Recent Research Articles from UNTHSC

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

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Assessment of impact of DNA extraction methods on analysis of human remain samples on massively parallel sequencing success.

Thu, 04/04/2019 - 06:17
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Assessment of impact of DNA extraction methods on analysis of human remain samples on massively parallel sequencing success.

Int J Legal Med. 2019 Jan;133(1):51-58

Authors: Zeng X, Elwick K, Mayes C, Takahashi M, King JL, Gangitano D, Budowle B, Hughes-Stamm S

Abstract
Skeletal remains recovered from missing persons' cases are often exposed to harsh environmental conditions resulting in the DNA being damaged, degraded, and/or the samples containing PCR inhibitors. In this study, the efficacy of common extraction methods was evaluated to remove high levels of PCR inhibitors commonly encountered with human remains, and their downstream compatibility with the two leading sequencing chemistries and platforms for human identification purposes. Blood, hair, and bone samples were spiked with high levels of inhibitors commonly identified in each particular substrate in order to test the efficiency of various DNA extraction methods prior to sequencing. Samples were extracted using three commercial extraction kits (DNA IQ™, DNA Investigator, and PrepFiler® BTA), organic (blood and hair only), and two total demineralization protocols (bone only)). Massively parallel sequencing (MPS) was performed using two different systems: Precision ID chemistry and a custom AmpliSeq™ STR and iiSNP panel on the Ion S5™ System and the ForenSeq DNA Signature Prep Kit on the MiSeq FGx™. The overall results showed that all DNA extraction methods were efficient and are fully compatible with both MPS systems. Key performance indicators such as STR and SNP reportable alleles, read depth, and heterozygote balance were comparable for each extraction method. In samples where CE-based STRs yielded partial profiles (bone), MPS-based STRs generated more complete or full profiles. Moreover, MPS panels contain more STR loci than current CE-based STR kits and also include SNPs, which can further increase the power of discrimination obtained from these samples, making MPS a desirable choice for the forensic analysis of such challenging samples.

PMID: 30341454 [PubMed - indexed for MEDLINE]

Obstetrics and Gynecology and Family Medicine Residents' Training and Knowledge on Emergency Contraception.

Wed, 04/03/2019 - 06:06
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Obstetrics and Gynecology and Family Medicine Residents' Training and Knowledge on Emergency Contraception.

J Womens Health (Larchmt). 2019 Apr 02;:

Authors: Rapkin RB, Griner SB, Godcharles CL, Vamos CA, Neelamegam M, Thompson EL, Daley EM

Abstract
BACKGROUND: Emergency contraception (EC) has the potential to play a vital role in preventing unintended pregnancies after unprotected sexual intercourse or contraceptive failure. Residency training can influence practice behaviors, however, the extent to which EC-related information is taught in training programs remains unknown. This study examined where residents obtain information about EC and whether knowledge differs by resident program characteristics.
MATERIALS AND METHODS: Program coordinators of Obstetrics and Gynecology (OB/GYN) and Family Medicine residency programs (n = 689) were emailed and requested to forward the survey link to residents. The survey included measures of EC education (hours, sources, including lectures, grand rounds), and EC-related knowledge. EC knowledge items assessed the three methods of EC (copper intrauterine device, ulipristal acetate, and oral levonorgestrel), effectiveness, mechanism of action, contraindications, and side effects. t-Tests and analysis of variances were used to compare mean knowledge scores (maximum = 20; higher scores indicating higher knowledge).
RESULTS: Among participants (n = 676), 61% were Family Medicine residents, 66% were white, and 72% were female. Overall, 34% received <1 hour of EC education, with OB/GYN residents receiving significantly more hours than Family Medicine residents. OB/GYN residents (mean = 14.40, standard deviation [SD] = 2.69) had a significantly higher mean knowledge score than Family Medicine residents (12.12, SD = 2.63; p < 0.000). Mean knowledge score differences were found by region of residency program, with residents in the Northeast reporting higher knowledge.
CONCLUSIONS: Overall, residents received very little EC education, with OB/GYN residents receiving more training and having higher knowledge than their Family Medicine counterparts. Additional training is needed to ensure that residents are knowledgeable about this effective method to decrease unintended pregnancies.

PMID: 30939069 [PubMed - as supplied by publisher]

An ensemble-based likelihood ratio approach for family-based genomic risk prediction.

Tue, 04/02/2019 - 05:54
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An ensemble-based likelihood ratio approach for family-based genomic risk prediction.

J Zhejiang Univ Sci B. 2018 Dec.;19(12):935-947

Authors: An H, Wei CS, Wang O, Wang DH, Xu LW, Lu Q, Ye CY

Abstract
OBJECTIVE: As one of the most popular designs used in genetic research, family-based design has been well recognized for its advantages, such as robustness against population stratification and admixture. With vast amounts of genetic data collected from family-based studies, there is a great interest in studying the role of genetic markers from the aspect of risk prediction. This study aims to develop a new statistical approach for family-based risk prediction analysis with an improved prediction accuracy compared with existing methods based on family history.
METHODS: In this study, we propose an ensemble-based likelihood ratio (ELR) approach, Fam-ELR, for family-based genomic risk prediction. Fam-ELR incorporates a clustered receiver operating characteristic (ROC) curve method to consider correlations among family samples, and uses a computationally efficient tree-assembling procedure for variable selection and model building.
RESULTS: Through simulations, Fam-ELR shows its robustness in various underlying disease models and pedigree structures, and attains better performance than two existing family-based risk prediction methods. In a real-data application to a family-based genome-wide dataset of conduct disorder, Fam-ELR demonstrates its ability to integrate potential risk predictors and interactions into the model for improved accuracy, especially on a genome-wide level.
CONCLUSIONS: By comparing existing approaches, such as genetic risk-score approach, Fam-ELR has the capacity of incorporating genetic variants with small or moderate marginal effects and their interactions into an improved risk prediction model. Therefore, it is a robust and useful approach for high-dimensional family-based risk prediction, especially on complex disease with unknown or less known disease etiology.

PMID: 30507077 [PubMed - indexed for MEDLINE]

Selectively Inhibiting the Median Preoptic Nucleus Attenuates Angiotensin II and Hyperosmotic-Induced Drinking Behavior and Vasopressin Release in Adult Male Rats.

Sat, 03/30/2019 - 05:23
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Selectively Inhibiting the Median Preoptic Nucleus Attenuates Angiotensin II and Hyperosmotic-Induced Drinking Behavior and Vasopressin Release in Adult Male Rats.

eNeuro. 2019 Mar-Apr;6(2):

Authors: Marciante AB, Wang LA, Farmer GE, Cunningham JT

Abstract
The median preoptic nucleus (MnPO) is a putative integrative region that contributes to body fluid balance. Activation of the MnPO can influence thirst, but it is not clear how these responses are linked to body fluid homeostasis. We used designer receptors exclusively activated by designer drugs (DREADDs) to determine the role of the MnPO in drinking behavior and vasopressin release in response to peripheral angiotensin II (ANG II) or 3% hypertonic saline (3% HTN) in adult male Sprague Dawley rats (250-300 g). Rats were anesthetized with isoflurane and stereotaxically injected with an inhibitory DREADD (rAAV5-CaMKIIa-hM4D(Gi)-mCherry) or control (rAAV5-CaMKIIa-mCherry) virus in the MnPO. After two weeks' recovery, a subset of rats was used for extracellular recordings to verify functional effects of ANG II or hyperosmotic challenges in MnPO slice preparations. Remaining rats were used in drinking behavior studies. Each rat was administered either 10 mg/kg of exogenous clozapine-N-oxide (CNO) to inhibit DREADD-expressing cells or vehicle intraperitoneal followed by a test treatment with either 2-mg/kg ANG II or 3% HTN (1 ml/100-g bw, s.c.), twice per week for two separate treatment weeks. CNO-induced inhibition during either test treatment significantly attenuated drinking responses compared to vehicle treatments and controls. Brain tissue processed for cFos immunohistochemistry showed decreased expression with CNO-induced inhibition during either test treatment in the MnPO and downstream nuclei compared to controls. CNO-mediated inhibition significantly attenuated treatment-induced increases in plasma vasopressin compared to controls. The results indicate inhibition of CaMKIIa-expressing MnPO neurons significantly reduces drinking and vasopressin release in response to ANG II or hyperosmotic challenge.

PMID: 30923740 [PubMed - in process]

A proteomic signature for dementia with Lewy bodies.

Sat, 03/30/2019 - 05:23
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A proteomic signature for dementia with Lewy bodies.

Alzheimers Dement (Amst). 2019 Dec;11:270-276

Authors: O'Bryant SE, Ferman TJ, Zhang F, Hall J, Pedraza O, Wszolek ZK, Como T, Julovich D, Mattevada S, Johnson LA, Edwards M, Hall J, Graff-Radford NR

Abstract
Introduction: We sought to determine if a proteomic profile approach developed to detect Alzheimer's disease would distinguish patients with Lewy body disease from normal controls, and if it would distinguish dementia with Lewy bodies (DLB) from Parkinson's disease (PD).
Methods: Stored plasma samples were obtained from 145 patients (DLB n = 57, PD without dementia n = 32, normal controls n = 56) enrolled from patients seen in the Behavioral Neurology or Movement Disorders clinics at the Mayo Clinic, Florida. Proteomic assays were conducted and analyzed as per our previously published protocols.
Results: In the first step, the proteomic profile distinguished the DLB-PD group from controls with a diagnostic accuracy of 0.97, sensitivity of 0.91, and specificity of 0.86. In the second step, the proteomic profile distinguished the DLB from PD groups with a diagnostic accuracy of 0.92, sensitivity of 0.94, and specificity of 0.88.
Discussion: These data provide evidence of the potential utility of a multitiered blood-based proteomic screening method for detecting DLB and distinguishing DLB from PD.

PMID: 30923734 [PubMed]

Inline flow sensor for ventriculoperitoneal shunts: Experimental evaluation in swine.

Sat, 03/30/2019 - 05:23
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Inline flow sensor for ventriculoperitoneal shunts: Experimental evaluation in swine.

Med Eng Phys. 2019 Mar 25;:

Authors: Qin C, Olivencia-Yurvati AH, Williams AG, Eskildsen D, Mallet RT, Dasgupta PK

Abstract
Shunts are commonly employed to treat hydrocephalus, a severe central nervous disease caused by the buildup of cerebrospinal fluid in the brain. These shunts divert excessive cerebrospinal fluid from brain ventricles to other body cavities, thereby relieving the symptoms. However, these shunts are highly prone to failure due to obstruction from cellular debris, leading to cerebrospinal fluid accumulation in the brain and exacerbation of neurological symptoms. Therefore, there is a clinical need for a reliable, non-invasive method of monitoring shunt performance. Recently, a simple inline flow sensor was reported for monitoring ventriculoperitoneal shunting of cerebrospinal fluid in hydrocephalus treatment. The present work aimed to evaluate performance of the device in an animal model of hydrocephalus. Sensor-equipped shunt tubes were placed in anesthetized, juvenile swine. The flows reported by the sensor were compared with gravimetric flow measurements. Robust correlations (r ≈ 0.87-0.96) between the gravimetric and sensor-reported flows were obtained in 4 of the 6 experiments. The mean slope of the linear relationship of the gravimetrically determined vs. sensor flow rates was 0.98 ± 0.09 in the 6 experiments, indicating the sensor accurately reported shunt flows up to 35 ml/h. The sensor responded immediately to abrupt flow changes following cerebroventricular fluid injections. Minor hardware problems were identified and corrected. These experiments provide practical guidance for future preclinical testing of the device.

PMID: 30922842 [PubMed - as supplied by publisher]

Arterial Baroreflex Resetting during Exercise in Humans: Underlying Signaling Mechanisms.

Fri, 03/29/2019 - 05:16

Arterial Baroreflex Resetting during Exercise in Humans: Underlying Signaling Mechanisms.

Exerc Sport Sci Rev. 2019 Mar 27;:

Authors: Raven PB, Young BE, Fadel PJ

Abstract
The arterial baroreflex (ABR) resets during exercise in an intensity-dependent manner to operate around a higher blood pressure with maintained sensitivity. This review provides a historical perspective of ABR resetting, and the involvement of other neural reflexes in mediating exercise resetting. Furthermore, we discuss potential underlying signaling mechanisms that may contribute to exercise ABR resetting in physiological and pathophysiological conditions.

PMID: 30921029 [PubMed - as supplied by publisher]

Neuronal deletion of phosphatase and tensin homolog results in cerebellar motor learning dysfunction and alterations in intracellular signaling.

Fri, 03/29/2019 - 05:16

Neuronal deletion of phosphatase and tensin homolog results in cerebellar motor learning dysfunction and alterations in intracellular signaling.

Neuroreport. 2019 Mar 26;:

Authors: Nolan SO, Jefferson TS, Reynolds CD, Smith GD, Holley AJ, Hodges SL, Lugo JN

Abstract
The purpose of this investigation was to examine cerebellar levels of several molecular signaling pathways, including PI3K/AKT/mammalian target of rapamycin (mTOR) signaling and markers of neuronal migration, following loss of the phosphatase and tensin homolog (PTEN) gene in a subset of neurons, as well as the accompanying behavior phenotype in mice. Motor coordination and learning were measured by the sticker removal task and the accelerating rotarod. Western blots were conducted on cerebellar tissue samples. We demonstrated that neuron subset-specific deletion of PTEN in mice led to deficits in motor coordination. These changes were accompanied by alterations in many different proteins, including the PI3K/AKT/mTOR signaling pathway, FMRP, glutamate receptors, and neuronal migration markers. These data firstly support a role for hyperactivation of mTOR in the cerebellum following the loss of PTEN, accompanied by behavioral deficits. Moreover, the results of the current study support a broader role for PTEN signaling in early neuronal migration and organization of the cerebellum, and point to a putative role for PTEN in many neuropsychiatric conditions.

PMID: 30920436 [PubMed - as supplied by publisher]

Weighing the evidence for using vascular conductance, not resistance, in comparative cardiovascular physiology.

Fri, 03/29/2019 - 05:16

Weighing the evidence for using vascular conductance, not resistance, in comparative cardiovascular physiology.

J Exp Biol. 2019 Mar 27;222(Pt 6):

Authors: Joyce W, White DW, Raven PB, Wang T

Abstract
Vascular resistance and conductance are reciprocal indices of vascular tone that are often assumed to be interchangeable. However, in most animals in vivo, blood flow (i.e. cardiac output) typically varies much more than arterial blood pressure. When blood flow changes at a constant pressure, the relationship between conductance and blood flow is linear, whereas the relationship between resistance and blood flow is non-linear. Thus, for a given change in blood flow, the change in resistance depends on the starting point, whereas the attendant change in conductance is proportional to the change in blood flow regardless of the starting conditions. By comparing the effects of physical activity at different temperatures or between species - concepts at the heart of comparative cardiovascular physiology - we demonstrate that the difference between choosing resistance or conductance can be marked. We also explain here how the ratio of conductance in the pulmonary and systemic circulations provides a more intuitive description of cardiac shunt patterns in the reptilian cardiovascular system than the more commonly used ratio of resistance. Finally, we posit that, although the decision to use conductance or resistance should be made on a case-by-case basis, in most circumstances, conductance is a more faithful portrayal of cardiovascular regulation in vertebrates.

PMID: 30918087 [PubMed - in process]

Microbial enrichment and gene functional categories revealed on the walls of a spent fuel pool of a nuclear power plant.

Tue, 03/26/2019 - 07:45
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Microbial enrichment and gene functional categories revealed on the walls of a spent fuel pool of a nuclear power plant.

PLoS One. 2018;13(10):e0205228

Authors: Silva R, de Almeida DM, Cabral BCA, Dias VHG, Mello ICTE, Ürményi TP, Woerner AE, Neto RSM, Budowle B, Nassar CAG

Abstract
Microorganisms developing in the liner of the spent fuel pool (SFP) and the fuel transfer channel (FTC) of a Nuclear Power Plant (NPP) can form high radiation resistant biofilms and cause corrosion. Due to difficulties and limitations to obtain large samples from SFP and FTC, cotton swabs were used to collect the biofilm from the wall of these installations. Molecular characterization was performed using massively parallel sequencing to obtain a taxonomic and functional gene classification. Also, samples from the drainage system were evaluated because microorganisms may travel over the 12-meter column of the pool water of the Brazilian Nuclear Power Plant (Angra1), which has been functioning since 1985. Regardless of the treatment of the pool water, our data reveal the unexpected presence of Fungi (Basidiomycota and Ascomycota) as the main contaminators of the SFP and FTC. Ustilaginomycetes (Basidiomycota) was the major class contributor (70%) in the SFP and FTC reflecting the little diversity in these sites; nevertheless, Proteobacteria, Actinobacteria, Firmicutes (Bacilli) were present in small proportions. Mapping total reads against six fungal reference genomes indicate that there is, in fact, a high abundance of fungal sequences in samples collected from SFP and FTC. Analysis of the ribosomal internal transcribed spacer (ITS) 1 and 2 regions and the protein found in the mitochondria of eukaryotic cells, cytochrome b (cytb) grouped our sample fungi in the clade 7 as Ustilago and Pseudozyma. In contrast, in the drainage system, Alphaproteobacteria were present in high abundances (55%). The presence of Sphingopyxis, Mesorhizobium, Erythrobacter, Sphingomonas, Novosphingobium, Sphingobium, Chelativorans, Oceanicaulis, Acidovorax, and Cyanobacteria was observed. Based on genomic annotation data, the assessment of the biological function found a higher proportion of protein-coding sequences related to respiration and protein metabolism in SFP and FTC samples. The knowledge of this biological inventory present in the system may contribute to further studies of potential microorganisms that might be useful for bioremediation of nuclear waste.

PMID: 30286173 [PubMed - indexed for MEDLINE]

Letter to the Editor. Ventricular catheter tip proximity to choroid plexus is a key factor in shunt failure.

Tue, 03/26/2019 - 07:45
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Letter to the Editor. Ventricular catheter tip proximity to choroid plexus is a key factor in shunt failure.

J Neurosurg Pediatr. 2017 12;20(6):614-616

Authors: Dickerman R, Reynolds A

PMID: 28937314 [PubMed - indexed for MEDLINE]

An Institutional Coordinated Plan for Effective Partnerships to Achieve Health Equity and Biomedical Workforce Diversity.

Mon, 03/25/2019 - 13:39
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An Institutional Coordinated Plan for Effective Partnerships to Achieve Health Equity and Biomedical Workforce Diversity.

Ethn Dis. 2019;29(Suppl 1):129-134

Authors: Vishwanatha JK, Basha R, Nair M, Jones HP

Abstract
The rapid growth and accumulation of specialized knowledge in today's biomedical fields, combined with entrenched and emerging health issues that persist among certain groups within the US population, emphasizes the significant need to diversify the nation's biomedical science workforce. The under-representation of minorities in science results in inadequate scientific input from divergent social or cultural perspectives and detracts from our nation's ability to resolve health disparities. The University of North Texas Health Science Center at Fort Worth has developed a coordinated approach with local, regional, and national partners to increase participation of underrepresented students along the career pathway from K-12 to faculty level. Career stage specific activities that include research, mentoring, networking, career development, grantsmanship and health disparities curriculum are provided for participants. Successful outcomes from our coordinated plan includes an increase in participant self-efficacy, research presentation awards, increase in grant awards and publications, and career advancement. Through partnerships within our institution, local school districts, and minority serving institutions nationwide, our coordinated plan provides mutually beneficial co-learning experiences to increase the number of under-represented individuals entering translational research focused on increasing the biomedical research workforce diversity and achieving health equity.

PMID: 30906161 [PubMed - in process]

A Novel Serum Free Primary Astrocyte Culture Method that Mimic Quiescent Astrocyte Phenotype.

Mon, 03/25/2019 - 13:39
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A Novel Serum Free Primary Astrocyte Culture Method that Mimic Quiescent Astrocyte Phenotype.

J Neurosci Methods. 2019 Mar 20;:

Authors: Prah J, Winters A, Chaudhari K, Hersh J, Liu R, Yang SH

Abstract
BACKGROUND: Primary astrocyte cultures have been used for decades to study astrocyte functions in health and disease. The current primary astrocyte cultures are mostly maintained in serum-containing medium which produces astrocytes with a reactive phenotype as compared to in vivo quiescent astrocytes. The aim of this study was to establish a serum-free astrocyte culture medium that maintains primary astrocytes in a quiescent state.
NEW METHOD: Serum free astrocyte base medium (ABM) supplemented with basic fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) (ABM-FGF2-EGF) or serum supplemented DMEM (MD-10%FBS) was used to culture primary astrocytes isolated from cerebral cortex of postnatal day 1 C57BL/6 mice.
RESULTS: Compared to astrocytes cultured in MD-10%FBS medium, astrocytes in ABM-FGF2-EGF had higher process bearing morphologies similar to in vivo astrocytes. Western blot, immunostaining, quantitative polymerase chain reaction and metabolic assays revealed that astrocytes maintained in ABM-FGF2-EGF had enhanced glycolytic metabolism, higher glycogen content, lower GFAP expression, increased glutamine synthase, and glutamate transporter-1 mRNA levels as compared to astrocytes cultured in MD-10% FBS medium.
COMPARISON TO EXISTING METHODS: These observations suggest that astrocytes cultured in ABM-FGF2-EGF media compared to the usual FBS media promote quiescent and biosynthetic phenotype similar to in vivo astrocytes.
CONCLUSION: This media provides a novel method for studying astrocytes functions in vitro under physiological and pathological conditions.

PMID: 30904500 [PubMed - as supplied by publisher]

Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma.

Sat, 03/23/2019 - 07:15
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Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma.

Mol Cancer. 2018 08 17;17(1):124

Authors: Timani KA, Győrffy B, Liu Y, Mohammad KS, He JJ

Abstract
Tip110, an important regulator of several oncogenic proteins, was significantly downregulated in human metastatic melanoma cells exposed to a hypoxic condition. Therefore, in this study, we set to determine whether differential expression of Tip110 could be an important indicator for melanoma tumorigenesis and metastasis. We found that in melanoma, but not in other cancer types, Tip110 knockdown enhanced significant expression and secretion of IL-8 and melanoma cells invasions. This induction was further potentiated under hypoxia and by inflammatory cytokine and found independent of TNF-α autocrine signaling. We further showed that Tip110 knockdown-mediated IL-8 induction involved IL-8 mRNA stability. Furthermore, the transcriptomic profiling data and survival from 455 melanoma patients demonstrated that the correlation between Tip110 expression and the clinical outcomes in melanoma was stage-dependent. These findings uncover important roles of Tip110 in melanoma tumorigenesis and metastasis through regulation of IL-8 and hope to provide new clues for future therapeutic strategies.

PMID: 30119675 [PubMed - indexed for MEDLINE]

Glycemic Management in the Bariatric Surgery Population: A Review of the Literature.

Sat, 03/23/2019 - 07:15
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Glycemic Management in the Bariatric Surgery Population: A Review of the Literature.

Pharmacotherapy. 2018 06;38(6):663-673

Authors: Howard ML, Steuber TD, Nisly SA

Abstract
Obesity is a worldwide epidemic often complicated by multiple comorbidities, including type 2 diabetes mellitus (T2DM). Bariatric surgery is an increasingly common and effective weight-loss strategy for obese patients that may result in resolution of metabolic-related disease states, such as T2DM. Although bariatric surgery has many positive outcomes for patients, dietary and pathophysiologic changes can create difficult-to-control blood glucose, especially in the immediate perioperative setting. Depending on oral antidiabetic agent and insulin needs preoperatively, many patients require cessation of oral agents and reduction or cessation of insulin. Unfortunately, despite available perioperative bariatric surgery guidelines, no specific recommendations for perioperative oral antidiabetic agent or insulin management exist. The purpose of this article is to review the current body of evidence for blood glucose management in the setting of bariatric surgery. An English-language PubMed and MEDLINE search was conducted from 1964 through March 2018 using the following search terms alone and in various combinations: bariatric surgery, gastric banding, laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), glucose management, insulin, and oral antidiabetic agent. Five articles were identified evaluating insulin management in the perioperative bariatric surgery setting, which were separated into two categories: immediate perioperative insulin management and long-term postoperative insulin management. Overall, various blood glucose management insulin protocols were evaluated. All studies included some type of insulin reduction in the perioperative setting. No studies identified specifically evaluated down-titration or discontinuation of oral antidiabetic agents. Given the lack of specific guideline recommendations, limitations of standardized insulin protocols, and inconsistency of outcomes studied, perioperative insulin at reduced doses compared to previous maintenance doses coupled with frequent blood glucose monitoring is reasonable. An opportunity exists for successful protocols to be addressed in future, larger studies.

PMID: 29722910 [PubMed - indexed for MEDLINE]

Early Nutrition Intervention Attenuates Weight Gain for Pediatric Acute Lymphoblastic Leukemia Patients in Maintenance Therapy.

Fri, 03/22/2019 - 07:06
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Early Nutrition Intervention Attenuates Weight Gain for Pediatric Acute Lymphoblastic Leukemia Patients in Maintenance Therapy.

J Pediatr Hematol Oncol. 2018 03;40(2):104-110

Authors: Hill R, Hamby T, Bashore L, Rapisand S, Galipp K, Heym K, Bowman WP

Abstract
Obesity following treatment of pediatric acute lymphoblastic leukemia (ALL) has become a significant long-term concern. Excessive weight gain often occurs during treatment, particularly during induction and the first 6 months of maintenance therapy, and it may be potentially modifiable. This retrospective study aimed to evaluate the impact of an early, 3-visit nutrition intervention on weight gain during maintenance therapy in ALL patients. Medical records of the intervention group were compared with historical controls who were treated on the same ALL treatment protocols during an earlier time period. Anthropometrics were collected throughout intensive therapy and at every monthly visit during the first 12 months of maintenance therapy. In total, 67 patients were evaluated (33 in the intervention group and 34 in the control group). After controlling for significant predictors of body mass index (BMI) z-scores in maintenance therapy-including higher BMI at diagnosis and weight gain throughout intensive therapy-the intervention group demonstrated more controlled weight gain during maintenance therapy (P<0.0001). A 3-visit nutrition intervention was effective in attenuating weight gain trends during ALL maintenance therapy.

PMID: 29045268 [PubMed - indexed for MEDLINE]

Angiotensin Type 1a Receptors in the Median Preoptic Nucleus Support Intermittent Hypoxia-Induced Hypertension.

Thu, 03/21/2019 - 06:57
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Angiotensin Type 1a Receptors in the Median Preoptic Nucleus Support Intermittent Hypoxia-Induced Hypertension.

Am J Physiol Regul Integr Comp Physiol. 2019 Mar 20;:

Authors: Shell B, Farmer GE, Nedungadi TP, Wang LA, Marciante AB, Snyder BD, Cunningham RL, Cunningham JT

Abstract
Chronic Intermittent Hypoxia (CIH) is a model of the hypoxemia from sleep apnea that causes a sustained increase in blood pressure. Inhibition of the central renin-angiotensin system or FosB in the median preoptic nucleus (MnPO) prevents the sustained hypertensive response to CIH. We tested the hypothesis that angiotensin type 1a (AT1a) receptors in the MnPO, which are upregulated by CIH, contribute to this hypertension. In preliminary experiments, retrograde tract tracing studies showed AT1a receptor expression in MnPO neurons projecting to the paraventricular nucleus. Adult male rats were exposed to 7 days of intermittent hypoxia (cycling between 21% and 10% O2 every 6 min., 8 hours/day during light phase). Seven days of CIH was associated with a FosB dependent increase in AT1a receptor mRNA without changes in the permeability of the blood-brain-barrier in the MnPO. Separate groups of rats were injected in the MnPO with an AAV containing shRNA against AT1a receptors to test their role in intermittent hypoxia hypertension. Injections of shRNA against AT1a in MnPO blocked the increase in mRNA associated with CIH, prevented the sustained component of the hypertension during normoxia, and reduced circulating advanced oxidation protein products, an indicator of oxidative stress. Rats injected with shRNA against AT1a and exposed to CIH had less FosB staining in MnPO and the rostral ventrolateral medulla after intermittent hypoxia than rats injected with the control vector that were exposed to CIH. Our results indicate AT1a receptors in the MnPO contribute to the sustained blood pressure increase to intermittent hypoxia.

PMID: 30892911 [PubMed - as supplied by publisher]

The Probabilistic Genotyping Software STRmix: Utility and Evidence for its Validity.

Thu, 03/21/2019 - 06:57
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The Probabilistic Genotyping Software STRmix: Utility and Evidence for its Validity.

J Forensic Sci. 2019 Mar;64(2):393-405

Authors: Buckleton JS, Bright JA, Gittelson S, Moretti TR, Onorato AJ, Bieber FR, Budowle B, Taylor DA

Abstract
Forensic DNA interpretation is transitioning from manual interpretation based usually on binary decision-making toward computer-based systems that model the probability of the profile given different explanations for it, termed probabilistic genotyping (PG). Decision-making by laboratories to implement probability-based interpretation should be based on scientific principles for validity and information that supports its utility, such as criteria to support admissibility. The principles behind STRmix™ are outlined in this study and include standard mathematics and modeling of peak heights and variability in those heights. All PG methods generate a likelihood ratio (LR) and require the formulation of propositions. Principles underpinning formulations of propositions include the identification of reasonably assumed contributors. Substantial data have been produced that support precision, error rate, and reliability of PG, and in particular, STRmix™. A current issue is access to the code and quality processes used while coding. There are substantial data that describe the performance, strengths, and limitations of STRmix™, one of the available PG software.

PMID: 30132900 [PubMed - indexed for MEDLINE]

Establishment of a conditionally immortalized mouse optic nerve astrocyte line.

Thu, 03/21/2019 - 06:57
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Establishment of a conditionally immortalized mouse optic nerve astrocyte line.

Exp Eye Res. 2018 11;176:188-195

Authors: Liu Y, Patel GC, Mao W, Clark AF

Abstract
Optic nerve astrocytes play a major role in axonal degeneration and regeneration. Astrocyte lines are an important tool to elucidate the responsible cellular mechanisms. In this study, we established a conditionally immortalized mouse optic nerve astrocyte line. Astrocytes were cultured from explants derived from postnatal day 4-5 H-2kb-tsA58 transgenic mouse optic nerves. Cells were cultured in defined astrocyte culture medium under permissive (33 °C) or non-permissive (38.5 °C) temperatures with or without interferon-ɤ (IFN-ɤ). Astrocytes were characterized by immunocytochemistry staining using antibodies against glial fibrillary acidic protein (GFAP) and neural cell adhesion molecule (NCAM). Cell proliferation rates were determined by cell growth curves and percentage of Ki67 positive cells. Karyotyping was performed to validate the mouse origin of established cell line. Conditional immortalization was assessed by western blot-determined expression levels of SV40 large T antigen (TAg), p53, GFAP and NCAM in non-permissive culture conditions. In addition, phagocytic activity of immortalized cells was determined by flow cytometry-based pHrodo fluorescence analysis. After 5 days in culture, cells migrated out from optic nerve explants. Immunocytochemistry staining showed that migrating cells expressed astrocyte makers, GFAP and NCAM. In permissive conditions, astrocytes had increased expression levels of TAg and p53, exhibited a greater cell proliferation rate as well as a higher percentage of Ki67 positive cells (n = 3, p < 0.05) compared to cells cultured in non-permissive conditions. One cell line (ImB1ON) was further maintained through 60 generations. Karyotyping showed that ImB1ON was of mouse origin. Flow cytometry-based pHrodo fluorescence analysis demonstrated phagocytic activity of ImB1ON cells. Quantitative PCR showed mRNA expression of trophic factors. Non-permissive culture conditions decreased expression of TAg and p53 in ImB1ON, and increased the expression of NCAM. A conditionally immortalized mouse optic nerve astrocyte line was established. This cell line provides an important tool to study astrocyte biological processes.

PMID: 30006274 [PubMed - indexed for MEDLINE]

Students' versus residency programs' perceptions of a high-quality PGY1 residency applicant.

Thu, 03/21/2019 - 06:57
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Students' versus residency programs' perceptions of a high-quality PGY1 residency applicant.

Curr Pharm Teach Learn. 2018 02;10(2):137-145

Authors: Gibson CM, Elrod S

Abstract
INTRODUCTION: Securing a pharmacy residency position is highly competitive, and pharmacy students must work throughout pharmacy school to ensure their applications are as competitive as possible. Several surveys asking residency programs to describe the most crucial qualities of a high-quality residency candidate have been conducted. However, no study has investigated whether congruency exists between pharmacy students' and residency programs' perceptions of these sought-after qualities.
METHODS: We surveyed pharmacy students to compare their perceptions of important qualities of residency candidates for securing an interview and ultimately being ranked by residency programs. The results were compared to results of an identical previously-published survey of residency program directors.
RESULTS: Student and program perceptions of important qualities of residency candidates were mostly in agreement. Students' perceptions of qualities considered for final ranking of candidates are similar among pharmacy students in professional years 1-3 (P1-P3). However, P3 students' perceptions of qualities important for interview invitations are better aligned with residency programs than P1 and P2 students.
DISCUSSION: Students' and programs' perceptions of important qualities for residency candidates were well aligned on most items. However, only students perceived a letter of recommendation from the dean and North American Pharmacist Licensure Examination (NAPLEX) scores as an important factor for residency. As the pharmacy curriculum progresses, students' and residency programs' perceptions of the most important qualities used to ultimately rank candidates appear to converge; however, perceptions of important characteristics for an interview invitation were consistent over time.
CONCLUSIONS: Overall, perceptions of components of a high-quality residency applicant are congruent between residency programs and students.

PMID: 29706267 [PubMed - indexed for MEDLINE]

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