Recent Research Articles from UNTHSC

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

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Updated: 1 hour 10 min ago

The human cost of global warming: Deadly landslides and their triggers (1995-2014).

Tue, 05/28/2019 - 12:41
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The human cost of global warming: Deadly landslides and their triggers (1995-2014).

Sci Total Environ. 2019 Apr 01;682:673-684

Authors: Haque U, da Silva PF, Devoli G, Pilz J, Zhao B, Khaloua A, Wilopo W, Andersen P, Lu P, Lee J, Yamamoto T, Keellings D, Jian-Hong W, Glass GE

Abstract
Worldwide, landslides incur catastrophic and significant economic and human losses. Previous studies have characterized the patterns in landslides' fatalities, from all kinds of triggering causes, at a continental or global scale, but they were based on data from periods of <10 years. The research herein presented hypothesizes that climate change associated with extreme rainfall and population distribution is contributing to a higher number of deadly landslides worldwide. This study maps and identified deadly landslides in 128 countries and it encompasses their role, for a 20 years' period from January/1995 to December/2014, considered representative for establishing a relationship between landslides and their meteorological triggers. A database of georeferenced landslides, their date, and casualties' information, duly validated, was implemented. A hot spot analysis for the daily record of landslide locations was performed, as well as a percentile-based approach to evaluate the trend of extreme rainfall events for each occurrence. The relationship between casualty, population distribution, and rainfall was also evaluated. For 20 years, 3876 landslides caused a total of 163,658 deaths and 11,689 injuries globally. They occurred most frequently between June and December in the Northern Hemisphere, and between December and February in the Southern Hemisphere. A significant global rise in the number of deadly landslides and hotspots across the studied period was observed. Analysis of daily rainfall confirmed that more than half of the events were in areas exposed to the risk of extreme rainfall. The relationships established between extreme rainfall, population distribution, seasonality, and landslides provide a useful basis for efforts to model the adverse impacts of extreme rainfall due to climate change and human activities and thus contribute towards a more resilient society.

PMID: 31129549 [PubMed - as supplied by publisher]

Setting-Based Prioritization for Birth Cohort Hepatitis C Virus Testing in the United States.

Tue, 05/28/2019 - 12:41
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Setting-Based Prioritization for Birth Cohort Hepatitis C Virus Testing in the United States.

Clin Infect Dis. 2019 May 24;:

Authors: MacDonald BR, Chu TC, Stewart RA, Ojha RP

PMID: 31125407 [PubMed - as supplied by publisher]

Patients and providers' knowledge, attitudes, and beliefs regarding immediate postpartum long-acting reversible contraception: a systematic review.

Tue, 05/28/2019 - 12:41
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Patients and providers' knowledge, attitudes, and beliefs regarding immediate postpartum long-acting reversible contraception: a systematic review.

Women Health. 2019 May 23;:1-18

Authors: Thompson EL, Vamos CA, Logan RG, Bronson EA, Detman LA, Piepenbrink R, Daley EM, Sappenfield WM

Abstract
The American College of Obstetricians and Gynecologists recommends long-acting reversible contraception (LARC) immediately postpartum for preventing unintended pregnancy. This systematic review identified patients' and providers' knowledge, attitudes, and beliefs regarding immediate postpartum LARC use. Web of Science, Embase, PubMed, PsychInfo, and CINHAL databases (from inception to December 2018) were searched using LARC and immediate postpartum as search terms. The inclusion criteria were observational US studies, peer-reviewed, and English language, and the exclusion criterion was published abstracts only. The search yielded 4140 articles, and 18 articles were included in the final sample. Articles focused on women (n = 6) emphasizing patient preferences about the use of postpartum intrauterine devices (IUDs) and comprised samples of postpartum women. Among articles focused on providers (n = 12), knowledge regarding immediate postpartum LARCs varied. Providers reported lack of training and lack of comfort with regard to counseling and insertion as barriers to providing postpartum IUDs. This review identified literature regarding patient and provider perspectives on immediate postpartum LARC. Future work should ascertain patients' and providers' needs and preferences for integrating LARC counseling as a viable contraception option during the immediate postpartum period, ultimately promoting optimal inter-pregnancy intervals and overall health for women and future offspring.

PMID: 31122167 [PubMed - as supplied by publisher]

Genistein: mechanisms of action for a pleiotropic neuroprotective agent in stroke.

Fri, 05/24/2019 - 05:51
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Genistein: mechanisms of action for a pleiotropic neuroprotective agent in stroke.

Nutr Neurosci. 2019 Jun;22(6):375-391

Authors: Schreihofer DA, Oppong-Gyebi A

Abstract
Genistein is a plant estrogen promoted as an alternative to post-menopausal hormone therapy because of a good safety profile and its promotion as a natural product. Several preclinical studies of cerebral ischemia and other models of brain injury support a beneficial role for genistein in protecting the brain from injury whether administered chronically or acutely. Like estrogen, genistein is a pleiotropic molecule that engages several different mechanisms to enhance brain health, including reduction of oxidative stress, promotion of growth factor signaling, and immune suppression. These actions occur in endothelial, glial, and neuronal cells to provide a coordinated beneficial action to ischemic challenge. Though many of these protective actions are associated with estrogen-like actions of genistein, additional activities on other receptors and intracellular targets suggest that genistein is more than a mere estrogen-mimic. Importantly, genistein lacks some of the detrimental effects associated with post-menopausal estrogen treatment and may provide an alternative to hormone therapy in those patients at risk for ischemic events.

PMID: 29063799 [PubMed - indexed for MEDLINE]

Development of zebrafish demyelination model for evaluation of remyelination compounds and RORγt inhibitors.

Wed, 05/22/2019 - 05:24

Development of zebrafish demyelination model for evaluation of remyelination compounds and RORγt inhibitors.

J Pharmacol Toxicol Methods. 2019 May 18;:106585

Authors: Zhu XY, Guo SY, Xia B, Li CQ, Wang L, Wang YH

Abstract
RAR-related orphan receptor-γt (RORγt) directs differentiation of proinflammatory T helper 17 cells and is a potential therapeutic target for chronic autoimmune and inflammatory diseases including multiple sclerosis. In this study, zebrafish at days post fertilization treated with ethidium bromide (EB) at a concentration of 75 μM for 72 h were determined as the optimum conditions for the demyelination model development. Zebrafish motility was recorded automatically using a video-track motion detector and quantitative myelin assay was measured by FluoroMyelin staining. A well-known remyelination agent thyroxine (T4) was tested to confirm whether EB-induced motility and myelin damage could be rescued. Two RORγt lead inhibitors GSK805 and SR1001 were assessed for their therapeutic effects on remyelination, axon regeneration, motor neuron promotion and anti-inflammation. T4 significantly improved EB-induced motility dysfunction and myelin damage and promoted myelin basic protein (MBP) regeneration in the demyelinated zebrafish. GSK805 and SR1001 enhanced remyelination in a dose-dependent manner and promoted MBP regeneration. Both GSK805 and SR1001 markedly recovered EB-induced axon and motor neuron damage, and exhibited significantly inhibitory effects of neutrophil infiltration and macrophage recruitment. These results indicate that EB treatment can induce zebrafish demyelination; and the zebrafish demyelination model in combination with quantitative motility and myelin assays is a predictive, reproducible and relatively high throughput screening for rapidly in vivo identification of remyelination compounds and RORγt inhibitors.

PMID: 31112751 [PubMed - as supplied by publisher]

Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes.

Wed, 05/22/2019 - 05:24
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Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes.

Curr Eye Res. 2018 07;43(7):921-933

Authors: Dibas A, Millar C, Al-Farra A, Yorio T

Abstract
PURPOSE: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs) after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of ASIC1a provides RGC neuroprotection.
METHODS: Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. RGC function was measured by Pattern electroretinography (PERG). In addition, retinal ASIC1a and ASIC2 were observed by immunohistochemistry and western blot. Changes in calpain, fodrin, heat shock protein 70 (HSP70), Brn3a, super oxide dismutase-1 (SOD1), catalase, and glutathione perioxidase-4 (GPX4) protein levels were assessed by western blot. RGC numbers were measured by immunohistochemistry on whole retinal flat mounts using anti-RNA binding protein with multiple splicing (RBPMS) antibodies. Intravitreal injection of psalmotoxin-1, a selective ASIC1a blocker, was used to assess the neuroprotective effect of ASIC1a inhibition.
RESULTS: Levels of ASIC1a and ASIC2 after I/R increased in RGCs. Upregulation of ASIC1a but not ASIC2 was attenuated by intravitreal injection of psalmotoxin-1. I/R induced activation of calpain and degradation of fodrin, HSP70, and reduction in Brn3a. In contrast, while psalmotoxin-1 attenuated calpain activation and increased Brn3a levels, it failed to block HSP70 degradation. Unlike SOD1 protein which was reduced, catalase protein levels increased after I/R. Psalmotoxin-1, although not affecting SOD1 and GPX4, increased catalase levels significantly. Psalmotoxin-1 also increased RBPMS-labeled RGCs following I/R as judged by immunohistochemistry of retinal flat mounts. Finally, psalmotoxin-1 enhanced the amplitude of PERG following I/R, suggesting partial rescue of RGC function.
CONCLUSION: Psalmotoxin-1 appears to exert a neuroprotective effect under ischemic insults and targeting inhibition of ASICs may represent a new therapeutic approach in ischemic retinal diseases.

PMID: 29595330 [PubMed - indexed for MEDLINE]

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

Tue, 05/21/2019 - 05:15
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Successful management of early gastrogastric fistula using fully covered esophageal stent.

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

Authors: Jafri SA, Jay Roberts DO, Smith A

PMID: 30545597 [PubMed - indexed for MEDLINE]

Years of Life Lost, Age Discrimination, and the Myth of Productivity.

Tue, 05/21/2019 - 05:15
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Years of Life Lost, Age Discrimination, and the Myth of Productivity.

Am J Public Health. 2017 10;107(10):1535-1537

Authors: Brenner MH

PMID: 28902541 [PubMed - indexed for MEDLINE]

Limited Intragenerational Mobility of Surgical Caseload of Iowa Hospitals.

Mon, 05/20/2019 - 05:04

Limited Intragenerational Mobility of Surgical Caseload of Iowa Hospitals.

J Med Syst. 2019 May 18;43(7):187

Authors: O'Neill L, Dexter F, Epstein RH

Abstract
We previously calculated the Gini index for 121 Iowa hospitals over the ten-year period 2007-2016. The Gini index is a statistic used in economics to assess difference in the distribution of wealth among groups. We reported a high degree of "inequality" among hospitals. In this paper, we extend this work by calculating the intragenerational mobility for the hospitals present in 2007-2008 and 2015-2016. Whereas in economics intragenerational mobility often is measured as changes in income over time within a group, we study changes in hospitals' surgical caseloads. Intragenerational mobility was quantified using the Spearman rank correlation, the slope of the ordinary least squares (OLS) regression line in the log scale, and the Shorrocks trace index. The results were consistent across the three measures. There was a low degree of mobility for the surgical caseloads of the hospitals during the 10-year period under study. For example, based on the slope of the OLS regression, intragenerational mobility was not significantly different from zero (P > 0.05). None (0%) of the 113 hospitals with at least 10 cases both periods increased from the 1st to 5th quintile, 1st to 4th quintile, 2nd to 5th quintile, 2nd to 4th quintile, or even from 3rd to 5th quintile. The results show the importance of hospitals not investing irrationally based on false hope of surgical growth.

PMID: 31104154 [PubMed - in process]

Responses of cerebral blood velocity and tissue oxygenation to low frequency oscillations during simulated hemorrhagic stress in humans.

Thu, 05/16/2019 - 07:38
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Responses of cerebral blood velocity and tissue oxygenation to low frequency oscillations during simulated hemorrhagic stress in humans.

Exp Physiol. 2019 May 15;:

Authors: Anderson GK, Sprick JD, Park FS, Rosenberg AJ, Rickards CA

Abstract
NEW FINDINGS: What is the central question of this study? Do low frequency oscillations in arterial pressure and cerebral blood velocity protect cerebral blood velocity and oxygenation during central hypovolaemia? What is the main finding and its importance? Low frequency oscillations in arterial pressure and cerebral blood velocity attenuate reductions in cerebral oxygen saturation but do not protect absolute cerebral blood velocity during central hypovolaemia. This finding points to the potential importance of hemodynamic oscillations in maintaining cerebral oxygenation and therefore viability of tissues during challenges to cerebral blood flow and oxygen delivery.
ABSTRACT: Tolerance to both actual and simulated haemorrhage varies between individuals. Exaggerated low frequency (∼0.1 Hz) oscillations in mean arterial pressure (MAP) and brain blood flow (indexed via middle cerebral artery velocity, MCAv) have been associated with improved tolerance to reduced central blood volume. The mechanism for this association has not been explored. We hypothesized that inducing low frequency oscillations in arterial pressure and cerebral blood velocity would attenuate reductions in cerebral blood velocity and oxygenation during simulated haemorrhage. Fourteen subjects (11 M/3F) were exposed to oscillatory (0.1 Hz, 0.05 Hz) and non-oscillatory (0 Hz) lower body negative pressure (LBNP) profiles with an average chamber pressure of -60 mmHg (randomized and counterbalanced order). Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe (ScO2 ) via near infrared spectroscopy. Tolerance was higher during the two oscillatory profiles compared with the 0 Hz profile (0.05 Hz, P = 0.04; 0.1 Hz, P = 0.09), accompanied by attenuated reductions in stroke volume (P < 0.001) and ScO2 (P≤0.02). No differences were observed between profiles for reductions in MAP (P = 0.17) and MCAv (P = 0.30). In partial support of our hypothesis, cerebral oxygenation, but not cerebral blood velocity, was protected during the oscillatory profiles. Interestingly, more subjects tolerated the oscillatory profiles compared to the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of haemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissues during haemorrhagic stress. This article is protected by copyright. All rights reserved.

PMID: 31090115 [PubMed - as supplied by publisher]

Severe hypercholesterolemia in a 2-year-old.

Thu, 05/16/2019 - 07:38
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Severe hypercholesterolemia in a 2-year-old.

J Clin Lipidol. 2019 Mar 27;:

Authors: Horner S, Hamilton L, Hamby T, Wilson DP

Abstract
Routine and selective cholesterol screening of children is an effective tool to help identify those with familial hypercholesterolemia. In children found to have elevated levels of cholesterol, secondary causes should be excluded, including hypothyroidism. Thyroid hormone has multiple effects on the regulation of lipid synthesis, absorption, and metabolism. In this case report, we described a 2-year-old with a history of congenital hypothyroidism who was found to have severe hypercholesterolemia. A detailed medical history and appropriate screening tests are important in determining the underlying cause of elevated low-density lipoprotein cholesterol to help inform clinical decision-making.

PMID: 31088731 [PubMed - as supplied by publisher]

Prenatal therapeutics and programming of cardiovascular function.

Wed, 05/15/2019 - 07:30
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Prenatal therapeutics and programming of cardiovascular function.

Pharmacol Res. 2019 01;139:261-272

Authors: Brennan LJ, 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 - indexed for MEDLINE]

Potential two-step proteomic signature for Parkinson's disease: Pilot analysis in the Harvard Biomarkers Study.

Tue, 05/14/2019 - 07:21
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Potential two-step proteomic signature for Parkinson's disease: Pilot analysis in the Harvard Biomarkers Study.

Alzheimers Dement (Amst). 2019 Dec;11:374-382

Authors: O'Bryant SE, Edwards M, Zhang F, Johnson LA, Hall J, Kuras Y, Scherzer CR

Abstract
Introduction: We sought to determine if our previously validated proteomic profile for detecting Alzheimer's disease would detect Parkinson's disease (PD) and distinguish PD from other neurodegenerative diseases.
Methods: Plasma samples were assayed from 150 patients of the Harvard Biomarkers Study (PD, n = 50; other neurodegenerative diseases, n = 50; healthy controls, n = 50) using electrochemiluminescence and Simoa platforms.
Results: The first step proteomic profile distinguished neurodegenerative diseases from controls with a diagnostic accuracy of 0.94. The second step profile distinguished PD cases from other neurodegenerative diseases with a diagnostic accuracy of 0.98. The proteomic profile differed in step 1 versus step 2, suggesting that a multistep proteomic profile algorithm to detecting and distinguishing between neurodegenerative diseases may be optimal.
Discussion: These data provide evidence of the potential use of a multitiered blood-based proteomic screening method for detecting individuals with neurodegenerative disease and then distinguishing PD from other neurodegenerative diseases.

PMID: 31080873 [PubMed]

Exploring the 1000 Genomes Project haplotype reporting for the CYP2D6 pharmacogene.

Tue, 05/14/2019 - 07:21
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Exploring the 1000 Genomes Project haplotype reporting for the CYP2D6 pharmacogene.

Int J Legal Med. 2019 05;133(3):807-810

Authors: Wendt FR, Woerner AE, Sajantila A, Moura-Neto RS, Budowle B

PMID: 29860596 [PubMed - indexed for MEDLINE]

Racial and ethnic disparities in a state-wide registry of patients with pancreatic cancer and an exploratory investigation of cancer cachexia as a contributor to observed inequities.

Sat, 05/11/2019 - 06:44
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Racial and ethnic disparities in a state-wide registry of patients with pancreatic cancer and an exploratory investigation of cancer cachexia as a contributor to observed inequities.

Cancer Med. 2019 May 09;:

Authors: Permuth JB, Clark Daly A, Jeong D, Choi JW, Cameron ME, Chen DT, Teer JK, Barnett TE, Li J, Powers BD, Kumar NB, George TJ, Ali KN, Huynh T, Vyas S, Gwede CK, Simmons VN, Hodul PJ, Carballido EM, Judge AR, Fleming JB, Merchant N, Trevino JG

Abstract
Pancreatic cancer (PC) is characterized by racial/ethnic disparities and the debilitating muscle-wasting condition, cancer cachexia. Florida ranks second in the number of PC deaths and has a large and understudied minority population. We examined the primary hypothesis that PC incidence and mortality rates may be highest among Black Floridians and the secondary hypothesis that biological correlates of cancer cachexia may underlie disparities. PC incidence and mortality rates were estimated by race/ethnicity, gender, and county using publicly available state-wide cancer registry data that included approximately 2700 Black, 25 200 Non-Hispanic White (NHW), and 3300 Hispanic/Latino (H/L) Floridians diagnosed between 2004 and 2014. Blacks within Florida experienced a significantly (P < 0.05) higher incidence (12.5/100 000) and mortality (10.97/100 000) compared to NHW (incidence = 11.2/100 000; mortality = 10.3/100 000) and H/L (incidence = 9.6/100 000; mortality = 8.7/100 000), especially in rural counties. To investigate radiologic and blood-based correlates of cachexia, we leveraged data from a subset of patients evaluated at two geographically distinct Florida Cancer Centers. In Blacks compared to NHW matched on stage, markers of PC-induced cachexia were more frequent and included greater decreases in core musculature compared to corresponding healthy control patients (25.0% vs 10.1% lower), greater decreases in psoas musculature over time (10.5% vs 4.8% loss), lower baseline serum albumin levels (3.8 vs 4.0 gm/dL), and higher platelet counts (332.8 vs 268.7 k/UL). Together, these findings suggest for the first time that PC and cachexia may affect Blacks disproportionately. Given its nearly universal contribution to illness and PC-related deaths, the early diagnosis and treatment of cachexia may represent an avenue to improve health equity, quality of life, and survival.

PMID: 31074202 [PubMed - as supplied by publisher]

Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats.

Sat, 05/11/2019 - 06:44
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Role of the afferent renal nerves in sodium homeostasis and blood pressure regulation in rats.

Exp Physiol. 2019 May 10;:

Authors: Frame AA, Carmichael CY, Kuwabara JT, Cunningham JT, Wainford RD

Abstract
NEW FINDINGS: What is the central question of this study? These studies were designed to determine the differential roles of the mechanosensitive and chemosensitive afferent renal nerves in the reno-renal reflex that promotes natriuresis, sympathoinhibition, and normotension during acute and chronic challenges to sodium homeostasis. What is the main finding and its importance? The mechanosensitive afferent renal nerves contribute to an acute natriuretic sympathoinhibitory reno-renal reflex that may be integrated within the paraventricular nucleus of the hypothalamus. Critically, the afferent renal nerves are required for the maintenance of salt resistance in Sprague Dawley and Dahl Salt Resistant rats and attenuate the development of Dahl Salt Sensitive hypertension.
ABSTRACT: These studies tested the hypothesis that in normotensive salt resistant rat phenotypes the mechanosensitive afferent renal nerve (ARN) reno-renal reflex promotes natriuresis, sympathoinhibition and normotension during acute and chronic challenges to fluid and electrolyte homeostasis. Selective ARN ablation was conducted prior to 1) an acute isotonic volume expansion (VE) or 1 M NaCl infusion in Sprague Dawley (SD) rats and 2) chronic high salt intake in SD, Dahl Salt Resistant (DSR), and Dahl Salt Sensitive (DSS) rats. ARN responsiveness following high salt intake was assessed ex-vivo in response to norepinephrine and sodium concentration (SD, DSR and DSS) and via in-vivo manipulation of renal pelvic pressure and sodium concentration (SD and DSS). ARN ablation attenuated the natriuretic and sympathoinhibitory responses to an acute VE (peak natriuresis [μeq/min] sham 52 ± 5 vs. ARN ablation 28 ± 3 p < 0.05), but not a hypertonic saline infusion in SD rats. High salt (HS) intake enhanced ARN reno-renal reflex mediated natriuresis in response to direct increases in renal pelvic pressure (mechanoreceptor stimulus) in-vivo and ARN responsiveness to norepinephrine ex-vivo in SD, but not DSS, rats. In-vivo and ex-vivo ARN responsiveness to increased renal pelvic sodium concentration (chemoreceptor stimulus) was unaltered during HS intake. ARN ablation evoked sympathetically-mediated salt sensitive hypertension in SD rats (MAP [mmHg] sham normal salt 102 ± 2 vs. sham HS 104 ± 2 vs. ARN ablation normal salt 103 ± 2 vs. ARN ablation HS 121 ± 2 p < 0.05) and DSR rats and exacerbated DSS hypertension. The mechanosensitive ARN mediate an acute sympathoinhibitory natriuretic reflex and counter the development of salt sensitive hypertension. This article is protected by copyright. All rights reserved.

PMID: 31074108 [PubMed - as supplied by publisher]

Wearable Devices for Single-Cell Sensing and Transfection.

Sat, 05/11/2019 - 06:44
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Wearable Devices for Single-Cell Sensing and Transfection.

Trends Biotechnol. 2019 May 06;:

Authors: Chang L, Wang YC, Ershad F, Yang R, Yu C, Fan Y

Abstract
Wearable healthcare devices are mainly used for biosensing and transdermal delivery. Recent advances in wearable biosensors allow for long-term and real-time monitoring of physiological conditions at a cellular resolution. Transdermal drug delivery systems have been further scaled down, enabling wide selections of cargo, from natural molecules (e.g., insulin and glucose) to bioengineered molecules (e.g., nanoparticles). Some emerging nanopatches show promise for precise single-cell gene transfection in vivo and have advantages over conventional tools in terms of delivery efficiency, safety, and controllability of delivered dose. In this review, we discuss recent technical advances in wearable micro/nano devices with unique capabilities or potential for single-cell biosensing and transfection in the skin or other organs, and suggest future directions for these fields.

PMID: 31072609 [PubMed - as supplied by publisher]

Zika Virus Infects Trabecular Meshwork and Causes Trabeculitis and Glaucomatous Pathology in Mouse Eyes.

Fri, 05/10/2019 - 06:35
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Zika Virus Infects Trabecular Meshwork and Causes Trabeculitis and Glaucomatous Pathology in Mouse Eyes.

mSphere. 2019 May 08;4(3):

Authors: Singh PK, Kasetti RB, Zode GS, Goyal A, Juzych MS, Kumar A

Abstract
Zika virus (ZIKV) infection during pregnancy leads to devastating fetal outcomes, including neurological (microcephaly) and ocular pathologies such as retinal lesions, optic nerve abnormalities, chorioretinal atrophy, and congenital glaucoma. Only clinical case reports have linked ZIKV infection to causing glaucoma, a major blinding eye disease. In the present study, we have investigated the role of ZIKV in glaucoma pathophysiology using in vitro and in vivo experimental models. We showed that human primary trabecular meshwork (Pr. TM) cells, as well as a human GTM3 cell line, were permissive to ZIKV infection. ZIKV induced the transcription of various genes expressing pattern recognition receptors (TLR2, TLR3, and RIG-I), cytokines/chemokines (TNF-α, IL-1β, CCL5, and CXCL10), interferons (IFN-α2, IFN-β1, and IFN-γ), and interferon-stimulated genes (ISG15 and OAS2) in Pr. TM cells. ZIKV infection in IFNAR1-/- and wild-type (WT) mouse eyes resulted in increased intraocular pressure (IOP) and the development of chorioretinal atrophy. Anterior chamber (AC) inoculation of ZIKV caused infectivity in iridocorneal angle and TM, leading to the death of TM cells in the mouse eyes. Moreover, anterior segment tissue of infected eyes exhibited increased expression of inflammatory mediators and interferons. Furthermore, ZIKV infection in IFNAR1-/- mice resulted in retinal ganglion cell (RGC) death and loss, coinciding with optic nerve infectivity and disruption of anterograde axonal transport. Because of similarity in glaucomatous pathologies in our study and other experimental glaucoma models, ZIKV infection can be used to study infectious triggers of glaucoma, currently an understudied area of investigation.IMPORTANCE Ocular complications due to ZIKV infection remains a major public health concern because of their ability to cause visual impairment or blindness. Most of the previous studies have shown ZIKV-induced ocular pathology in the posterior segment (i.e., retina) of the eye. However, some recent clinical reports from affected countries highlighted the importance of ZIKV in affecting the anterior segment of the eye and causing congenital glaucoma. Because glaucoma is the second leading cause of blindness worldwide, it is imperative to study ZIKV infection in causing glaucoma to identify potential targets for therapeutic intervention. In this study, we discovered that ZIKV permissively infects human TM cells and evokes inflammatory responses causing trabeculitis. Using a mouse model, we demonstrated that ZIKV infection resulted in higher IOP, increased RGC loss, and optic nerve abnormalities, the classical hallmarks of glaucoma. Collectively, our study provides new insights into ocular ZIKV infection resulting in glaucomatous pathology.

PMID: 31068433 [PubMed - in process]

Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior.

Fri, 05/10/2019 - 06:35
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Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior.

Acta Biomater. 2018 04 15;71:444-459

Authors: Raghunathan VK, Benoit J, Kasetti R, Zode G, Salemi M, Phinney BS, Keller KE, Staverosky JA, Murphy CJ, Acott T, Vranka J

Abstract
Ocular hypertension is a causal risk-factor to developing glaucoma. This is associated with stiffening of the trabecular meshwork (TM), the primary site of resistance to aqueous-humor-outflow. The mechanisms underlying this stiffening or how pathologic extracellular matrix (ECM) affects cell function are poorly understood. It is recognized that mechanotransduction systems allow cells to sense and translate the intrinsic biophysical properties of ECM into intracellular signals to control gene transcription, protein expression, and cell behavior. Using an anterior segment perfusion model, we document that there are significantly more low flow regions that are much stiffer, and fewer high flow regions that are less stiff in glaucomatous TM (GTM) when compared to non-glaucomatous TMs (NTM). GTM tissue also has fewer cells overall when compared with NTM tissue. In order to study the role of pathologic ECM in glaucoma disease progression, we conducted studies using cell derived matrices (CDM). First, we characterized the mechanics, composition and organization of fibronectin in ECM deposited by GTM and NTM cells treated with glucocorticosteroids. Then, we determined that these GTM-derived ECM are able to induce stiffening of normal NTM cells, and alter their gene/protein expression to resemble that of a glaucomatous phenotype. Further, we demonstrate that GTM-derived ECM causes endoplasmic reticular stress in NTM. They also became resistant to being reorganized by these NTM cells. These phenomena were exacerbated by ECMs obtained from steroid treated glaucoma model groups. Collectively, our data demonstrates that CDMs represent a novel tool for the study of bidirectional interactions between TM cells and their immediate microenvironment.
STATEMENT OF SIGNIFICANCE: Extracellular matrix (ECM) changes are prevalent in a number of diseases. The precise mechanisms by which changes in the ECM contribute to disease progression is unclear, primarily due to absence of appropriate models. Here, using glaucoma as a disease model, we document changes in cell derived matrix (CDM) and tissue mechanics that contribute to the pathology. Subsequently, we determine the effect that ECMs from diseased and healthy individuals have on healthy cell behaviors. Data emanating from this study demonstrate that CDMs are a potent tool for the study of cell-ECM interactions.

PMID: 29524673 [PubMed - indexed for MEDLINE]

Livingston et al. Respond.

Fri, 05/10/2019 - 06:35
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Livingston et al. Respond.

Am J Public Health. 2018 03;108(3):e12-e13

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

PMID: 29412728 [PubMed - indexed for MEDLINE]

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