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]
Updated: 1 hour 17 min ago

Fluorescence lifetime imaging with time-gated detection of hyaluronidase using a long lifetime azadioxatriangulenium (ADOTA) fluorophore.

Fri, 10/05/2018 - 07:28
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Fluorescence lifetime imaging with time-gated detection of hyaluronidase using a long lifetime azadioxatriangulenium (ADOTA) fluorophore.

Methods Appl Fluoresc. 2016 11 17;4(4):047001

Authors: Chib R, Requena S, Mummert M, Strzhemechny YM, Gryczynski I, Borejdo J, Gryczynski Z, Fudala R

Abstract
A fluorescence lifetime imaging probe with a long lifetime was used in combination with time-gating for the detection of hyaluronidase using hyaluronic acid as the probe template. This probe was developed by heavily labeling hyaluronic acid with long lifetime azadioxatriangulenium fluorophores (ADOTA). We used this probe to image hyaluronidase produced by DU-145 prostate cancer cells.

PMID: 28192308 [PubMed - indexed for MEDLINE]

Contraceptive Use Effectiveness and Pregnancy Prevention Information Preferences Among Heterosexual and Sexual Minority College Women.

Thu, 10/04/2018 - 07:28
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Contraceptive Use Effectiveness and Pregnancy Prevention Information Preferences Among Heterosexual and Sexual Minority College Women.

Womens Health Issues. 2018 Jul - Aug;28(4):342-349

Authors: Blunt-Vinti HD, Thompson EL, Griner SB

Abstract
BACKGROUND: Previous research shows that sexual minority women have higher rates of unintended pregnancy than heterosexual women, but has not considered the wide range of contraceptive method effectiveness when exploring this disparity. We examine contraceptive use effectiveness and desire for pregnancy prevention information among college women across sexual orientation identity as a risk factor for unintended pregnancy.
METHODS: Using the National College Health Assessment Fall 2015 dataset, restricted to women who reported engaging in vaginal sex and not wanting to be pregnant (N = 6,486), logistic regression models estimated the odds of contraceptive method effectiveness and desire for pregnancy prevention information by sexual orientation.
RESULTS: Most women (57%) reported using a moderately effective contraceptive method (e.g., pill, patch, ring, shot) at last vaginal sex. Compared with heterosexual women, bisexual (adjusted odds ratio [aOR], 0.48; 95% confidence interval [CI], 0.37-0.62), lesbian (aOR, 0.03; 95% CI, 0.02-0.06), pansexual/queer (aOR, 0.38; 95% CI, 0.25-.56), and other (aOR, 0.50; 95% CI, 0.30-0.81) women were significantly less likely to have used a moderately effective method compared with no method. Only 9% of the sample used a highly effective method; asexual (aOR, 0.58; 95% CI, 0.37-0.92) and lesbian (aOR, 0.07; 95% CI, 0.03-0.20) women were significantly less likely than heterosexual women to have used these methods. Pansexual/queer and bisexual women were more likely than heterosexual women to desire pregnancy prevention information.
CONCLUSIONS: Several groups of sexual minority women were less likely than heterosexual women to use highly or moderately effective contraceptive methods, putting them at increased risk for unintended pregnancy, but desired pregnancy prevention information. These findings bring attention to the importance of patient-centered sexual and reproductive care to reduce unintended pregnancy.

PMID: 29666034 [PubMed - indexed for MEDLINE]

Vascular endothelium: a potential source of podocalyxin in serum from pregnancies with preeclampsia.

Thu, 10/04/2018 - 07:28
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Vascular endothelium: a potential source of podocalyxin in serum from pregnancies with preeclampsia.

J Hypertens. 2017 11;35(11):2176-2177

Authors: Goulopoulou S

PMID: 28953590 [PubMed - indexed for MEDLINE]

Humanin Attenuates NMDA-Induced Excitotoxicity by Inhibiting ROS-dependent JNK/p38 MAPK Pathway.

Wed, 10/03/2018 - 07:29
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Humanin Attenuates NMDA-Induced Excitotoxicity by Inhibiting ROS-dependent JNK/p38 MAPK Pathway.

Int J Mol Sci. 2018 Sep 29;19(10):

Authors: Yang X, Zhang H, Wu J, Yin L, Yan LJ, Zhang C

Abstract
Humanin (HN) is a novel 24-amino acid peptide that protects neurons against N-methyl-d-aspartate (NMDA)-induced toxicity. However, the contribution of the different mitogen-activated protein kinases (MAPKs) signals to HN neuroprotection against NMDA neurotoxicity remains unclear. The present study was therefore aimed to investigate neuroprotective mechanisms of HN. We analyzed intracellular Ca2+ levels, reactive oxygen species (ROS) production, and the MAPKs signal transduction cascade using an in vitro NMDA-mediated excitotoxicity of cortical neurons model. Results showed that: (1) HN attenuated NMDA-induced neuronal insults by increasing cell viability, decreasing lactate dehydrogenase (LDH) release, and increasing cell survival; (2) HN reversed NMDA-induced increase in intracellular calcium; (3) pretreatment by HN or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, decreased ROS generation after NMDA exposure; (4) administration of HN or N-Acetyl-l-cysteine (NAC), a ROS scavenger, inhibited NMDA-induced JNK and p38 MAPK activation. These results indicated that HN reduced intracellular elevation of Ca2+ levels, which, in turn, inhibited ROS generation and subsequent JNK and p38 MAPK activation that are involved in promoting cell survival in NMDA-induced excitotoxicity. Therefore, the present study suggests that inhibition of ROS-dependent JNK/p38 MAPK signaling pathway serves an effective strategy for HN neuroprotection against certain neurological diseases.

PMID: 30274308 [PubMed - in process]

Limb Ischemic Conditioning Improved Cognitive Deficits via eNOS-Dependent Augmentation of Angiogenesis after Chronic Cerebral Hypoperfusion in Rats.

Tue, 10/02/2018 - 16:31

Limb Ischemic Conditioning Improved Cognitive Deficits via eNOS-Dependent Augmentation of Angiogenesis after Chronic Cerebral Hypoperfusion in Rats.

Aging Dis. 2018 Oct;9(5):869-879

Authors: Ren C, Li N, Li S, Han R, Huang Q, Hu J, Jin K, Ji X

Abstract
Intracranial and extracranial arterial stenosis, the primary cause of chronic cerebral hypoperfusion (CCH), is a critical reason for the pathogenesis of vascular dementia and Alzheimer's disease characterized by cognitive impairments. Our previous study demonstrated that limb remote ischemic conditioning (LRIC) improved cerebral perfusion in intracranial arterial stenosis patients. The current study aimed to test whether LRIC promotes angiogenesis and increases phosphorylated endothelial nitric oxide synthase (p-eNOS) activity in CCH rat model. Adult male Sprague-Dawley rats were randomly assigned to three different groups: sham group, bilateral carotid artery occlusion (2VO) group and 2VO+LRIC group. Cerebral Blood Flow (CBF) was measured with laser speckle contrast imager at 4 weeks. Cognitive testing was performed at four and six weeks after 2VO surgery. We demonstrated that LRIC treatment increased cerebral perfusion and improved the CCH induced spatial learning and memory impairment. Immunohistochemistry confirmed that LRIC prevented cell death in the CA1 region, and increased the number of vessels and angiogenesis in the hippocampus after 2VO. Western blot analysis shows that LRIC therapy significantly increased p-eNOS expression in the hippocampus when compared with 2VO rats. Moreover, eNOS inhibitor reduced the effect of LRIC on angiogenesis in the hippocampus and spatial learning and memory function. Our data suggested that LRIC promoted angiogenesis, which is mediated, in part, by eNOS/NO.

PMID: 30271664 [PubMed]

Androgens modulate chronic intermittent hypoxia effects on brain and behavior.

Mon, 10/01/2018 - 07:28
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Androgens modulate chronic intermittent hypoxia effects on brain and behavior.

Horm Behav. 2018 Sep 27;:

Authors: Snyder B, Duong P, Trieu J, Cunningham RL

Abstract
Sleep apnea is associated with testosterone dysregulation as well as increased risk of developing neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). A rodent model of the hypoxic events of sleep apnea, chronic intermittent hypoxia (CIH), has been previously documented to impair cognitive function and elevate oxidative stress in male rats, while simultaneously decreasing testosterone. Therefore, androgens may modulate neuronal function under CIH. To investigate the role of androgens during CIH, male rats were assigned to one of four hormone groups: 1) gonadally intact, 2) gonadectomized (GDX), 3) GDX + testosterone (T) supplemented, or 4) GDX + dihydrotestosterone (DHT) supplemented. Each group was exposed to either normal room air or CIH exposure for one week, followed by memory and motor task assessments. Brain regions associated with AD and PD (entorhinal cortex, dorsal hippocampus, and substantia nigra) were examined for oxidative stress and inflammatory markers, key characteristics of AD and PD. Gonadally intact rats exhibited elevated oxidative stress due to CIH, but no significant memory and motor impairments. GDX increased memory impairments, regardless of CIH exposure. T preserved memory function and prevented detrimental CIH-induced changes. In contrast, DHT was not protective, as evidenced by exacerbated oxidative stress under CIH. Further, CIH induced significant spatial memory impairment in rats administered DHT. These results indicate androgens can have both neuroprotective and detrimental effects under CIH, which may have clinical relevance for men with untreated sleep apnea.

PMID: 30268884 [PubMed - as supplied by publisher]

Establishing a multidisciplinary framework to study drug-drug interactions of hormonal contraceptives: an invitation to collaborate.

Fri, 09/28/2018 - 07:29
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Establishing a multidisciplinary framework to study drug-drug interactions of hormonal contraceptives: an invitation to collaborate.

CPT Pharmacometrics Syst Pharmacol. 2018 Sep 27;:

Authors: Lesko LJ, Vozmediano V, Brown JD, Winterstein A, Zhao P, Lippert J, Höchel J, Chaturvedula A, White A, Schmidt S

Abstract
Hormonal contraceptive agents (HCAs) are widely used throughout the world, and women taking HCAs are likely to take other medications. However, little is known about clinical effect of most drug-drug interactions (DDIs) associated with HCAs. A team of interdisciplinary outcomes and pharmacometric researchers from academia and industry jointly engage in a research project to (1) quantitatively elucidate DDI impacts on unintended pregnancies and breakthrough bleeding, and (2) establish a DDI-prediction framework to inform optimal use of HCAs. This article is protected by copyright. All rights reserved.

PMID: 30260082 [PubMed - as supplied by publisher]

Vasodilator Function is Impaired in Burn Injury Survivors.

Thu, 09/27/2018 - 07:29
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Vasodilator Function is Impaired in Burn Injury Survivors.

Am J Physiol Regul Integr Comp Physiol. 2018 Sep 26;:

Authors: Romero SA, Moralez G, Jaffery MF, Huang M, Crandall CG

Abstract
The effect of severe burn injury on vascular health is unknown. We tested the hypothesis that, compared with non-burn control subjects, vasodilator function would be reduced and that pulse wave velocity (a measure of arterial stiffness) would be increased in individuals with prior burn injuries, the extent of which would be associated with the magnitude of body surface area having sustained a severe burn injury. Pulse wave velocity, macro- (flow-mediated dilation) and microvascular (reactive hyperemia) dilator functions were assessed in 14 non-burned control subjects and 32 age-matched subjects with well-healed burn injuries. Fifteen subjects with burn injuries covering 17-40% body surface area were assigned to a moderate burn injury group and 17 subjects with burn injuries covering >40% body surface area were assigned to a high burn injury group. Pulse wave velocity (central, P = 0.3; peripheral, P = 0.3) did not differ between the three groups. Compared with the control group, macrovascular dilator function was reduced in the moderate burn injury group (P = 0.07) and high burn injury group (P < 0.05). Likewise, peak vascular conductance during post-occlusive reactive hyperemia, differed from the moderate burn injury group (P = 0.08 vs. control) and the high burn injury group (P < 0.05 vs. control). These data suggest that vasodilator function is impaired in well-healed burn injury survivors, the extent of which is not dependent on the magnitude of body surface area having sustained a severe burn injury.

PMID: 30256680 [PubMed - as supplied by publisher]

Improved glucose homeostasis in male obese Zucker rats coincides with enhanced baroreflexes and activation of the nucleus tractus solitarius.

Thu, 09/27/2018 - 07:29
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Improved glucose homeostasis in male obese Zucker rats coincides with enhanced baroreflexes and activation of the nucleus tractus solitarius.

Am J Physiol Regul Integr Comp Physiol. 2018 Sep 26;:

Authors: Chaudhary P, Schreihofer AM

Abstract
Young adult male obese Zucker rats (OZR) develop insulin resistance and hypertension with impaired baroreflex-mediated bradycardia and activation of nucleus tractus solitarius (NTS). Because type 1 diabetic rats also develop impaired baroreflex-mediated NTS activation, we hypothesized that improving glycemic control in OZR would enhance compromised baroreflexes and NTS activation. Fasting blood glucose measured by telemetry was comparable in OZR and LZR at 12-17 weeks. However, with access to food, OZR were chronically hyperglycemic throughout this age range. By 15-17 weeks of age, tail samples yielded higher glucose values than those measured by telemetry in OZR but not LZR, consistent with reports of exaggerated stress responses in OZR. Injection of glucose (1g/kg, i.p.) produced larger rises in glucose and areas under the curve in OZR than LZR. Treatment with metformin (300 mg/kg/day) or pioglitazone (5 mg/kg/day) in drinking water for 2-3 weeks normalized fed glucose levels in OZR with no effect in LZR. After metformin treatment, area under the curve for blood glucose after glucose injection was reduced in OZR and comparable to LZR. Hyperinsulinemia was slightly reduced by each treatment in OZR, but insulin was still greatly elevated compared to LZR. Neither treatment reduced hypertension in OZR, but both treatments significantly improved the blunted phenylephrine-induced bradycardia and NTS c-Fos expression in OZR with no effect in LZR. These data suggest that restoring glycemic control in OZR enhances baroreflex control of heart rate by improving the response of the NTS to raising AP even in the presence of hyperinsulinemia and hypertension.

PMID: 30256679 [PubMed - as supplied by publisher]

How often parents make decisions with their children is associated with obesity.

Thu, 09/27/2018 - 07:29
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How often parents make decisions with their children is associated with obesity.

BMC Pediatr. 2018 Sep 25;18(1):311

Authors: Rahman A, Fulda KG, Franks SF, Fernando SI, Habiba N, Muzaffar O

Abstract
BACKGROUND: Evidence supports that better parental involvement and communication are related to reduced obesity in children. Parent-child collaborative decision-making is associated with lower BMI among children; while child-unilateral and parent-unilateral decision-making are associated with overweight children. However, little is known about associations between joint decision-making and obesity among Hispanic youth. The purpose of this analysis was to determine the relationship between parent-child decision making and obesity in a sample of predominantly Hispanic adolescents.
METHODS: Data from two studies focused on risk for type II diabetes were analyzed. A total of 298 adolescents 10-14 years of age and their parent/legal guardian were included. Parents completed questionnaires related to psychosocial, family functioning, and environmental factors. Multiple logistic regression was used to determine the association between obesity (≥ 95th percentile for age and gender), the dependent variable, and how often the parent felt they made decisions together with their child (rarely/never, sometimes, usually, always), the primary independent variable. Covariates included gender, age, ethnicity, total family income, and days participated in a physical activity for at least 20 min. ORs and 95% CIs were calculated.
RESULTS: Adolescent participants were predominantly Hispanic n = 233 (78.2%), and approximately half n = 150 (50.3%) were female. In multivariate analyses, adolescents who rarely/never made decisions together with their family had significantly higher odds (OR = 3.50; 95% CI [1.25-9.83]) of being obese than those who always did. No association was observed between either those who sometimes make decisions together or those who usually did and those that always did.
CONCLUSIONS: Parents and children not making decisions together, an essential aspect of parent-child communication, is associated with increased childhood obesity. The results of our study contribute to evidence of parental involvement in decision-making as an important determinant of adolescent health. Further studies should explore temporal relationships between parenting or communication style and obesity.

PMID: 30253768 [PubMed - in process]

The influence of the carotid baroreflex on dynamic regulation of cerebral blood flow and cerebral tissue oxygenation in humans at rest and during exercise.

Thu, 09/27/2018 - 07:29
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The influence of the carotid baroreflex on dynamic regulation of cerebral blood flow and cerebral tissue oxygenation in humans at rest and during exercise.

Eur J Appl Physiol. 2018 May;118(5):959-969

Authors: Purkayastha S, Maffuid K, Zhu X, Zhang R, Raven PB

Abstract
PURPOSE: This preliminary study tested the hypothesis that the carotid baroreflex (CBR) mediated sympathoexcitation regulates cerebral blood flow (CBF) at rest and during dynamic exercise.
METHODS: In seven healthy subjects (26 ± 1 years), oscillatory neck pressure (NP) stimuli of + 40 mmHg were applied to the carotid baroreceptors at a pre-determined frequency of 0.1 Hz at rest, low (10 ± 1W), and heavy (30 ± 3W) exercise workloads (WLs) without (control) and with α - 1 adrenoreceptor blockade (prazosin). Spectral power analysis of the mean arterial blood pressure (MAP), mean middle cerebral artery blood velocity (MCAV), and cerebral tissue oxygenation index (ScO2) in the low-frequency range (0.07-0.20 Hz) was estimated to examine NP stimuli responses.
RESULTS: From rest to heavy exercise, WLs resulted in a greater than three-fold increase in MCAV power (42 ± 23.8-145.2 ± 78, p < 0.01) and an almost three-fold increase in ScO2 power (0.51 ± 0.3-1.53 ± 0.8, p = 0.01), even though there were no changes in MAP power (from 24.5 ± 21 to 22.9 ± 11.9) with NP stimuli. With prazosin, the overall MAP (p = 0.0017), MCAV (p = 0.019), and ScO2 (p = 0.049) power was blunted regardless of the exercise conditions. Prazosin blockade resulted in increases in the Tf gain index between MAP and MCAV compared to the control (p = 0.03).
CONCLUSION: CBR-mediated changes in sympathetic activity contribute to dynamic regulation of the cerebral vasculature and CBF at rest and during dynamic exercise in humans.

PMID: 29497836 [PubMed - indexed for MEDLINE]

The effects of state rules on opioid prescribing in Indiana.

Thu, 09/27/2018 - 07:29
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The effects of state rules on opioid prescribing in Indiana.

BMC Health Serv Res. 2018 01 18;18(1):29

Authors: Al Achkar M, Grannis S, Revere D, MacKie P, Howard M, Gupta S

Abstract
BACKGROUND: Prescription opioids have been linked to over half of the 28,000 opioid overdose deaths in 2014. High rates of prescription opioid non-medical use have continued despite nearly all states implementing large-scale prescription drug monitoring programs (PDMP), which points to the need to examine the impact of state PDMP's on curbing inappropriate opioid prescribing. In the short-term, PDMPs have been associated with short-term prescribing declines. Yet little is known about how such policies differentially impact patient subgroups or are interpreted by prescribing providers. Our objective was to compare volumes of prescribed opioids before and after Indiana implemented opioid prescribing emergency rules and stratify the changes in opioid prescribing by patient and provider subgroups.
METHODS: An interrupted time series analysis was conducted using data obtained from the Indiana PDMP. Prescription level data was merged with census data to characterize patient socioeconomic status. Analyses were stratified by patients' gender, age, opioid dosage, and payer. The primary outcome indicator was the total morphine equivalent dose (MED) of dispensed opioids per day in the state of Indiana. Also considered were number of unique patients, unique providers, and prescriptions; MED per transaction and per day; and number of days supplied.
RESULTS: After controlling for time trends, we found that total MED for opioids decreased after implementing the new emergency rules, differing by patient gender, age, and payer. The effect was larger for males than females and almost 10 times larger for 0-20 year olds as compared to the 60+ age range. Medicare and Medicaid patients experienced more decline in prescribing than patients with private insurance. Patients with prescriptions paid for by workers' comp experienced the most significant decline. The emergency rules were associated with decline in both the number of prescribers and the number of day supply.
CONCLUSIONS: Although the Indiana opioid prescribing emergency rules impacted statewide prescribing behavior across all individual patient and provider characteristics, the emergency rules' effect was not consistent across patient characteristics. Further studies are needed to assess how individual patient characteristics influence the interpretation and application of state policies on opioid prescribing.

PMID: 29347984 [PubMed - indexed for MEDLINE]

Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.

Thu, 09/27/2018 - 07:29
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.

World J Biol Psychiatry. 2018 06;19(4):244-328

Authors: Lewczuk P, Riederer P, O'Bryant SE, Verbeek MM, Dubois B, Visser PJ, Jellinger KA, Engelborghs S, Ramirez A, Parnetti L, Jack CR, Teunissen CE, Hampel H, Lleó A, Jessen F, Glodzik L, de Leon MJ, Fagan AM, Molinuevo JL, Jansen WJ, Winblad B, Shaw LM, Andreasson U, Otto M, Mollenhauer B, Wiltfang J, Turner MR, Zerr I, Handels R, Thompson AG, Johansson G, Ermann N, Trojanowski JQ, Karaca I, Wagner H, Oeckl P, van Waalwijk van Doorn L, Bjerke M, Kapogiannis D, Kuiperij HB, Farotti L, Li Y, Gordon BA, Epelbaum S, Vos SJB, Klijn CJM, Van Nostrand WE, Minguillon C, Schmitz M, Gallo C, Lopez Mato A, Thibaut F, Lista S, Alcolea D, Zetterberg H, Blennow K, Kornhuber J, Members of the WFSBP Task Force Working on this Topic: Peter Riederer, Carla Gallo, Dimitrios Kapogiannis, Andrea Lopez Mato, Florence Thibaut

Abstract
In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.

PMID: 29076399 [PubMed - indexed for MEDLINE]

An investigation of the Plasmodium falciparum malaria epidemic in Kavango and Zambezi regions of Namibia in 2016.

Wed, 09/26/2018 - 10:29

An investigation of the Plasmodium falciparum malaria epidemic in Kavango and Zambezi regions of Namibia in 2016.

Trans R Soc Trop Med Hyg. 2018 Sep 25;:

Authors: Chanda E, Arshad M, Khaloua A, Zhang W, Namboze J, Uusiku P, Angula AH, Gausi K, Tiruneh D, Islam QM, Kolivras K, Haque U

Abstract
Background: Namibia is one of the countries among the eight that are targeting malaria elimination in southern Africa. However, the country has encountered malaria epidemics in recent years. The objective of this study was to investigate malaria epidemics and to contribute to strengthening malaria surveillance and control in an effort to move Namibia toward eliminating malaria.
Method: Malaria epidemiology data for 2014-2015 were collected from the weekly surveillance system. All consenting household members within a 100-m radius of index households were screened in 2016 using a Carestart malaria HRP2/pLDH combined rapid diagnostic test after epidemics. All houses within this radius were sprayed in 2016 with the pyrethroid deltamethrin and K-Othrine WG 250. Anopheles mosquito-positive breeding sites were identified and treated with the organophosphate larvicide temephos. Insecticide susceptibility and bioassay tests were conducted.
Results: During the epidemic response period in 2016, 56 parasitologically confirmed Plasmodium falciparum malaria cases in the Zambezi region were detected from active screening. The majority of those cases (83%) were asymptomatic infections. In the Kavango region, the malaria epidemic persisted, with 228 P. falciparum malaria cases recorded, but only 97 were investigated. In Namibia, malaria vector susceptibility was detected to 4% dichlorodiphenyltrichloroethane. Indoor residual spraying was conducted in 377 (90%) of the targeted households along with community awareness through health education of 1499 people and distribution of more than 2000 information, education and communication materials. The P. falciparum malaria cases in the Zambezi decreased from 122 in week 9 to 97 after week 15.
Conclusions: Malaria epidemics along with the persistence of asymptomatic reservoir infections pose a serious challenge in Namibia's elimination effort. The country needs to ensure sustainable interventions to target asymptomatic reservoir infections and prevent epidemics in order to successfully achieve its goal of eliminating malaria.

PMID: 30252108 [PubMed - as supplied by publisher]

Surgical management of giant intrapetrous internal carotid aneurysm presenting with coil exposure after endovascular treatment.

Wed, 09/26/2018 - 10:29
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Surgical management of giant intrapetrous internal carotid aneurysm presenting with coil exposure after endovascular treatment.

Neurosurg Rev. 2018 Jul;41(3):891-894

Authors: Yu LB, Zhang D, Yang SH, Zhao JZ

Abstract
Giant intrapetrous internal carotid aneurysms (petrous ICA aneurysm) are rare. A giant petrous ICA aneurysm presenting with otorrhagia and coil exposure to the external auditory meatus (EAM) after endovascular treatment has never been documented before. The authors report here a case of successful surgical trapping with bypass intervention of a giant petrous ICA aneurysm presenting with coil exposure after endovascular treatment. A 58-year-old man presented with persistent otorrhagia having been admitted to our hospital because of the recurrence of a giant petrous ICA aneurysm after repeated embolization treatments with coils. An electronic otoscope examination demonstrated that a piece of coil escaped into his right EAM. After multidisciplinary consultation, an extracranial-intracranial (EC-IC) bypass with ICA occlusion and coil removal with a closed EAM filling were performed in stages. The patient recovered quickly without any neurological deficits. A digital subtraction angiography confirmed the absence of the aneurysm and patency of the bypass graft.

PMID: 29572579 [PubMed - indexed for MEDLINE]

Children with Autism Spectrum Disorder, Developmental Coordination Disorder, and typical development differ in characteristics of dynamic postural control: A preliminary study.

Tue, 09/25/2018 - 07:29
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Children with Autism Spectrum Disorder, Developmental Coordination Disorder, and typical development differ in characteristics of dynamic postural control: A preliminary study.

Gait Posture. 2018 Sep 14;67:9-11

Authors: Miller HL, Caçola PM, Sherrod GM, Patterson RM, Bugnariu NL

Abstract
BACKGROUND: Autism Spectrum Disorder (ASD) and Developmental Coordination Disorder (DCD) are developmental disorders with distinct definitions and symptoms. However, both conditions share difficulties with motor skills, including impairments in postural control. While studies have explored postural sway variables in children with DCD and ASD as compared to typical development (TD), few have used kinematic data to assess the magnitude of differences between these two neurodevelopmental conditions. There are few sensitive and specific measures available to assess balance impairment severity in these populations.
RESEARCH QUESTION: Do individuals with ASD, DCD, and TD differ in dynamic postural control?
METHODS: We quantified postural control differences between ASD, DCD, and TD during a dynamic balance task. 10 ASD, 10 DCD, and 8 TD agematched children completed a dynamic postural control task in a virtual environment. They leaned to shift their center of pressure (CoP) to match a user-controlled object to an oscillating target (0.1 Hz-0.8 Hz).
RESULTS: The DCD group had higher CoP accelerations compared to ASD or TD. While the DCD and TD groups did not differ in their medial-lateral velocity, the ASD group had low medial-lateral velocity and acceleration as compared to DCD and TD. ASD group velocity and acceleration did not differ from that of the TD group in the anterior-posterior direction. Higher accelerations in the DCD group reflected non-fluid movements; by contrast, the ASD group had slower, more fluid movements. Results may reflect differences in how children with ASD and DCD plan, execute, and modify motor actions.
SIGNIFICANCE: This study demonstrates the potential utility of CoP acceleration and velocity as a sensitive and specific means of differentiating between ASD, DCD, and TD. Results indicating group differences between ASD and DCD in velocity and acceleration profiles represent an important step toward understanding how these populations modify motor plans during dynamic tasks.

PMID: 30245240 [PubMed - as supplied by publisher]

Effects of temperature on bacterial microbiome composition in Ixodes scapularis ticks.

Sat, 09/22/2018 - 07:28
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Effects of temperature on bacterial microbiome composition in Ixodes scapularis ticks.

Microbiologyopen. 2018 Sep 21;:e00719

Authors: Thapa S, Zhang Y, Allen MS

Abstract
Ixodes scapularis, the blacklegged deer tick, is the principal vector of Lyme disease in North America. Environmental factors are known to influence regional and seasonal incidence of Lyme disease and possibly the endemicity of the disease to the northeastern and upper mid-western regions of the United States. With a goal to understand the impact of environmental temperature on microbial communities within the tick, we investigated the bacterial microbiome of colony-reared I. scapularis ticks statically incubated at different temperatures (4, 20, 30, and 37°C) at a constant humidity in a controlled laboratory setting by comparison of sequenced amplicons of the bacterial 16S V4 rRNA gene to that of the untreated baseline controls. The microbiomes of colony-reared I. scapularis males were distinct than that of females, which were entirely dominated by Rickettsia. In silico removal of Rickettsia sequences from female data revealed the underlying bacterial community, which is consistent in complexity with those seen among male ticks. The bacterial community composition of these ticks changes upon incubation at 30°C for a week and 37°C for more than 5 days. Moreover, the male ticks incubated at 30 and 37°C exhibited significantly different bacterial diversity compared to the initial baseline microbiome, and the change in bacterial diversity was dependent upon duration of exposure. Rickettsia-free data revealed a significantly different bacterial diversity in female ticks incubated at 37°C compared to that of 4 and 20°C treatments. These results provide experimental evidence that environmental temperature can impact the tick bacterial microbiome in a laboratory setting.

PMID: 30239169 [PubMed - as supplied by publisher]

Aptamer-based search for correlates of plasma and serum water T2: implications for early metabolic dysregulation and metabolic syndrome.

Sat, 09/22/2018 - 07:28
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Aptamer-based search for correlates of plasma and serum water T2: implications for early metabolic dysregulation and metabolic syndrome.

Biomark Res. 2018;6:28

Authors: Patel V, Dwivedi AK, Deodhar S, Mishra I, Cistola DP

Abstract
Background: Metabolic syndrome is a cluster of abnormalities that increases the risk for type 2 diabetes and atherosclerosis. Plasma and serum water T2 from benchtop nuclear magnetic resonance relaxometry are early, global and practical biomarkers for metabolic syndrome and its underlying abnormalities. In a prior study, water T2 was analyzed against ~ 130 strategically selected proteins and metabolites to identify associations with insulin resistance, inflammation and dyslipidemia. In the current study, the analysis was broadened ten-fold using a modified aptamer (SOMAmer) library, enabling an unbiased search for new proteins correlated with water T2 and thus, metabolic health.
Methods: Water T2 measurements were recorded using fasting plasma and serum from non-diabetic human subjects. In parallel, plasma samples were analyzed using a SOMAscan assay that employed modified DNA aptamers to determine the relative concentrations of 1310 proteins. A multi-step statistical analysis was performed to identify the biomarkers most predictive of water T2. The steps included Spearman rank correlation, followed by principal components analysis with variable clustering, random forests for biomarker selection, and regression trees for biomarker ranking.
Results: The multi-step analysis unveiled five new proteins most predictive of water T2: hepatocyte growth factor, receptor tyrosine kinase FLT3, bone sialoprotein 2, glucokinase regulatory protein and endothelial cell-specific molecule 1. Three of the five strongest predictors of water T2 have been previously implicated in cardiometabolic diseases. Hepatocyte growth factor has been associated with incident type 2 diabetes, and endothelial cell specific molecule 1, with atherosclerosis in subjects with diabetes. Glucokinase regulatory protein plays a critical role in hepatic glucose uptake and metabolism and is a drug target for type 2 diabetes. By contrast, receptor tyrosine kinase FLT3 and bone sialoprotein 2 have not been previously associated with metabolic conditions. In addition to the five most predictive biomarkers, the analysis unveiled other strong correlates of water T2 that would not have been identified in a hypothesis-driven biomarker search.
Conclusions: The identification of new proteins associated with water T2 demonstrates the value of this approach to biomarker discovery. It provides new insights into the metabolic significance of water T2 and the pathophysiology of metabolic syndrome.

PMID: 30237882 [PubMed]

Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia.

Sat, 09/22/2018 - 07:28
Related Articles

Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia.

Proc Natl Acad Sci U S A. 2018 Sep 20;:

Authors: Nguyen T, Su C, Singh M

Abstract
Progesterone (P4) is a potent neuroprotectant and a promising therapeutic for stroke treatment. However, the underlying mechanism(s) remain unclear. Our laboratory recently reported that brain-derived neurotrophic factor (BDNF) is a critical mediator of P4's protective actions and that P4-induced BDNF release from cortical astrocytes is mediated by a membrane-associated progesterone receptor, Pgrmc1. Here, we report that the microRNA (miRNA) let-7i is a negative regulator of Pgrmc1 and BDNF in glia and that let-7i disrupts P4-induced BDNF release and P4's beneficial effects on cell viability and markers of synaptogenesis. Using an in vivo model of ischemia, we demonstrate that inhibiting let-7i enhances P4-induced neuroprotection and facilitates functional recovery following stroke. The discovery of such factors that regulate the cytoprotective effects of P4 may lead to the development of biomarkers to differentiate/predict those likely to respond favorably to P4 versus those that do not.

PMID: 30237284 [PubMed - as supplied by publisher]

Promoting guideline-based cancer genetic risk assessment for hereditary breast and ovarian cancer in ethnically and geographically diverse cancer survivors: Rationale and design of a 3-arm randomized controlled trial.

Sat, 09/22/2018 - 07:28
Related Articles

Promoting guideline-based cancer genetic risk assessment for hereditary breast and ovarian cancer in ethnically and geographically diverse cancer survivors: Rationale and design of a 3-arm randomized controlled trial.

Contemp Clin Trials. 2018 Sep 17;:

Authors: Kinney AY, Howell R, Ruckman R, McDougall JA, Boyce TW, Vicuña B, Lee JH, Guest DD, Rycroft R, Valverde PA, Gallegos KM, Meisner A, Wiggins CL, Stroup A, Paddock LE, Walters ST

Abstract
BACKGROUND: Although national guidelines for cancer genetic risk assessment (CGRA) for hereditary breast and ovarian cancer (HBOC) have been available for over two decades, less than half of high-risk women have accessed these services, especially underserved minority and rural populations. Identification of high-risk individuals is crucial for cancer survivors and their families to benefit from biomedical advances in cancer prevention, early detection, and treatment.
METHODS: This paper describes community-engaged formative research and the protocol of the ongoing randomized 3-arm controlled Genetic Risk Assessment for Cancer Education and Empowerment (GRACE) trial. Ethnically and geographically diverse breast and ovarian cancer survivors at increased risk for hereditary cancer predisposition who have not had a CGRA are recruited through the three statewide cancer registries. The specific aims are to: 1) compare the effectiveness of a targeted intervention (TP) vs. a tailored counseling and navigation(TCN) intervention vs. usual care (UC) on CGRA utilization at 6 months post-diagnosis (primary outcome); compare the effectiveness of the interventions on genetic counseling uptake at 12 months after removal of cost barriers (secondary outcome); 2) examine potential underlying theoretical mediating and moderating mechanisms; and 3) conduct a cost evaluation to guide dissemination strategies.
DISCUSSION: The ongoing GRACE trial addresses an important translational gap by developing and implementing evidence-based strategies to promote guideline-based care and reduce disparities in CGRA utilization among ethnically and geographically diverse women. If effective, these interventions have the potential to reach a large number of high-risk families and reduce disparities through broad dissemination.
TRIAL REGISTRATION NUMBER: NCT03326713; clinicaltrials.gov.

PMID: 30236776 [PubMed - as supplied by publisher]

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