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 55 min ago

Use of Complementary Health Approaches for Chronic Low-Back Pain: A Pain Research Registry-Based Study.

Sat, 03/14/2020 - 07:03
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Use of Complementary Health Approaches for Chronic Low-Back Pain: A Pain Research Registry-Based Study.

J Altern Complement Med. 2020 Mar 11;:

Authors: Licciardone JC, Pandya V

Abstract
Objectives: To measure the use of complementary health approaches (CHAs) recommended in recent clinical practice guidelines relating to low-back pain, multivariate factors associated with their use, and clinical outcomes of CHA users and nonusers. Design: Observational cross-sectional study. Settings/Location: The Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Subjects: A total of 568 patients with chronic low-back pain. Interventions: Massage therapy, spinal manipulation, yoga, and acupuncture. Outcome measures: The numerical rating scale for low-back pain intensity, Roland-Morris Disability Questionnaire for back-related disability, and the Patient-Reported Outcomes Measurement Information System with 29 items for quality-of-life deficits relating to sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue. Results: The distribution of the number of different CHAs used by patients for low-back pain was as follows: 0, 179 (31.5%); 1, 139 (24.5%); 2, 160 (28.2%); 3, 70 (12.3%); and 4, 20 (3.5%). The numbers of patients using the specific CHAs were as follows: massage therapy, 271 (47.7%); spinal manipulation, 238 (41.9%); yoga, 144 (25.4%); and acupuncture, 96 (16.9%). Opioids had been used for low-back pain by 415 (73.1%) patients. Higher levels of education and higher pain self-efficacy scores were associated with greater use of any CHA, whereas increasing age and being Black were associated with lesser use of any CHA. Any CHA use was associated with lesser low-back pain intensity and lesser back-related disability. Patients who used massage therapy reported better clinical outcomes across all three dimensions. Patient pain self-efficacy also enhanced the effect of CHA use. Conclusions: The use of CHAs relative to opioids for low-back pain was inconsistent with recommendations from recent clinical practice guidelines despite clinical benefits with CHA use in this study. More research is needed on ways to improve the uptake of CHAs recommended for low-back pain, particularly among older and Black patients.

PMID: 32167785 [PubMed - as supplied by publisher]

Retrospective data analyses of social and environmental determinants of malaria control for elimination prospects in Eritrea.

Sat, 03/14/2020 - 07:03
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Retrospective data analyses of social and environmental determinants of malaria control for elimination prospects in Eritrea.

Parasit Vectors. 2020 Mar 12;13(1):126

Authors: Mihreteab S, Lubinda J, Zhao B, Rodriguez-Morales AJ, Karamehic-Muratovic A, Goitom A, Shad MY, Haque U

Abstract
BACKGROUND: The present study focuses on both long- and short-term malaria transmission in Eritrea and investigates the risk factors. Annual aggregates of information on malaria cases, deaths, diagnostics and control interventions from 2001 to 2008 and monthly reported data from 2009 to 2017 were obtained from the National Malaria Control Programme. We used a generalized linear regression model to examine the associations among total malaria cases, death, insecticide-treated net coverage, indoor residual spraying and climatic parameters.
RESULTS: Reduction in malaria mortality is demonstrated by the milestone margins of over 97% by the end of 2017. Malaria incidence likewise declined during the period (from 33 to 5 per 1000 population), representing a reduction of about 86% (R2 = 0.3) slightly less than the decline in mortality. The distribution of insecticide treated nets generally declined between 2001 and 2014 (R2 = 0.16) before increasing from 2015 to 2017, while the number of people protected by indoor residual spraying slightly increased (R2 = 0.27). Higher rainfall was significantly associated with an increased number of malaria cases. The covariates rainfall and temperature are a better pair than IRS and LLIN to predict incidences. On the other hand, IRS and LLIN is a more significant pair to predict mortality cases.
CONCLUSIONS: While Eritrea has made significant progress towards malaria elimination, this progress should be maintained and further improved. Distribution, coverage and utilization of malaria control and elimination tools should be optimized and sustained to safeguard the gains made. Additionally, consistent annual performance evaluation of malaria indicators would ensure a continuous learning process from gains/threats of epidemics and resurgence in regions already earmarked for elimination.

PMID: 32164770 [PubMed - in process]

Influence of neurovascular mechanisms on response to tDCS: an exploratory study.

Sat, 03/14/2020 - 07:03
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Influence of neurovascular mechanisms on response to tDCS: an exploratory study.

Exp Brain Res. 2019 Nov;237(11):2829-2840

Authors: Iyer PC, Rosenberg A, Baynard T, Madhavan S

Abstract
The beneficial effects of transcranial direct current stimulation (tDCS) for stroke rehabilitation are limited by the variability in changes in corticomotor excitability (CME) after tDCS. Neuronal activity is closely related to cerebral blood flow; however, the cerebral hemodynamics of neuromodulation in relation to neural effects have been less explored. In this study, we examined the effects of tDCS on cerebral blood velocity (CBv) in chronic stroke survivors using transcranial Doppler (TCD) ultrasound in relation to changes in CME and described the neurovascular characteristics of tDCS responders. Middle cerebral artery (MCA) CBv, cerebrovascular resistance (CVRi) and other cerebral hemodynamics-related variables were continuously measured before and after 15 min of 1 mA anodal tDCS to the lesioned lower limb M1. tDCS did not modulate CBv in the whole group and upon TMS-based stratification of responders and non-responders. However, at baseline, responders demonstrated lower CME levels, lower CBv and higher CVRi as compared to non-responders. These results indicate a possible difference in baseline CME and CBv in tDCS responders that may influence their response to neuromodulation. Future trials with a large sample size and repeated baseline measurements may help validate these findings and establish a relationship between neuromodulation and neurovascular mechanisms in stroke.

PMID: 31455998 [PubMed - indexed for MEDLINE]

When Memory Does Not Serve You Well.

Fri, 03/13/2020 - 06:49
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When Memory Does Not Serve You Well.

Circ Res. 2020 Mar 13;126(6):722-724

Authors: Shimoura CG, Mathis KW

PMID: 32163345 [PubMed - as supplied by publisher]

Protective Behavioral Strategies Scale-20: Psychometric properties of a French and German version among young males in Switzerland.

Fri, 03/13/2020 - 06:49
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Protective Behavioral Strategies Scale-20: Psychometric properties of a French and German version among young males in Switzerland.

Int J Methods Psychiatr Res. 2019 09;28(3):e1777

Authors: Grazioli VS, Studer J, Larimer ME, Lewis MA, Marmet S, Lemoine M, Daeppen JB, Gmel G

Abstract
OBJECTIVE: The Protective Behavioral Strategies Scale (PBSS-20) is one of the most commonly used measures of engagement in protective behavioral strategies (PBS). This research aimed to examine the psychometric properties of a French and German version of the PBSS-20 in a large sample of young males in Switzerland.
METHOD: The sample included 5,017 young males (mean age = 25.44) participating in the Cohort Study on Substance Use Risk Factors in Switzerland. Measures of PBS use, total drinks per week, and alcohol-related consequences were used from a second follow-up assessment.
RESULTS: Confirmatory factor analysis testing different models previously documented in the literature provided initial support for a four-factor model. Fit statistics indicated that this model adequately reflects the structure of data. Further findings also provided support for adequate internal consistency and for convergent validity of this four-factor model, whereas metric-but not scalar-measurement invariance across linguistic regions was demonstrated.
CONCLUSION: Although further research testing measurement invariance across linguistic regions and gender is warranted, results of the current study suggest that the French and German PBSS-20 is reliable and that it may represent a promising research and clinical tool that can be used in both French- and German-speaking countries.

PMID: 30848002 [PubMed - indexed for MEDLINE]

HEART Score Risk Stratification of Low-Risk Chest Pain Patients in the Emergency Department: A Systematic Review and Meta-Analysis.

Fri, 03/13/2020 - 06:49
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HEART Score Risk Stratification of Low-Risk Chest Pain Patients in the Emergency Department: A Systematic Review and Meta-Analysis.

Ann Emerg Med. 2019 08;74(2):187-203

Authors: Laureano-Phillips J, Robinson RD, Aryal S, Blair S, Wilson D, Boyd K, Schrader CD, Zenarosa NR, Wang H

Abstract
STUDY OBJECTIVE: The objectives of this systematic review and meta-analysis are to appraise the evidence in regard to the diagnostic accuracy of a low-risk History, ECG, Age, Risk Factors, and Troponin (HEART) score for prediction of major adverse cardiac events in emergency department (ED) patients. These included 4 subgroup analyses: by geographic region, the use of a modified low-risk HEART score (traditional HEART score [0 to 3] in addition to negative troponin results), using conventional versus high-sensitivity troponin assays in the HEART score, and a comparison of different post-ED-discharge patient follow-up intervals.
METHODS: We searched MEDLINE, EBSCO, Web of Science, and Cochrane Database for studies on the diagnostic performance of low-risk HEART scores to predict major adverse cardiac events among ED chest pain patients. Two reviewers independently screened articles for inclusion, assessed the quality of studies with both an adapted Quality Assessment of Diagnostic Accuracy Studies version 2 tool and an internally developed tool that combined components of the Quality in Prognostic Studies; Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies; and Grading of Recommendations Assessment, Development and Evaluation. Pooled sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios were calculated.
RESULTS: There were 25 studies published from 2010 to 2017, with a total of 25,266 patients included in the final meta-analysis, of whom 9,919 (39.3%) were deemed to have low-risk HEART scores (0 to 3). Among patients with low-risk HEART scores, short-term major adverse cardiac events (30 days to 6 weeks) occurred in 2.1% of the population (182/8,832) compared with 21.9% of patients (3,290/15,038) with non-low-risk HEART scores (4 to 10). For patients with HEART scores of 0 to 3, the pooled sensitivity of short-term major adverse cardiac event predictions was 0.96 (95% confidence interval [CI] 0.93 to 0.98), specificity was 0.42 (95% CI 0.36 to 0.49), positive predictive value was 0.19 (95% CI 0.14 to 0.24), negative predictive value was 0.99 (95% CI 0.98 to 0.99), positive likelihood ratio was 1.66 (95% CI 1.50 to 1.85), and negative likelihood ratio was 0.09 (95% CI 0.06 to 0.15). Subgroup analysis showed that lower short-term major adverse cardiac events occurred among North American patients (0.7%), occurred when modified low-risk HEART score was used (0.8%), or occurred when high-sensitivity troponin was used for low-risk HEART score calculations (0.8%).
CONCLUSION: In this meta-analysis, despite its use in different patient populations, the troponin type used, and timeline of follow-up, a low-risk HEART score had high sensitivity, negative predictive value, and negative likelihood ratio for predicting short-term major adverse cardiac events, although risk of bias and statistical heterogeneity were high.

PMID: 30718010 [PubMed - indexed for MEDLINE]

Functional connectome biotypes of chemotherapy-related cognitive impairment.

Thu, 03/12/2020 - 06:37
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Functional connectome biotypes of chemotherapy-related cognitive impairment.

J Cancer Surviv. 2020 Mar 10;:

Authors: Kesler SR, Petersen ML, Rao V, Harrison RA, Palesh O

Abstract
PURPOSE: Cancer-related cognitive impairment (CRCI) is a common neurotoxicity among patients with breast and other cancers. Neuroimaging studies have demonstrated measurable biomarkers of CRCI but have largely neglected the potential heterogeneity of the syndrome.
METHODS: We used retrospective functional MRI data from 80 chemotherapy-treated breast cancer survivors to examine neurophysiologic subtypes or "biotypes" of CRCI. The breast cancer group consisted of training (N = 57) and validation (N = 23) samples.
RESULTS: An unsupervised clustering approach using connectomes from the training sample identified three distinct biotypes. Cognitive performance (p < 0.05, corrected) and regional connectome organization (p < 0.001, corrected) differed significantly between the biotypes and also from 103 healthy female controls. We then built a random forest classifier using connectome features to distinguish between the biotypes (accuracy = 91%) and applied this to the validation sample to predict biotype assignment. Cognitive performance (p < 0.05, corrected) and regional connectome organization (p < 0.005, corrected) differed significantly between the predicted biotypes and healthy controls. Biotypes were also characterized by divergent clinical and demographic factors as well as patient reported outcomes.
CONCLUSIONS: Neurophysiologic biotypes may help characterize the heterogeneity associated with CRCI in a data-driven manner based on neuroimaging biomarkers.
IMPLICATIONS FOR CANCER SURVIVORS: Our novel findings provide a foundation for detecting potential risk and resilience factors that warrant further study. With further investigation, biotypes might be used to personalize assessments of and interventions for CRCI.

PMID: 32157609 [PubMed - as supplied by publisher]

A current snapshot of the state of 3D printing in hand rehabilitation.

Thu, 03/12/2020 - 06:37
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A current snapshot of the state of 3D printing in hand rehabilitation.

J Hand Ther. 2020 Mar 07;:

Authors: Patterson RM, Salatin B, Janson R, Salinas SP, Mullins MJS

Abstract
3D printing is often discussed in the field of hand rehabilitation, yet many hand therapists are unaware of this technology and how it either is used or could potentially be used in rehabilitation. To shed some light on the state of 3D printing in hand rehabilitation, we sought insight from a rehabilitation engineer, occupational therapy educator, clinician, and hospital administrator to provide a comprehensive look at the state of 3D printing today.

PMID: 32156576 [PubMed - as supplied by publisher]

Artificial fingerprints for cross-comparison of forensic DNA and protein recovery methods.

Thu, 03/12/2020 - 06:37
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Artificial fingerprints for cross-comparison of forensic DNA and protein recovery methods.

PLoS One. 2019;14(10):e0223170

Authors: LeSassier DS, Schulte KQ, Manley TE, Smith AR, Powals ML, Albright NC, Ludolph BC, Weber KL, Woerner AE, Gardner MW, Hewitt FC

Abstract
Quantitative genomic and proteomic evaluation of human latent fingerprint depositions represents a challenge within the forensic field, due to the high variability in the amount of DNA and protein initially deposited. To better assess recovery techniques for touch depositions, we present a method to produce simple and customizable artificial fingerprints. These artificial fingerprint samples include the primary components of a typical latent fingerprint, specifically sebaceous fluid, eccrine perspiration, extracellular DNA, and proteinaceous epidermal skin material (i.e., shed skin cells). A commercially available emulsion of sebaceous and eccrine perspiration material provides a chemically-relevant suspension solution for fingerprint deposition, simplifying artificial fingerprint production. Extracted human genomic DNA is added to accurately mimic the extracellular DNA content of a typical latent print and comparable DNA yields are recovered from the artificial prints relative to human prints across surface types. Capitalizing on recent advancements in the use of protein sequence identification for human forensic analysis, these samples also contain a representative quantity of protein, originating from epidermal skin cells collected from the fingers and palms of volunteers. Proteomic sequencing by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis indicates a high level of protein overlap between artificial and latent prints. Data are available via ProteomeXchange with identifier PXD015445. By including known quantities of DNA and protein into each artificial print, this method enables total DNA and protein recovery to be quantitatively assessed across different sample collection and extraction methods to better evaluate extraction efficiency. Collectively, these artificial fingerprint samples are simple to make, highly versatile and customizable, and accurately represent the biochemical composition and biological signatures of human fingerprints.

PMID: 31581206 [PubMed - indexed for MEDLINE]

Mobile Assessment of Acute Effects of Marijuana on Cognitive Functioning in Young Adults: Observational Study.

Wed, 03/11/2020 - 06:13

Mobile Assessment of Acute Effects of Marijuana on Cognitive Functioning in Young Adults: Observational Study.

JMIR Mhealth Uhealth. 2020 Mar 10;8(3):e16240

Authors: Chung T, Bae SW, Mun EY, Suffoletto B, Nishiyama Y, Jang S, Dey AK

Abstract
BACKGROUND: Mobile assessment of the effects of acute marijuana on cognitive functioning in the natural environment would provide an ecologically valid measure of the impacts of marijuana use on daily functioning.
OBJECTIVE: This study aimed to examine the association of reported acute subjective marijuana high (rated 0-10) with performance on 3 mobile cognitive tasks measuring visuospatial working memory (Flowers task), attentional bias to marijuana-related cues (marijuana Stroop), and information processing and psychomotor speed (digit symbol substitution task [DSST]). The effect of distraction as a moderator of the association between the rating of subjective marijuana high and task performance (ie, reaction time and number of correct responses) was explored.
METHODS: Young adults (aged 18-25 years; 37/60, 62% female) who reported marijuana use at least twice per week were recruited through advertisements and a participant registry in Pittsburgh, Pennsylvania. Phone surveys and mobile cognitive tasks were delivered 3 times per day and were self-initiated when starting marijuana use. Completion of phone surveys triggered the delivery of cognitive tasks. Participants completed up to 30 days of daily data collection. Multilevel models examined associations between ratings of subjective marijuana high (rated 0-10) and performance on each cognitive task (reaction time and number of correct responses) and tested the number of distractions (rated 0-4) during the mobile task session as a moderator of the association between ratings of subjective marijuana high and task performance.
RESULTS: Participants provided 2703 data points, representing 451 reports (451/2703, 16.7%) of marijuana use. Consistent with slight impairing effects of acute marijuana use, an increase in the average rating of subjective marijuana high was associated with slower average reaction time on all 3 tasks-Flowers (B=2.29; SE 0.86; P=.008), marijuana Stroop (B=2.74; SE 1.09; P=.01), and DSST (B=3.08; SE 1.41; P=.03)-and with fewer correct responses for Flowers (B=-0.03; SE 0.01; P=.01) and DSST (B=-0.18; SE 0.07; P=.01), but not marijuana Stroop (P=.45). Results for distraction as a moderator were statistically significant only for certain cognitive tasks and outcomes. Specifically, as hypothesized, a person's average number of reported distractions moderated the association of the average rating of subjective marijuana high (over and above a session's rating) with the reaction time for marijuana Stroop (B=-52.93; SE 19.38; P=.006) and DSST (B=-109.72; SE 42.50; P=.01) and the number of correct responses for marijuana Stroop (B=-0.22; SE 0.10; P=.02) and DSST (B=4.62; SE 1.81; P=.01).
CONCLUSIONS: Young adults' performance on mobile cognitive tasks in the natural environment was associated with ratings of acute subjective marijuana high, consistent with slight decreases in cognitive functioning. Monitoring cognitive functioning in real time in the natural environment holds promise for providing immediate feedback to guide personal decision making.

PMID: 32154789 [PubMed - as supplied by publisher]

Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

Wed, 03/11/2020 - 06:13
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Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

Int J Mol Sci. 2020 Mar 05;21(5):

Authors: Nahomi RB, Nam MH, Rankenberg J, Rakete S, Houck JA, Johnson GC, Stankowska DL, Pantcheva MB, MacLean PS, Nagaraj RH

Abstract
BACKGROUND: Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients. We investigated the role of the neuroprotective kynurenic acid (KYNA) in RGC death against retinal ischemia/reperfusion (I/R) injury.
METHODS: We injected KYNA intravenously or intravitreally to mice. We generated a knockout mouse strain of kynurenine 3-monooxygenase (KMO), an enzyme in the kynurenine pathway that produces neurotoxic 3-hydroxykynurenine. To test the effect of mild hyperglycemia on RGC protection, we used streptozotocin (STZ) induced diabetic mice. Retinal I/R injury was induced by increasing intraocular pressure for 60 min followed by reperfusion and RGC numbers were counted in the retinal flat mounts.
RESULTS: Intravenous or intravitreal administration of KYNA protected RGCs against I/R injury. The I/R injury caused a greater loss of RGCs in wild type than in KMO knockout mice. KMO knockout mice had mildly higher levels of fasting blood glucose than wild type mice. Diabetic mice showed significantly lower loss of RGCs when compared with non-diabetic mice subjected to I/R injury.
CONCLUSION: Together, our study suggests that the absence of KMO protects RGCs against I/R injury, through mechanisms that likely involve higher levels of KYNA and glucose.

PMID: 32151061 [PubMed - in process]

Pharmacological, Toxicological, and Dose Range Assessment of OG716, a Novel Lantibiotic for the Treatment of Clostridium difficile-Associated Infection.

Wed, 03/11/2020 - 06:13
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Pharmacological, Toxicological, and Dose Range Assessment of OG716, a Novel Lantibiotic for the Treatment of Clostridium difficile-Associated Infection.

Antimicrob Agents Chemother. 2019 04;63(4):

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

Abstract
Lantibiotics present an attractive scaffold for the development of novel antibiotics. We report here a novel lantibiotic for the treatment of Clostridium difficile infection. The lead compounds were selected from a library of over 700 single- and multiple-substitution variants of the lantibiotic mutacin 1140 (MU1140). The best performers in vitro and in vivo were further used to challenge Golden Syrian hamsters orally in a Golden Syrian hamster model of Clostridium difficile-associated disease (CDAD) in a dose-response format, resulting in the selection of OG716 as the lead compound. This lantibiotic was characterized by a 50% effective dose of 23.85 mg/kg of body weight/day (10.97 μmol/kg/day) in this model. Upon oral administration of the maximum feasible dose (≥1,918 mg/kg/day), no observable toxicities or side effects were noted, and no effect on intestinal motility was observed. Compartmentalization to the gastrointestinal tract was confirmed. MU1140-derived variants offer a large pipeline for the development of novel antibiotics for the treatment of several indications and are particularly attractive considering their novel mechanism of action. Based on the currently available data, OG716 has an acceptable profile for further development for the treatment of CDAD.

PMID: 30670434 [PubMed - indexed for MEDLINE]

Hypothalamic Paraventricular Nucleus Gαi2 (Guanine Nucleotide-Binding Protein Alpha Inhibiting Activity Polypeptide 2) Protein-Mediated Neural Control of the Kidney and the Salt Sensitivity of Blood Pressure.

Tue, 03/10/2020 - 06:01

Hypothalamic Paraventricular Nucleus Gαi2 (Guanine Nucleotide-Binding Protein Alpha Inhibiting Activity Polypeptide 2) Protein-Mediated Neural Control of the Kidney and the Salt Sensitivity of Blood Pressure.

Hypertension. 2020 Mar 09;:HYPERTENSIONAHA11913777

Authors: Carmichael CY, Kuwabara JT, Pascale CL, Moreira JD, Mahne SE, Kapusta DR, Rosene DL, Williams JS, Cunningham JT, Wainford RD

Abstract
We have previously reported that in salt-resistant rat phenotypes brain, Gαi2 (guanine nucleotide-binding protein alpha inhibiting activity polypeptide 2) proteins are required to maintain blood pressure and sodium balance. However, the impact of hypothalamic paraventricular nucleus (PVN) Gαi2 proteins on the salt sensitivity of blood pressure is unknown. Here, by the bilateral PVN administration of a targeted Gαi2 oligodeoxynucleotide, we show that PVN-specific Gαi2 proteins are required to facilitate the full natriuretic response to an acute volume expansion (peak natriuresis [μeq/min] scrambled (SCR) oligodeoxynucleotide 41±3 versus Gαi2 oligodeoxynucleotide 18±4; P<0.05) via a renal nerve-dependent mechanism. Furthermore, in response to chronically elevated dietary sodium intake, PVN-specific Gαi2 proteins are essential to counter renal nerve-dependent salt-sensitive hypertension (mean arterial pressure [mm Hg] 8% NaCl; SCR oligodeoxynucleotide 128±2 versus Gαi2 oligodeoxynucleotide 147±3; P<0.05). This protective pathway involves activation of PVN Gαi2 signaling pathways, which mediate sympathoinhibition to the blood vessels and kidneys (renal norepinephrine [pg/mg] 8% NaCl; SCR oligodeoxynucleotide 375±39 versus Gαi2 oligodeoxynucleotide 850±27; P<0.05) and suppression of the activity of the sodium chloride cotransporter assessed as peak natriuresis to hydrochlorothiazide. Additionally, central oligodeoxynucleotide-mediated Gαi2 protein downregulation prevented PVN parvocellular neuron activation, assessed by FosB immunohistochemistry, in response to increased dietary salt intake. In our analysis of the UK BioBank data set, it was observed that 2 GNAI2 single nucleotide polymorphism (SNP) (rs2298952, P=0.041; rs4547694, P=0.017) significantly correlate with essential hypertension. Collectively, our data suggest that selective targeting and activation of PVN Gαi2 proteins is a novel therapeutic approach for the treatment of salt-sensitive hypertension.

PMID: 32148128 [PubMed - as supplied by publisher]

Building a Culture of Safety: Relearning Organizational Behavior.

Tue, 03/10/2020 - 06:01
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Building a Culture of Safety: Relearning Organizational Behavior.

Int Anesthesiol Clin. 2019;57(3):12-24

Authors: DeSocio PA, Garzon MP, Hicks MR

PMID: 31577234 [PubMed - indexed for MEDLINE]

Neural Control of Blood Pressure is Altered Following Isolated Leg Heating in Aged Humans.

Sat, 03/07/2020 - 07:09
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Neural Control of Blood Pressure is Altered Following Isolated Leg Heating in Aged Humans.

Am J Physiol Heart Circ Physiol. 2020 Mar 06;:

Authors: Engelland RE, Hemingway HW, Tomasco OG, Olivencia-Yurvati AH, Romero SA

Abstract
There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. We tested the hypothesis that acute leg heating would decrease arterial blood pressure in aged adults secondary to sympathoinhibition. Thirteen young and 10 aged adults were exposed to 45 min of leg heating. Muscle sympathetic nerve activity (radial nerve) was measured before leg heating (Pre-heat) and 30 min after (Recovery), and is expressed as burst frequency. Neurovascular transduction was examined by assessing the slope of the relation between muscle sympathetic nerve activity and leg vascular conductance measured at rest and during isometric handgrip exercise performed to fatigue. Arterial blood pressure was well maintained in young adults (Pre-heat, 86 ± 6 mmHg vs. Recovery, 88 ± 7 mmHg; P = 0.4) due to increased sympathetic nerve activity (Pre-heat, 16 ± 7 bursts min-1 vs. Recovery, 22 ± 10 bursts min-1; P < 0.01). However, in aged adults, sympathetic nerve activity did not differ from Pre-heat (37 ± 5 bursts min-1) to Recovery (33 ± 6 bursts min-1, P = 0.1), despite a marked reduction in arterial blood pressure (Pre-heat, 101 ± 7 mmHg vs. Recovery, 94 ± 6 mmHg; P < 0.01). Neurovascular transduction did not differ from Pre-heat to Recovery for either age group (P ≥ 0.1). The reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating is mediated, in part, by a sympathoinhibitory effect that alters the compensatory neural response to hypotension.

PMID: 32142377 [PubMed - as supplied by publisher]

Primary care clinics can be a source of exposure to virulent Clostridium (now Clostridioides) difficile: An environmental screening study of hospitals and clinics in Dallas-Fort Worth region.

Fri, 03/06/2020 - 15:59
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Primary care clinics can be a source of exposure to virulent Clostridium (now Clostridioides) difficile: An environmental screening study of hospitals and clinics in Dallas-Fort Worth region.

PLoS One. 2019;14(8):e0220646

Authors: Simecka JW, Fulda KG, Pulse M, Lee JH, Vitucci J, Nguyen P, Taylor P, Filipetto F, Espinoza AM, Sharma S

Abstract
C. difficile is an endospore-forming pathogen, which is becoming a common cause of microbial health-care associated gastrointestinal disease in the United States. Both healthy and symptomatic patients can shed C. difficile spores into the environment, which can survive for long periods, being resistant to desiccation, heat, and disinfectants. In healthcare facilities, environmental contamination with C. difficile is a major concern as a potential source of exposure to this pathogen and risk of disease in susceptible patients. Although hospital-acquired infection is recognized, community-acquired infection is an increasingly recognized health problem. Primary care clinics may be a significant source of exposure to this pathogen; however, there are limited data about presence of environmental C. difficile within clinics. To address the potential for primary care clinics as a source of environmental exposure to virulent C. difficile, we measured the frequency of environmental contamination with spores in clinic examination rooms and hospital rooms in Dallas-Fort Worth (DFW) area of Texas. The ribotypes and presence of toxin genes from some environmental isolates were compared. Our results indicate primary care clinics have higher frequencies of contamination than hospitals. After notification of the presence of C. difficile spores in the clinics and an educational discussion to emphasize the importance of this infection and methods of infection prevention, environmental contamination in clinics was reduced on subsequent sampling to that found in hospitals. Thus, primary care clinics can be a source of exposure to virulent C. difficile, and recognition of this possibility can result in improved infection prevention, potentially reducing community-acquired C. difficile infections and subsequent disease.

PMID: 31415582 [PubMed - indexed for MEDLINE]

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

Fri, 03/06/2020 - 15:59
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Selectively Inhibiting the Median Preoptic Nucleus Attenuates Angiotensin II and Hyperosmotic-Induced Drinking Behavior and Vasopressin Release in Adult Male Rats.

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

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

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

PMID: 30923740 [PubMed - indexed for MEDLINE]

Inhibition of p-mTOR represses PS1 transcription by reducing p-JNK.

Tue, 03/03/2020 - 06:20
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Inhibition of p-mTOR represses PS1 transcription by reducing p-JNK.

Front Biosci (Landmark Ed). 2020 Mar 01;25:1297-1304

Authors: Das HK, Hontiveros SS

Abstract
Presenilin-1 (PS1) is the catalytic subunit of gamma-secretase. PS1 cleaves beta-amyloid precursor protein (APP) to produce Abeta peptide and Notch 1 receptor to release Notch intracellular domain (NICD) in the cytoplasm. We have previously shown that rapamycin inhibits p-mTOR to repress PS1 transcription and Notch 1-signaling. But the exact mechanism by which rapamycin inhibits PS1 transcription is not known. We have also published that inhibition of basal activity of c-jun-NH2-terminal kinase (JNK) with JNK-specific inhibitor SP600125 represses PS1 transcription by reducing p-JNK and via p53 dependent mechanism. We now report that rapamycin inhibits the phosphorylation of both mTOR (p-mTOR) and JNK (p-JNK). It appears that rapamycin represses PS1 transcription by inhibiting the expression of p-JNK in SK-N-SH cells under non-stressed condition. Consequently, one of the mechanisms of inhibition of PS1 transcription by rapamycin is similar to the mechanism of repression of PS1 transcription by JNK-specific inhibitor SP600125. We also report that JNK-inhibitor SP6000125 decreases both p-JNK and p-mTOR protein levels. These results suggest that JNK and mTOR may potentially activate each other by mutual phosphorylation.

PMID: 32114433 [PubMed - in process]

Inhibition of p-mTOR represses transcription of PS1 and Notch 1-signaling.

Tue, 03/03/2020 - 06:20
Related Articles

Inhibition of p-mTOR represses transcription of PS1 and Notch 1-signaling.

Front Biosci (Landmark Ed). 2020 Mar 01;25:1172-1183

Authors: Das HK, Hontiveros SS

Abstract
Presenilin-1 (PS1) protein is the catalytic subunit of the gamma-secretase, and participates in the processing of beta-amyloid precursor protein (APP) to produce Abeta peptide and Notch 1 receptor to release Notch intracellular domain (NICD) in the cytoplasm. NICD migrates to the nucleus and causes Notch signaling by increasing the expression of the Hes1 gene. The mammalian target of rapamycin (mTOR) controls cellular homeostasis, and its activity is inhibited by rapamycin. The buildup of Abeta increases the mTOR signaling, whereas decreasing mTOR signaling reduces Abeta levels suggesting an interrelationship between mTOR signaling and Abeta. Administration of rapamycin in 3XTg-AD mouse model of Alzheimer's disease (AD) rescues cognitive deficits and ameliorates Abeta and Tau pathology. We have dissected the mechanisms by which rapamycin inhibits PS1 expression and Notch1 signaling. Our results demonstrated that rapamycin efficiently suppressed phosphorylation of mTOR (p-mTOR), and decreased expression of PS1-mRNA as well as p-p70S6K1, 4EBP1, PS1, NICD, and Hes1 protein levels. Therefore, rapamycin decreased PS1 protein levels and Notch 1 processing by inhibiting PS1 transcription.

PMID: 32114428 [PubMed - in process]

Dental opinion leaders' perspectives on barriers and facilitators to HPV-related prevention.

Tue, 03/03/2020 - 06:20
Related Articles

Dental opinion leaders' perspectives on barriers and facilitators to HPV-related prevention.

Hum Vaccin Immunother. 2019;15(7-8):1856-1862

Authors: Griner SB, Thompson EL, Vamos CA, Chaturvedi AK, Vazquez-Otero C, Merrell LK, Kline NS, Daley EM

Abstract
Evidence suggests a causal connection between the Human Papillomavirus (HPV) and oropharyngeal cancers. HPV-related oropharyngeal cancers are increasing and are the most common HPV-associated cancer. Previous research suggests that dental professionals recognize a role in the prevention of HPV and oropharyngeal cancers. As an initial step to investigating effective mechanisms of incorporating HPV prevention into dental practices, including the HPV vaccine, this qualitative study explored dental opinion leaders' perspectives on barriers and facilitators to HPV-related prevention in the dental profession. Dental opinion leaders were identified through: (1) national professional organizations and advocacy groups, (2) by indication of an expert panel, and (3) focus groups conducted with oral health providers. Thirteen participants representing 11 organizations were interviewed via telephone. Interview recordings were transcribed verbatim and thematically coded using a priori and emergent codes. Opinion leaders described multi-level factors influencing dental providers' HPV-related prevention practice behaviors. Barriers included HPV as a sensitive topic and the need for HPV-related education and skills. Facilitators included perceptions of HPV prevention as part of the dental providers' role and the potential development of passive educational methods to provide HPV-related information to patients. Opinion leaders reported dental providers have a role in the prevention of HPV and oropharyngeal cancer; yet, to fully incorporate this topic into their practice, dental providers need further education and skill-based training. Opinion leaders have significant role in shaping this topic as a priority and identifying potential interventions to assist dental providers' HPV-related prevention. Future research should maximize the role of opinion leaders as key change agents.

PMID: 30735476 [PubMed - indexed for MEDLINE]

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