Neurosciences Commons^™

Associations Between Metabolomic Biomarkers Of Avocado Intake And Glycemia In The Multi-Ethnic Study Of Atherosclerosis, Alexis C Wood, Mark O Goodarzi, Mackenzie K Senn, Meghana D Gadgil, Goncalo Graca, Matthew A Allison, Ioanna Tzoulaki, Michael Y Mi, Philip Greenland, Timothy Ebbels, Paul Elliott, Russell P Tracy, David M Herrington, Jerome I Rotter

Faculty, Staff and Students Publications

BACKGROUND: Avocado consumption is linked to better glucose homeostasis, but small associations suggest potential population heterogeneity. Metabolomic data capture the effects of food intake after digestion and metabolism, thus accounting for individual differences in these processes.

OBJECTIVES: To identify metabolomic biomarkers of avocado intake and to examine their associations with glycemia.

METHODS: Baseline data from 6224 multi-ethnic older adults (62% female) included self-reported avocado intake, fasting glucose and insulin, and untargeted plasma proton nuclear magnetic resonance metabolomic features (metabolomic data were available for a randomly selected subset; N = 3438). Subsequently, incident type 2 diabetes (T2D) was assessed over an …

Association Between Alcohol Consumption And Ectopic Fat In The Multi-Ethnic Study Of Atherosclerosis, Richard Kazibwe, Parag A Chevli, Joni K Evans, Matthew Allison, Erin D Michos, Alexis C Wood, Jingzhong Ding, Michael D Shapiro, Morgana Mongraw-Chaffin

Faculty, Staff and Students Publications

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 >(light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and …

Genome-Wide Association Studies And Fine-Mapping Identify Genomic Loci For N-3 And N-6 Polyunsaturated Fatty Acids In Hispanic American And African American Cohorts, Chaojie Yang, Jenna Veenstra, Traci M Bartz, Matthew C Pahl, Brian Hallmark, Yii-Der Ida Chen, Jason Westra, Lyn M Steffen, Christopher D Brown, David Siscovick, Michael Y Tsai, Alexis C Wood, Stephen S Rich, Caren E Smith, Timothy D O'Connor, Dariush Mozaffarian, Struan F A Grant, Floyd H Chilton, Nathan L Tintle, Rozenn N Lemaitre, Ani Manichaikul

Faculty, Staff and Students Publications

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play critical roles in human health. Prior genome-wide association studies (GWAS) of n-3 and n-6 PUFAs in European Americans from the CHARGE Consortium have documented strong genetic signals in/near the FADS locus on chromosome 11. We performed a GWAS of four n-3 and four n-6 PUFAs in Hispanic American (n = 1454) and African American (n = 2278) participants from three CHARGE cohorts. Applying a genome-wide significance threshold of P < 5 × 10

Unraveling The Serotonin Saga: From Discovery To Weight Regulation And Beyond – A Comprehensive Scientific Review, Kristine Conde, Shuzheng Fang, Yong Xu

Faculty, Staff and Students Publications

The prevalence of obesity is rapidly increasing worldwide, while the development of effective obesity therapies lags behind. Although new therapeutic targets to alleviate obesity are identified every day, and drug efficacy is improving, adverse side effects and increased health risks remain serious issues facing the weight-loss industry. Serotonin, also known as 5-HT, has been extensively studied in relation to appetite reduction and weight loss. As a result, dozens of upstream and downstream neural targets of 5-HT have been identified, revealing a multitude of neural circuits involved in mediating the anorexigenic effect of 5-HT. Despite the rise and fall of several …

An Sms Text Message-Based Type 2 Diabetes Prevention Program For Hispanic Adolescents With Obesity: Qualitative Co-Design Process, Erica Soltero, Callie Lopez, Sandra Mihail, Ayleen Hernandez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: SMS text message-based interventions are a promising approach for reaching and engaging high-risk youths, such as Hispanic adolescents with obesity, in health promotion and disease prevention opportunities. This is particularly relevant, given that SMS text messaging is widely accessible and available and that adolescents are frequent texters. Including youths in the development of SMS text message content can lead to more acceptable and relevant messaging; however, few studies include this group as cocollaborators.

OBJECTIVE: This study aimed to use a co-design process to inform the development of SMS text messages that promote healthy physical activity (PA) and sleep behaviors …

Avocado Consumption And Markers Of Inflammation: Results From The Multi-Ethnic Study Of Atherosclerosis (Mesa), Feon W Cheng, Nikki A Ford, Alexis C Wood, Russell Tracy

Faculty, Staff and Students Publications

Purpose

Since avocado consumption has been linked to a possible reduction in inflammation, we investigated associations between avocado consumption and markers of inflammation in a population-based multi-ethnic cohort [Multi-Ethnic Study of Atherosclerosis (MESA)].

Methods

We used a food frequency questionnaire (FFQ) at MESA exam 1 to capture avocado/guacamole consumption. To calculate daily servings of avocado/guacamole, we used both frequency and serving size data from the FFQ. We classified participants into three consumer groups: rare or never (daily serving ≤ 0.03), medium (0.03 < daily serving < 0.1), and heavy (0.1 ≤ daily serving). Inflammation was estimated by natural log-transformed inflammatory biomarkers (CRP, IL-2, IL-6, homocysteine, fibrinogen, TNF-a soluble receptors). We used multivariate general linear regression models to assess associations accounting for age, sex, race/ethnicity, educational level, income, energy intake, smoking status, physical activity, diet quality, body mass index, and diabetes type.

Results

Among 5794 MESA participants, the average age and BMI were 62.25 y ± 10.26 and 28.28 ± …

Prematurity Blunts Protein Synthesis In Skeletal Muscle Independently Of Body Weight In Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

Background

Postnatal growth failure in premature infants is associated with reduced lean mass accretion. Prematurity impairs the feeding-induced stimulation of translation initiation and protein synthesis in the skeletal muscle of neonatal pigs. The objective was to determine whether body weight independently contributes to the blunted postprandial protein synthesis.

Methods

Preterm and term pigs that were either fasted or fed were stratified into quartiles according to birth weight to yield preterm and term groups of similar body weight; first and second quartiles of preterm pigs and third and fourth quartiles of term pigs were compared (preterm-fasted, n = 23; preterm-fed, n …

Dietary Sources Of Linoleic Acid (La) Differ By Race/Ethnicity In Adults Participating In The National Health And Nutrition Examination Survey (Nhanes) Between 2017-2018, Shabnam R Momin, Mackenzie K Senn, Ani Manichaikul, Chaojie Yang, Rasika Mathias, Mimi Phan, Stephen S Rich, Susan Sergeant, Michael Seeds, Lindsay Reynolds, Floyd H Chilton, Alexis C Wood

Faculty, Staff and Students Publications

Linoleic acid (LA) is a primary n-6 polyunsaturated fatty acid (PUFA), which is of interest to nutritional professionals as it has been associated with health outcomes. However, as some LA-rich foods offer protection against chronic diseases such as CVD (e.g., fatty fish), while others increase risk (e.g., red meat), the individual foods contributing to LA intake may be an important factor to consider. Therefore, this analysis sought to examine whether there are racial/ethnic differences in the proportion of overall LA intake accounted for by individual food groups, via a cross-sectional analysis of 3815 adults participating in the National Health …

Diet Quality Among Pre-Adolescent African American Girls In A Randomized Controlled Obesity Prevention Intervention Trial, Debbe Thompson, Yiming Mirabile, Noemi Islam, Chishinga Callender, Salma M A Musaad, Julie Miranda, Jennette P Moreno, Jayna M Dave, Tom Baranowski

Faculty, Staff and Students Publications

Consuming an unhealthy diet increases health risks. This study assessed the impact of a culturally adapted behaviorally innovative obesity prevention intervention (The Butterfly Girls and the Quest for Founder’s Rock) on diet quality in pre-adolescent non-Hispanic Black/African American girls. The RCT consisted of three groups (experimental, comparison, and waitlist control); block randomization allocated participants to each group. The two treatment groups varied in terms of whether or not they set goals. Data were collected at baseline (prior to receiving the intervention), post 1 (3 months post-baseline), and post 2 (6 months post-baseline). Two dietitian-assisted 24 h dietary recalls …

Preterm Birth Alters The Feeding-Induced Activation Of Akt Signaling In The Muscle Of Neonatal Piglets, Agus Suryawan, Marko Rudar, Jane K Naberhuis, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Postnatal lean mass accretion is commonly reduced in preterm infants. This study investigated mechanisms involved in the blunted feeding-induced activation of Akt in the skeletal muscle of preterm pigs that contributes to lower protein synthesis rates.

METHODS: On day 3 following cesarean section, preterm and term piglets were fasted or fed an enteral meal. Activation of Akt signaling pathways in skeletal muscle was determined.

RESULTS: Akt1 and Akt2, but not Akt3, phosphorylation were lower in the skeletal muscle of preterm than in term pigs (P < 0.05). Activation of Akt-positive regulators, PDK1 and mTORC2, but not FAK, were lower in preterm than in term (P < 0.05). The formation of Akt complexes with GAPDH and Hsp90 and the abundance of Ubl4A were lower in preterm than in term (P < 0.05). The abundance of Akt inhibitors, PHLPP and SHIP2, but not PTEN and IP6K1, were higher in preterm than in term pigs (P < 0.05). PP2A activation was inhibited by feeding in term but not in preterm pigs (P < 0.05).

CONCLUSIONS: Our results suggest that preterm birth impairs regulatory components involved in Akt activation, …

Examination Of Parent-Reported Differences In Children’S Daily Screen Use, Sleep, And Sleep Hygiene Behaviors During The School Year And Summer And Their Association With Bmi, Jennette P Moreno, Alexis C Wood, Brooke Reichek, Hafza Dadabhoy, Tom Baranowski, Debbe Thompson, Teresia M O'Connor

Faculty, Staff and Students Publications

OBJECTIVE: The current study examined school-summer differences in children's sleep patterns and sleep hygiene. Cross-sectional relationships with children's sleep, sleep hygiene, and weight status were explored during the school year and summer.

METHODS: Children (5-8 years) and their parents (n = 197 dyads) were recruited from 4 schools in southeastern Texas and via Facebook. Parents reported children's school year and summer sleep, sleep hygiene, and screen media use. Children's body mass index (BMI) was objectively assessed at the beginning and end of the summer. Associations between children's sleep hygiene and screen media use, sleep duration, and weight status were explored. …

Lateral Septum As A Melanocortin Downstream Site In Obesity Development, Yuanzhong Xu, Zhiying Jiang, Hongli Li, Jing Cai, Yanyan Jiang, Joshua Otiz-Guzman, Yong Xu, Benjamin R Arenkiel, Qingchun Tong

Faculty, Staff and Students Publications

The melanocortin pathway is well established to be critical for body-weight regulation in both rodents and humans. Despite extensive studies focusing on this pathway, the downstream brain sites that mediate its action are not clear. Here, we found that, among the known paraventricular hypothalamic (PVH) neuron groups, those expressing melanocortin receptors 4 (PVHMc4R) preferably project to the ventral part of the lateral septum (LSv), a brain region known to be involved in emotional behaviors. Photostimulation of PVHMc4R neuron terminals in the LSv reduces feeding and causes aversion, whereas deletion of Mc4Rs or disruption of glutamate release from LSv-projecting PVH neurons …

The Metreleptin Effectiveness And Safety Registry (Measure): Concept, Design And Challenges, Morey W Haymond, David Araújo-Vilar, John Balser, James H Lewis, Ruth Louzado, Carla Musso, Julia Von Schnurbein, Martin Wabitsch

Faculty, Staff and Students Publications

BACKGROUND: Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin deficiency in patients with lipodystrophy - a group of rare diseases characterized by a paucity of adipose tissue. MEASuRE (Metreleptin Effectiveness And Safety Registry) is a post-authorization, voluntary registry that gathers long-term safety and effectiveness data on metreleptin. Here, we present the aims and evolution of MEASuRE.

METHODS: MEASuRE was established to collect data from patients receiving commercially supplied metreleptin in the United States (US) and European Union (EU). MEASuRE aims to determine the incidence and severity of …

Associations Between Avocado Intake And Lower Rates Of Incident Type 2 Diabetes In Us Adults With Hispanic/Latino Ancestry, Alexis C Wood, Mackenzie K Senn, Jerome I Rotter

Faculty, Staff and Students Publications

BACKGROUND/PURPOSE: Hispanic/Latinos in the US are at increased risk for type 2 diabetes (T2D). Data suggest that avocado intake is associated with better glycemic control, but whether this translates to protection from T2D has not been studied. The goal of the current analyses was to examine whether consuming avocados at baseline is associated with lower incident T2D over a six-year period, compared to not consuming avocados at baseline.

SUBJECTS/METHODS: Using data from a large population of US adults with Hispanic ancestry, without known or unknown T2D at baseline (N=6,159), participants were classified as avocado consumers (N=983) or non-consumers (N=5,176) based …

Identification Of A Gabaergic Neural Circuit Governing Leptin Signaling Deficiency-Induced Obesity, Yong Han, Yang He, Lauren Harris, Yong Xu, Qi Wu

Faculty, Staff and Students Publications

The hormone leptin is known to robustly suppress food intake by acting upon the leptin receptor (LepR) signaling system residing within the agouti-related protein (AgRP) neurons of the hypothalamus. However, clinical studies indicate that leptin is undesirable as a therapeutic regiment for obesity, which is at least partly attributed to the poorly understood complex secondary structure and key signaling mechanism of the leptin-responsive neural circuit. Here, we show that the LepR-expressing portal neurons send GABAergic projections to a cohort of α3-GABAA receptor expressing neurons within the dorsomedial hypothalamic nucleus (DMH) for the control of leptin-mediated obesity phenotype. We identified the …

Fit24, A Digital Health Intervention To Reduce Type 2 Diabetes Risk Among Hispanic Youth: Protocol For A Feasibility Pilot Study, Erica G Soltero, Callie Lopez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: Poor physical activity (PA) and sleep behaviors in Hispanic adolescents contributes to increased risk for type 2 diabetes. Commonly owned digital devices and services like smartphones and text-messaging are highly used among adolescents and are promising intervention tools for reaching this age group. Personal activity trackers assess activity and sleep, making them ideal tools for addressing these behaviors. We propose to examine the feasibility of a 12-week intervention that uses theoretically grounded text messages and a Fitbit device to improve PA and sleep among Hispanic adolescents with obesity, as compared to a wait-list control group with a Fitbit device …

Soybean Gmsaul1, A Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely Through Repressing The Activation Of Gmmpk3, Jun-Mei Li, Mei-Yan Ye, Chaofeng Wang, Xiao-Han Ma, Ni-Ni Wu, Chen-Li Zhong, Yanjun Zhang, Ninghui Cheng, Paul A Nakata, Lirong Zeng, Jian-Zhong Liu

Faculty, Staff and Students Publications

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, …

In Vivo Functional Characterization Of Egfr Variants Identifies Novel Drivers Of Glioblastoma, Kwanha Yu, Kathleen Kong, Brittney Lozzi, Estefania Luna-Figueroa, Alexis Cervantes, Rachel Curry, Carrie A Mohila, Ganesh Rao, Ali Jalali, Gordon B Mills, Kenneth L Scott, Benjamin Deneen

Faculty, Staff and Students Publications

BACKGROUND: Glioblastoma is the most common and aggressive primary brain tumor. Large-scale sequencing initiatives have cataloged its mutational landscape in hopes of elucidating mechanisms driving this deadly disease. However, a major bottleneck in harnessing this data for new therapies is deciphering "driver" and "passenger" events amongst the vast volume of information.

METHODS: We utilized an autochthonous, in vivo screening approach to identify driver, EGFR variants. RNA-Seq identified unique molecular signatures of mouse gliomas across these variants, which only differ by a single amino acid change. In particular, we identified alterations to lipid metabolism, which we further validated through an unbiased …

Child Weight Status: The Role Of Feeding Styles And Highly Motivated Eating In Children, Maria A Papaioannou, Thomas G Power, Teresia M O'Connor, Jennifer O Fisher, Nilda E Micheli, Sheryl O Hughes

Faculty, Staff and Students Publications

Although parental feeding plays an important role in child eating and weight status, high food motivation among children may also be a factor shaping how feeding impacts child weight. This study explored whether individual differences in preschool children’s food motivation interacted with mothers’ feeding styles in predicting subsequent child weight status. Participants included 129 Hispanic Head Start mother/child dyads. Data were collected at ages 4–5 years (Time 1) and 7–9 (Time 3). Staff measured heights/weights and observed children in an eating in the absence of hunger task. Mothers reported on feeding styles/practices and children’s eating behaviors. A principal components analysis …

Asprosin Promotes Feeding Through Sk Channel-Dependent Activation Of Agrp Neurons, Bing Feng, Hesong Liu, Ila Mishra, Clemens Duerrschmid, Peiyu Gao, Pingwen Xu, Chunmei Wang, Yanlin He

Faculty, Staff and Students Publications

Asprosin, a recently identified adipokine, activates agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARH) via binding to protein tyrosine phosphatase receptor δ (Ptprd) to increase food intake. However, the intracellular mechanisms responsible for asprosin/Ptprd-mediated activation of AgRPARH neurons remain unknown. Here, we demonstrate that the small-conductance calcium-activated potassium (SK) channel is required for the stimulatory effects of asprosin/Ptprd on AgRPARH neurons. Specifically, we found that deficiency or elevation of circulating asprosin increased or decreased the SK current in AgRPARH neurons, respectively. AgRPARH-specific deletion of SK3 (an SK channel subtype highly expressed in AgRPARH neurons) blocked asprosin-induced …

Tfeb-Mediated Lysosomal Exocytosis Alleviates High-Fat Diet-Induced Lipotoxicity In The Kidney, Jun Nakamura, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Satoshi Minami, Atsushi Takahashi, Jun Matsuda, Shinsuke Sakai, Hiroaki Yonishi, Shihomi Maeda, Sho Matsui, Isao Matsui, Takayuki Hamano, Masatomo Takahashi, Maiko Goto, Yoshihiro Izumi, Takeshi Bamba, Miwa Sasai, Masahiro Yamamoto, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Shuhei Nakamura, Tamotsu Yoshimori, Andrea Ballabio, Yoshitaka Isaka

Duncan NRI Faculty and Staff Publications

Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic target of rapamycin kinase complex 1 pathway in a Rag GTPase-dependent manner, though these effects gradually diminished after extended treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney …

Comparison Of Percentile Tables And Algorithm-Based Calculators For Classification Of Blood Pressures In Children And Adolescents With Obesity: A Secondary Analysis Of A Clinical Trial, William J Pitts, Tami L Cave, Alana Cavadino, Roman J Shypailo, Sarah E Maessen, Paul L Hofman, William Wong, Yvonne C Anderson

Faculty, Staff and Students Publications

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines.

METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification …

Brain Nuclear Receptors And Cardiovascular Function, Mengjie Wang, Yongjie Yang, Yong Xu

Faculty, Staff and Students Publications

Brain-heart interaction has raised up increasing attentions. Nuclear receptors (NRs) are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis, etc. In this review, we will elaborate recent findings that have established the physiological relevance of brain NRs in the context of cardiovascular function. In addition, we will discuss the currently available evidence regarding the distinct neuronal populations that respond to brain NRs in the cardiovascular control. These findings suggest connections between cardiac control and brain dynamics through NR signaling, which …

Association Of Omega 3 Polyunsaturated Fatty Acids With Incident Chronic Kidney Disease: Pooled Analysis Of 19 Cohorts, Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C Van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji De Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H De Boer, David S Siscovick, Dariush Mozaffarian, Jason Hy Wu

Faculty, Staff and Students Publications

OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).

DESIGN: Pooled analysis.

DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.

STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.

DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were …

Increased Camkk2 Expression Is An Adaptive Response That Maintains The Fitness Of Tumor-Infiltrating Natural Killer Cells, Patrick K Juras, Luigi Racioppi, Debarati Mukherjee, Sandeep Artham, Xia Gao, Laura Akullian D'Agostino, Ching-Yi Chang, Donald P Mcdonnell

Faculty, Staff and Students Publications

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) …

Adolescence, Alcohol, And Astrocytes: The Impact Of Adolescent Alcohol Use On Astrocyte-Synaptic Interactions, Structure, Function, And Behavior, Christopher Douglas Walker

Theses, Dissertations and Capstones

Alcohol is the third leading cause of preventable death in the United States and has substantial social and economic burdens. Excessive alcohol consumption in the form of binge drinking is highly prevalent among adolescents and emerging adults. Binge drinking is a form of excessive drinking, defined as consuming enough alcohol on a single occasion to result in blood alcohol concentrations above 0.08%. Approximately 55% of full-time college students aged 18- 22 years old have reported consuming alcohol in a binge manner. Furthermore, studies have shown that approximately 20% of college students meet the criteria for an alcohol use disorder (AUD). …

Sex-Specific Associations Between Urinary Bisphenols Concentrations During Pregnancy And Problematic Child Behaviors At Age 2 Years, Sarah Dee Geiger, Salma Musaad, Jennifer Hill, Andréa Aguiar, Susan Schantz

Faculty, Staff and Students Publications

Effects of prenatal bisphenol A (BPA) exposure on child behavior are mixed with some reports suggesting increased problematic behaviors in girls (e.g., aggression and emotional reactivity) and in boys (i.e., externalizing behaviors), while other reports suggest decreased problematic behaviors in girls. Little is known about the potential impact of pregnancy bisphenol S (BPS) exposure on child behavior. In a prospective cohort study (n=68), five maternal spot urine samples collected across pregnancy were pooled and analyzed for BPA and BPS. Child behavior at 2 years was assessed using the Child Behavior Checklist (CBCL). Linear regression models were used to assess associations …

Cerebral Microdialysis And Glucopenia In Traumatic Brain Injury: A Review, Himanshu Sharma, John P Mcginnis, Katherine E Kabotyanski, Shankar P Gopinath, Jerry C Goodman, Claudia Robertson, Jovany Cruz Navarro

Faculty, Staff and Students Publications

Traditionally, intracranial pressure (ICP) and partial brain tissue oxygenation (PbtO2) have been the primary invasive intracranial measurements used to guide management in patients with severe traumatic brain injury (TBI). After injury however, the brain develops an increased metabolic demand which may require an increment in the oxidative metabolism of glucose. Simultaneously, metabolic, and electrical dysfunction can lead to an inability to meet these demands, even in the absence of ischemia or increased intracranial pressure. Cerebral microdialysis provides the ability to accurately measure local concentrations of various solutes including lactate, pyruvate, glycerol and glucose. Experimental and clinical data demonstrate that such …

Chronic Stress May Disrupt Covariant Fluctuations Of Vitamin D And Cortisol Plasma Levels And Placentome Formation In Pregnant Sheep During The Last Trimester: A Methodological Approach And Preliminary Report, Colin Wakefield

Tower Health Research Day

No abstract provided.

Phenotypic And Genetic Spectrum Of Atp6v1a Encephalopathy: A Disorder Of Lysosomal Homeostasis, Renzo Guerrini, Davide Mei, Katalin Kerti-Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, Kimberly Mcdonald, Janice Baker, Vikas Bhambhani, Zöe Powis, Lance Rodan, Rima Nabbout, Giulia Barcia, Jill A Rosenfeld, Carlos A Bacino, Cyril Mignot, Lillian H Power, Catharine J Harris, Dragan Marjanovic, Rikke S Møller, Trine B Hammer, Riikka Keski Filppula, Päivi Vieira, Clara Hildebrandt, Stephanie Sacharow, Luca Maragliano, Fabio Benfenati, Katherine Lachlan, Andreas Benneche, Florence Petit, Jean Madeleine De Sainte Agathe, Barbara Hallinan, Yue Si, Ingrid M Wentzensen, Fanggeng Zou, Vinodh Narayanan, Naomichi Matsumoto, Alessandra Boncristiano, Giancarlo La Marca, Mitsuhiro Kato, Kristin Anderson, Carmen Barba, Luisa Sturiale, Domenico Garozzo, Roberto Bei, Laura Masuelli, Valerio Conti, Gaia Novarino, Anna Fassio

Faculty, Staff and Student Publications

Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease. Here we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased …