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Item 12-Lipoxygenase Promotes Obesity-Induced Oxidative Stress in Pancreatic Islets(American Society for Microbiology (ASM), 2014-10) Tersey, Sarah A.; Maier, Bernhard; Nishiki, Yurika; Maganti, Aarthi V.; Nadler, Jerry L.; Mirmira, Raghavendra G.; Department of Pediatrics, IU School of MedicineHigh-fat diets lead to obesity, inflammation, and dysglycemia. 12-Lipoxygenase (12-LO) is activated by high-fat diets and catalyzes the oxygenation of cellular arachidonic acid to form proinflammatory intermediates. We hypothesized that 12-LO in the pancreatic islet is sufficient to cause dysglycemia in the setting of high-fat feeding. To test this, we generated pancreas-specific 12-LO knockout mice and studied their metabolic and molecular adaptations to high-fat diets. Whereas knockout mice and control littermates displayed identical weight gain, body fat distribution, and macrophage infiltration into fat, knockout mice exhibited greater adaptive islet hyperplasia, improved insulin secretion, and complete protection from dysglycemia. At the molecular level, 12-LO deletion resulted in increases in islet antioxidant enzymes Sod1 and Gpx1 in response to high-fat feeding. The absence or inhibition of 12-LO led to increases in nuclear Nrf2, a transcription factor responsible for activation of genes encoding antioxidant enzymes. Our data reveal a novel pathway in which islet 12-LO suppresses antioxidant enzymes and prevents the adaptive islet responses in the setting of high-fat diets.Item A Study of the Correlation of Incisive Biting Forces with Age, Sex and Anterior Occlusion(1971) Kotwal, Navroze Shavak; Standish, S. Miles; Chalian, Varoujan A.; Shanks, James C.This study was designed to prove or disprove the fact that incisive biting force can be correlated with the variables chosen which were age, sex and anterior occlusion (overjet, overbite and cuspid relation). The amount of linear contact made by the incisal edges of the upper and lower incisors was also included as one of the variables. One hundred and fifty individuals, 80 males and 70 females, between the ages of 10 and 25 were selected for this study. This was a cross sectional study in which four readings of the maximum biting ability were recorded for every individual just once during the study and an average of the four recordings was taken. An intra-oral force transducer using strain gages was employed to record incisive biting forces. The results indicated that age, sex and amount of linear contact were correlated with biting force when considered singly. When the variables were considered jointly through a stepwise regression analysis overbite also entered as a significant predictor of biting force in addition to the three mentioned variables. Multiple correlation coefficient R was 0.54 for the four entered variables (age squared, sex, overbite and linear contact squared) with biting force. The R squared value was 0.29 so that 29 percent of the variation in incisive biting force of this sample was due to these four variables. The correlated R-squared value indicates a large error of prediction and a low degree of precision in estimating biting force from these four variables. Therefore, a regression equation is not demonstrated.Item Alcohol reinstatement after prolonged abstinence from alcohol drinking by female adolescent rats: Roles of cyclooxygenase-2 and the prostaglandin E2 receptor 1(Elsevier, 2022) Kline, Hannah L.; Yamamoto, Bryan K.; Pharmacology and Toxicology, School of MedicineBackground: Adolescent alcohol misuse is a global problem that can significantly increase the reinstatement of alcohol drinking during re-exposure after abstinence, but the mechanism that causes this increase is unknown. Female adolescents are an understudied population but they are particularly vulnerable to adolescent-onset alcohol abuse. We aimed to determine how adolescent-onset alcohol drinking affects pro-inflammatory mediators endothelin-1 (ET-1), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) in the brain and the role of COX-2 and PGE2 in EtOH reinstatement in adolescent females. Methods: Adolescent female rats were exposed to a 2-bottle choice paradigm of water vs 5% ethanol (EtOH) every other day over a 21 day period. ET-1 and COX-2 proteins were measured in the dorsal striatum (DS) after a 4 week abstinence from EtOH drinking. The COX-2 inhibitor nimesulide was then administered during abstinence prior to an EtOH reinstatement or sucrose preference or to measure PGE2 content. The PGE2 receptor 1 (EP1) antagonist SC-51089 was then administered prior to EtOH reinstatement during which EtOH intake was measured. Results: EtOH drinking significantly increased ET-1 by 33.8 ± 8.9% and COX-2 by 71.4 ± 24.3% in the DS. Treatment with nimesulide during abstinence attenuated EtOH intake during reinstatement after prolonged abstinence by 40.3 ± 12.4% compared to saline controls. Adolescent EtOH drinking and abstinence increased PGE2 150.5 ± 30.9% in the DS and nimesulide attenuated this increase. SC-51089 treatment during abstinence attenuated EtOH reinstatement by 48.1 ± 8.4% compared to DMSO controls. Conclusions: These experiments identified a prostaglandin-mediated mechanism that offers a putative pharmacological target to attenuate EtOH reinstatement after adolescent-onset EtOH drinking.Item Amyloid-β precursor protein synthesis inhibitors for Alzheimer's disease treatment(Wiley, 2014-10) Greig, Nigel H.; Sambamurti, Kumar; Lahiri, Debomoy K.; Becker, Robert E.; Department of Psychiatry, IU School of MedicineItem An Investigation of the Effects of Incisal Overjet on Mandibular Movement During Speech(1979) Lipken, Neil A.The objective of this study was to explore the possible existence of mandibular protrusion during speech for those subjects possessing at least three millimeters of incisal overjet. The most important clinical consequence would be the question of whether or not temporomandibular joint symptomatology becomes manifest with advancing age in these subjects. If proof of a “speech protrusion” were to be found in the course of this research, a future investigation would be in order using an older group of subjects with incisal overjet to answer the above question. A Class I control group was gathered, consisting of ten female subjects, all of whom had zero incisal overjet. Ten female subjects also made up a Class II group, with the criterion being a minimum of three millimeters of incisal overjet. The age range of all the subjects, with one exception, was 17 to 30, none of the subjects had any perceptible speech defects. In both groups, a wide range of overbite was sought and obtained. Models as well as lateral headplates were taken for all twenty subjects. The test instrument was the Mandibular Kinesiograph located in the Complete Denture Department of the Indiana University School of Dentistry. The test parameter components included “s,” a consonant, and the three vowels representing the extremes of the vowel diagram, “ee,” “oo,” and “ah.” These were combined to yield three consonant-vowel combinations, namely “ee-see,” “oo-soo,” and “ah-sah.” After making a reference scribe which consisted of habitual occlusion, a protrusive slide to the end-to-end incisal position, and a retrusive slide, if present, back to centric occlusion, a given subject was asked to repeat each of the consonant-vowel combinations five times. Thus for each subject there were three tracings, each with five trials and a reference scribe. The data were collected by a tape recorder attached to the Kinesiograph, and the subsequent tape sent to Pharmadynamics Research, Inc. in West Lafayette, Indiana, for computer analysis. The computer’s first step was to take each set of five trials for a given consonant-vowel combination and produce one averaged curve. As a result, each subject was left with three curves. Using the end-to-end incisal position, habitual occlusion, and when present, centric occlusion, as reference points, for all subjects anteroposterior distance measurements were made for “s,” and both anteroposterior and vertical distance measurements were made for “ee,” “oo,” and “ah.” These distances were then compared using F-tests and t-tests both between and among the classes (Class I and Class II groups). Statistically significant differences, or lack of, were searched for in evaluating the t-test results. Although the basic purpose of the research was to seek proof of a Class II mandibular protrusion, during “s” to a typical Class I anteroposterior “s” posture, other secondary findings centered around the anteroposterior and vertical positions of “ee,” “oo,” and “ah” relative to habitual occlusion and centric occlusion. The results of the research were as follows: (1) Class II subjects demonstrated complete anterior translation of the mandible during “s” production, validifying the main hypothesis of the study. There was no statistical significance between Class I and Class II “s” position. (2) For the Class I group only, the “oo-soo” “s” mandibular position was statistically posterior to the “ee-see” “s,” with the “ah-sah” “s” appearing to be in an intermediate anteroposterior position. (3) The Class II “ah” mandibular position was more inferior than that of the class I “ah.” (4) For both class I and Class II, the order of mandibular position from superior to inferior was “oo,” “ee,” and then “ah.” (5) The class I “ee” mandibular position was posterior to that of the Class II “ee.” (6) For both Class I and Class II, then mandibular position of “ah” was posterior to that of both “ee” and “oo.”Item Atomoxetine improved attention in children and adolescents with attention-deficit/hyperactivity disorder and dyslexia in a 16 week, acute, randomized, double-blind trial(Mary Ann Liebert, 2013-11) Wietecha, Linda; Williams, David; Shaywitz, Sally; Shaywitz, Bennett; Hooper, Stephen R.; Wigal, Sharon B.; Dunn, David; McBurnett, Keith; Pediatrics, School of MedicineOBJECTIVE: The purpose of this study was to evaluate atomoxetine treatment effects in attention-deficit/hyperactivity disorder (ADHD-only), attention-deficit/hyperactivity disorder with comorbid dyslexia (ADHD+D), or dyslexia only on ADHD core symptoms and on sluggish cognitive tempo (SCT), working memory, life performance, and self-concept. METHODS: Children and adolescents (10-16 years of age) with ADHD+D (n=124), dyslexia-only (n=58), or ADHD-only (n=27) received atomoxetine (1.0-1.4 mg/kg/day) or placebo (ADHD-only subjects received atomoxetine) in a 16 week, acute, randomized, double-blind trial with a 16 week, open-label extension phase (atomoxetine treatment only). Changes from baseline were assessed to weeks 16 and 32 in ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv); ADHD Rating Scale-IV-Teacher-Version (ADHDRS-IV-Teacher-Version); Life Participation Scale-Child- or Parent-Rated Version (LPS); Kiddie-Sluggish Cognitive Tempo (K-SCT) Interview; Multidimensional Self Concept Scale (MSCS); and Working Memory Test Battery for Children (WMTB-C). RESULTS: At week 16, atomoxetine treatment resulted in significant (p<0.05) improvement from baseline in subjects with ADHD+D versus placebo on ADHDRS-IV-Parent:Inv Total (primary outcome) and subscales, ADHDRS-IV-Teacher-Version Inattentive subscale, K-SCT Interview Parent and Teacher subscales, and WMTB-C Central Executive component scores; in subjects with Dyslexia-only, atomoxetine versus placebo significantly improved K-SCT Youth subscale scores from baseline. At Week 32, atomoxetine-treated ADHD+D subjects significantly improved from baseline on all measures except MSCS Family subscale and WMTB-C Central Executive and Visuo-spatial Sketchpad component scores. The atomoxetine-treated dyslexia-only subjects significantly improved from baseline to week 32 on ADHDRS-IV-Parent:Inv Inattentive subscale, K-SCT Parent and Teacher subscales, and WMTB-C Phonological Loop and Central Executive component scores. The atomoxetine-treated ADHD-only subjects significantly improved from baseline to Week 32 on ADHDRS-Parent:Inv Total and subscales, ADHDRS-IV-Teacher-Version Hyperactive/Impulsive subscale, LPS Self-Control and Total, all K-SCT subscales, and MSCS Academic and Competence subscale scores. CONCLUSIONS: Atomoxetine treatment improved ADHD symptoms in subjects with ADHD+D and ADHD-only, but not in subjects with dyslexia-only without ADHD. This is the first study to report significant effects of any medication on SCT.Item Authorship Trends Over the Past 30-Years in the Annals of Biomedical Engineering(Springer, 2019-05) Aguilar, Izath Nizeet; Ganesh, Venkateswaran; Mannfeld, Rachel; Gorden, Riley; Hatch, Jennifer M.; Lunsford, Shatoria; Whipple, Elizabeth C.; Loder, Randall T.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineIn academia, manuscripts serve as an important component of career development. The past several years have seen heightened evaluation of the role of the gender gap in career advancement, as well as other bibliometric changes in publications. We therefore analyzed authorship and publication trends in the Annals of Biomedical Engineering over the past three decades (one complete year of manuscripts for each decade; 1986, 1996, 2006, and 2016). The variables analyzed were number of authors per manuscript, numerical position of the corresponding author, number of collaborating institutions and countries, number of references, and number of citations per manuscript. The gender of both the first and corresponding authors was identified and analyzed over time and by region. Globally, the percentage of female first and corresponding authors significantly increased from 0% in 1986 to 28.6% (p = 0.003) and 20.4% (p = 0.0009), respectively, in 2016. Although there were significant differences regarding female first and corresponding author over time, they did not vary by region of origin (p = 0.5 and 0.2, respectively). Overall, these findings highlight the improvements made and the challenges that still exist related to publishing within the bioengineering field.Item Changes in Device Uptake and Glycemic Control Among Pregnant Women With Type 1 Diabetes: Data From the T1D Exchange(Sage, 2021) Levy, Carol J.; Foster, Nicole C.; DuBose, Stephanie N.; Agarwal, Shivani; Lyons, Sarah K.; Peters, Anne L.; Uwaifo, Gabriel I.; DiMeglio, Linda A.; Sherr, Jennifer L.; Polsky, Sarit; Pediatrics, School of MedicineObjectives: To examine changes in device use and glycemic outcomes for pregnant women from the T1D Exchange Clinic Registry between the years 2010-2013 and 2016-2018. Methods: Participant-reported device use and glycemic outcomes were compared for women aged 16-40 years who were pregnant at the time of survey completion, comparing 2010-2013 (cohort 1) and 2016-2018 (cohort 2). Hemoglobin A1c results within 30 days prior to survey completion were obtained from medical records. Results: There were 208 pregnant women out of 5,236 eligible participants completing the questionnaire in cohort 1 and 47 pregnant women out of 2,818 eligible participants completing the questionaire in cohort 2. Continuous glucose monitor (CGM) use while pregnant trended upward among cohort 2 (70% vs 37%, P = .02), while reported continuous subcutaneous insulin infusion (CSII) use while pregnant declined (76% vs 64%, P = .04). HbA1c levels trended downward (6.8% cohort 1 vs 6.5% cohort 2, P = .07). Conclusions: Self-reported CGM use while pregnant increased over the studied intervals whereas CSII use decreased. Additional evaluation of device use and the potential benefits for T1D pregnancies is needed.Item Clinical features of young children referred for impairing temper outbursts(Mary Ann Liebert, 2013-11) Roy, Amy K.; Klein, Rachel G.; Angelosante, Aleta; Bar-Haim, Yair; Leibenluft, Ellen; Hulvershorn, Leslie; Dixon, Erica; Dodds, Alice; Spindel, Carrie; Psychiatry, School of MedicineOBJECTIVE: In light of the current controversy about whether severe temper outbursts are diagnostic of mania in young children, we conducted a study to characterize such children, focusing on mania and other mood disorders, emotion regulation, and parental psychiatric history. METHODS: Study participants included 51 5-9-year-old children with frequent, impairing outbursts (probands) and 24 non-referred controls without outbursts. Parents completed a lifetime clinical interview about their child, and rated their child's current mood and behavior. Teachers completed a behavior rating scale. To assess emotion regulation, children were administered the Balloons Game, which assesses emotion expressivity in response to frustration, under demands of high and low regulation. Parental lifetime diagnoses were ascertained in blind clinical interviews. RESULTS: No child had bipolar disorder, bipolar disorder not otherwise specified (NOS), or major depression (MDD). The most prevalent disorder was oppositional defiant disorder (88.2%), followed by attention-deficit/hyperactivity disorder (74.5%), anxiety disorders (49.0%), and non-MDD depressive disorders (33.3%). Eleven probands (21.6%) met criteria for severe mood dysregulation. During the Balloons Game, when there were no demands for self-regulation, children with severe outbursts showed reduced positive expressivity, and also showed significant deficits in controlling negative facial expressions when asked to do so. Anxiety disorders were the only diagnoses significantly elevated in probands' mothers. CONCLUSIONS: Overall, young children with severe temper outbursts do not present with bipolar disorder. Rather, disruptive behavior disorders with anxiety and depressive mood are common. In children with severe outbursts, deficits in regulating emotional facial expressions may reflect deficits controlling negative affect. This work represents a first step towards elucidating mechanisms underlying severe outbursts in young children.Item A Comparison Study of Temporomandibular Joint Symptoms in Patients Following Mandibular Advancement by Bilateral Sagittal Split Osteotomies: Rigid Fixation Versus Nonrigid Fixation(1989) Flynn, Brent Cameron; Roberts, W. Eugene; Brown, David T.; Nelson, Charles L.; Shanks, James C.; Hennon, David K.Primary consideration must be given to the temporomandibular joint when planning and performing orthognathic surgical procedures. It has long been understood that the status of the temporomandibular joint can easily and unintentionally be altered during orthognathic surgery, regardless of the method of fixation used. With the advent of modern fixation techniques, many clinicians and investigators have questioned the effects of rigid fixation on the temporomandibular joint. To investigate this, a clinical study of 40 patients treated with mandibular advancement for retrognathism was performed. Twenty patients were treated with rigid fixation while another 20 patients had inferior border wires placed with anterior skeletal fixation. All patients were asked questions regarding the history of their temporomandibular joints. In addition, all patients received a clinical postoperative temporomandibular joints. In addition, all patients received a clinical postoperative temporomandibular joint evaluation. The results were statistically analyzed with the Chi-square analysis and Standard T test. It was determined that the Null Hypothesis could not be rejected for any of the symptoms evaluated in this study. The results support the belief that rigid fixation is no different when compared to wire osteosynthesis in terms of prevalence of temporomandibular joint symptoms.