Average Z-score Research Articles

QOL-22. Neurocognitive performance in survivors of pediatric brain tumors with neurocutaneous syndromes

Abstract BACKGROUND: Pediatric brain tumors (PBT) in children with neurocutaneous syndromes are typically low-grade and survival rates are close to 100%. Neurocutaneous syndromes are associated with neurocognitive and behavioral problems, and a diagnosis of brain tumor adds to the total neurocognitive burden. The aim of this study was to describe neurocognitive performance in survivors of PBT with a neurocutaneous syndrome and to find associated factors. METHOD: Neurocognitive data (verbal and non-verbal reasoning, cognitive processing speed, working memory, and executive function) on 20 survivors of brain tumors with neurocutaneous syndromes were collected from medical logs. Results were converted to z-scores (m=0, sd=1) using age-adjusted national norms. Generalized linear models were built to find factors associated with neurocognitive performance. Most survivors had received several assessments and all assessments were added to the model together with time since diagnosis at assessment. RESULTS: Seventeen of the survivors (85%) had undergone 1-3 assessments and 3 survivors had undergone 4-5 assessments. Six survivors (30%) had a diagnosis of intellectual disability, and neurocognitive scores were low at all assessment points: average z-score across all datapoints(sd): verbal reasoning -1.1(1.2); non-verbal reasoning -1.2(0.9); working memory -1.9(0.7); cognitive processing speed -1.0 (1.0); executive function -0.6 (1.0)). Factors associated with worse neurocognitive performance were young age at brain tumor diagnosis, larger tumors, epilepsy, and longer time span between diagnosis and assessment. CONCLUSIONS: Survivors of PBT with neurocutaneous syndromes are at risk for neurocognitive deficits that might worsen over time. These survivors need personalized neurocognitive follow-up. When examining neurocognitive performance and associated factors in survivors of PBT special consideration needs to be taken to survivors with neurocutaneous syndrome since these survivors receive limited cancer treatment and still have neurocognitive deficits.

Brain-derived neurotrophic factor and neurofilament light chain in cerebrospinal fluid are inversely correlated with cognition in Multiple Sclerosis at the time of diagnosis

BackgroundCognitive performance may be impaired in MS even at the earliest stages of disease. We tested whether brain-derived neurotrophic factor and neurofilament light chain levels in serum and cerebrospinal fluid (CSF) samples (sNfL/cNfL/sBDNF/cBDNF) collected at the time of diagnosis are associated with cognitive performance. MethodsWe measured sNfL/cNfL/sBDNF/cBDNF using single-molecule array (Simoa) in 47 newly diagnosed patients (32 relapsing-remitting MS/6 primary progressive MS/9 clinically isolated syndrome). Partial correlations between average z-score on neuropsychological tests and sNfL/sBDNF/cNfL/cBDNF were computed after adjusting for covariates. Multivariate analysis of covariance determined the effect of cognitive status on biomarker levels. A composite measure of NfL and BDNF was submitted to similar exploratory analysis. ResultsCognitive performance correlated inversely with cNfL (r=-0.451/q=0.032) and cBDNF (r=-0.406/q=0.034). Impairment in at least two different tests was linked to higher cNfL (p=0.011) and cBDNF (p=0.035) levels compared to impairment in only one test and for cNfL also compared to no impairment at all (p=0.01). Composite CSF biomarker measure accounting for both cNfL and cBDNF correlated more strongly with tests of information processing (p=0.048) and verbal learning/memory consolidation (p = 0.02) as compared to the single CSF biomarkers. ConclusionsCSF BDNF and NfL levels measured at the time of diagnosis are inversely associated with cognitive performance in MS. Our findings suggest that CSF biomarkers linked to different pathophysiological processes reflect neuropsychological impairment in the earliest stages of the disease. Combining different CSF measures might facilitate the developing of a better biomarker of cognition in MS.

Exploring species-specific inhibitors with multiple target sites on S. aureus pyruvate kinase using a computational workflow

Experimental evidence indicated that bacterial pyruvate kinase of glycolysis can be evaluated as an alternative target to eliminate infections, while antibiotic resistance poses a global threat. Here, we use a computational workflow to reveal and investigate the potential allosteric sites of methicillin-resistant S. aureus PK, which can help in designing species-specific drugs to inhibit activity of this organism. Residue interaction networks point to a known allosteric site at the small C-C interface, a potential allosteric site near the small interface (site #1), and a second potential allosteric site at the large interface (site #2). 2 µs-long molecular dynamics (MD) simulations with AMBER16 generate different conformations of one narrow target site. Known and potential allosteric sites on the selected conformers are investigated using ensemble docking with AutoDock Vina and a library of 2447 FDA-approved drugs. We determine 18 hits, comprising ergot-alkaloids, anti-cancer-agents, antivirals, analgesics, cardiac glycosides, all with a high docking z-score for three sites. 5 selected compounds with high, average and low z-scores are subjected to 50 ns-long MD simulations for MM-GBSA calculations. ΔGbind values up to −49.3 kcal/mol at the C-C interface, up to −32.7 kcal/mol at site #1, and up to −53.3 kcal/mol at site #2 support the docking calculations. We investigate mitapivat and TT-232 as reference compounds under clinical trial, targeting human PK isomers. We suggest 18 FDA-approved hits from the docking calculations and TT-232 as potential inhibitors with multiple target sites on S. aureus PK. This study also proposes pharmacophores models for de novo drug design. Communicated by Ramaswamy H. Sarma

Dual Banking System Stability Index in the Shadow of COVID-19 Pandemic

The financial system is categorized as stable if there is no excessive volatility from financial pressures or crises. The IMF indicates that the crisis is not only related to one element but more than two or three elements of the crisis. The banking system's stability is measured by the banking stability index, gauging the effectiveness of monetary policy and financial risk. This study aims to measure the stability of the Indonesian banking system in the dual banking system model. The indicator to measure banking stability used the Z-score statistic based on fluctuations of Return on Assets for each type of bank. The Markov Switching Vector Autoregressive (MSVAR) model method was used to analyze the volatility of banking stability. Independent variables used included credit risk (NPL), Loan to Deposit Ratio, Liquidity Risk, Net Interest Margin, Capital Adequacy Ratio, Money Market Rate, Inflation, Gross Domestic Product, Federal Reserve rate, and Exchange Rate. The results of the regime switch analysis concluded that Indonesia's banking stability experienced a structural break due to the effects of the pandemic in April 2020. Based on the average Z-score value, the Islamic banking stability index was higher than conventional banking. In other words, Islamic banking was more stable than the conventional banking system. The Islamic banking stability index (iZscore) was significantly influenced by the level of Net Operating Margin, Financing to deposit ratio, Potential Loss Profit Sharing, Islamic Money Market Rate, and Exchange Rate. However, non-performing financing did not affect Islamic banking stability since the profit-sharing system implemented by Islamic banking stability was more influenced by the ratio of potential loss and profit-sharing system.

Prevalence of Female Athlete Triad Risk Factors among Female International Volunteers and College Age-Matched Controls.

This study retrospectively compared the prevalence of factors related to the female athlete triad (low energy availability, secondary amenorrhea (SA), low bone mineral density (BMD)), and post-study BMD of female college students and female international volunteer missionaries (volunteers). Female college students (21–26 years) completed a survey that retrospectively assessed an 18-month study period (volunteer service or first 18 months of college); Diet History Questionnaire III (DHQ III) and Dual-Energy X-ray Absorptiometry (DXA) scan were optional. One-way ANOVAs and chi-squared distributions assessed group differences. Logistic regression assessed covariates of SA and BMD; corresponding odds ratios (OR) and confidence intervals (CI) were calculated. Statistical significance was set at p < 0.001. 3683 participants (58.8% volunteers, 31.5% non-volunteers, 9.8% others) provided complete survey data; 246 completed the DHQ III, and 640 had a post-study DXA scan. Volunteers had higher metabolic equivalent (MET) hours than non-volunteers and others (p < 0.001), and higher prevalence of food insecurity (p < 0.001) and SA (p < 0.001). Volunteers had higher odds of SA (OR = 2.17, CI = 1.75–2.62) than non-volunteers. Weight loss, body satisfaction, “other” weight loss methods, increased MET hours, and vomiting during the study period increased participants’ odds of SA. Participants’ average BMD Z-scores were within the expected range at all sites, with no significant group differences. Volunteers’ higher MET hours and higher prevalence of food insecurity and SA did not result in significantly lower post-study period BMD.

Analisis Kesehatan Keuangan dan Prediksi Kebangkrutan Perusahaan PT Pertamina (persero) Periode 2017-2020

The purpose of this study is to determine the financial health of pertamina (persero) and predict the company’s bankruptcy from 2017 to 2020 based on Surat Keputusan Menteri BUMN Nomor:KEP-100/MBU/2002 and Altman Z-Score Analysis. The type of data used in this study is company’s audited financial statement for the period 2017-2020. Data Collection technique in this study is to analyze the company’s audited financial statement from 2017-2020. The result showed that based on the ratio in SK Menteri BUMN Nomor:KEP-100/MBU/2002 based on the financial aspect with indicators namely ROE, ROI, Cash Ratio, Current Ratio, Collection Periods, Inventory Turnover, TATO, and Total Equity to Total Assets, the level of soundness of the company PT Pertamina (persero) from 2017 to 2020 it is in the unhealthy category because the total score of the health assessment level obtained from these 8 indicators is less than 65 from the total score it should be, which in 70. The prediction of PT Pertamina (persero) bankruptcy, the average Z-Score analysis value in 2017 to 2019 up 2,0 with the category of a zone of ignorance or grey area, while in 2020 when during the corona pandemic the lowest score of 1,82 in the category of a zone of ignorance or grey area, therefore the company PT Pertamina (persero) is expected to be able to improve the level of financial health and financial performance so that the company can achieve a healthy predicate or category.

Employing Google Trends to Assess Concussion Search Popularity, Seasonality, and Association With High School Sports Participation.

This investigation employs 2004-2020 Google Trends data to correlate concussion search popularity and high school sports participation while assessing search seasonality and factors associated with search escalation. Events linked to concussions, from news to entertainment, altered public perception of concussions and discouraged high-risk activities. Such sentiment likely promoted high school football's 2004-2018 8% decrease in participation, despite simultaneous 8% increase for sports overall. Google Trends (GT) analysis calculates distinct subjects' popularity scores (0-100) by normalizing Google search frequency with other subjects in the same topic. With 35% of patients researching their conditions using Google, tracking concussion popularity scores allows robust analysis of event-driven fluctuation, seasonal variation, and sports impact. Worldwide GT analysis was conducted for the disease topic "Concussion" with the categorical filter "Health" from 2004 to 2020. This period's monthly popularity scores with annual averages and annual high school sports participation data were subsequently obtained from Google Trends and the National Federation of State High School Associations, respectively. Concurrence of significant score changes with CTE studies' publication, release of 2015 film Concussion, and the COVID-19 pandemic validates GT's measurement of public interest. From 2006 to 2016, Pearson's correlation coefficients demonstrated strong negative correlation between GT popularity scores for "Concussion" with total number of high school football participants overall (R2 = 0.8553) and participants per school (R2 = 0.9533). Confirming football-related seasonality, one-way ANOVA regression analysis concluded 2004-2020's mean change in month-specific popularity score is not the same (p = 3.193E-08), and months during football season had statistically significant variability (September: p = 4.389E-05) with elevated average z-scores. Coupled with ANOVA regression and normalized analyses, strong negative correlations between concussion popularity score and high school football participation produce quantitative measures of a long-suspected relationship. Tracking concussion popularity and seasonality with Google Trends provides insight into how, when, and why patients are educating themselves online.

Urine tricarboxylic acid cycle signatures of early-stage diabetic kidney disease.

Urine tricarboxylic acid (TCA) cycle organic anions (OAs) are elevated in diabetes and may be biomarkers for diabetic kidney disease (DKD) progression. We assessed associations of 10 urine TCA cycle OAs with estimated glomerular filtration rate (eGFR) and eGFR slope. This study is ancillary to the Simultaneous Risk Factor Control Using Telehealth to SlOw Progression of Diabetic Kidney Disease (STOP-DKD) Trial-a randomized trial of pharmacist-led medication and behavior management in 281 patients with early to moderate DKD at Duke from 2014 to 2015. We used linear mixed models to assess associations of urine TCA cycle OAs with outcomes and modelled TCA cycle OAs as: (1) the average of z-scores for each OA; and (2) principal component (PC) scores derived by principal component analysis (PCA). Untargeted urine metabolomics were added for additional discovery. Among 132 participants with 24h urine samples (50% men; 58% Black; mean age 64years [SD 9]; mean eGFR 74ml/min/1.73m2 [SD 21] and medianurine albumin-to-creatinine [UACR] 20mg/g [IQR 8-95]), PCA identified 3 OA metabolite PCs. Malate, fumarate, pyruvate, α-ketoglutarate, lactate, succinate and citrate/isocitrate loaded positively on PC1; methylsuccinate, ethylmalonate and succinate loaded positively on PC2; and methylmalonate, ethylmalonate and citrate/isocitrate loaded negatively on PC3. Over a median follow-up of 1.8years (IQR, 1.2 to 2.2), higher average OA z-score was strongly associated with higher eGFR after covariate adjustment (p = 0.01), but not with eGFR slope (p = 0.9). Higher PC3, but not other PCs, was associated with lower eGFR (p < 0.001). Conditional random forests and smooth clipped absolute deviation models confirmed methylmalonate, citrate/isocitrate, and ethylmalonate, and added lactate as top ranked metabolites in models of baseline eGFR (R-squared 0.32 and 0.33, respectively). Untargeted urine metabolites confirmed association of urine TCA cycle OAs with kidney function. Thus, lower urine TCA cycle OAs, most notably lower methylmalonate, ethylmalonate and citrate/isocitrate, are potential indicators of kidney impairment in early stage DKD.

Hypertensive Retinopathy Is Associated With Worse Cognitive Function in Women: The SWAN Study

Based on the 2018 American Academy of Neurology guideline, the prevalence of mild cognitive impairment (CI) increases from 6.7% at 60-64 years to 25.2% at 80-84 years. There is interest to identify potential biomarkers in the retina for CI and dementia. The aims of this analysis was to test whether hypertensive retinopathy (HR) was associated with cognitive function using data from the Study of Women’s Health Across the Nation (SWAN), Michigan cohort. SWAN, launched in 1996/97, is a longitudinal study of women traversing midlife and into late adulthood. Starting in 2000, cognitive function tests were administered: East Boston Memory Test immediate (EBMTi) and 10-minute delay (EBMTd) for verbal episodic memory; digit span backwards (DSB) for working memory; and symbol digits modalities test (SDMT) for perception speed, motor speed, and visual scanning. Z-scores were calculated for EBMTi, EBMTd, DSB and SDMT and averaged at follow-up visit 15 (2015/16). Eye exams were performed on 255 women (66 + 2.6 years) at follow-up visit 16 (2016/17). HR was based on presence/absence of arteriovenous nicking. Logistic regression showed a statistically significant association of lower average cognitive Z-score with HR (p-value 0.03, beta=-0.21 [95% confidence interval: -0.40 to -0.02]) adjusting for measured hypertension or anti-hypertensive drugs, years of measured hypertension, race, education, and age. Preliminary results indicate that HR is associated with lower cognitive test scores in women in their 60s-70s. This association between a simple ophthalmic exam finding of systemic hypertension, i.e., arteriovenous nicking, and lower cognitive function is consistent with a cerebrovascular mechanism of CI.

Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial

Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized trial of vitamin D3 (2000 IU/day of cholecalciferol) and fish oil supplements: 3424 had cognitive assessments by phone (eight neuropsychologic tests; 2.8 years follow-up) and 794 had in-person assessments (nine tests; 2.0 years follow-up). The primary, pre-specified outcome was decline over two assessments in global composite score (average z-scores of all tests); substudy-specific results were meta-analyzed. The pooled mean difference in annual rate of decline (MD) for vitamin D3 versus placebo was 0.01 (95% CI − 0.01, 0.02; p = 0.39). We observed no interaction with baseline 25-hydroxyvitamin-D levels (p-interaction = 0.84) and a significant interaction with self-reported race (p-interaction = 0.01). Among Black participants (19%), those assigned vitamin D3 versus placebo had better cognitive maintenance (MD = 0.04, 95% CI 0.01, 0.08, similar to that observed for Black participants 1.2 years apart in age). Thus, vitamin D3 (2000 IU/day cholecalciferol) supplementation was not associated with cognitive decline over 2–3 years among community-dwelling older participants but may provide modest cognitive benefits in older Black adults, although these results need confirmation.Trial registration ClinicalTrials.gov; VITAL (NCT01169259), VITAL-DEP (NCT01696435) and VITAL-Cog (NCT01669915); the date the registration for the parent trial (NCT01169259) was submitted to the registry: 7/26/2010 and the date of first patient enrollment in either of the ancillary studies for cognitive function in a subset of eligible VITAL participants: 9/14/2011.

Differences in birthweight by maternal and paternal nativity status in Canada.

Parental nativity, as well as duration of residence of foreign-born parents in the host country, has been shown to be associated with size at birth. However, most studies have focused on maternal nativity status only and have not accounted for important characteristics of both parents. To explore whether maternal and paternal nativity and length of residence (LOR) are independently associated with birthweight for gestational age in a representative sample of infants in Canada. We compared mean differences in sex- and gestational age-standardised birthweight z-score by nativity status of both parents in a nationally representative sample of 130,532singleton infants born between May 2004 and May 2006 to mothers residing in Canada. We categorised parental nativity status into four groups (both parents Canada-born, mother only foreign-born, father only foreign-born and both parents foreign-born) and parents' LOR into three (both ≤10years, only one parent ≤10years and both >10years). We estimated mean differences in birthweight z-score and their 95% confidence intervals in linear regression models adjusted for parity, parents' ages, education, ethnicity and marital status of the mother. Compared with babies of Canada-born couples, those of two foreign-born parents had on average smaller birthweight z-score, -0.23 (95% CI -0.28, -0.25). However, after adjustment, the mean difference in z-score was -0.02 (95% CI -0.05, 0.00). Infants born to parents who had both resided in Canada for ≤10years had a unadjusted mean difference in z-score of -0.27 (95% CI -0.29, -0.26), compared infants whose parents were both Canada-born, but the difference became negligible (-0.02, 95% CI -0.04, 0.01) after adjustment. The birthweight differences by parental nativity or length of residence observed in our study population could be attributed to differences in the distribution of other parental characteristics that affect birthweight.

Early high-energy feeding in infants following cardiac surgery: a randomized controlled trial.

BackgroundEffective nutrition programs are beneficial for nutritional recovery in infants. Few studies have focused on the effect of early high-energy feeding after open heart surgery. This study sought to assess the effects of early high-energy feeding in infants after congenital heart surgery.MethodsPatients at a tertiary pediatric cardiology center who underwent open heart surgery between July 2016 and July 2018 were recruited and randomly allocated to 1 of the following 2 groups: (I) the intervention group (postoperative early high-energy feeding; n=124); and (II) the control group (no intervention; n=120).The primary endpoints of average energy delivery and growth Z-scores [i.e., weight-for-height Z-score (WHZ), weight-for-age Z-score (WAZ), and height-for-age Z-score (HAZ)] were recorded preoperatively, during the intensive care unit (ICU) stay, at discharge, and at 1 and 3 months postoperatively. The secondary endpoints of malnutrition recovery, ventilator support time, infection rate, and cardiac ICU (CICU) stay were also recorded.ResultsA total of 244 infants were included in the study. There were no significant differences in the baseline features between the 2 groups. The intervention group received higher calories on average than the control group (44.5 vs. 34.7; P<0.001). At discharge from the ICU, the WHZ (−2.29 vs. −2.76; P<0.001) and WAZ (−3.08 vs. −3.43; P=0.005) of patients in the intervention group were higher than those of patients in the control group. Ventilator support time (P=0.004), CICU stay (P=0.045), and infection rate (P=0.001) were significantly lower in the intervention group than the control group. At 3 months post-surgery, the intervention group exhibited a higher malnutrition recovery rate than the control group (19.4% vs. 6.5%; P=0.002).ConclusionsThe administration of early high-energy feeding to infants after congenital heart surgery is associated with improved growth, reduced CICU stay, decreased ventilator support time, and reduced postoperative infection rates.Trial RegistrationClinicalTrials NCT04609358.

Effet du régime alimentaire seul ou combiné à l’activité physique sur l’obésité et le surpoids chez les adolescents à Kinshasa, RD Congo

Context and objective. Knowledge of therapeutic interventions to treat obesity among sub-Saharan African adolescents is limited. The present study aimed to evaluate the effects of diet and/or physical activity on overweight and obesity among teenagers. Methods. In prospective cohort study, we conducted 6 months long, three-arm randomized trial, to determine the effects of diet (A), aerobic exercise program (B), or the combination of both interventions (C) on change in body weight in Kinshasa, capital of DR Congo from July 15th, 2019 to February 18th, 2020. Results. A total of 64 overweight and obese adolescents were enrolled. Globally, their average BMI, BMI z-score and weight significantly decreased -0.5± 0.1 Kg / m², -0.10 ± 0.16 and -1.9 ± 2.6 Kg, respectively. Average loss weight at 6 months was -1.86 ±1.2 Kg, -1.14±0.99 Kg and -0.88±1.05 in group C (A+B), B and A, respectively. In contrast, in the control group D, the average weight slightly increased (+0.02 ± 0.01 Kg). Conclusion. Among overweight and obese adolescents, lifestyle change including diet, exercise, or both combined over 6 months improves the loss of body weight, mainly from the combined intervention. Keywords: Diet, Physical activity, Obesity, Adolescents, DR Congo Received: April 19th, 2021 Accepted: June 18th, 2021 https://dx.doi.org/10.4314/aam.v14i4.2

824 MOLECULAR UNDERPINNINGS OF NEUROENDOCRINE DIFFERENTIATION IN ESOPHAGEAL ADENOCARCINOMA AND ITS PROGNOSTIC SIGNIFICANCE

Abstract The presence of neuroendocrine (NE) differentiation has been previously reported in both morphological subtypes, (intestinal and diffuse), of esophageal adenocarcinoma, (EAC). This is more commonly seen in the post-treatment setting and is thought to confer a more aggressive phenotype. However, the molecular underpinning and therapeutic implications of NE differentiation within EAC is poorly understood. Herein, the goal is to understand the molecular mechanisms, evolution and the prognostic significance of NE development in EAC tumours. Methods We interrogated a previously published transcriptome dataset with matched H&amp;E slides, TCGA EAC (N = 86). Moreover, we have begun reviewing H&amp;E slides from EAC patients from UHN (N = 50). We created a NE gene expression signature (N = 25 genes) from the literature as an initial proof of concept. We quantified the presence of a NET-like/organoid morphology in the matched H&amp;E slides and correlated it with the average z-score of the NE gene signature calculated from the matched transcriptome data. Results NE differentiation was present in 27/86 cases with a mean of 21.01% +/− 20.9 within the tumour area. We compared the expression of our NE gene signature with the proportion of NE morphology and observed a moderate correlation between morphology with the gene expression (R^2 = 0.546, P &amp;lt; 0.001 ordinary least squares regression), providing validation that the organoid/NET-like morphological pattern correlates with NE differentiation. Furthermore, we have validated the presence of NE morphology in a subset of the UHN samples using electron microscopy and immunohistochemistry (chromogranin and synaptophysin). Conclusion This is a first of a kind study to profile a specific morphology with a transcriptional signature within EAC across a large cohort of patient samples. Correlation of NE-features with clinical outcome together with treatment resistant implications is currently underway.

Do Zinc Supplementation and Physical Exercise Affect Height, H/A z-score, and Academic Performance of Stunted Children in Coronavirus Disease 2019 Pandemic?

BACKGROUND: Stunting in children remains to be a global issue that requires to be addressed. Zinc plays a role in stimulating children’s growth. Research on zinc supplementation and physical exercise in stunted children remains limited in number, specifically during the COVID-19 pandemic.&#x0D; AIM: This study aims to analyze the effect of zinc supplementation and physical exercise on height, H/A z-score, and academic performance of stunted children in the COVID-19 pandemic.&#x0D; METHODS: The design used in this study was a randomized pre-post test control group design. A total of 30 stunted children aged 8-12 years was divided into 2 groups. The treatment group received 5 ml of zinc syrup 3 times/week for 3 months and practiced physical exercise 3 times/week for 3 months. The control group only practiced physical exercise 3 times/week for 3 months. The analysis of change difference in average height, H/A z-score, and academic performance between the treatment and control groups was performed using independent t-test.&#x0D; RESULTS: There was no significant difference in the increase in average height between treatment and control groups (p&gt;0.05). There was increase in the average z-score of H/A in treatment group (0.19) which was higher than in control group (0.14), but the result of independent t-test showed that the mean difference was not significant (p&gt;0.05). The result of independent t-test showed that there was no significant difference in the change in average academic performance scores between treatment and control groups (p&gt;0.05).&#x0D; CONCLUSION: There was no significant difference in the increase in height, H/A z-score, and academic performance of stunted children between the treatment and control groups. Further study is necessary to conduct with a minimum of 6 months of intervention in the non-pandemic period.

Associations between dietary fatty acid patterns and cognitive function in the Hispanic Community Health Study/Study of Latinos.

Our objective was to quantify the cross-sectional associations between dietary fatty acid (DFA) patterns and cognitive function among Hispanic/Latino adults. This study included data from 8,942 participants of the Hispanic Community Health Study/Study of Latinos, a population-based cohort study (weighted age 56.2 y and proportion female 55.2%). The NCI (National Cancer Institute) method was used to estimate dietary intake from two 24-hr recalls. We derived DFA patterns using principal components analysis with 26 fatty acid and total plant and animal monounsaturated fatty acid (MUFA) input variables. Global cognitive function was calculated as the average z-score of 4 neurocognitive tests. Survey linear regression models included multiple potential confounders such as age, sex, education, depressive symptoms, physical activity, energy intake, and cardiovascular disease. DFA patterns were characterized by consumption of long-chain saturated fatty acids (SFA), animal-based MUFA, and trans fatty acids (Factor 1); short to medium-chain SFA (Factor 2); very-long-chain omega-3 polyunsaturated fatty acids (PUFA) (Factor 3); very-long-chain SFA and plant-based MUFA and PUFA (Factor 4). Factor 2 was associated with greater scores for global cognitive function (β=0.037 ± 0.012) and the Digit Symbol Substitution (DSS) (β=0.56±0.17), Brief Spanish English Verbal Learning-Sum (B-SEVLT) (β=0.23 ± 0.11), and B-SEVLT-Recall (β=0.11 ± 0.05) tests (P<0.05 for all). Factors 1 (β=0.04 ± 0.01) and 4 (β=0.70 ± 0.18) were associated with the DSS test (P<0.05 for all). Consumption of short to medium-chain SFA may be associated with higher cognitive function among U.S.-residing Hispanic/Latino adults. Prospective studies are necessary to confirm these findings.

Single leaflet reconstruction in paediatric aortic regurgitation using the Ozaki procedure

Aortic valve repair in children is still a challenge. The aim of this study was to analyse the surgical results of children with aortic regurgitation who underwent single leaflet reconstruction using the Ozaki procedure in our medical centre. A retrospective study was conducted of nine children with aortic regurgitation who received single leaflet reconstruction from May 2017 to September 2019. Paired t-tests and Wilcoxon signed rank tests were used to compare the data at different time points. The median surgical age was 4.7 (3.5, 6.4) years. Eight patients were pre-operatively diagnosed with severe aortic regurgitation, while one had moderate regurgitation. The left ventricles were significantly enlarged, with an average z-score of 3.8. Single leaflet reconstruction was carried out using glutaraldehyde-treated autologous pericardium under the standard Ozaki procedure. The median follow-up was 22 (14, 33) months. There was no post-operative death or re-intervention. One patient had moderate or more aortic regurgitation during the follow-up. The average degree of aortic regurgitation was mild, and the average z-score of the left ventricle decreased to -0.2 in the last follow-up. Single leaflet reconstruction using the Ozaki procedure was an effective surgical method for treating children with aortic regurgitation in our centre with satisfactory short-term results.

Implications of congenital heart disease on growth and development of paediatric cardiac surgical patients

Background: To identify the prevalence, predictors and implications of malnutrition and failure to thrive (FTT) in paediatric cardiac surgical patients.Methods: Observational retrospective analysis of data of paediatric patients presenting for cardiac surgery at Queen Alia heart institute/Amman/Jordan between April 2020 and October 2020. Patients' ages, anthropometric measurements, diagnoses, type of surgical intervention, ICU stay and perioperative outcomes were recorded on a special form designed for the purpose of this study. Prevalence of malnutrition based on world health organization (WHO) and centers for disease control (CDC) growth charts was determined using height-for-age z-score (HAZ) and percentile, weight-for-age z-score (WAZ) and percentile, weight-for-height z-score (WHZ) and percentile. BMI was used for patients above 2 years of age in 109 paediatric cardiac surgical patients. Prevalence of malnutrition and FTT was examined according to age category and cardiac pathology). Patients were divided according to heart pathology into cyanotic and acyanotic CHD.Results: One hundred and nine pediatric cardiac surgical patients were presented for cardiac surgery (59 males and 50 females). Patients' age ranged from 2 days to 17 years (mean 3.7 years, SD±4.5 years). Patients' body weight ranged from 2.7 to 70 kg (mean 14.98 kg, SD±14.2 kg). Average weight percentile was 19.26 (SD±20.01) and ranged between 0.1 and 88.5 and the average Z-score for weight was -1.274±1.037 (mean±SD). The overall height percentile for the all patients with CHD averaged 18.53±17.1 (mean±SD) and the average Z-score for height was -1.1029±0.743 (mean±SD). Prevalence of isolated malnutrition and FTT was 33.2% and 20.2%. Normal nutritional status was found in 46.78%. Cyanotic type CHD was more commonly associated with FTT (p=0.001), longer cardiopulmonary bypass (p=0.001), higher intraoperative lactate (p=0.012) and aortic cross clamp times (p=0.001). Patients with malnutrition and FTT had average ICU stay of 4.32±2.219 days and averaged 4.772±2.065 days (mean±SD) respectively, which was almost double of the ICU stay of patients who had normal nutritional status 2.32±2.261 days (mean±SD).Conclusions: Prevalence of malnutrition and FTT is high in paediatric patients with CHD at time of presentation for surgery. Predicting factors for malnutrition and FTT are cyanotic type of CHD and smaller age. Malnutrition was associated with longer ICU stay.

Abstract 626: The neoantigen and immune landscape of epithelial mesenchymal transition (EMT) low and high score serous ovarian cancers

Abstract Background: Apart from its role in ovarian cancer progression, epithelial-mesenchymal transition (EMT) can promote chemotherapy resistance. We aimed to analyze how the EMT score would affect the tumor microenvironment in ovarian cancer. Methods: cBioportal was queried to obtain The Cancer Genome Atlas (TCGA) data for the serous ovarian cancer (SOC) cohort (TCGA, 585 patients). The neoantigen prediction data was derived from the CloudNeo pipeline using TCGA mutation calling. EMT scores were calculated by subtracting the average RNA-seq z-scores of three epithelial marker genes from the average RNA-seq z-scores of 13 mesenchymal marker genes as described in the previous study. Patient samples were grouped as either EMT-high (highest 1/3) or EMT-low (lowest 1/3). CIBERSORT was applied to predict the tumor-infiltrating immune cells. Results: Among the 585 SOC patients, only 256 patients had mutation data available for our analysis. The EMT-low group had a significantly higher mutation count (p value=0.0004) and cytolytic score (p value=0.032) than the EMT-high group. In addition, the EMT-low samples were associated with improved overall survival in SOC patients (HR, 0.55; 95% CI, 0.39-0.78; P &amp;lt; 0.001). The median survival of EMT-low was 57.40, and EMT-high was 41.06 months. Neoantigen counts and PD-L1 express level tended to be higher in the EMT-high group although failed to show statistical significance. The immune cell infiltration rates were not different between both groups. Conclusions: Our study is the first to describe the association between the EMT potential, neoantigen counts, and cytolytic scores in SOC. In our analyses, tumors with low EMT potential had a significantly higher neoantigen burden and higher cytolytic scores, suggesting that tumors with low EMT potentials tend to be more immunogenic. Further studies are warranted to explore the utility of EMT scores as biomarkers to predict the treatment response to immunotherapy in SOC. The immunologic characteristics of EMT low and high SOCNumber of patientsNeoantigen countp-valueMutation countp-valueCytolytic scorep-valuePD-L1 expressionp-valueEMT low6088.190.183783.190.0004183.40.032190.0663EMT high5867.7472.7486.3515.52 Citation Format: Won Kyung Hur, Jin Young Hwang, Leeseul Kim, Myungwoo Nam, William H. Bae, Yoonhee Choi, Yeun Ho Lee, Heayoon S. Cho, Emma Yu, Chan Mi Jung, William Cheng, Eugene Kim, Christmann Low, Victor Wang, Jeff Chuang, Young Kwang Chae. The neoantigen and immune landscape of epithelial mesenchymal transition (EMT) low and high score serous ovarian cancers [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 626.

Beneficial effects of a nano formulation of pomegranate seed oil, GranaGard, on the cognitive function of multiple sclerosis patients

BackgroundThough often neglected, cognitive impairment is a common feature of multiple sclerosis in 43–70% of patients. None of the novel MS treatment seems to substantially affect or restore cognitive disability in MS. GranaGard (Granalix Bio Technologies LTD) is a food supplement shown to prevent neuronal death in several animal models of neurological diseases. Capsules of GranaGard comprise a self-emulsion nano formulation of pomegranate seed oil (PSO). This oil contains 80–90% of Punicic Acid (PA), one of the strongest natural antioxidants. In animal experiments, administration of GranaGard results in conjugation with linoleic acid (CLA), the main metabolite of PA, which is a well-known neuroprotective agent. AimsTo investigate whether GranaGard administration has an effect on the cognitive state of MS patients. MethodsThis is a single center, randomized double blind clinical trial that started in May 2018. The study included 30 MS patients; half of them (Group-A) were given GranaGard for the first three months and then placebo pills containing soybean oil for additional three months. Patients in Group-B received placebo for the first three months, and GranaGard for the following three months. GranaGard was administrated in addition to their immunomodulatory MS-treatments. Subsequently, all patients received GranaGard for additional six months. Patients were required to visit the neurologist at baseline (inclusion, visit 1) and at 3 months after treatment-initiation at each cycle of the trial (visits 2 and 3). During the follow up visits, clinical and cognitive examinations were performed, including Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC: 25 ft walking test, 9 PEG hole test & PASAT). Cognitive tests included The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery: 1) Symbol Digit Modalities Test (SDMT); 2) California Verbal Learning Test – Second Edition (CVLT-II); 3) and Brief Visuospatial Memory Test – Revised (BVMT-R). Cognitive outcomes were normalized to the healthy population and expressed as z-scores, depended on age, gender and education. Short quality of life and fatigue questionnaires (SF-12, MFIS-5) were also provided by the participants. ResultsNo serious adverse effects, related to the product, were observed during the study period. All patients receiving GranaGard reported a ‘’positive‘’ effect in their ADL while using the product. While there were no significant differences in the clinical parameters of disability (EDSS scores) between the treatment groups, there was a trend of beneficial effect of GranaGard, on the verbal testing during the first 3-month period of treatment. The z score for CVLT-II, significantly increased (from 0.891 to 1.415, p = 0.012, Wilcoxon rank test) at 3-months in the group of patients who were treated with GranaGard, as compared to baseline. A similar (but not statistically significant) trend was seen also in the BVMTr testing during the same 3 months-period, whereas there was no change in the SDMT. The overall average z-score of all three cognitive functions was significantly improved in the three months of Granagard treatment (-0.0077 at 3 months vs 0.462 at baseline, p = 0.034, Wilcoxon rank test). During the same 3-months period there were no significant changes in the placebo-treated group. For the patients receiving GranaGard in the initial 3 months, the value of z score of CVLT-II remained high (z = 1.415) also at the following three months (while they received placebo), suggesting a longer lasting effect for at least 3 months after discontinuation of the drug. ConclusionThis is the first study in which GranaGard, a brain targeted nano-formulation of PSO, was tested in humans. Our results in this small pilot, controlled trial provide indications that GranaGard administration to MS patients might improve/stabilize cognitive disability. Larger studies with longer duration, are needed to confirm these initial observations.