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

Recent Research Articles from UNTHSC - Fri, 12/07/2018 - 09:58
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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 - in process]

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors.

Recent Research Articles from UNTHSC - Fri, 12/07/2018 - 09:58
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Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transcription Factors.

Cell Physiol Biochem. 2018 Nov 30;51(4):1894-1907

Authors: Hurtado M, Sankpal UT, Kaba A, Mahammad S, Chhabra J, Brown DT, Gurung RK, Holder AA, Vishwanatha JK, Basha R

Abstract
BACKGROUND/AIMS: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated.
METHODS: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks.
RESULTS: The IC50 value for Cu-TA was about half than TA.Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G2/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring.
CONCLUSION: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth.

PMID: 30504717 [PubMed - as supplied by publisher]

Impact of Environmental Stressors on Tolerance to Hemorrhage in Humans.

Recent Research Articles from UNTHSC - Thu, 12/06/2018 - 09:54

Impact of Environmental Stressors on Tolerance to Hemorrhage in Humans.

Am J Physiol Regul Integr Comp Physiol. 2018 Dec 05;:

Authors: Crandall CG, Rickards CA, Johnson BD

Abstract
Hemorrhage is a leading cause of death in the military and civilian settings and approximately 85% of potentially survivable battlefield deaths are hemorrhage related. Both Soldiers and civilians are exposed to a number of environmental and physiological conditions that have the potential to alter tolerance to a hemorrhagic insult. The objective of this review article is to summarize the known impact of commonly encountered environmental and physiological conditions on hemorrhagic tolerance, primarily in humans. The majority of the presented studies use lower-body negative pressure (LBNP) to simulate a hemorrhagic insult, although some studies employed incremental blood withdrawal. This review first addresses the use of LBNP as a model of hemorrhage-induced central hypovolemia, and then addresses the effects of the following conditions on tolerance to LBNP: passive and exercise-induced heat stress with and without accompanying hypohydration/dehydration, hypothermic exposure, and altitude/hypoxia exposure. By understanding the effects of these environmental and physiological conditions on responses to a hemorrhagic challenge, including tolerance, targeted strategies and interventions can be developed and applied to reduce the impact of such conditions on tolerance to a hemorrhagic insult, and ultimately improve survival from blood loss injuries.

PMID: 30517019 [PubMed - as supplied by publisher]

Nanopore sequencing: An enrichment-free alternative to mitochondrial DNA sequencing.

Recent Research Articles from UNTHSC - Wed, 12/05/2018 - 09:50

Nanopore sequencing: An enrichment-free alternative to mitochondrial DNA sequencing.

Electrophoresis. 2018 Dec 04;:

Authors: Zascavage RR, Thorson K, Planz JV

Abstract
Mitochondrial DNA sequence data is often utilized in disease studies, conservation genetics and forensic identification. The current approaches for sequencing the full mtGenome typically require several rounds of PCR enrichment during Sanger or MPS protocols followed by fairly tedious assembly and analysis. Here we describe an efficient approach to sequencing directly from genomic DNA samples without prior enrichment or extensive library preparation steps. A comparison is made between libraries sequenced directly from native DNA and the same samples sequenced from libraries generated with nine overlapping mtDNA amplicons on the Oxford Nanopore MinION device. The native and amplicon library preparation methods and alternative base calling strategies were assessed to establish error rates and identify trends of discordance between the two library preparation approaches. For the complete mtGenome, 16,569 nucleotides, an overall error rate of approximately 1.00% was observed. As expected with mtDNA, the majority of error was detected in homopolymeric regions. The use of a modified basecaller that corrects for ambiguous signal in homopolymeric stretches reduced the error rate for both library preparation methods to approximately 0.30%. Our study indicates that direct mtDNA sequencing from native DNA on the minION device provides comparable results to those obtained from common mtDNA sequencing methods and is a reliable alternative to approaches using PCR-enriched libraries. This article is protected by copyright. All rights reserved.

PMID: 30511783 [PubMed - as supplied by publisher]

Use of the Muddiest Point Technique as an exam review in an integrated pharmacotherapy course.

Recent Research Articles from UNTHSC - Sat, 12/01/2018 - 09:32
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Use of the Muddiest Point Technique as an exam review in an integrated pharmacotherapy course.

Curr Pharm Teach Learn. 2018 Sep;10(9):1295-1302

Authors: Bullock KC, Gibson C, Howard M, Liu J, Tatachar A, Yuet WC

Abstract
BACKGROUND AND PURPOSE: The objective of this study was to evaluate the impact in student pharmacists' exam performance learning outcomes and satisfaction after integrating the Muddiest Point assessment technique into exam reviews.
EDUCATIONAL ACTIVITY AND SETTING: In 2016, the Muddiest Point, a formative assessment tool, was used to develop exam review sessions for second-year student pharmacists in an integrated pharmacotherapy course focused on the cardiovascular system. Performance scores on all four exams were compared between students in the 2015 and 2016 courses. Students' complexity of learning was categorized using a taxonomy of learning structure. A survey was used to evaluate student perceptions of exam reviews and the Muddiest Point technique (MPT).
FINDINGS: Scores were higher on the second exam for the 83 students in the 2016 course (78.0% vs. 86.0%, p<0.001). There was no difference on other exam scores or overall course failures. Muddiest points submitted by students demonstrated a variety of taxonomy of learning levels. Student pharmacists surveyed at the conclusion of the course agreed that exam reviews were helpful for their preparation for exams and that the MPT was a valuable use of class time.
SUMMARY: Incorporating the MPT into exam reviews maintained exam scores and supported evaluation of student learning. In addition, student pharmacists were satisfied with this exam review method.

PMID: 30497634 [PubMed - in process]

Current state of Alzheimer's fluid biomarkers.

Recent Research Articles from UNTHSC - Fri, 11/30/2018 - 09:29
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Current state of Alzheimer's fluid biomarkers.

Acta Neuropathol. 2018 Nov 28;:

Authors: Molinuevo JL, Ayton S, Batrla R, Bednar MM, Bittner T, Cummings J, Fagan AM, Hampel H, Mielke MM, Mikulskis A, O'Bryant S, Scheltens P, Sevigny J, Shaw LM, Soares HD, Tong G, Trojanowski JQ, Zetterberg H, Blennow K

Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

PMID: 30488277 [PubMed - as supplied by publisher]

ANXA2 expression in African American triple-negative breast cancer patients.

Recent Research Articles from UNTHSC - Wed, 11/28/2018 - 06:21
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ANXA2 expression in African American triple-negative breast cancer patients.

Breast Cancer Res Treat. 2018 Nov 26;:

Authors: Gibbs LD, Chaudhary P, Mansheim K, Hare RJ, Mantsch RA, Vishwanatha JK

Abstract
PURPOSE: Our aim was to determine the role of Annexin A2 (AnxA2), which we have previously found to contribute to the aggressiveness of TNBC, with AA TNBC patients and clinical outcome.
METHODS: We analyzed TCGA breast cancer database (n = 1098) to observe AnxA2 expression within breast cancer subtypes and is correlation with overall survival. Further, we examined breast tissue specimens (n = 119) through chromogenic in situ hybridization (CISH) and specimen were scored independently by two pathologists in a blinded study.
RESULTS: In our TCGA analysis, high expression of AnxA2 was correlated with poor survival in patients with TNBC. AnxA2 gene expression was not correlated with poor survival in other breast cancer subtypes. AnxA2 average CISH intensity score (CISH score = 0, null expression to 3, high expression) for TNBC was significantly higher in comparison to estrogen receptor and/or progesterone receptor positive, human epidermal growth factor positive, and non-malignant tissues. Furthermore, AnxA2 average score was significantly higher in AA TNBC patients (CISH average score = 2.45 ± 0.3266) in comparison to Caucasian TNBC patients (CISH average score = 1.1 ± 0.4069).
CONCLUSION: AnxA2 is overexpressed in TNBC, implicating AnxA2 as a contributor to the aggressive biology of TNBC in AA women.

PMID: 30478786 [PubMed - as supplied by publisher]

OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections.

Recent Research Articles from UNTHSC - Wed, 11/28/2018 - 06:21
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OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections.

PLoS One. 2018;13(6):e0197467

Authors: Kers JA, DeFusco AW, Park JH, Xu J, Pulse ME, Weiss WJ, Handfield M

Abstract
Lantibiotics continue to offer an untapped pipeline for the development of novel antibiotics. We report here the discovery of a novel lantibiotic for the treatment of C. difficile infection (CDI). The leads were selected from a library of over 300 multiple substitution variants of the lantibiotic Mutacin 1140 (MU1140). Top performers were selected based on testing for superior potency, solubility, manufacturability, and physicochemical and/or metabolic stability in biologically-relevant systems. The best performers in vitro were further evaluated orally in the Golden Syrian hamster model of CDAD. In vivo testing ultimately identified OG716 as the lead compound, which conferred 100% survival and no relapse at 3 weeks post infection. MU1140-derived variants are particularly attractive for further clinical development considering their novel mechanism of action.

PMID: 29894469 [PubMed - indexed for MEDLINE]

Hospitalized Patients With and Without Hemodialysis Have Markedly Different Vancomycin Pharmacokinetics: A Population Pharmacokinetic Model-Based Analysis.

Recent Research Articles from UNTHSC - Wed, 11/28/2018 - 06:21
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Hospitalized Patients With and Without Hemodialysis Have Markedly Different Vancomycin Pharmacokinetics: A Population Pharmacokinetic Model-Based Analysis.

Ther Drug Monit. 2018 04;40(2):212-221

Authors: Goti V, Chaturvedula A, Fossler MJ, Mok S, Jacob JT

Abstract
BACKGROUND: Despite being in clinical use for about 6 decades, vancomycin dosing remains perplexing and complex.
METHODS: A population pharmacokinetic modeling and simulation approach was used to evaluate the efficiency of the current nomogram-based dosing of vancomycin. Serum vancomycin concentrations were obtained as a part of routine therapeutic drug monitoring from two 500-bed academic medical centers. A population pharmacokinetic model was first built using these therapeutic drug monitoring data. Population pharmacokinetic modeling was conducted using NONMEM (7.2 and 7.3). The forward addition-backward elimination approach was used to test the covariate effects. Appropriate numerical and visual criteria were used as model diagnostics for checking model appropriateness and model qualification. The current nomogram efficiency was evaluated by determining the percentage of subjects in the therapeutic range (10-20 mg/L).
RESULTS: A 2-compartment model with between-subject variability on clearance (CL), central volume of distribution (Vc), and peripheral volume of distribution best fit the data. Blood urea nitrogen, age, creatinine clearance, and hemodialysis status were significant covariates on clearance. Hemodialysis status was a significant covariate on Vc and peripheral volume of distribution. In the final model, creatinine clearance was retained as a covariate on CL whereas hemodialysis status was retained as covariate on both CL and Vc. Using Monte Carlo simulations, the current nomogram was optimized by the addition of a loading dose and reducing the maintenance doses. The current nomogram is suboptimal. Optimization of the nomogram resulted in >40% subjects consistently being in the therapeutic range at troughs collected after the first 6 doses.
CONCLUSIONS: CL and Vc differ markedly between patients undergoing hemodialysis and those not undergoing hemodialysis. Dosing nomogram based on these covariate relationships may potentially help in accurate dosing of vancomycin.

PMID: 29470227 [PubMed - indexed for MEDLINE]

Livedoid Vasculopathy Presenting in a Patient With Sickle Cell Disease.

Recent Research Articles from UNTHSC - Tue, 11/27/2018 - 06:18
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Livedoid Vasculopathy Presenting in a Patient With Sickle Cell Disease.

Am J Dermatopathol. 2018 Sep;40(9):682-685

Authors: Reagin H, Marks E, Weis S, Susa J

Abstract
We report a case in which a 43-year-old African American male with medical history of sickle cell disease (SCD) presented with a nonhealing ulcer. Biopsy revealed features of livedoid vasculopathy. Previously, livedoid vasculopathy had only been described in a patient with sickle cell trait, but never in a patient with SCD. Livedoid vasculopathy most commonly affects the distal lower extremities and is characterized by irregular, punched-out, painful ulcers that heal with stellate white scars of atrophie blanche. Histologically, it reveals segmental hyalinizing vessels, focal thrombosis, and endothelial proliferation. The etiology is currently unclear, but it has been shown to be related to procoagulant states and a diagnosis of livedoid vasculopathy should prompt a thorough hypercoagulable workup, including testing for SCD in high-risk patients.

PMID: 29533274 [PubMed - indexed for MEDLINE]

Rat Strain and Housing Conditions Alter Oxidative Stress and Hormone Responses to Chronic Intermittent Hypoxia.

Recent Research Articles from UNTHSC - Thu, 11/22/2018 - 05:54
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Rat Strain and Housing Conditions Alter Oxidative Stress and Hormone Responses to Chronic Intermittent Hypoxia.

Front Physiol. 2018;9:1554

Authors: Snyder B, Duong P, Tenkorang M, Wilson EN, Cunningham RL

Abstract
Sleep apnea has been associated with elevated risk for metabolic, cognitive, and cardiovascular disorders. Further, the role of hypothalamic-pituitary-adrenal (HPA) activation in sleep apnea has been controversial in human studies. Chronic intermittent hypoxia (CIH) is a rodent model, which mimics the hypoxemia experienced by patients with sleep apnea. Most studies of CIH in rats have been conducted in the Sprague Dawley rat strain. Previously published literature suggests different strains of rats exhibit various responses to disease models, and these effects can be further modulated by the housing conditions experienced by each strain. This variability in response is similar to what has been observed in clinical populations, especially with respect to the HPA system. To investigate if strain or housing (individual or pair-housed) can affect the results of CIH (AHI 8 or 10) treatment, we exposed individual and pair-housed Sprague Dawley and Long-Evans male rats to 7 days of CIH treatment. This was followed by biochemical analysis of circulating hormones, oxidative stress, and neurodegenerative markers. Both strain and housing conditions altered oxidative stress generation, hyperphosphorylated tau protein (tau tangles), circulating corticosterone and adrenocorticotropic hormone (ACTH), and weight metrics. Specifically, pair-housed Long-Evans rats were the most sensitive to CIH, which showed a significant association between oxidative stress generation and HPA activation under conditions of AHI of 8. These results suggest both strain and housing conditions can affect the outcomes of CIH.

PMID: 30459637 [PubMed]

Probabilistic genotyping software: An overview.

Recent Research Articles from UNTHSC - Wed, 11/21/2018 - 05:49

Probabilistic genotyping software: An overview.

Forensic Sci Int Genet. 2018 Nov 11;38:219-224

Authors: Coble MD, Bright JA

Abstract
The interpretation of mixed profiles from DNA evidentiary material is one of the more challenging duties of the forensic scientist. Traditionally, analysts have used a "binary" approach to interpretation where inferred genotypes are either included or excluded from the mixture using a stochastic threshold and other biological parameters such as heterozygote balance, mixture ratio, and stutter ratios. As the sensitivity of STR multiplexes and capillary electrophoresis instrumentation improved over the past 25 years, coupled with the change in the type of evidence being submitted for analysis (from high quality and quantity (often single-source) stains to low quality and quantity (often mixed) "touch" samples), the complexity of DNA profile interpretation has equally increased. This review provides a historical perspective on the movement from binary methods of interpretation to probabilistic methods of interpretation. We describe the two approaches to probabilistic genotyping (semi-continuous and fully continuous) and address issues such as validation and court acceptance. Areas of future needs for probabilistic software are discussed.

PMID: 30458407 [PubMed - as supplied by publisher]

PRENATAL THERAPEUTICS AND PROGRAMMING OF CARDIOVASCULAR FUNCTION.

Recent Research Articles from UNTHSC - Wed, 11/21/2018 - 05:49

PRENATAL THERAPEUTICS AND PROGRAMMING OF CARDIOVASCULAR FUNCTION.

Pharmacol Res. 2018 Nov 17;:

Authors: Brennan L, Goulopoulou S, Bourque SL

Abstract
Cardiovascular diseases (CVD) are a leading cause of mortality worldwide. Despite recognizing the importance of risk factors in dictating CVD susceptibility and onset, patient treatment remains a challenging endeavor. Increasingly, the benefits of prevention and mitigation of risk factors earlier in life are being acknowledged. The developmental origins of health and disease posits that insults during specific periods of development can influence long-term health outcomes; this occurs because the developing organism is highly plastic, and hence vulnerable to environmental perturbations. By extension, targeted therapeutics instituted during critical periods of development may confer long-term protection, and thus reduce the risk of CVD in later life. This review provides a brief overview of models of developmental programming, and then discusses the impact of perinatal therapeutic interventions on long-term cardiovascular function in the offspring. The discussion focuses on bioactive food components, as well as pharmacological agents currently approved for use in pregnancy; in short, those agents most likely to be used in pregnancy and early childhood.

PMID: 30458216 [PubMed - as supplied by publisher]

Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension in mice.

Recent Research Articles from UNTHSC - Tue, 11/20/2018 - 05:45
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Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension in mice.

Sci Rep. 2018 01 16;8(1):862

Authors: Patel GC, Liu Y, Millar JC, Clark AF

Abstract
Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent vision loss. The alternatively spliced isoform of glucocorticoid receptor GRβ acts as dominant negative regulator of GR activity, and it has been shown that overexpressing GRβ in trabecular meshwork (TM) cells inhibits GC-induced glaucomatous damage in TM cells. The purpose of this study was to use viral vectors to selectively overexpress the GRβ isoform in the TM of mouse eyes treated with GCs, to precisely dissect the role of GRβ in regulating steroid responsiveness. We show that overexpression of GRβ inhibits GC effects on MTM cells in vitro and GC-induced OHT in mouse eyes in vivo. Ad5 mediated GRβ overexpression reduced the GC induction of fibronectin, collagen 1, and myocilin in TM of mouse eyes both in vitro and in vivo. GRβ also reversed DEX-Ac induced IOP elevation, which correlated with increased conventional aqueous humor outflow facility. Thus, GRβ overexpression reduces effects caused by GCs and makes cells more resistant to GC treatment. In conclusion, our current work provides the first evidence of the in vivo physiological role of GRβ in regulating GC-OHT and GC-mediated gene expression in the TM.

PMID: 29339763 [PubMed - indexed for MEDLINE]

The shear complexity of insulin-stimulated vasodilation.

Recent Research Articles from UNTHSC - Sun, 11/18/2018 - 05:36
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The shear complexity of insulin-stimulated vasodilation.

J Physiol. 2018 Nov 17;:

Authors: Lalande S, Romero SA

PMID: 30447000 [PubMed - as supplied by publisher]

Effect of video-assisted patient education on compliance with therapy, quality of life, psychomorbidity and cost of illness in Irritable Bowel Syndrome.

Recent Research Articles from UNTHSC - Sun, 11/18/2018 - 05:36
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Effect of video-assisted patient education on compliance with therapy, quality of life, psychomorbidity and cost of illness in Irritable Bowel Syndrome.

Postgrad Med. 2018 Nov 16;:

Authors: Kamat N, Rajan Mallayasamy S, Sharma P, Kamath A, Pai G

Abstract
Background Patient education is important in Irritable bowel syndrome (IBS), but its effects on outcomes have not been studied extensively. Methods Patients were enrolled and prospectively divided into an interventional and usual care group. Both received standard of care, but the former additionally received video-assisted patient education. Self-administered questionnaires IBS-QOL, Beck Anxiety-Depression Inventory II (BAI, BDI) and Hospital Anxiety and Depression Scale (HADS) were administered at baseline, 3 and 6 months. Compliance was defined as drug intake of > 80% of the prescribed dose. COI included prospective, prevalence based, societal perspective. Results Of the 107 patients included, 84 [78.5%; male = 66 (78.57%); median age = 44 (range 20 - 77 years)] completed the follow up. While the median (IQR) QOL scores decreased significantly in both the groups (p<0.001 for either group), the final scores were significantly better in the interventional group [49 (44 - 52.5) versus 80 (76-103) respectively; p<0.005]. There was a significant improvement in the BDI; p<0.001]. However, the rest did not achieve statistical significance. At 6 months total median (IQR) semi-annual cost per patient was INR 14639 (8253-17909) [USD $240 (135-294]. Conclusion Video-assisted patient education should be a part of the treatment of IBS since it improves the QOL and depression scores. Keywords: Irritable Bowel Syndrome, patient education, cost of illness, psychomorbidity.

PMID: 30445893 [PubMed - as supplied by publisher]

Intracranial atherosclerotic disease.

Recent Research Articles from UNTHSC - Fri, 11/16/2018 - 05:25

Intracranial atherosclerotic disease.

Neurobiol Dis. 2018 Nov 12;:

Authors: Wang Y, Meng R, Liu G, Cao C, Chen F, Jin K, Ji X, Cao G

Abstract
Intracranial atherosclerosis (ICAS) is a progressive pathological process that causes progressive stenosis and cerebral hypoperfusion and is a major cause of stroke occurrence and recurrence around the world. Multiple factors contribute to the development of ICAS. Angiography imaging techniques can improve the diagnosis of and the selection of appropriate treatment regimens for ICAS. Neither aggressive medication nor endovascular interventions can eradicate stroke recurrence in patients with ICAS. Non-pharmacological therapies such as remote ischemic conditioning and hypothermia are emerging. Comprehensive therapy with medication in combination with endovascular intervention and/or non-pharmacological treatment may be a potential strategy for ICAS treatment in the future. We summarized the epidemiology, pathophysiological mechanisms, risk factors, biomarkers, imaging and management of ICAS.

PMID: 30439443 [PubMed - as supplied by publisher]

Cannabinoid-like Effects of Five Novel Carboxamide Synthetic Cannabinoids.

Recent Research Articles from UNTHSC - Fri, 11/16/2018 - 05:25

Cannabinoid-like Effects of Five Novel Carboxamide Synthetic Cannabinoids.

Neurotoxicology. 2018 Nov 12;:

Authors: Gatch MB, Forster MJ

Abstract
A new generation of novel cannabinoid compounds have been developed as marijuana substitutes to avoid drug control laws and cannabinoid blood tests. 5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liability. Locomotor activity in mice was tested to screen for locomotor depressant effects and to identify behaviorally-active dose ranges and times of peak effect. Discriminative stimulus effects were tested in rats trained to discriminate Δ9-tetrahydrocannabinol (3 mg/kg, 30-min pretreatment). 5F-MDMB-PINACA (ED50 = 1.1 mg/kg) and MDMB-CHIMICA (ED50 = 0.024 mg/kg) produced short-acting (30 min) depression of locomotor activity. ADB-FUBINACA (ED50 = 0.19 mg/kg), and AMB- FUBINACA (ED50 = 0.19 mg/kg) depressed locomotor activity for 60-90 min; whereas MDMB-FUBINACA (ED50 = 0.04 mg/kg) depressed locomotor activity for 150 min. AMB-FUBINACA produced tremors at the highest dose tested. 5F-MDMB-PINACA (ED50 = 0.07), MDMB-CHIMICA (ED50 = 0.01 mg/kg), MDMB-FUBINACA (ED50 = 0.051 mg/kg), ADB-FUBINACA (ED50 = 0.075 mg/kg) and AMB-FUBINACA (ED50 = 0.029) fully substituted for the discriminative stimulus effects of Δ9-THC following 15-min pretreatment. All 5 compounds decreased locomotor activity and produced discriminative stimulus effects similar to those of Δ9-THC, which suggests they may have abuse liability similar to that of Δ9-THC. AMB-FUBINACA may have an increased risk of toxicities in recreational users.

PMID: 30439379 [PubMed - as supplied by publisher]

Efficacy of curcumin for age-associated cognitive decline: a narrative review of preclinical and clinical studies.

Recent Research Articles from UNTHSC - Fri, 11/16/2018 - 05:25
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Efficacy of curcumin for age-associated cognitive decline: a narrative review of preclinical and clinical studies.

Geroscience. 2018 04;40(2):73-95

Authors: Sarker MR, Franks SF

Abstract
Processes such as aberrant redox signaling and chronic low-grade systemic inflammation have been reported to modulate age-associated pathologies such as cognitive impairment. Curcumin, the primary therapeutic component of the Indian spice, Turmeric (Curcuma longa), has long been known for its strong anti-inflammatory and antioxidant activity attributable to its unique molecular structure. Recently, an interest in this polyphenol as a cognitive therapeutic for the elderly has emerged. The purpose of this paper is to critically review preclinical and clinical studies that have evaluated the efficacy of curcumin in ameliorating and preventing age-associated cognitive decline and address the translational progress of preclinical to clinical efficacy. PubMed, semantic scholar, and Google scholar searches were used for preclinical studies; and clinicaltrials.gov , the Australian and New Zealand clinical trials registry, and PubMed search were used to select relevant completed clinical studies. Results from preclinical studies consistently demonstrate curcumin and its analogues to be efficacious for various aspects of cognitive impairment and processes that contribute to age-associated cognitive impairment. Results of published clinical studies, while mixed, continue to show promise for curcumin's use as a therapeutic for cognitive decline but overall remain inconclusive at this time. Both in vitro and in vivo studies have found that curcumin can significantly decrease oxidative stress, systemic inflammation, and obstruct pathways that activate transcription factors that augment these processes. Future clinical studies would benefit from including evaluation of peripheral and cerebrospinal fluid biomarkers of dementia and behavioral markers of cognitive decline, as well as targeting the appropriate population.

PMID: 29679204 [PubMed - indexed for MEDLINE]

Temperature as a Causative Factor in Diabetic Foot Ulceration: A Call to Revisit Ulcer Pathomechanics.

Recent Research Articles from UNTHSC - Thu, 11/15/2018 - 05:20

Temperature as a Causative Factor in Diabetic Foot Ulceration: A Call to Revisit Ulcer Pathomechanics.

J Am Podiatr Med Assoc. 2018 Nov 14;:

Authors: Yavuz M, Ersen A, Hartos J, Lavery LA, Wukich DK, Hirschman GB, Armstrong DG, Quiben MQ, Adams LS

Abstract
BACKGROUND: Diabetic foot ulcers are a major burden to patients and to the healthcare systems of many countries. To prevent and/or treat ulcers more effectively, predictive biomarkers are needed. We examined temperature as a biomarker and as a causative factor in ulcer development.
METHODS: 37 individuals with diabetes were enrolled in this observational case-control study: nine with diabetic neuropathy and ulcer history (DFU), 14 with diabetic neuropathy (DN), and 14 non-neuropathic participants (DC). Resting barefoot plantar temperatures were recorded using an infrared thermal camera. Mean temperature in each region was determined based on 4 anatomical regions; hallux, medial forefoot, central forefoot, and lateral forefoot and separate linear models with specified contrasts between DFU, DN, and DC groups were set to reveal mean differences for each foot region, while controlling for group characteristics.
RESULTS: Mean temperature readings in each foot region was higher than 30.0°C in the DFU and DN compared to the DC group with all temperatures below 30.0°C. Mean differences were greatest between the DFU and the DC group, with mean differences ranging from 3.2°C in the medial forefoot to 4.9°C in the hallux.
CONCLUSIONS: Increased plantar temperatures in individuals with a history of ulcers may include acute temperature increases from plantar stresses, chronic inflammation from prolonged stresses, and impairment in temperature regulation from autonomic neuropathy. Diabetic foot temperatures, particularly in those with previous ulcers, may easily reach hazard thresholds indicated by prior pressure ulcer studies. The results necessitate further exploration of temperature in diabetic foot and how it may contribute to ulceration.

PMID: 30427732 [PubMed - as supplied by publisher]

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