compared to the obese and overweight categories based on BMI, significantly higher scores of PFI were observed for males and females.

Prospective association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity

BackgroundMitochondria are multifunctional energy-producing and signaling organelles that support life and contribute to stress adaptation. There is a growing understanding of the dynamic relationship between stress exposure and mitochondrial biology; however, the influence of stress on key domains of mitochondrial biology during early-life, particularly the earliest phases of intra-uterine/prenatal period remains largely unknown. Thus, the goal of this study was to examine the impact of fetal exposure to stress (modeled as the biological construct allostatic load) upon mitochondrial biology in early childhood. MethodsIn n = 30 children (range: 3.5–6 years, 53% male), we quantified mitochondrial content via citrate synthase (CS) activity and mtDNA copy number (mtDNAcn), and measured mitochondrial bioenergetic capacity via respiratory chain enzyme activities (complexes I (CI), II (CII), and IV (CIV)) in platelet-depleted peripheral blood mononuclear cells (PBMCs). In a cohort of healthy pregnant women, maternal allostatic load was operationalized as a latent variable (sum of z-scores) representing an aggregation of early-, mid- and late-gestation measures of neuroendocrine (cortisol), immune (interleukin-6, C-reactive protein), metabolic (homeostasis model assessment of insulin resistance, free fatty acids), and cardiovascular (aggregate systolic and diastolic blood pressure) systems, as well as an anthropometric indicator (pre-pregnancy body mass index [BMI]). ResultsAn interquartile increase in maternal allostatic load during pregnancy was associated with higher mitochondrial content (24% and 15% higher CS and mtDNAcn), and a higher mitochondrial bioenergetic capacity (16%, 23%, and 25% higher CI, CII and CIV enzymatic activities) in child leukocytes. The positive association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity remained significant after accounting for the effects of key pre- and post-natal maternal and child covariates (p’s < 0.05, except CI p = 0.073). ConclusionWe report evidence that prenatal biological stress exposure, modeled as allostatic load, was associated with elevated child mitochondrial content and bioenergetic capacity in early childhood. This higher mitochondrial content and bioenergetic capacity (per leukocyte) may reflect increased energetic demands at the immune or organism level, and thus contribute to wear-and-tear and pathophysiology, and/or programmed pro-inflammatory phenotypes. These findings provide potential mechanistic insight into the cellular processes underlying developmental programming, and support the potential role that changes in mitochondrial content and bioenergetic functional capacity may play in altering life-long susceptibility for health and disease.

Metabolic risk is associated with sociodemographic characteristics in adolescents from both rural and urban regions from southern Brazil

BackgroundThe prevalence of several cardiovascular metabolic disorders are increasingly cause for concern in adolescents worldwide. Given the complex interrelations between metabolic risk (MR) and sociodemographic variables, the present study aims to examine the association between the presence of MR with sociodemographic characteristics (sex, skin color, residential area, and parental socioeconomic status) in adolescents from Southern Brazil.MethodsCross-sectional study conducted with 1,152 adolescents (507 males) aged between 12 and 17 years. MR was assessed using a continuous score (cMetS; sum of Z-scores of the following variables: waist circumference, systolic blood pressure (SBP), glucose, high-density lipoprotein cholesterol [HDL-C, inverse], triglycerides [TG], and estimated cardiorespiratory fitness [CRF, inverse]). Poisson regression was used to examine associations between sociodemographic variables with the dichotomized cMetS and separate metabolic variables. The results were expressed with prevalence ratios (PR) and 95% confidence intervals (CI).ResultsThe presence of MR (evaluated by the cMetS) was observed in 8.7% of adolescents. Higher MR was less prevalent among non-white adolescents (PR: 0.96; 95% CI: 0.93; 0.99). Adolescents living in rural areas had a lower prevalence of the following metabolic variables; low HDL-C (PR: 0.95; 95% CI: 0.94; 0.97), elevated TG (PR: 0.95; 95% CI: 0.92; 0.99), elevated glucose (PR: 0.96; 95% CI: 0.95; 0.98), and low CRF levels (PR: 0.88; 95% CI: 0.85; 0.92). Whereas, SBP was higher in those living in rural areas (PR: 1.11; 95% CI: 1.05; 1.17). In girls, there was a higher prevalence of raised TG (PR: 1.06; 95% CI: 1.02; 1.10) and lower levels of CRF (PR: 1.20; 95% CI: 1.16; 1.24), but a lower prevalence of elevated glucose (PR: 0.97; 95% CI: 0.97; 0.99).ConclusionHigher MR prevalence was lower in those self-reporting non-white skin color and selected MR factors were less prevalent in those living in rural areas. The identification of groups at higher MR is important for early prevention and monitoring strategies for both Type 2 diabetes and later cardiovascular disease. Future studies should be conducted to assess the socio-cultural aspects of the relationships between MR and socio-cultural and lifestyle variables.

Adherence to a healthy dietary pattern is associated with greater anti-oxidant capacity and improved glycemic control in Iraqi patients with type 2 diabetes

BACKGROUND: Healthy dietary patterns are typically associated with improved metabolic and cardiovascular health in population-based cohorts. This study aims to investigate whether a healthy dietary score, derived from UK Diabetes and Diet Questionnaire (UKDDQ), is significantly associated with measures of metabolic health and nutritional status in patients with T2DM. METHODS: This cross-sectional study included 85 patients with T2DM (age: 51.7±9.4, BMI: 30.6±5.3) and 20 healthy volunteers (age: 48.4±8.6, BMI: 29.5±5) recruited from the Al-Hassan Diabetes and Endocrinology Specialized Center, Karbala, Iraq. Body weight, height and body mass index (BMI) and resting clinic blood pressure were measured. All participants completed the UKDDQ to assess the quality of the diet. Metabolic and nutritional biomarkers were measured in fasting blood samples. A composite nutritional heathy index score (CNHI-score) based on the sum of z-scores for plasma vitamin A, C and E concentrations was derived. RESULTS: In patients with T2DM the UKDDQ score was associated with lower fasting blood glucose (FBG) (r = –0.33; P &lt; 0.01), hemoglobin A1C (r = –0.49; P &lt; 0.001), total cholesterol (TC) (r = –0.26; P = 0.02) concentrations. In patients with T2DM, the CNHI-score significantly associated with UKDDQ (r = 0.43; P &lt; 0.001). In addition, a higher CNHI-score was associated with FBG (r = –0.61; P &lt; 0.001), HbA1C (r = –0.83; P &lt; 0.001), TC (r = –0.30; P &lt; 0.01) and triglyceride (r = –0.30; P &lt; 0.01) concentrations. CONCLUSIONS: A healthy diet is associated with a higher concentration of anti-oxidant vitamins and better glycemic and lipid profile in healthy subjects and in patients with T2DM.

ProFitFun: a protein tertiary structure fitness function for quantifying the accuracies of model structures.

An accurate estimation of the quality of protein model structures typifies as a cornerstone in protein structure prediction regimes. Despite the recent groundbreaking success in the field of protein structure prediction, there are certain prospects for the improvement in model quality estimation at multiple stages of protein structure prediction and thus, to further push the prediction accuracy. Here, a novel approach, named ProFitFun, for assessing the quality of protein models is proposed by harnessing the sequence and structural features of experimental protein structures in terms of the preferences of backbone dihedral angles and relative surface accessibility of their amino acid residues at the tripeptide level. The proposed approach leverages upon the backbone dihedral angle and surface accessibility preferences of the residues by accounting for its N-terminal and C-terminal neighbors in the protein structure. These preferences are used to evaluate protein structures through a machine learning approach and tested on an extensive dataset of diverse proteins. The approach was extensively validated on a large test dataset (n = 25005) of protein structures, comprising 23661 models of 82 non-homologous proteins and 1344 non-homologous experimental structures. In addition, an external dataset of 40000 models of 200 non-homologous proteins was also used for the validation of the proposed method. Both datasets were further used for benchmarking the proposed method with four different state-of-the-art methods for protein structure quality assessment. In the benchmarking, the proposed method outperformed some state-of-the-art methods in terms of Spearman's and Pearson's correlation coefficients, average GDT-TS loss, sum of z-scores and average absolute difference of predictions over corresponding observed values. The high accuracy of the proposed approach promises a potential use of the sequence and structural features in computational protein design. http://github.com/KYZ-LSB/ProTerS-FitFun. Supplementary data are available at Bioinformatics online.

Composite Score of Readiness (CSR) as Holistic Profiling of Functional Deficits in Footballers Following ACL Reconstruction.

Background: The decision to return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction is difficult; thus, coaching staff require a readable, easy-to-use, and holistic indication of an athlete’s readiness to play. Purpose: To present the Composite Score of Readiness (CSR) as a method providing a single score for RTS tests after ACL reconstruction. Methods: The study comprised 65 male football players (age 18–25 years), divided into three groups: ACL group—subjects after ACL rupture and reconstruction, Mild Injury (MI) group—subjects after mild lower limb injuries, and Control (C) group—subjects without injuries. The CSR was calculated based on three performed tests (Y-balance test, Functional Movement Screen, and Tuck Jump Assessment) and expressed as the sum of z-scores. The CSR index allows highlighting an athlete’s functional deficits across tests relative to the evaluated group. Results: The CSR indicated that relative to the group of athletes under the study, similar functional deficits were present. Comparing athletes following ACL reconstruction to both the MI and C groups, in the majority of subjects, the CSR index was below zero. The correlation between CSR and raw tests results indicated that the CSR is most strongly determined by YBT. Conclusion: The CSR is a simple way to differentiate people after serious injuries (with large functional deficits) from people without injuries or with only small deficits. Because the CSR is a single number, it allows us to more easily interpret the value of functional deficits in athletes, compared to rating those deficits based on raw tests results.

Abstract 872: Pathogenesis underlying the bidirectional relationship between non-Hodgkin lymphomas and primary Sjögren's Syndrome

Abstract Introduction: Bidirectional relationship between non-Hodgkin lymphomas (NHLs) and Sjögren's syndrome (SS) has been recognized in large scale cohort studies. To investigate the underlying pathogenesis of this association, we identified highly expressed genes and altered pathways with RNA-sequencing (RNA-seq) data from SS and NHLs patients. Methods: Canonical pathway analysis was conducted by comparing RNA-seq data from whole-transcriptome expression profiling to identify underlying pathogenesis among NHL patients with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL), and SS patients. Collected biopsies included lymphoma biopsies for NHLs, including BL (n = 59), DLBCL (n = 88), FL (n = 65), MCL (n = 43), and MZL (n = 23), sorted B cells from healthy donors (n=10), as well as parotid gland tissues for SS (n=17). Fold changes and z-scores were derived after normalized by the expression levels among controls. RNA-seq data with P values less than 0.05 or -log10(P) values larger than 1.3 were considered significantly expressed. Positive z-scores indicated up-regulation while negative z-scores indicated down-regulation. Results: There were 17 identified significantly expressed genes (P &amp;lt; 0.05 for all NHLs and SS), including well-known cancer-associated genes CXCL13, COL1A1, IGFBP7, COL3A1, CXCL9, CXCL12, CCL19, and CLU. Among them, CXCL13 was the most expressed gene involved in NHLs and SS. The fold changes of CXCL13 were 14.09, 465.57, 319.51, 369.70, 817.63, and 4.03 for BL, DLBCL, FL, MCL, MZL, and SS, respectively. Among all identified pathways underlying SS and NHL development, which were ordered based on the sum of z-scores, the endocannabinoid system-driven cancer inhibition pathways were the most significantly altered in both SS and NHLs, followed by interferon-involved antiviral responses, when compared to matched healthy controls. The z-scores of the cancer inhibition pathways were -0.14 for BL (-log10(P) = 4.54), -1.30 for DLBCL (-log10(P) = 3.00), -0.33 for FL (-log10(P) = 4.67), -0.87 for MCL (-log10(P) =3.77), -2.61 for MZL (-log10(P) = 4.31), and -1 for SS (-log10(P) = 1.44). Conclusion: The underlying pathogenesis for SS-associated NHL development involved 17 highly expressed genes, including CXCL13, and down-regulated cancer inhibition pathways. Citation Format: Kevin Sheng-Kai Ma, Cho-Han Chiang, Li-Tzu Wang. Pathogenesis underlying the bidirectional relationship between non-Hodgkin lymphomas and primary Sjögren's Syndrome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 872.

Increased particle size of triglyceride remnant lipoproteins, but not their plasma concentration or lipid content, augment risk prediction of incident diabetes: prospective results from ELSA-Brasil

Abstract Importance Predicting risk of Type 2 Diabetes Mellitus (T2DM) accurately allows allocation of resources to prevent its development. Fasting blood triglycerides are highly predictive for T2DM. Triglyceride remnant lipoproteins (TRL) more accurately reflect pathophysiological changes that underlie progression to T2DM, such as pancreatic steatosis and inflammation. We hypothesized TRL-related factors could improve risk prediction for development of T2DM. Methods We included individuals aged 35–74 years from the ELSA-Brasil cohort who had HbA1c and an oral glucose tolerance test at baseline. Regression models were used to predict incident T2DM, starting with medical history, metabolic syndrome traits (age, sex, hypertension, waist circumference [WC], HbA1c, triglycerides) and hsCRP, adding TRL-related measurements, including plasma concentration, particle size, as well as cholesterol and triglyceride content. TRL features were measured by NMR spectroscopy. Discrimination was assessed with area under receiver operator curves (AUROCs). Results Among 4,466 individuals at-risk, there were 353 new cases of T2DM after 3.7 (SD=0.6) years follow-up. We derived an 8-variable model with AUROC 0.891 (95% CI: 0.870–0.913). Overall TRL-related markers did not improve predictive capacity for T2DM. However, TRL particle diameter (TRLZ) increased AUROC, particularly in individuals without glucose abnormalities at baseline (Hba1c &amp;lt;5.7%). In this subgroup, AUROC increased from 0.761 (95% CI: 0.739–0.798 – Baseline-model) to 0.823 (95% CI: 0.783–0.862 – TRLZ model) (p-value=0.00006). Consistently, the net reclassification improvent (NRI) of the model with TRLZ improved by 10.27% (95% CI: 1.0–24.1, p=0.00041). In subjects with pre-diabetes at baseline, TRLZ is highly correlated with obesity, insulin resistance and inflammation (sum of z-scores for WC + HOMA-IR + hsPCR: R2=0.25), but this was less important in individuals with Hba1c &amp;lt;5.7% (R2=0.15). Sensitivity analyzes confirmed the results with different inclusion criteria (pre-diabetes defined with TTGO only) and excluding patients diagnosed with DM2 incident based only on fasting blood glucose. Conclusions TRL particle diameter improves prediction of T2DM, particularly in subjects with no glycemic abnormalities at baseline. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Brazilian Ministry of Health (Department of Science and Technology), Ministry of Science, Technology and Innovation, and the National Council for Scientific and Technological Development (CNPq)

The Relationships Between King-devick And SCAT5 Scores In High-school Athletes

Preseason testing is important when developing concussion-related safety programs in high-school athletics. However, the relationships between many commonly-used and valid-baseline assessments are unknown PURPOSE: To determine the relationships between King-Devick (KD) and the Sport Concussion Assessment Tool - 5thEdition (SCAT5), commonly used as part of a pre-season concussion-safety program for high-school athletes. METHODS: SCAT5 and KD baseline scores from high-school athletes (n = 404, 28 = female, aged 16 ±1 years) were recorded and later analyzed. KD testing required participants to complete two, error-free trials, which were reported to the nearest 0.0 s and a single SCAT5 assessment completed one-on-one with a physician or athletic trainer. The SCAT5 test is composed of several relevant neurocognitive components (concentration, current number of symptoms, symptom severity, orientation, memory, neurological screening, balance, and recall). Due to the dichotomous nature of the neurological screening component, those data were excluded from this analysis (n = 9 scored in the abnormal category). Pearson-product moment correlations were calculated between the best-baseline KD score and SCAT5’s component tests, including a composite score. The composite score was calculated as a sum of z-scores from each individual test making up the SCAT5. RESULTS: The mean ± standard deviation of the KD test were 52.5 ± 13.3 s. Pearson-product moment correlations revealed a weak-negative relationship with the SCAT5 component - Concentration (r = - 0.12, p = 0.02). However, no other meaningful relationships were detected [number of symptoms (r = - 0.04, p = 0.48), symptom severity (r = - 0.06, p = 0.22), orientation (r = - 0.07, p = 0.14), memory (r = - 0.02, p = 0.63), balance (r = - 0.04, p = 0.39), recall (r = 0.01, p = 0.88), and composite z-score (r = - 0.05, p = 0.30)] CONCLUSIONS:These data show that KD and SCAT5 scores are generally unrelated in this sample of high-school athletes. Clinically, the data support the true utility of neurocognitive testing resides in one’s ability to use the same test to directly compare pre- vs. post-test scores in diagnosing and monitoring recovery in athletes suspected of having a concussion. King-Devick provided access to testing services - free of charge.

The association between BMI and health-related physical fitness among Chinese college students: a cross-sectional study

BackgroundExisting studies reporting on the levels of physical fitness among college students used relatively few fitness tests as a reflection of physical fitness, which could not comprehensively evaluate the levels of physical fitness. Thus, the current study aimed to investigate the cross-sectional relationship between body mass index (BMI) and a physical fitness index (PFI) based on six indicators of fitness in Chinese college students.MethodAnthropometric measurements and six measures of physical fitness (Vital capacity, 50-m sprint, sit and reach, standing long jump, 800/1000-m run, pull-up/bent-leg sit-up) were measured. BMI was calculated to classify individuals into underweight, normal weight, overweight, and obesity groups. Z-scores based on sex-specific mean and standard deviation were calculated, and the sum of z-scores for the six fitness tests was used as a PFI. Three models (a linear regression model, polynomial regression model with a second-order BMI term and a restricted cubic spline regression model) were fitted to discuss the potential relation between BMI and PFI. We compared the models using Akaike Information Criterion (AIC) and R square.ResultsTotally, 8548 freshmen from the years 2014 to 2016 in a medical college completed the physical fitness tests. There was a decreasing trend of physical fitness index from the years 2014 to 2016 (P for trend < 0.01). More male than female students were overweight or obese (23.5% vs. 11.9%), but more female than male students were normal weight (74.7% vs. 64.8%). A restricted cubic spline regression model was superior to linear and polynomial regression model with lower AIC and higher R square.ConclusionsThe relationships between BMI and PFI in college students were non-linear. Underweight, overweight and obese students had poorer performance in physical fitness index than normal weight students. Future prospective, longitudinal cohort studies to identify the causal relations and potential mechanism in a good manner are required.

Abstract P421: Alternate Health Eating Index &amp; Cognitive Function Among Middle-aged and Older Hispanics/ Latinos: The Hispanic Community Health Study/ Study of Latinos

Introduction: A healthy diet may promote healthy cognitive aging; however, little is known about associations between diet quality and cognition in Hispanics/Latinos. Hypothesis: Higher diet quality (2010 Alternative Healthy Eating Index; AHEI-2010) is associated with better global cognition and performance on specific cognitive tests (verbal learning, memory, verbal fluency, and processing speed) in Hispanics/Latinos. Methods: Data from HCHS/SOL Visit 1 (2008-2011; n=8461; ages 45-74 years) were analyzed. The global cognition score was computed as the sum of z-scores for the individual tests. Dietary intake was assessed via two 24-hour recalls. Total AHEI-2010 score was categorized into quintiles (Q); higher Q represents higher diet quality. Cross-sectional associations between AHEI-2010 and each cognitive test were examined using survey-weighted linear regression models adjusted for age, sex, education, and total daily energy intake (Model 1); and Model 1 plus Hispanic/Latino heritage, annual household income, language preference, type 2 diabetes, smoking, and depressive symptoms (Model 2). Results: In minimally-adjusted models (Table 1), global cognition, verbal learning, verbal memory, verbal fluency, and processing speed scores were significantly higher by 1.32, 2.38, 1.40, 2.33, and 1.34 units for Q5 (vs. Q1). In fully-adjusted models, global cognitive function scores were significantly higher by 0.28, 0.52, and 0.48 units for Q2 through Q4 (vs. Q1; p -trend= 0.042). Verbal learning scores were significantly higher by 0.60, 0.62, 0.92, and 0.88 units for Q2 through Q5 (vs. Q1; p -trend= 0.020). Verbal memory scores were significantly higher by 0.33, 0.40, 0.52, and 0.46 units for Q2 through Q5 (vs. Q1; p -trend= 0.007). AHEI-2010 was not associated with verbal fluency and processing speed in Model 2. Conclusions: Among middle-aged and older Hispanics/Latinos, higher diet quality was associated with better global cognition, verbal learning, and memory, but not with verbal fluency, or processing speed.

Predicting Soldier Task Performance From Physical Fitness Tests: Reliability and Construct Validity of a Soldier Task Test Battery.

Spiering, BA, Walker, LA, Larcom, K, Frykman, PN, Allison, SC, and Sharp, MA. Predicting soldier task performance from physical fitness tests: reliability and construct validity of a soldier task test battery. J Strength Cond Res 35(10): 2749-2755, 2021-The purpose of this study was to determine the reliability and construct validity of a battery of tests designed to assess soldier task performance. In the first part of the study (designed to assess test-retest reliability), 33 enlisted soldiers (31 men, 2 women; 23 ± 3 years; 1.75 ± 0.08 m; and 81.4 ± 12.8 kg) completed a 4-event "soldier task test battery" (STTB) on 4 occasions, each separated by at least 1 week. The STTB consisted of the following tests, in order: (a) 30-m grenade throw for accuracy; (b) running long jump while wearing a 20.5-kg load; (c) 1 repetition maximum box lift; and (d) 3.2-km load carriage time trial while wearing a 33-kg load. In the second part of the study (designed to assess construct validity), 41 male soldiers (22 ± 3 years; 1.75 ± 0.08 m; and 81.4 ± 12.9 kg) completed the STTB and a series of physical fitness tests. The physical fitness tests included measurements of body composition, muscular strength, muscular power, muscular endurance, and cardiovascular endurance. Overall performance on the STTB (reflected by the sum of z-scores across individual tests) demonstrated an intraclass correlation coefficient of 0.95 and was correlated to lean mass, V˙o2peak, and measures of muscular strength and power. Lean body mass and standing long jump predicted performance on the STTB (R2 = 0.41). In conclusion, this STTB can reliably assess performance of soldiering tasks. The relationships between the STTB and physical fitness tests can be used to develop training programs to prepare soldiers to perform physically demanding tasks.

Cardiometabolic correlates of sleep-disordered breathing in renal transplant children.

Sleep-disordered breathing, a prevalent condition among adult renal transplant (RTx) recipients, has become an established independent risk factor of MetS, and furthermore, it might contribute to increased CV risk. Despite the proven correlations in adults, there is a lack of evidence for its significance in the pediatric RTx population. In this study, we aimed at assessing the prevalence and the clinical correlates of SDB in RTx children. Data of 13 patients (age [mean±SD]: 14.2±2.7years) were analyzed. SDB was evaluated by PSG, as severity score OAHI was applied. Carbohydrate metabolism was characterized by OGTT, whereas CV status was studied by ABPM. Three composite end-points were calculated as sum of z-scores: daytime systolic and diastolic BP; nighttime systolic and diastolic BP; and glucose and insulin levels at 120minutes. Eight patients (61.5%) were diagnosed with SDB of whom five patients (38.5%) had moderate or severe SDB. In linear regression analysis, OAHI during REM was associated with the CV variables (daytime BP P=0.032, ß=0.748; nighttime BP P=0.041, ß=0.715), and the correlations remained significant after adjustments for BMI. However, we did not confirm a significant association with the metabolic variables. The prevalence of SDB was high, and its severity during REM was a predictor of the BP suggesting that RTx children with SDB might be at risk of developing CV complications, especially HTN similarly to adults.

The triple variable index combines information generated over time from common monitoring variables to identify patients expressing distinct patterns of intraoperative physiology

BackgroundMean arterial pressure (MAP), bispectral index (BIS), and minimum alveolar concentration (MAC) represent valuable, yet dynamic intraoperative monitoring variables. They provide information related to poor outcomes when considered together, however their collective behavior across time has not been characterized.MethodsWe have developed the Triple Variable Index (TVI), a composite variable representing the sum of z-scores from MAP, BIS, and MAC values that occur together during surgery. We generated a TVI expression profile, defined as the sequential TVI values expressed across time, for each surgery where concurrent MAP, BIS, and MAC monitoring occurred in an adult patient (≥18 years) at the University of Pittsburgh Medical Center between January and July 2014 (n = 5296). Patterns of TVI expression were identified using k-means clustering and compared across numerous patient, procedure, and outcome characteristics. TVI and the triple low state were compared as prediction models for 30-day postoperative mortality.ResultsThe median frequency MAP, BIS, and MAC were recorded was one measurement every 3, 5, and 5 min. Three expression patterns were identified: elevated, mixed, and depressed. The elevated pattern displayed the highest average MAP, BIS, and MAC values (86.5 mmHg, 45.3, and 0.98, respectively), while the depressed pattern displayed the lowest values (76.6 mmHg, 38.0, 0.66). Patterns (elevated, mixed, depressed) were distinct across the following characteristics: average patient age (52, 53, 54 years), American Society of Anesthesiologists Physical Status 4 (6.7, 16.1, 27.3%) and 5 (0.1, 0.6, 1.6%) categories, cardiac (2.2, 6.5, 16.1%) and emergent (5.8, 10.5, 12.8%) surgery, cardiopulmonary bypass use (0.3, 2.6, 9.8%), intraoperative medication administration including etomidate (3.0, 7.3, 12.6%), hydromorphone (47.6, 26.3, 25.2%), ketamine (11.2, 4.6, 3.0%), dexmedetomidine (18.4, 16.6, 13.6%), phenylephrine (74.0, 74.8, 83.0), epinephrine (2.0, 6.0, 18.0%), norepinephrine (2.4, 7.5, 21.2%), vasopressin (3.4, 7.6, 21.0%), succinylcholine (74.0, 69.0, 61.9%), intraoperative hypotension (28.8, 33.0, 52.3%) and the triple low state (9.4, 30.3, 80.0%) exposure, and 30-day postoperative mortality (0.8, 2.7, 5.6%). TVI was a better predictor of patients that died or survived in the 30 days following surgery compared to cumulative triple low state exposure (AUC 0.68 versus 0.62, p < 0.05).ConclusionsSurgeries that share similar patterns of TVI expression display distinct patient, procedure, and outcome characteristics.

Abstract 027: Life-course Cardiovascular Risk Mobility in the International Childhood Cardiovascular Cohort (i3C) Consortium

Background: We previously adapted a methodology from literature on socioeconomic mobility (the “American Dream”) to develop an analogous concept of Cardiovascular (CV) Risk Mobility (CRM: movement across CV risk rankings during aging) in the Bogalusa Heart Study (BHS). We found high mobility, such that childhood CV risk burden tracks into adulthood, but not so strongly that a low CV-risk stratum in adulthood is unreachable. Because geopolitical, ethnic, and healthcare differences may affect mobility in life course CV health, we sought to further test CRM using an international consortium. Methods: We used prospective data from n=20,685 children followed into adulthood (inverse probability weighted, n=6,029 with adult follow-up) from the 1970s-2010s in three of the i3C Consortium cohorts: BHS, the Young Finns Study (YFS), and the Muscatine Study. During childhood (age 5-18 yr), participants were percentile-ranked by their CV risk factor burden using an age- and sex-adjusted sum of z-scores from total cholesterol, systolic blood pressure, BMI, and triglycerides. During adult follow-up (age 40-55 yr), participants were percentile-ranked using the Framingham score. The rank-rank slope (β) from the regression of adult/child percentile rankings forms the measure of CRM. Results: Patterns of CRM were similar to BHS in both YFS [β=.15 (95% CI: .12, .18) at age 10] and Muscatine [β=.14 (95% CI: .09, .19) at age 10]. Pooled results of age/rank interaction were significant ( p =0.005), indicating a pattern of lower CRM (more tracking) earlier in childhood. The pooled β=.15 (95% CI: .14, .16)], meaning that a child ranked 10 percentiles better was only 1.5 percentiles better as an adult. Conclusions: Populations in the developed world track, yet exhibit large mobility in CV risk. Children are readily able to move from both high to low and low to high CV risk strata over the life course. The earlier children develop a high CV risk factor burden relative to their peers, the lower their mobility, or opportunity to “catch up,” into adulthood.

Association between the consumption of antioxidant nutrients with lipid alterations and cardiometabolic risk in adolescents

ABSTRACT Objective This study aimed at validating the associations between the consumption of antioxidant nutrients as well as lipid alterations and cardiometabolic risks in adolescents. Methods This cross-sectional study included 327 adolescents aged 14-19 years. Sociodemographic and dietary information, anthropometric and blood pressure measurements, and biochemical data were obtained. Cardiometabolic risk was calculated by aggregating the risk factors, which were expressed as the sum of Z-scores. Poisson regression was performed to estimate the prevalence ratios. Results In boys, low intake of zinc was associated with elevated total cholesterol and triglyceride levels, whereas it was associated with low high-density lipoprotein cholesterol levels and high low-density lipoprotein cholesterol and total cholesterol levels in girls, thus indicating a cardiometabolic risk. Furthermore, low intake of copper was associated with high triglyceride levels and cardiometabolic risk in girls. The high prevalence ratios of high low-density lipoprotein cholesterol and total cholesterol levels and cardiometabolic risk were higher in those with low intake of vitamin A. Among girls, associations were also observed between lower intake of vitamin A and high triglyceride levels. Low intake of vitamin C among boys was associated with elevated high low-density lipoprotein cholesterol and triglyceride levels. Among girls, the intake of this vitamin was associated with lower low high-density lipoprotein cholesterol levels. In girls, low intake of vitamin E was associated with low low high-density lipoprotein cholesterol levels and high total cholesterol levels. Conclusion The associations between antioxidant micronutrients as well as lipid alterations and cardiometabolic risk emphasize the importance of encouraging the consumption of foods that are rich in these nutrients to modulate lipid alterations and cardiometabolic risk.