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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Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine.

Tue, 10/17/2017 - 07:34
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Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine.

Neuropharmacology. 2017 Oct 12;:

Authors: Kopra J, Villarta-Aguilera M, Savolainen M, Weingerl S, Myöhänen TT, Rannanpää S, Salvatore MF, Andressoo JO, Piepponen TP

Abstract
Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons.

PMID: 29031851 [PubMed - as supplied by publisher]

Methylene Blue Ameliorates Ischemia/Reperfusion-Induced Cerebral Edema: An MRI and Transmission Electron Microscope Study.

Sun, 10/15/2017 - 13:40
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Methylene Blue Ameliorates Ischemia/Reperfusion-Induced Cerebral Edema: An MRI and Transmission Electron Microscope Study.

Acta Neurochir Suppl. 2016;121:227-36

Authors: Fang Q, Yan X, Li S, Sun Y, Xu L, Shi Z, Wu M, Lu Y, Dong L, Liu R, Yuan F, Yang SH

Abstract
The neuroprotective effect of methylene blue (MB) has been identified against various brain disorders, including ischemic stroke. In the present study, we evaluated the effects of MB on postischemic brain edema using magnetic resonance imaging (MRI) and transmission electron microscopy (TEM). Adult male rats were subjected to transient focal cerebral ischemia induced by 1 h middle cerebral artery occlusion (MCAO), followed by reperfusion. MB was infused intravenously immediately after reperfusion (3 mg/kg) and again at 3 h post-occlusion (1.5 mg/kg). Normal saline was administered as vehicle control. Sequential MRIs, including apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI), were obtained at 0.5, 2.5, and 48 h after the onset of stroke. Separated groups of animals were sacrificed at 2.5 and 48 h after stroke for ultrastructural analysis by TEM. In addition, final lesion volumes were analyzed by triphenyltetrazolium chloride (TTC) staining at 48 h after stroke. Ischemic stroke induced ADC lesion volume at 0.5 h during MCAOs that were temporally recovered at 1.5 h after reperfusion. No significant difference in ADC-defined lesion was observed between vehicle and MB treatment groups. At 48 h after stroke, MB significantly reduced ADC lesion and T2WI lesion volume and attenuated cerebral swelling. Consistently, MB treatment significantly decreased TTC-defined lesion volume at 48 h after stroke. TEM revealed remarkable swollen astrocytes, astrocytic perivascular end-feet, and concurrent shrunken neurons in the penumbra at 2.5 and 48 h after MCAO. MB treatment attenuated astrocyte swelling, the perivascular astrocytic foot process, and endothelium and also alleviated neuron degeneration. This study demonstrated that MB could decrease postischemic brain edema and provided additional evidence that future clinical investigation of MB for the treatment of ischemic stroke is warrented.

PMID: 26463954 [PubMed - indexed for MEDLINE]

Direct costs for nonsurgical management of Chronic Pancreatitis in a tertiary care teaching hospital.

Fri, 10/13/2017 - 07:34

Direct costs for nonsurgical management of Chronic Pancreatitis in a tertiary care teaching hospital.

Expert Rev Pharmacoecon Outcomes Res. 2017 Oct 12;:1-6

Authors: Kamat N, Pai G, Mallayasamy SR, Kamath A, S R

Abstract
BACKGROUND: Chronic pancreatitis (CP) is a leading cause of hospitalization among gastrointestinal diseases resulting in considerable financial burden to patients. However the direct costs for nonsurgical management in CP remains unexplored.
METHODS: A cross sectional study was carried out (2011-14) in the Department of Gastroenterology, Kasturba Hospital, Manipal, India. Demographic and clinical data on laboratory investigations, interventions and follow up were obtained from the medical records department. Item costs were derived from the hospital electronic billing section. Cost was expressed as median annual cost per patient.
RESULTS: 65 (male 48; 73.8%) patients were included. Their median age was 31 (range 12-68) years. The annual median (IQR) total cost per patient was INR 88,892 (70,550.5-116,004); [USD 1410(1119-1841); € 1155(916-1507)], comprising of INR 61,089 (39,102.5-90,360.5) [USD 970 (621-1434); € 793(508-1174)] for outpatient management and INR 32,450 (11,016-46,958) [USD 515 (175-745); €421(143-610)] for hospitalization. 69.5% of the treatment cost was attributed to outpatient treatment. Drugs contributed to 54%, hospitalization incurred 30.5%, investigations 12% and professional fees (3.5%) of the total cost. Pancreatic enzyme replacement therapy (PERT) cost contributed to three-quarters of drug therapy. Use of rabeprazole as against pantoprazole reduced the overall annual cost of therapy by 4%.
CONCLUSIONS: This study depicts the first nonsurgical management of accrued direct costs associated with CP due to expensive medications. Due to the high cost for PERT, its usefulness needs proper validation by cost benefit analysis.

PMID: 29022830 [PubMed - as supplied by publisher]

Implantable Medical Device Website Efficacy in Informing Consumers Weighing Benefits/Risks of Health Care Options.

Fri, 10/13/2017 - 07:34
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Implantable Medical Device Website Efficacy in Informing Consumers Weighing Benefits/Risks of Health Care Options.

J Health Commun. 2016;21(sup2):121-126

Authors: Wagner T, Lindstadt C, Jeon Y, Mackert M

Abstract
As more individuals turn to the Internet for health-related information and technology increases the availability and use of implantable medical devices (IMDs), the websites marketing these devices will increase. Healthy People 2020 mandates increased understandability and usability of health-related websites. This project used social cognitive theory (SCT) and health literacy constructs from the Institute of Medicine and National Institutes of Health to analyze eight IMD websites. Despite current recommendations, none of the websites considered for this study offered content of an appropriate reading level in conjunction with the United States average of eighth grade, and 75% of the sites failed to satisfy more than one health literacy construct. Most of the websites lacked many of the SCT constructs. More attention is needed to improve the usability of these and future IMD websites to simultaneously meet the goal of marketing IMDs and the Healthy People 2020 goals to educate patients and promote public health.

PMID: 27662117 [PubMed - indexed for MEDLINE]

Recreational Cannabis Legalization and Opioid-Related Deaths in Colorado, 2000-2015.

Thu, 10/12/2017 - 07:37

Recreational Cannabis Legalization and Opioid-Related Deaths in Colorado, 2000-2015.

Am J Public Health. 2017 Nov;107(11):1827-1829

Authors: Livingston MD, Barnett TE, Delcher C, Wagenaar AC

Abstract
OBJECTIVES: To examine the association between Colorado's legalization of recreational cannabis use and opioid-related deaths.
METHODS: We used an interrupted time-series design (2000-2015) to compare changes in level and slope of monthly opioid-related deaths before and after Colorado stores began selling recreational cannabis. We also describe the percent change in opioid-related deaths by comparing the unadjusted model-smoothed number of deaths at the end of follow-up with the number of deaths just prior to legalization.
RESULTS: Colorado's legalization of recreational cannabis sales and use resulted in a 0.7 deaths per month (b = -0.68; 95% confidence interval = -1.34, -0.03) reduction in opioid-related deaths. This reduction represents a reversal of the upward trend in opioid-related deaths in Colorado.
CONCLUSIONS: Legalization of cannabis in Colorado was associated with short-term reductions in opioid-related deaths. As additional data become available, research should replicate these analyses in other states with legal recreational cannabis.

PMID: 29019782 [PubMed - in process]

Administration of 5-methoxyindole-2-carboxylic acid that potentially targets mitochondrial dihydrolipoamide dehydrogenase confers cerebral preconditioning against ischemic stroke injury.

Thu, 10/12/2017 - 07:37

Administration of 5-methoxyindole-2-carboxylic acid that potentially targets mitochondrial dihydrolipoamide dehydrogenase confers cerebral preconditioning against ischemic stroke injury.

Free Radic Biol Med. 2017 Oct 07;:

Authors: Wu J, Li R, Li W, Ren M, Thangthaeng N, Sumien N, Liu R, Yang S, Simpkins JW, Forster MJ, Yan LJ

Abstract
The objective of this study was to investigate a possible role of mitochondrial dihydrolipoamide dehydrogenase (DLDH) as a chemical preconditioning target for neuroprotection against ischemic injury. We used 5-methoxyindole-2-carboxylic acid (MICA), a reportedly reversible DLDH inhibitor, as the preconditioning agent and administered MICA to rats mainly via dietary intake. Upon completion of 4 week's MICA treatment, rats underwent 1h transient ischemia and 24h reperfusion followed by tissue collection. Our results show that MICA protected the brain against ischemic stroke injury as the infarction volume of the brain from the MICA-treated group was significantly smaller than that from the control group. Data were then collected without or with stroke surgery following MICA feeding. It was found that in the absence of stroke following MICA feeding, DLDH activity was lower in the MICA treated group than in the control group, and this decreased activity could be partly due to DLDH protein sulfenation. Moreover, DLDH inhibition by MICA was also found to upregulate the expression of NAD(P)H-ubiquinone oxidoreductase 1(NQO1) via the Nrf2 signaling pathway. In the presence of stroke following MICA feeding, decreased DLDH activity and increased Nrf2 signaling were also observed along with increased NQO1 activity, decreased oxidative stress, decreased cell death, and increased mitochondrial ATP output. We also found that MICA had a delayed preconditioning effect four weeks post MICA treatment. Our study indicates that administration of MICA confers chemical preconditioning and neuroprotection against ischemic stroke injury.

PMID: 29017857 [PubMed - as supplied by publisher]

Fast STR allele identification with STRait Razor 3.0.

Thu, 10/12/2017 - 07:37
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Fast STR allele identification with STRait Razor 3.0.

Forensic Sci Int Genet. 2017 Sep;30:18-23

Authors: Woerner AE, King JL, Budowle B

Abstract
The short tandem repeat allele identification tool (STRait Razor), a program used to characterize the haplotypes of short tandem repeats (STRs) in massively parallel sequencing (MPS) data, was redesigned. STRait Razor v3.0 performs ∼660× faster allele identification than its previous version (v2s), a speedup that is largely due to a novel indexing strategy used to perform "fuzzy" (approximate) string matching of anchor sequences. Written in a portable compiled language, C++, STRait Razor v3.0 functions on all major operating systems including Microsoft Windows, and it has cross-platform multithreading support. In silico estimates of precision and accuracy of STRait Razor v3.0 were 100% in this evaluation and results were highly concordant with those of Strait Razor v2s. STRait Razor v3.0 adds several key features that simplify the haplotype reporting process, including simple filters to remove low frequency haplotypes as well as merging haplotypes within a locus encoded on opposite strands of the DNA molecule.

PMID: 28605651 [PubMed - indexed for MEDLINE]

Methamphetamine Augments Concurrent Astrocyte Mitochondrial Stress, Oxidative Burden, and Antioxidant Capacity: Tipping the Balance in HIV-Associated Neurodegeneration.

Wed, 10/11/2017 - 07:42

Methamphetamine Augments Concurrent Astrocyte Mitochondrial Stress, Oxidative Burden, and Antioxidant Capacity: Tipping the Balance in HIV-Associated Neurodegeneration.

Neurotox Res. 2017 Oct 09;:

Authors: Borgmann K, Ghorpade A

Abstract
Methamphetamine (METH) use, with and without human immunodeficiency virus (HIV)-1 comorbidity, exacerbates neurocognitive decline. Oxidative stress is a probable neurotoxic mechanism during HIV-1 central nervous system infection and METH abuse, as viral proteins, antiretroviral therapy and METH have each been shown to induce mitochondrial dysfunction. However, the mechanisms regulating mitochondrial homeostasis and overall oxidative burden in astrocytes are not well understood in the context of HIV-1 infection and METH abuse. Here, we report METH-mediated dysregulation of astrocyte mitochondrial morphology and function during prolonged exposure to low levels of METH. Mitochondria became larger and more rod shaped with METH when assessed by machine learning, segmentation analyses. These changes may be mediated by elevated mitofusin expression coupled with inhibitory phosphorylation of dynamin-related protein-1, which regulate mitochondrial fusion and fission, respectively. While METH decreased oxygen consumption and ATP levels during acute exposure, chronic treatment of 1 to 2 weeks significantly enhanced both when tested in the absence of METH. Together, these changes significantly increased not only expression of antioxidant proteins, augmenting the astrocyte's oxidative capacity, but also oxidative damage. We propose that targeting astrocytes to reduce their overall oxidative burden and expand their antioxidant capacity could ultimately tip the balance from neurotoxicity towards neuroprotection.

PMID: 28993979 [PubMed - as supplied by publisher]

Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?

Wed, 10/11/2017 - 07:42
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Can Ceftazidime-Avibactam and Aztreonam Overcome β-Lactam Resistance Conferred by Metallo-β-Lactamases in Enterobacteriaceae?

Antimicrob Agents Chemother. 2017 Apr;61(4):

Authors: Marshall S, Hujer AM, Rojas LJ, Papp-Wallace KM, Humphries RM, Spellberg B, Hujer KM, Marshall EK, Rudin SD, Perez F, Wilson BM, Wasserman RB, Chikowski L, Paterson DL, Vila AJ, van Duin D, Kreiswirth BN, Chambers HF, Fowler VG, Jacobs MR, Pulse ME, Weiss WJ, Bonomo RA

Abstract
Based upon knowledge of the hydrolytic profile of major β-lactamases found in Gram-negative bacteria, we tested the efficacy of the combination of ceftazidime-avibactam (CAZ-AVI) with aztreonam (ATM) against carbapenem-resistant enteric bacteria possessing metallo-β-lactamases (MBLs). Disk diffusion and agar-based antimicrobial susceptibility testing were initially performed to determine the in vitro efficacy of a unique combination of CAZ-AVI and ATM against 21 representative Enterobacteriaceae isolates with a complex molecular background that included blaIMP, blaNDM, blaOXA-48, blaCTX-M, blaAmpC, and combinations thereof. Time-kill assays were conducted, and the in vivo efficacy of this combination was assessed in a murine neutropenic thigh infection model. By disk diffusion assay, all 21 isolates were resistant to CAZ-AVI alone, and 19/21 were resistant to ATM. The in vitro activity of CAZ-AVI in combination with ATM against diverse Enterobacteriaceae possessing MBLs was demonstrated in 17/21 isolates, where the zone of inhibition was ≥21 mm. All isolates demonstrated a reduction in CAZ-AVI agar dilution MICs with the addition of ATM. At 2 h, time-kill assays demonstrated a ≥4-log10-CFU decrease for all groups that had CAZ-AVI with ATM (8 μg/ml) added, compared to the group treated with CAZ-AVI alone. In the murine neutropenic thigh infection model, an almost 4-log10-CFU reduction was noted at 24 h for CAZ-AVI (32 mg/kg every 8 h [q8h]) plus ATM (32 mg/kg q8h) versus CAZ-AVI (32 mg/kg q8h) alone. The data presented herein require us to carefully consider this new therapeutic combination to treat infections caused by MBL-producing Enterobacteriaceae.

PMID: 28167541 [PubMed - indexed for MEDLINE]

Biomechanical behavior of novel composite PMMA-CaP bone cements in an anatomically accurate cadaveric vertebroplasty model.

Wed, 10/11/2017 - 07:42
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Biomechanical behavior of novel composite PMMA-CaP bone cements in an anatomically accurate cadaveric vertebroplasty model.

J Orthop Res. 2017 Sep;35(9):2067-2074

Authors: Aghyarian S, Hu X, Haddas R, Lieberman IH, Kosmopoulos V, Kim HKW, Rodrigues DC

Abstract
Vertebral compression fractures are caused by many factors including trauma and osteoporosis. Osteoporosis induced fractures are a result of loss in bone mass and quality that weaken the vertebral body. Vertebroplasty and kyphoplasty, involving cement augmentation of fractured vertebrae, show promise in restoring vertebral mechanical properties. Some complications however, are reported due to the performance characteristics of commercially available bone cements. In this study, the biomechanical performance characteristics of two novel composite (PMMA-CaP) bone cements were studied using an anatomically accurate human cadaveric vertebroplasty model. The study involves mechanical testing on two functional cadaveric spinal unit (2FSU) segments which include monotonic compression and cyclical fatigue tests, treatment by direct cement injection, and microscopic visualization of sectioned vertebrae. The 2FSU segments were fractured, treated, and mechanically tested to investigate the stability provided by two novel bone cements; using readily available commercial acrylic cement as a control. Segment height and stiffness were tracked during the study to establish biomechanical performance. The 2FSU segments were successfully stabilized with all three cement groups. Stiffness values were restored to initial levels following fatigue loading. Cement interdigitation was observed with all cement groups. This study demonstrates efficient reinforcement of the fractured vertebrae through stiffness restoration. The pre-mixed composite cements were comparable to the commercial cement in their performance and interdigitative ability, thus holding promise for future clinical use. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2067-2074, 2017.

PMID: 27891670 [PubMed - indexed for MEDLINE]

Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.

Wed, 10/11/2017 - 07:42
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Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.

Alzheimers Dement. 2017 Jan;13(1):45-58

Authors: O'Bryant SE, Mielke MM, Rissman RA, Lista S, Vanderstichele H, Zetterberg H, Lewczuk P, Posner H, Hall J, Johnson L, Fong YL, Luthman J, Jeromin A, Batrla-Utermann R, Villarreal A, Britton G, Snyder PJ, Henriksen K, Grammas P, Gupta V, Martins R, Hampel H, Biofluid Based Biomarker Professional Interest Area

Abstract
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.

PMID: 27870940 [PubMed - indexed for MEDLINE]

HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression.

Wed, 10/11/2017 - 07:42
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HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression.

J Neuroinflammation. 2016 Sep 15;13(1):247

Authors: Rahimian P, He JJ

Abstract
BACKGROUND: Synaptodendritic damage is a pathological hallmark of HIV-associated neurocognitive disorders, and HIV-1 Tat protein is known to cause such injury in the central nervous system. In this study, we aimed to determine the molecular mechanisms of Tat-induced neurite shortening, specifically the roles of miR-132, an important regulator of neurite morphogenesis in this process.
METHODS: The relationship between Tat expression and miR-132 expression was first determined using reverse transcription quantitative PCR (qRT-PCR) in Tat-transfected astrocytes and neurons, astrocytes from Tat-transgenic mice, and HIV-infected astrocytes. qRT-PCR and Western blotting were performed to determine Tat effects on expression of miR-132 target genes methyl CpG-binding protein 2, Rho GTPase activator p250GAP, and brain-derived neurotrophic factor. Exosomes were isolated from Tat-expressing astrocytes, and exosomal microRNA (miRNA) uptake into neurons was studied using miRNA labeling and flow cytometry. The lactate dehydrogenase release was used to determine the cytotoxicity, while immunostaining was used to determine neurite lengths and synapse formation. Tat basic domain deletion mutant and miR-132 mimic and inhibitor were used to determine the specificity of the relationship between Tat and miR-132 and its effects on astrocytes and neurons and the underlying mechanisms of Tat-induced miR-132 expression.
RESULTS: Tat significantly induced miR-132 expression, ensuing down-regulation of miR-132 target genes in astrocytes and neurons. miR-132 induction was associated with phosphorylation of cAMP response element-binding protein and required the basic domain of Tat. miRNA-132 induction had no effects on astrocyte activation or survival but was involved in the direct neurotoxicity of Tat. miR-132 was present in astrocyte-derived exosomes and was taken up by neurons, causing neurite shortening.
CONCLUSIONS: Tat-induced miR-132 expression contributes to both direct and astrocyte-mediated Tat neurotoxicity and supports the important roles of miR-132 in controlling neurite outgrowth.

PMID: 27634380 [PubMed - indexed for MEDLINE]

CRISPR-Cas9-based treatment of myocilin-associated glaucoma.

Thu, 10/05/2017 - 07:39

CRISPR-Cas9-based treatment of myocilin-associated glaucoma.

Proc Natl Acad Sci U S A. 2017 Oct 02;:

Authors: Jain A, Zode G, Kasetti RB, Ran FA, Yan W, Sharma TP, Bugge K, Searby CC, Fingert JH, Zhang F, Clark AF, Sheffield VC

Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-of-function mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular meshwork (TM), the tissue that regulates IOP. We use CRISPR-Cas9-mediated genome editing in cultured human TM cells and in a MYOC mouse model of POAG to knock down expression of mutant MYOC, resulting in relief of ER stress. In vivo genome editing results in lower IOP and prevents further glaucomatous damage. Importantly, using an ex vivo human organ culture system, we demonstrate the feasibility of human genome editing in the eye for this important disease.

PMID: 28973933 [PubMed - as supplied by publisher]

First-year Student Pharmacists' Spirituality and Perceptions Regarding the Role of Spirituality in Pharmacy Education.

Wed, 10/04/2017 - 07:43

First-year Student Pharmacists' Spirituality and Perceptions Regarding the Role of Spirituality in Pharmacy Education.

Am J Pharm Educ. 2017 Aug;81(6):108

Authors: Jacob B, White A, Shogbon A

Abstract
Objective: To measure student pharmacists' spirituality utilizing validated survey instruments and to determine perceptions regarding the anticipated role of spirituality in academic course work and professional practice. Methods: This was a cross-sectional, descriptive study. The survey was offered to all first-year student pharmacists during the first week of the fall semester (2012-2015). Descriptive and inferential statistics were used to analyze data. Results: A total of 580 students (98%) participated. The majority of students reported having each of the spiritual experiences on most days of the week or more frequently (58% to 89% based on individual item). Furthermore, 57% of students anticipate that matters of spirituality would be significant components of academic course work and 75% anticipate they would be incorporated into eventual professional practice settings. These perceptions were positively correlated to measures of spirituality and religiosity. Conclusion: These findings suggest that faculty should evaluate current and future incorporation of topics related to spirituality and health in pharmacy curriculum.

PMID: 28970609 [PubMed - in process]

Age-related Impairment of Vascular Structure and Functions.

Tue, 10/03/2017 - 07:37

Age-related Impairment of Vascular Structure and Functions.

Aging Dis. 2017 Oct;8(5):590-610

Authors: Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, Xie L, Jin K

Abstract
Among age-related diseases, cardiovascular and cerebrovascular diseases are major causes of death. Vascular dysfunction is a key characteristic of these diseases wherein age is an independent and essential risk factor. The present work will review morphological alterations of aging vessels in-depth, which includes the discussion of age-related microvessel loss and changes to vasculature involving the capillary basement membrane, intima, media, and adventitia as well as the accompanying vascular dysfunctions arising from these alterations.

PMID: 28966804 [PubMed]

Aging Systemic Milieu Impairs Outcome after Ischemic Stroke in Rats.

Tue, 10/03/2017 - 07:37

Aging Systemic Milieu Impairs Outcome after Ischemic Stroke in Rats.

Aging Dis. 2017 Oct;8(5):519-530

Authors: Pan M, Wang P, Zheng C, Zhang H, Lin S, Shao B, Zhuge Q, Jin K

Abstract
Compelling evidence indicates that factors in the blood can profoundly reverse aging-related impairments, as exposure of aged mice to young blood rejuvenates adult stem cell function, improves cognition, and ameliorates cardiac hypertrophy. Systemic factors from mice can also extend the life span of a partner exposed to a lethal treatment or disease. These findings suggest that the systemic milieu of a healthy young partner may be beneficial for an aged organism. However, it is unknown whether a healthy young systemic milieu can improve functional recovery after ischemic stroke. Intraperitoneal administration of young plasma into aged rats after ischemic stroke induced by distal middle cerebral artery occlusion (dMCAO) reduced infarct volume and motor impairment, compared with vehicle group. On the contrary, intraperitoneal administration of plasma from aged rats into young ischemic rats worsened brain injury and motor deficits. Using a proteomic approach, we found that haptoglobin levels were significantly increased in serum of aged rats and that intraperitoneal administration of haptoglobin impaired outcome after ischemic stroke in young rats. Our data suggest that the aging systemic milieu plays a critical role in functional outcome after ischemic stroke.

PMID: 28966798 [PubMed]

Severe hypercholesterolemia and liver disease in a 3-year old.

Tue, 10/03/2017 - 07:37
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Severe hypercholesterolemia and liver disease in a 3-year old.

J Clin Lipidol. 2016 May-Jun;10(3):650-3

Authors: Patel AM, Brautbar A, Desai NK, Wilson DP

Abstract
Lipoprotein-X, which is composed of phospholipids and non-esterified cholesterol, is an abnormal lipoprotein with a density range similar to LDL-C. The two most common ways which lipoprotein-X accumulates is from reflux of bile salts into plasma or deficiency in lecithin cholesterol acyltransferase. This is a case of severe hypercholesterolemia and liver disease in a 3- year old male that presented with pruritus, pale stool, scleral ictus, and abdominal distention. He was diagnosed with primary sclerosing cholangitis which was confirmed by liver biopsy. Our patient was treated with steroids and immunomodulator therapy which was associated with significant reduction in cholestasis and LDL-C levels. Lipoprotein-X has several properties that make it anti-atherogenic, which raises the question if treatment for hypercholesterolemia should be initiated.

PMID: 27206954 [PubMed - indexed for MEDLINE]

Risk of psychological ill health and methods of organisational downsizing: a cross-sectional survey in four European countries.

Sun, 10/01/2017 - 07:36

Risk of psychological ill health and methods of organisational downsizing: a cross-sectional survey in four European countries.

BMC Public Health. 2017 Sep 29;17(1):758

Authors: Andreeva E, Brenner MH, Theorell T, Goldberg M

Abstract
BACKGROUND: The manner in which organizational downsizing is implemented can make a substantial difference as to whether the exposed workers will suffer from psychological ill health. Surprisingly, little research has directly investigated this issue. We examined the likelihood of psychological ill health associated with strategic and reactive downsizing.
METHODS: A cross-sectional survey included 1456 respondents from France, Sweden, Hungary and the United Kingdom: 681 employees in stable workplaces (reference group) and 775 workers from downsized companies. Reactive downsizing was exemplified by the exposures to compulsory redundancies of medium to large scale resulting in job loss or surviving a layoff while staying employed in downsized organizations. The workforce exposed to strategic downsizing was represented by surplus employees who were internally redeployed and supported through their career change process within a policy context of "no compulsory redundancy". Symptoms of anxiety, depression and emotional exhaustion were assessed in telephone interviews with brief subscales from Hospital Anxiety Scale (HADS-A), Hopkins Symptom Checklist (SCL-CD6) and Maslach Burnout Inventory (MBI-GS). Data were analyzed using logistic regression.
RESULTS: We observed no increased risk of psychological ill health in the case of strategic downsizing. The number of significant associations with psychological ill health was the largest for the large-scale reactive downsizing: surviving a layoff was consistently associated with all three outcome measures; returning to work after the job loss experience was related to anxiety and depression, while persons still unemployed at interview had elevated odds of anxiety. After reactive medium-scale downsizing, unemployment at interview was the only exposure associated with anxiety and depression.
CONCLUSIONS: The manner in which organizational downsizing is implemented can be important for the psychological wellbeing of workers. If downsizing is unavoidable, it should be achieved strategically. Greater attention is needed to employment and health policies supporting the workers after reactive downsizing.

PMID: 28962605 [PubMed - in process]

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

Sat, 09/30/2017 - 07:34
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Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

J Glaucoma. 2016 Oct;25(10):e834-e842

Authors: McDonnell FS, McNally SA, Clark AF, O'Brien CJ, Wallace DM

Abstract
BACKGROUND: Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma. The purpose of this study was to compare global DNA methylation levels in primary human normal (NLC) and glaucomatous (GLC) cells, and to investigate DNA methylation in driving fibrosis through regulation of transforming growth factor β1 (TGFβ1).
MATERIALS AND METHODS: LC cells were cultured from normal and glaucomatous human donors. Global methylation was assessed by ELISA. qPCR was conducted for DNA methyltransferases (DNMTs), methyl-CpG-binding protein 2 (MeCP2), TGFβ 1 and 2, collagen 1α1 (COL1A1), and α-smooth muscle actin (αSMA). TGFβ1 and DNMT1 were examined by immunofluorescence. Methylation of the TGFβ1 promoter was determined by methylation-specific PCR (MSP).
RESULTS: Global DNA methylation demonstrated an increase in GLC compared with NLC cells (P<0.05). The previously mentioned methylation and matrix genes were increased in GLC compared with NLC cells (P<0.05). Immunofluorescence showed increased TGFβ1 and DNMT1 in GLC compared with NLC cells. MSP showed increased unmethylated DNA in the TGFβ1 promoter of GLC compared with NLC cells.
CONCLUSIONS: We found increased expression of fibrotic genes in GLC cells and demonstrated an increase in global DNA methylation and in associated enzymes in GLC cells. Furthermore, we showed decreased promoter methylation of TGFβ1 in GLC cells. Determining a role for methylation in glaucoma and in regulating TGFβ1 may provide a novel therapeutic approach.

PMID: 27300643 [PubMed - indexed for MEDLINE]

Comparative tolerance of two massively parallel sequencing systems to common PCR inhibitors.

Fri, 09/29/2017 - 07:34
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Comparative tolerance of two massively parallel sequencing systems to common PCR inhibitors.

Int J Legal Med. 2017 Sep 27;:

Authors: Elwick K, Zeng X, King J, Budowle B, Hughes-Stamm S

Abstract
Human remains can be severely affected by the environment, and the DNA may be damaged, degraded, and/or inhibited. In this study, a DNA sample (at 1 ng DNA target input in triplicate) was spiked with five concentrations of five inhibitors (humic acid, melanin, hematin, collagen, and calcium) and sequenced with both the HID-Ion AmpliSeq™ Library Kit and ID panel on the Ion PGM™ System and the ForenSeq DNA Signature Prep Kit on the MiSeq FGx™. The objective of this study was to compare the baseline tolerance of the two sequencing chemistries and platforms to common inhibitors encountered in human remains recovered from missing person cases. The two chemistries generally were comparable but not always susceptible to the same inhibitors or at the same capacity. The HID-Ion AmpliSeq™ Library Kit and ID panel and the ForenSeq DNA Signature Prep Kit both were susceptible to humic acid, melanin, and collagen; however, the ForenSeq kit showed greater inhibition to melanin and collagen than the AmpliSeq™ kit. In contrast, the ForenSeq kit was resistant to the effects of hematin and calcium, whereas the AmpliSeq™ kit was highly inhibited by hematin. Short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) showed the same trend among inhibitors when using the ForenSeq kit. Generally, locus read depth, heterozygote allele balance, and the numbers of alleles typed were inversely correlated with increasing inhibitor concentration. The larger STR loci were affected more so by the presence of inhibitors compared to smaller STR amplicons and SNP loci. Additionally, it does not appear that sequence noise is affected by the inhibitors. The noise percentage, however, does increase as the inhibitor concentration increases, due to the decrease in locus read depth and not likely because of chemistry effects.

PMID: 28956146 [PubMed - as supplied by publisher]

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