Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
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Potential highly polymorphic short tandem repeat markers for enhanced forensic identity testing.

Thu, 01/03/2019 - 07:29
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Potential highly polymorphic short tandem repeat markers for enhanced forensic identity testing.

Forensic Sci Int Genet. 2018 11;37:162-171

Authors: Novroski NMM, Woerner AE, Budowle B

Abstract
Due to their polymorphic nature, short tandem repeats (STRs) are well-studied and routinely used genetic markers for forensic DNA typing. However, even the largest STR multiplexes are limited in their ability to parse out individuals in a DNA mixture sample, due to alleles shared by size detected by capillary electrophoresis and challenges in resolving minor alleles from stutter, and inherent heterozygote imbalance. In this study, STRs were explored in public datasets that displayed sequence variation and may have limited allele length spread. STRs were first selected using fundamental criteria of high heterozygosity, tetra-, penta-, or hexanucleotide repeat length, and overall relative narrow allele spread (based on length). All candidates were further scrutinized for chemistry compatibility. The resulting STRs were multiplexed and sequenced by massively parallel sequencing in a limited sample population set. Each candidate STR was evaluated for analytical performance and desired biological properties. The findings presented describe a refined set of 53 potential highly polymorphic STR markers (high sequence diversity and heterozygosity; reduced allele spread) that may be suitable to supplement the current core marker set(s) for possible enhanced characterization of complex DNA profiles.

PMID: 30176438 [PubMed - indexed for MEDLINE]

Ischemic and hypoxic conditioning: Potential for protection of vital organs.

Tue, 01/01/2019 - 07:28
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Ischemic and hypoxic conditioning: Potential for protection of vital organs.

Exp Physiol. 2018 Dec 31;:

Authors: Sprick JD, Mallet RT, Przyklenk K, Rickards CA

Abstract
NEW FINDINGS: What is the topic of this review? Paradoxically, ischemic and hypoxic conditioning paradigms protect vital organs from ischemic and hypoxic injury. In this Symposium Report, we focus on remote ischemic preconditioning (RIPC) and hypoxic preconditioning as novel therapeutic approaches for cardiac- and neuro-protection. What advances does it highlight? Growing interest in ischemic and hypoxic preconditioning has facilitated improved understanding of associated mechanisms and signaling pathways, and identified potential pitfalls with application of these therapies to clinical trials. Novel adaptations of preconditioning paradigms have also been developed, including intermittent hypoxia training, RIPC training, and RIPC-exercise, extending their utility to chronic settings.
ABSTRACT: Myocardial infarction and stroke remain leading causes of death worldwide, despite extensive resources directed towards developing effective treatments. In this Symposium Report we highlight the potential applications of intermittent ischemic and hypoxic conditioning protocols to combat the deleterious consequences of heart and brain ischemia. Insights into mechanisms underlying the protective effects of intermittent hypoxia training (IHT) are discussed, including the activation of hypoxia-inducible factor-1 and Nrf2 transcription factors, synthesis of antioxidant and ATP-generating enzymes, and a shift in microglia from pro- to anti-inflammatory phenotypes. Although there is little argument regarding the efficacy of remote ischemic preconditioning (RIPC) in pre-clinical models, this strategy has not consistently translated into the clinical arena. This lack of translation may be related to the patient populations targeted thus far, and the anesthetic regimen used in two of the major RIPC clinical trials. Additionally, we do not fully understand the mechanism through which RIPC protects the vital organs, and co-morbidities (e.g., hypercholesterolemia, diabetes) may interfere with its efficacy. Finally, novel adaptations have been made to extend RIPC to more chronic settings. One adaptation is RIPC-exercise (RIPC-X), an innovative paradigm that applies cyclical RIPC to blood flow restriction exercise (BFRE). Recent findings suggest that this novel exercise modality attenuates the exaggerated hemodynamic responses that may limit the use of conventional BFRE in some clinical settings. Collectively, intermittent ischemic and hypoxic conditioning paradigms remain an exciting frontier for the protection against ischemic injuries. This article is protected by copyright. All rights reserved.

PMID: 30597638 [PubMed - as supplied by publisher]

Failed Early Intervention of Pyomyositis in an Immunocompetent Individual.

Tue, 01/01/2019 - 07:28
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Failed Early Intervention of Pyomyositis in an Immunocompetent Individual.

Case Rep Infect Dis. 2018;2018:4296976

Authors: Al-Dossari R, Zekri S

Abstract
Pyomyositis is a purulent infection of striated muscle tissue that usually leads to an abscess, commonly due to S. aureus. Pyomyositis is typically found in tropic regions, but it is increasingly being recognized in temperate climates, especially in immunocompromised individuals. Patient presentation ranges from afebrile with mildly elevated WBC to frank sepsis. In many reported cases, patients may develop multiple abscesses at different sites. We report a case of a 54-year-old male with a history of chronic obstructive pulmonary disease (COPD) presenting with right pectoral infection. This case demonstrates the possibility that antibiotic therapy in early presentations may not effectively prevent abscess formation, contrary to treatment suggestions found in the literature.

PMID: 30595930 [PubMed]

Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice.

Tue, 01/01/2019 - 07:28
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Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice.

Sci Rep. 2017 06 23;7(1):4145

Authors: Li W, Ding Y, Smedley C, Wang Y, Chaudhari S, Birnbaumer L, Ma R

Abstract
The present study was conducted to determine if TRPC6 regulates glomerular filtration rate (GFR) and the contractile function of glomerular mesangial cells (MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in anesthetized rats with and without in vivo knockdown of TRPC6 in kidneys. We found that GFR was significantly greater, and serum creatinine level was significantly lower in TRPC6 deficient mice. Consistently, local knockdown of TRPC6 in kidney using TRPC6 specific shRNA construct significantly attenuated Ang II-induced GFR decline in rats. Furthermore, Ang II-stimulated contraction and Ca2+ entry were significantly suppressed in primary MCs isolated from TRPC6 deficient mice, and the Ca2+ response could be rescued by re-introducing TRPC6. Moreover, inhibition of reverse mode of Na+-Ca2+ exchange by KB-R7943 significantly reduced Ca2+ entry response in TRPC6-expressing, but not in TRPC6-knocked down MCs. Ca2+ entry response was also significantly attenuated in Na+ free solution. Single knockdown of TRPC6 and TRPC1 resulted in a comparable suppression on Ca2+ entry with double knockdown of both. These results suggest that TRPC6 may regulate GFR by modulating MC contractile function through multiple Ca2+ signaling pathways.

PMID: 28646178 [PubMed - indexed for MEDLINE]

Three-dimensional anatomy of the anthropoid bony pelvis.

Sat, 12/29/2018 - 19:30
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Three-dimensional anatomy of the anthropoid bony pelvis.

Am J Phys Anthropol. 2018 05;166(1):3-25

Authors: Ward CV, Maddux SD, Middleton ER

Abstract
OBJECTIVES: Pelvic form is hypothesized to reflect locomotor adaptation in anthropoids. Most observed variation is found in the ilium, which traditionally is thought to reflect thoracic and shoulder morphology. This article examines the articulated bony pelvis of anthropoids in three dimensions (3D) to test hypothesized variation in pelvic anatomy related to overall torso form.
MATERIALS AND METHODS: Sixty landmarks were collected on articulated pelves from 240 anthropoid individuals. Landmark data were subjected to a Generalized Procrustes Analysis. Principal Components Analysis was used to identify trends among taxa. Linear metrics were extracted, and bivariate allometric analysis was used to compare intergroup differences and scaling trends of specific dimensions.
RESULTS: The combination of 3D and bivariate allometric analysis demonstrates a complex pattern of locomotor/phylogenetic and allometric influences on pelvic morphology. Apes have relatively narrower dorsal interiliac spacing than do most monkeys, with relatively smaller spinal muscle attachment areas but only minimally wider ventral bi-iliac breadths. Hylobatids and atelids have a relatively more cranial position of their sacra than do other taxa, and hylobatids and cercopithecids relatively more retroflexed ischia. Within groups, the three pelvic joints (lumbosacral, sacroiliac, and hip) become relatively closer together with increasing body size.
CONCLUSIONS: A three-dimensional consideration of the articulated pelvis in anthropoids reveals determinants of pelvic variation not previously appreciated by studies of isolated hipbones. This study provides no support for the hypothesis that the ape pelvis is mediolaterally broader than that of monkeys in relative terms, as would be expected if iliac shape is related to hypothesized differences in thoracic breadth and shoulder orientation. Instead, apes, especially great apes, have relatively narrow sacra and longer lower pelves, related to their shorter, stiffer lumbar spines and torsos. This difference, coupled with strong positive allometry of iliac breadth and negative allometry of key pelvic lengths, along with some variation in ischial morphology in certain taxa, explains much of the variation in pelvic form among anthropoid primates.

PMID: 29417986 [PubMed - indexed for MEDLINE]

Personalized normative feedback for heavy drinking: An application of deviance regulation theory.

Tue, 12/25/2018 - 13:30
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Personalized normative feedback for heavy drinking: An application of deviance regulation theory.

Behav Res Ther. 2018 Nov 13;:

Authors: Neighbors C, DiBello AM, Young CM, Steers MN, Rinker DV, Rodriguez LM, Ryamond Knee C, Blanton H, Lewis MA

Abstract
Deviance Regulation Theory (DRT) proposes that individuals regulate their behavior to be in line with the behaviors of others. Specifically, individuals desire to stand out in positive way and not stand out in a negative way. DRT has been successfully applied to encourage other health behaviors and offers a unique method to utilize both injunctive norms in combination with descriptive norms in brief alcohol interventions. This randomized controlled trial evaluated a computer-delivered, norms-based personalized feedback intervention which systematically varied the focus on whether specific drinking behaviors were described as common or uncommon (a descriptive norm), whether the drinking behaviors were healthy versus unhealthy, and whether the drinking behaviors were positively or negatively framed (an injunctive norm). Nine-hundred and fifty-nine college drinkers completed baseline, three-month, and six-month follow-up assessments. Results indicated messages focusing on unhealthy drinking behaviors, particularly when described as uncommon, were most effective in reducing drinking and alcohol-related problems over time. This research utilizes deviance regulation theory as a way of improving personalized normative feedback by elucidating how to construct messages for brief interventions based on descriptive characteristics associated with specific target drinking behaviors in combination with perceptions of prevalence and acceptability of such drinking behaviors (an injunctive norm).

PMID: 30580836 [PubMed - as supplied by publisher]

Knockout of tissue transglutaminase ameliorates TGFβ2-induced ocular hypertension: A novel therapeutic target for glaucoma?

Sun, 12/23/2018 - 16:30
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Knockout of tissue transglutaminase ameliorates TGFβ2-induced ocular hypertension: A novel therapeutic target for glaucoma?

Exp Eye Res. 2018 06;171:106-110

Authors: Raychaudhuri U, Millar JC, Clark AF

Abstract
Glaucoma is a vision threatening optic neuropathy that affects millions of people worldwide. In primary open angle, increased intraocular pressure (IOP) is the main risk factor for the development of this disease. Studies investigating the causes and mechanisms of increased IOP show fibrotic changes in the trabecular meshwork (TM) that are different from those of age-matched controls. Tissue transglutaminase (TGM2), an extracellular matrix (ECM) crosslinking enzyme, covalently crosslinks ECM proteins and causes excessive ECM protein deposition in the TM that could cause increased IOP. Previous literature reports increased expression of TGM2 in glaucomatous eyes compared to controls. We recently have shown that overexpression of TGM2 causes increased ECM crosslinking in the TM, increases IOP, and decreases aqueous humor (AH) outflow facility in mouse eyes. Therefore, we wanted to study the effect of TGM2 knockout (KO) on IOP in TGM2 floxed mice. Ad5.Cre transduction caused partial KO of TGM2, which decreased TGM2 expression in the TM region of mouse eyes. TGM2 KO significantly decreased IOP by itself and also in TGFβ2 induced ocular hypertensive mice. TGM2 KO also restores the outflow facility in TGFβ2 transduced eyes. Overall, TGM2 KO rescued the TGFβ2-induced ocular hypertensive phenotype. Thus, TGM2 may offer potential as a new therapeutic target for glaucoma.

PMID: 29535003 [PubMed - indexed for MEDLINE]

Distinguishing genetically between the germlines of male monozygotic twins.

Fri, 12/21/2018 - 07:29
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Distinguishing genetically between the germlines of male monozygotic twins.

PLoS Genet. 2018 Dec;14(12):e1007756

Authors: Krawczak M, Budowle B, Weber-Lehmann J, Rolf B

Abstract
Identification of the potential donor(s) of human germline-derived cells is an issue in many criminal investigations and in paternity testing. The experimental and statistical methodology necessary to work up such cases is well established but may be more challenging if monozygotic (MZ) twins are involved. Then, elaborate genome-wide searches are required for the detection of early somatic mutations that distinguish the cell sample and its donor from the other twin, usually relying upon reference material other than semen (e.g. saliva). The first such cases, involving either criminal sexual offenses or paternity disputes, have been processed successfully by Eurofins Genomics and Forensics Campus. However, when presenting the experimental results in court, common forensic genetic practice requires that the residual uncertainty about donorship is quantified in the form of a likelihood ratio (LR). Hence, we developed a general mathematical framework for LR calculation, presented herein, which allows quantification of the evidence in favour of the true donor in the respective cases, based upon observed DNA sequencing read counts.

PMID: 30571769 [PubMed - in process]

Corticotropin-Releasing Hormone Projections from the Paraventricular Nucleus of the Hypothalamus to the Nucleus of the Solitary Tract Increases Blood Pressure.

Thu, 12/20/2018 - 10:29

Corticotropin-Releasing Hormone Projections from the Paraventricular Nucleus of the Hypothalamus to the Nucleus of the Solitary Tract Increases Blood Pressure.

J Neurophysiol. 2018 Dec 19;:

Authors: Wang LA, Nguyen DH, Mifflin SW

Abstract
Activation of corticotropin-releasing hormone (CRH) type 2 receptors (CRHR2) in the nucleus of the solitary tract (NTS) contributes to the development of hypertension, but the source of CRH inputs to the NTS that increases blood pressure remains unknown. This study tested the hypothesis that activation of CRH-containing projections from the paraventricular nucleus of the hypothalamus (PVN) to the NTS increase blood pressure. We expressed Channelrhodopsin 2 (ChR2), a light sensitive ion channel, into CRH-containing neurons in the PVN. This was achieved by injecting Cre-inducible virus expressing ChR2 into the PVN of CRH-Cre mice. CRH-Cre mice are genetically modified mice expressing Cre recombinase only in neurons producing CRH. We found that optogenetic stimulation of CRH-containing somas in the PVN or CRH-containing fibers in the NTS originating from the PVN significantly increased blood pressure and heart rate. Microinjection of K41498 (CRHR2 antagonist) into the NTS attenuated the pressor and tachycardiac responses induced by optogenetic stimulation of CRH-containing somas in the PVN. In vitro loose-patch recordings revealed that optogenetic stimulation of CRH-containing fibers in the NTS originating from the PVN significantly increased the discharge frequency of NTS neurons. This effect was attenuated by pretreatment of K41498 and was abolished by pretreatment of kynurenic acid (non-selective glutamate receptor antagonist). These results suggest that activation of PVN-NTS CRH-containing projections increases blood pressure and heart rate. The cardiovascular responses may be mediated at least in part by the co-release of CRH and glutamate from NTS CRH-containing axons originating from the PVN.

PMID: 30565964 [PubMed - as supplied by publisher]

Improving diagnosis by improving education: a policy brief on education in healthcare professions.

Thu, 12/20/2018 - 10:29
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Improving diagnosis by improving education: a policy brief on education in healthcare professions.

Diagnosis (Berl). 2018 09 25;5(3):107-118

Authors: Graber ML, Rencic J, Rusz D, Papa F, Croskerry P, Zierler B, Harkless G, Giuliano M, Schoenbaum S, Colford C, Cahill M, Olson APJ

PMID: 30145580 [PubMed - indexed for MEDLINE]

Opioids' Effect on Healing of Venous Leg Ulcers.

Thu, 12/20/2018 - 10:29
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Opioids' Effect on Healing of Venous Leg Ulcers.

J Invest Dermatol. 2017 12;137(12):2646-2649

Authors: Herskovitz I, MacQuhae FE, Dickerson JE, Cargill DI, Slade HB, Margolis DJ, Kirsner RS

PMID: 28842329 [PubMed - indexed for MEDLINE]

Differential effects of protein kinase C-eta on apoptosis versus senescence.

Wed, 12/19/2018 - 07:28
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Differential effects of protein kinase C-eta on apoptosis versus senescence.

Cell Signal. 2018 Dec 15;:

Authors: Basu A, Pal D, Blaydes R

Abstract
Protein kinase C-eta (PKCη) is considered an anti-apoptotic kinase, which promotes cell survival and chemoresistance in several cancers, including breast cancer. We have recently shown that PKCη positively regulates the anti-apoptotic protein Mcl-1 in breast cancer cells, and depletion of PKCη induced proteasomal degradation of Mcl-1. We therefore examined if depletion of PKCη would enhance cellular sensitivity to chemotherapeutic agents. Silencing of PKCη by siRNA attenuated apoptosis induced by doxorubicin and paclitaxel in both MCF-7 and T47D breast cancer cells. While silencing of Mcl-1 caused a substantial increase in apoptosis induced by doxorubicin, the combined knockdown of PKCη and Mcl-1 was less effective. Depletion of PKCη also caused an increase in the abundance of the cell cycle inhibitor p27 and a decrease in the clonogenic survival of MCF-7 and T47D cells. PKCη knockdown was associated with an increase in senescence-associated β-galactosidase (SA-β-gal) activity but this increase was attenuated by knockdown of p27. The suppression of doxorubicin-induced apoptosis by PKCη knockdown was partially relieved when p27 was depleted. Since loss of proliferative capacity during senescence could cause resistance to chemotherapeutic drugs, our results suggest that PKCη knockdown inhibits apoptosis by inducing p27-mediated senescence.

PMID: 30562553 [PubMed - as supplied by publisher]

Successful Remediation of an Advanced Pharmacy Practice Experience for an At-risk Student.

Wed, 12/19/2018 - 07:28
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Successful Remediation of an Advanced Pharmacy Practice Experience for an At-risk Student.

Am J Pharm Educ. 2018 Nov;82(9):6762

Authors: Martin RD, Wheeler E, White A, Killam-Worrall LJ

Abstract
Objective. To describe a successful remediation for an Acute Care Medicine advanced pharmacy practice experience (APPE) in a student with multiple learning deficits. Methods. A literature review of pharmacy and medical experiential remediation was conducted to identify best practices to implement prior to designing the remediation for our student case. Based on this search and experience as preceptors, a three-phase remediation was designed: one week for assessment, two weeks for development of learning skills and strategies and six weeks for an on-campus APPE. Success of the remediation was determined by student performance, as defined by the APPE preceptor, in all relevant 2013 Center for the Advancement of Pharmacy Education (CAPE) educational outcomes. Results. Baseline assessment indicated that the student was below minimal competency in six of 13 relevant 2013 CAPE educational outcomes. Upon completion of the three-part remediation, the student repeated the Acute Care Medicine APPE, achieving better than minimal competency in all 13 outcomes. The student demonstrated significant improvement in nine of 13 CAPE educational outcomes. Conclusion. This student case provides a novel and successful blueprint for remediation of APPE. However, more evidence-based literature is needed to guide educators in experiential remediation.

PMID: 30559502 [PubMed - in process]

Alcohol motivations and behaviors during months young adults experience social role transitions: Microtransitions in early adulthood.

Tue, 12/18/2018 - 07:28
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Alcohol motivations and behaviors during months young adults experience social role transitions: Microtransitions in early adulthood.

Psychol Addict Behav. 2018 Dec;32(8):895-903

Authors: Patrick ME, Rhew IC, Lewis MA, Abdallah DA, Larimer ME, Schulenberg JE, Lee CM

Abstract
The study examines how young adult transitions into and out of social roles (i.e., starting or ending a job, a romantic relationship, school) are associated with drinking motives (coping, enhancement, social, and conformity) and alcohol use in a given month. A community sample of young adult drinkers (N = 767; 56.3% female; 59.3% White; Ages 18-23) completed 24 consecutive months of online surveys (N = 15,333 months of data) about the previous month's experiences, social role transitions, and alcohol use. During the 2-year data collection window, participants reported starting/ending a job (10.0%/8.2%), a relationship (2.7%/4.3%), and school (9.2%/17.4%). Between persons, those who more often started jobs were more likely to drink and those who more often ended jobs had higher enhancement motives; those who more often ended relationships were more likely to drink, have a greater number of drinks when drinking, and have higher coping and enhancement motives; and those who more often started relationships had higher conformity motives. Within persons, during months when a relationship ended, participants reported stronger coping motives, and during months when a relationship started, they reported stronger social motives for drinking. During months when a relationship started or ended, participants also reported consuming a greater number of drinks when drinking. There were no differences based on starting or ending school. Young adult social role transitions are associated with concurrent changes in both alcohol use and motives for drinking. Understanding these contextual changes and their concomitant risks is key to providing salient interventions to reduce alcohol-related harm. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID: 30556714 [PubMed - in process]

Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Tue, 12/18/2018 - 07:28
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Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need.

Alzheimers Dement. 2018 Dec 13;:

Authors: Babulal GM, Quiroz YT, Albensi BC, Arenaza-Urquijo E, Astell AJ, Babiloni C, Bahar-Fuchs A, Bell J, Bowman GL, Brickman AM, Chételat G, Ciro C, Cohen AD, Dilworth-Anderson P, Dodge HH, Dreux S, Edland S, Esbensen A, Evered L, Ewers M, Fargo KN, Fortea J, Gonzalez H, Gustafson DR, Head E, Hendrix JA, Hofer SM, Johnson LA, Jutten R, Kilborn K, Lanctôt KL, Manly JJ, Martins RN, Mielke MM, Morris MC, Murray ME, Oh ES, Parra MA, Rissman RA, Roe CM, Santos OA, Scarmeas N, Schneider LS, Schupf N, Sikkes S, Snyder HM, Sohrabi HR, Stern Y, Strydom A, Tang Y, Terrera GM, Teunissen C, Melo van Lent D, Weinborn M, Wesselman L, Wilcock DM, Zetterberg H, O'Bryant SE, International Society to Advance Alzheimer's Research and Treatment, Alzheimer's Association

Abstract
Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.

PMID: 30555031 [PubMed - as supplied by publisher]

Compound stutter in D2S1338 and D12S391.

Mon, 12/17/2018 - 07:28
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Compound stutter in D2S1338 and D12S391.

Forensic Sci Int Genet. 2018 Dec 07;39:50-56

Authors: Woerner AE, King JL, Budowle B

Abstract
Compound repeats provide a testing ground for evaluating hypotheses on the causes and consequences of stutter. As compound repeats have two repeating motifs, each motif may produce stutter variants; thus as the repeat within the locus is compound, so is the resultant stutter. Further, the rates of stutter formation between these motifs may not be independent. This lack of independence may complicate modeling strategies, thus contributing to the challenges of mixture interpretation that rely on nucleotide sequence. This study evaluates compound stutter in two STR loci: D2S1338 and D12S391. The effects of flanking variation, as well as possible interactions between the two different uninterrupted stretches (US) and their respective stutter variants are assessed. Multivariate multiple linear regression (MMLR) was used to show that, as with simple repeats, the rate of stutter product formation of a particular repeating motif is not solely a function of the US of that repeat. The nucleotides adjacent to the repeating motif also appear to influence the rate of stutter formation of that motif, with those nucleotides sometimes including the other motif. MMLR was used to estimate the size of these effects and to construct an example of a two-dimensional (thus, a compound) stutter prediction. This example may merit further investigation in the application of massively parallel sequencing data to mixture interpretation and probabilistic genotyping.

PMID: 30554027 [PubMed - as supplied by publisher]

Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling.

Sat, 12/15/2018 - 07:29
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Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling.

Compr Physiol. 2018 Dec 13;9(1):375-411

Authors: Chaudhari S, Cushen SC, Osikoya O, Jaini PA, Posey R, Mathis KW, Goulopoulou S

Abstract
Epidemiological studies demonstrate disparities between men and women in cardiovascular disease prevalence, clinical symptoms, treatments, and outcomes. Enrollment of women in clinical trials is lower than men, and experimental studies investigating molecular mechanisms and efficacy of certain therapeutics in cardiovascular disease have been primarily conducted in male animals. These practices bias data interpretation and limit the implication of research findings in female clinical populations. This review will focus on the biological origins of sex differences in cardiovascular physiology, health, and disease, with an emphasis on the sex hormones, estrogen and testosterone. First, we will briefly discuss epidemiological evidence of sex disparities in cardiovascular disease prevalence and clinical manifestation. Second, we will describe studies suggesting sexual dimorphism in normal cardiovascular function from fetal life to older age. Third, we will summarize and critically discuss the current literature regarding the molecular mechanisms underlying the effects of estrogens and androgens on cardiac and vascular physiology and the contribution of these hormones to sex differences in cardiovascular disease. Fourth, we will present cardiovascular disease risk factors that are positively associated with the female sex, and thus, contributing to increased cardiovascular risk in women. We conclude that inclusion of both men and women in the investigation of the role of estrogens and androgens in cardiovascular physiology will advance our understanding of the mechanisms underlying sex differences in cardiovascular disease. In addition, investigating the role of sex-specific factors in the development of cardiovascular disease will reduce sex and gender disparities in the treatment and diagnosis of cardiovascular disease. © 2019 American Physiological Society. Compr Physiol 9:375-411, 2019.

PMID: 30549017 [PubMed - in process]

Successful management of early gastrogastric fistula using fully covered esophageal stent.

Fri, 12/14/2018 - 13:30
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Successful management of early gastrogastric fistula using fully covered esophageal stent.

Surg Obes Relat Dis. 2018 Dec;14(12):1911-1913

Authors: Jafri SA, Jay Roberts DO, Smith A

PMID: 30545597 [PubMed - in process]

[99mTc-HYNIC-N-dodecylamide]: a new hydrophobic tracer for labelling reconstituted high-density lipoproteins (rHDL) for radioimaging.

Fri, 12/14/2018 - 13:30
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[99mTc-HYNIC-N-dodecylamide]: a new hydrophobic tracer for labelling reconstituted high-density lipoproteins (rHDL) for radioimaging.

Nanoscale. 2018 Dec 13;:

Authors: Isaac-Olivé K, Ocampo-García BE, Aranda-Lara L, Santos-Cuevas CL, Jiménez-Mancilla NP, Luna-Gutiérrez MA, Medina LA, Nagarajan B, Sabnis N, Raut S, Prokai L, Lacko AG

Abstract
Despite the widespread use of nanotechnology in radio-imaging applications, lipoprotein based delivery systems have received only limited attention so far. These studies involve the synthesis of a novel hydrophobic radio-imaging tracer consisting of a hydrazinonicotinic acid (HYNIC)-N-dodecylamide and 99mTc conjugate that can be encapsulated into rHDL nanoparticles (NPs). These rHDL NPs can selectively target the Scavenger Receptor type B1 (SR-B1) that is overexpressed on most cancer cells due to excess demand for cholesterol for membrane biogenesis and thus can target tumors in vivo. We provide details of the tracer synthesis, characterization of the rHDL/tracer complex, in vitro uptake, stability studies and in vivo application of this new radio-imaging approach.

PMID: 30543234 [PubMed - as supplied by publisher]

Examining Changes in Prevention Guidelines in Maternal and Child Health: Development of a Teaching Activity.

Fri, 12/14/2018 - 13:30
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Examining Changes in Prevention Guidelines in Maternal and Child Health: Development of a Teaching Activity.

Matern Child Health J. 2018 09;22(9):1255-1259

Authors: Thompson EL, Vamos CA, Windsor-Hardy A, Griner SB, Daley EM

Abstract
Purpose Recent changes in preventive guidelines (e.g., pap testing, mammography) have resulted in confusion for both providers and patients. These changes have occurred either because new research has been introduced or because evidence for the practice is not established. Public health has the responsibility to promote the dissemination and implementation of changing guidelines into practice to improve the public's health. Health literacy may facilitate this process. The purpose of this study is to describe a teaching tool applying principles of health literacy to changes in prevention guidelines. The objectives of the teaching activity were to: (1) understand the development of evidence-informed prevention guidelines; and (2) use health literacy to evaluate the target population's perspectives on the guideline change using a health literacy approach. Description An interactive lecture and a practice-based assignment were created; the assignment was pilot-tested in graduate Women's Health classes. Multiple final products were developed in order to facilitate the lecture and assignment: (1) lesson plan; (2) slide presentation; (3) health literacy interview guide worksheet; and (4) grading rubric. After the presentation, students interviewed women from the guideline target population using health literacy constructs and synthesized their findings to create an overall assessment report. Assessment Feedback from the pilot test informed the revision of the teaching activity. Conclusions This teaching tool can be applied in a wide variety of settings in higher education, such as courses in public health, nursing, or medicine. As health literacy continues to be an important determinant of health status, integrating this determinant into the dissemination and communication of preventive guideline changes is needed.

PMID: 29946751 [PubMed - indexed for MEDLINE]

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