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: 52 min 35 sec ago

Serious mental illness and negative substance use consequences among adults on probation.

Sat, 03/24/2018 - 07:43

Serious mental illness and negative substance use consequences among adults on probation.

Health Justice. 2018 Mar 22;6(1):6

Authors: Rossheim ME, Livingston MD, Lerch JA, Taxman FS, Walters ST

Abstract
BACKGROUND: Adults on probation are at greater risk of both using substances and having a mental disorder compared to the general population. Several theories explain the relationship between substance use and poor mental health. However, the interaction between substance use, mental health, and substance-related consequences is not well understood. A better understanding of this relationship may help treatment programs become more responsive to people with serious mental illness (SMI).
METHOD: The current study used interview data from 313 adults on probation who reported recent substance use. We examined associations between SMI risk, substance use, and substance use consequences.
RESULTS: A substantial proportion of the sample (37.5%) screened at risk of having a SMI. Adjusting for type and amount of substance use, those who screened at risk of having a SMI reported more negative substance use consequences. Significant interaction effects were observed between use of alcohol or opiates and SMI risk. Alcohol use was associated with more negative substance use consequences among those at risk of SMI, while opiate use was associated with more consequences among those not at risk.
CONCLUSIONS: Programs are sorely needed to identify and treat adults with comorbid substance use and mental health symptoms, particularly for adults in the justice system. Clinicians should carefully consider how mental health may interact with substance use to exacerbate consequences.

PMID: 29569076 [PubMed]

Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2.

Sat, 03/24/2018 - 07:43
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Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2.

Stem Cells. 2017 Jul;35(7):1674-1686

Authors: Whitmill A, Liu Y, Timani KA, Niu Y, He JJ

Abstract
HIV-1 Tat-interacting protein of 110 kDa, Tip110, plays important roles in multiple biological processes. In this study, we aimed to characterize the function of Tip110 in embryonic development. Transgenic mice lacking expression of a functional Tip110 gene (Tip110-/- ) died post-implantation, and Tip110-/- embryos exhibited developmental arrest between 8.5 and 9.5 days post coitum. However, in vitro cultures of Tip110-/- embryos showed that Tip110 loss did not impair embryo growth from the zygote to the blastocyst. Extended in vitro cultures of Tip110-/- blastocysts showed that Tip110 loss impaired both blastocyst outgrowth and self-renewal and survival of blastocyst-derived embryonic stem cells. Microarray analysis of Tip110-/- embryonic stem cells revealed that Tip110 loss altered differentiation, pluripotency, and cycling of embryonic stem cells and was associated with downregulation of several major stem cell factors including Nanog, Oct4, and Sox2 through a complex network of signaling pathways. Taken together, these findings document for the first time the lethal effects of complete loss of Tip110 on mammalian embryonic development and suggest that Tip110 is an important regulator of not only embryonic development but also stem cell factors. Stem Cells 2017;35:1674-1686.

PMID: 28436127 [PubMed - indexed for MEDLINE]

Current Strategies for Brain Drug Delivery.

Wed, 03/21/2018 - 07:36

Current Strategies for Brain Drug Delivery.

Theranostics. 2018;8(6):1481-1493

Authors: Dong X

Abstract
The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

PMID: 29556336 [PubMed - in process]

The Radiographic Prepatellar Fat Thickness Ratio Correlates With Infection Risk After Total Knee Arthroplasty.

Wed, 03/21/2018 - 07:36

The Radiographic Prepatellar Fat Thickness Ratio Correlates With Infection Risk After Total Knee Arthroplasty.

J Arthroplasty. 2018 Feb 15;:

Authors: Wagner RA, Hogan SP, Burge JR, Bates CM, Sanchez HB

Abstract
BACKGROUND: Obesity has been associated with complications after a total knee arthroplasty (TKA). Surgical site infection (SSI) after TKA is one of the feared complications as it increases revision rates, costs, and stress to the patient. There is conflicting evidence in the literature regarding body mass index (BMI) and risk of infection after TKA, and some studies have suggested that site-specific fat distribution may be a better metric for determining risk of postoperative infections. Here, we investigate the correlation of soft tissue distribution about the knee to SSI after TKA.
METHODS: We retrospectively review 572 patients who underwent primary TKA at a single institution from 2006 to 2010. We introduce the prepatellar fat thickness ratio (PFTR) as a radiographic means to quantitatively assess fat distribution about the knee and evaluate this measurement's ability to assess the risk of developing an SSI after TKA.
RESULTS: The PFTR was shown to be a better predictor of SSI than BMI in both the univariate (P = .05) and multivariate (P = .01) analyses.
CONCLUSION: Although BMI cannot fully account for variations in adipose distribution, the PFTR may account for this variability and may be a helpful tool for assessing a patient's preoperative risk of SSI after TKA.

PMID: 29555491 [PubMed - as supplied by publisher]

Barriers for pregnant women living in rural, agricultural villages to accessing antenatal care in Cambodia: A community-based cross-sectional study combined with a geographic information system.

Tue, 03/20/2018 - 10:39

Barriers for pregnant women living in rural, agricultural villages to accessing antenatal care in Cambodia: A community-based cross-sectional study combined with a geographic information system.

PLoS One. 2018;13(3):e0194103

Authors: Yasuoka J, Nanishi K, Kikuchi K, Suzuki S, Ly P, Thavrin B, Omatsu T, Mizutani T

Abstract
BACKGROUND: Maternal morbidity and mortality is still a major public health issue in low- and middle-income countries such as Cambodia. Improving access to antenatal care (ANC) services for pregnant women has been widely recognized as one of the most effective means of reducing maternal mortality and morbidity. As such, this study examined the barriers for pregnant women living in rural, agricultural villages to accessing ANC based on data collected in the Ratanakiri province, one of the least developed provinces in Cambodia, using a combination of a community-based cross-sectional survey and a geographic information system (GIS).
METHODS: A community-based cross-sectional survey was conducted among 377 mothers with children under the age of two living in 62 villages in the Ratanakiri province, Cambodia, in December 2015. Face-to-face interviews were conducted to ask mothers about their ANC service use, knowledge of ANC, barriers to accessing health facilities, and complications they experienced during the most recent pregnancy. At the same time, GIS data were also collected using a Global Positioning System (GPS) to accurately measure actual travel distance of pregnant women to access health facilities and to examine geographical and environmental barriers in greater detail.
RESULTS: Only a third of the mothers met the recommendations made by the World Health Organization (WHO) of receiving ANC four times or more (achieved ANC4+), and a quarter of the mothers had never received ANC during their most recent pregnancy. Factors positively associated with achieving ANC4+ were mother's secondary or higher education (adjusted odds ratio [AOR] = 5.50, 95% confidence interval [CI]: 1.74, 17.37), being aware that receiving ANC is recommended (AOR = 2.74, 95% CI: 1.25, 6.00), and knowledge about the recommended frequency for ANC (AOR = 2.26, 95% CI: 7.22). Actual travel distance was negatively associated with achieving ANC4+. Mothers who had to travel 10.0-14.9 km were 68% less likely (AOR = 0.32, 95% CI: 0.10, 0.99), and those who had to travel 15.0 km or longer were 79% less likely (AOR = 0.21, 95% CI: 0.07, 0.62) to have achieved ANC 4+, both compared to those who travelled 5.0 km or less. While most previous studies have used a straight-line to measure distance traveled, this study much more accurately measured the actual distance traveled by using a GIS. As a result, there was a statistically significant discrepancy between actual travel distance and straight-line distance.
CONCLUSIONS: This study revealed promoting factors and barriers for ANC use among pregnant women living in remote, agricultural villages in Cambodia. Furthermore, this study highlights the importance of measuring travel distances accurately to ensure that targeted interventions for ANC are not misguided by straight-line distances. The methodology used in this study can be applied widely to other developing countries, especially in remote areas with limited road networks where there may be a large discrepancy between actual and straight-line distances.

PMID: 29554118 [PubMed - in process]

Knockout of tissue transglutaminase ameliorates TGFβ2-induced ocular hypertension: A novel therapeutic target for glaucoma?

Thu, 03/15/2018 - 07:36

Knockout of tissue transglutaminase ameliorates TGFβ2-induced ocular hypertension: A novel therapeutic target for glaucoma?

Exp Eye Res. 2018 Mar 10;:

Authors: Raychaudhuri U, Millar JC, Clark AF

Abstract
Glaucoma is a vision threatening optic neuropathy that affects millions of people worldwide. In primary open angle, increased intraocular pressure (IOP) is the main risk factor for the development of this disease. Studies investigating the causes and mechanisms of increased IOP show fibrotic changes in the trabecular meshwork (TM) that are different from those of age-matched controls. Tissue transglutaminase (TGM2), an extracellular matrix (ECM) crosslinking enzyme, covalently crosslinks ECM proteins and causes excessive ECM protein deposition in the TM that could cause increased IOP. Previous literature reports increased expression of TGM2 in glaucomatous eyes compared to controls. We have recently shown that overexpression of TGM2 causes increased ECM crosslinking in the TM, increases IOP, and decreases aqueous humor (AH) outflow facility in mouse eyes. Therefore, we wanted to study the effect of TGM2 knockout (KO) on IOP in TGM2 floxed mice. Ad5.Cre transduction caused partial KO of TGM2, which decreased TGM2 expression in the TM region of mouse eyes. TGM2 KO significantly decreased IOP by itself and also in TGFβ2 induced ocular hypertensive mice. TGM2 KO also modifies the outflow facility in TGFβ2 transduced eyes. Overall, TGM2 KO rescued the TGFβ2-induced ocular hypertensive phenotype. Thus, TGM2 may offer potential as a new therapeutic target for glaucoma.

PMID: 29535003 [PubMed - as supplied by publisher]

Copycats in Pilot Aircraft-Assisted Suicides after the Germanwings Incident.

Thu, 03/15/2018 - 07:36

Copycats in Pilot Aircraft-Assisted Suicides after the Germanwings Incident.

Int J Environ Res Public Health. 2018 Mar 11;15(3):

Authors: Laukkala T, Vuorio A, Bor R, Budowle B, Navathe P, Pukkala E, Sajantila A

Abstract
Aircraft-assisted pilot suicide is a rare but serious phenomenon. The aim of this study was to evaluate changes in pilot aircraft-assisted suicide risks, i.e., a copycat effect, in the U.S. and Germany after the Germanwings 2015 incident in the French Alps. Aircraft-assisted pilot suicides were searched in the U.S. National Transportation Safety Board (NTSB) accident investigation database and in the German Bundestelle für Flugunfalluntersuchung (BFU) Reports of Investigation database five years before and two years after the deliberate crash of the Germanwings flight into the French Alps in 2015. The relative risk (RR) of the aircraft-assisted pilot suicides was calculated. Two years after the incident, three out of 454 (0.66%) fatal incidents were aircraft-assisted suicides compared with six out of 1292 (0.46%) in the prior five years in the NTSB database. There were no aircraft-assisted pilot suicides in the German database during the two years after or five years prior to the Germanwings crash. The relative aircraft-assisted pilot suicide risk for the U.S. was 1.4 (95% CI 0.3-4.2) which was not statistically significant. Six of the pilots who died by suicide had told someone of their suicidal intentions. We consider changes in the rate to be within a normal variation. Responsible media coverage of aircraft incidents is important due to the large amount of publicity that these events attract.

PMID: 29534475 [PubMed - in process]

Livedoid Vasculopathy Presenting in a Patient With Sickle Cell Disease.

Wed, 03/14/2018 - 07:51

Livedoid Vasculopathy Presenting in a Patient With Sickle Cell Disease.

Am J Dermatopathol. 2018 Feb 28;:

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

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

PMID: 29533274 [PubMed - as supplied by publisher]

Chronic intermittent hypoxia induces hormonal and male sexual behavioral changes: Hypoxia as an advancer of aging.

Tue, 03/13/2018 - 07:34

Chronic intermittent hypoxia induces hormonal and male sexual behavioral changes: Hypoxia as an advancer of aging.

Physiol Behav. 2018 Mar 08;:

Authors: Nicole Wilson E, Anderson M, Snyder B, Duong P, Trieu J, Schreihofer DA, Cunningham RL

Abstract
Sleep apnea is a common sleep disorder characterized by intermittent periods of low blood oxygen levels. The risk for sleep apnea increases with age and is more prevalent in men than women. A common comorbidity of sleep apnea includes male sexual dysfunction, but it is not clear if a causal relationship exists between sleep apnea and sexual dysfunction. Possible mechanisms that link these two disorders include oxidative stress and testosterone. Oxidative stress is elevated in clinical patients with sleep apnea and in rodents exposed to chronic intermittent hypoxia (CIH), an animal model for apnea-induced hypopnea. Further, oxidative stress levels increase with age. Therefore, age may play a role in sleep apnea-induced sexual dysfunction and oxidative stress generation. To investigate this relationship, we exposed gonadally intact 3 (young) and 12 (middle-aged) month old male F344/BN F1 hybrid male rats to 8 days of CIH, and then examined male sexual function. Plasma was used to assess circulating oxidative stress and hormone levels. Middle-aged male rats had lower testosterone levels with increased sexual dysfunction and oxidative stress, independent of CIH. However, CIH decreased testosterone levels and increased sexual dysfunction and oxidative stress only in young gonadally intact male rats, but not in gonadectomized young rats with physiological testosterone replacement. In sum, CIH had a greater impact on younger gonadally intact animals, with respect to sexual behaviors, testosterone, and oxidative stress. Our data indicate CIH mimics the effects of aging on male sexual behavior in young gonadally intact male rats.

PMID: 29526572 [PubMed - as supplied by publisher]

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

Sun, 03/11/2018 - 07:43

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

Acta Biomater. 2018 Mar 07;:

Authors: Raghunathan V, 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 - as supplied by publisher]

The US Cancer Moonshot initiative.

Sat, 03/10/2018 - 07:49
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The US Cancer Moonshot initiative.

Lancet Oncol. 2016 05;17(5):e178-80

Authors: Aelion CM, Airhihenbuwa CO, Alemagno S, Amler RW, Arnett DK, Balas A, Bertozzi S, Blakely CH, Boerwinkle E, Brandt-Rauf P, Buekens PM, Chandler GT, Chang RW, Clark JE, Cleary PD, Curran JW, Curry SJ, Diez Roux AV, Dittus R, Ellerbeck EF, El-Mohandes A, Eriksen MP, Erwin PC, Evans G, Finnegan JR, Fried LP, Frumkin H, Galea S, Goff DC, Goldman LR, Guilarte TR, Rivera-Gutiérrez R, Halverson PK, Hand GA, Harris CM, Healton CG, Hennig N, Heymann J, Hunter D, Hwang W, Jones RM, Klag MJ, Klesges LM, Lahey T, Lawlor EF, Maddock J, Martin WJ, Mazzaschi AJ, Michael M, Mohammed SD, Nasca PC, Nash D, Ogunseitan OA, Perez RA, Perri M, Petersen DJ, Peterson DV, Philbert M, Pinto-Martin J, Raczynski JM, Raskob GE, Rimer BK, Rohrbach LA, Rudkin LL, Siminoff L, Szapocznik J, Thombs D, Torabi MR, Weiler RM, Wetle TF, Williams PL, Wykoff R, Ying J

PMID: 27301041 [PubMed - indexed for MEDLINE]

Blood-Based Biomarker Screening with Agnostic Biological Definitions for an Accurate Diagnosis Within the Dimensional Spectrum of Neurodegenerative Diseases.

Thu, 03/08/2018 - 07:34

Blood-Based Biomarker Screening with Agnostic Biological Definitions for an Accurate Diagnosis Within the Dimensional Spectrum of Neurodegenerative Diseases.

Methods Mol Biol. 2018;1750:139-155

Authors: Baldacci F, Lista S, O'Bryant SE, Ceravolo R, Toschi N, Hampel H, Alzheimer Precision Medicine Initiative (APMI)

Abstract
The discovery, development, and validation of novel candidate biomarkers in Alzheimer's disease (AD) and other neurodegenerative diseases (NDs) are increasingly gaining momentum. As a result, evolving diagnostic research criteria of NDs are beginning to integrate biofluid and neuroimaging indicators of pathophysiological mechanisms. More than 10% of people aged over 65 suffer from NDs. There is an urgent need for a refined two-stage diagnostic model to first initiate an early, sensitive, and noninvasive process in primary care settings. Individuals that meet detection criteria will then be channeled to more specific, costly (positron-emission tomography), and invasive (cerebrospinal fluid) assessment methods for confirmatory biological characterization and diagnosis.A reliable and sensitive blood test for AD and other NDs is not yet established; however, it would provide the golden screening gate for an efficient primary care management. A limitation to the development of a large-scale blood-screening biomarker-based test is the traditional application of clinically descriptive criteria for the categorization of single late-stage ND constructs. These are genetically and biologically heterogeneous, reflected in multiple pathophysiological mechanisms and subsequent pathologies throughout a dimensional continuum. Evidence suggests that a shared, "open-source" integrated multilevel categorization of NDs that clusters individuals based on descriptive clinical phenotypes and pathophysiological biomarker signatures will provide the next incremental step toward an improved diagnostic process of NDs. This intermediate objective toward unbiased biomarker-guided early detection of individuals at risk for NDs is currently carried out by the international pilot Alzheimer Precision Medicine Initiative Cohort Program (APMI-CP).

PMID: 29512070 [PubMed - in process]

Evaluating Personalized Feedback Intervention Framing with a Randomized Controlled Trial to Reduce Young Adult Alcohol-Related Sexual Risk Taking.

Thu, 03/08/2018 - 07:34

Evaluating Personalized Feedback Intervention Framing with a Randomized Controlled Trial to Reduce Young Adult Alcohol-Related Sexual Risk Taking.

Prev Sci. 2018 Mar 06;:

Authors: Lewis MA, Rhew IC, Fairlie AM, Swanson A, Anderson J, Kaysen D

Abstract
The purpose of this study was to evaluate personalized feedback intervention (PFI) framing with two web-delivered PFIs aimed to reduce young adult alcohol-related risky sexual behavior (RSB). Combined PFIs typically use an additive approach whereby independent components on drinking and components on RSB are presented without the discussion of the influence of alcohol on RSB. In contrast, an integrated PFI highlights the RSB-alcohol connection by presenting integrated alcohol and RSB components that focus on the role of intoxication as a barrier to risk reduction in sexual situations. In a randomized controlled trial, 402 (53.98% female) sexually active young adults aged 18-25 were randomly assigned to a combined PFI, an integrated PFI, or attention control. All assessment and intervention procedures were web-based. At the 1-month follow-up, those randomly assigned to the integrated condition had a lower likelihood of having any casual sex partners compared to those in the control group. At the 6-month follow-up, the combined condition had a lower likelihood of having any casual sex partners compared to those in the control group. When examining alcohol-related RSB, at the 1-month follow-up, both interventions showed a lower likelihood of any drinking prior to sex compared to the control group. When examining alcohol-related sexual consequences, results showed a reduction in the non-zero count of consequences in the integrated condition compared to the control at the 1-month follow-up. For typical drinks per week, those in the combined condition showed a greater reduction in the non-zero count of drinks than those in the control condition at the 1-month follow-up. While there were no significant differences between the two interventions, the current findings highlight the utility of two efficacious web-based alcohol and RSB interventions among a national sample of at-risk young adults.

PMID: 29511966 [PubMed - as supplied by publisher]

Alcohol use and alcohol/marijuana use during the most recent sexual experience differentially predict characteristics of the sexual experience among sexually active young adult drinkers.

Wed, 03/07/2018 - 07:38

Alcohol use and alcohol/marijuana use during the most recent sexual experience differentially predict characteristics of the sexual experience among sexually active young adult drinkers.

Addict Behav. 2018 Mar 03;82:105-108

Authors: Fairlie AM, Garcia TA, Lee CM, Lewis MA

Abstract
INTRODUCTION: Few studies have examined associations between using alcohol only and using both alcohol and marijuana with sexual behavior on specific occasions. The current study examined alcohol and marijuana use during the most recent sexual experience in association with relationship characteristics, psychological issues, and condom use.
METHODS: Young adult drinkers aged 18-25 who reported not using a condom during sex in the past month were recruited nationally. An analytic subsample (N = 378) was identified based on substance use during the most recent sexual experience [53% female, 70% Caucasian; mean age = 22.42 years (SD = 1.90)]. Using logistic regression, two dummy codes compared the alcohol use only group (n = 197) and the both alcohol and marijuana group (n = 95) to the group who used neither substance (n = 86). Participant sex, drinking frequency, and number of sexual partners were included as covariates.
RESULTS: The alcohol only group and the both alcohol and marijuana group had greater odds of being with a casual acquaintance and loss of respect compared to the group who used neither substance. The alcohol only group had greater odds of being with someone they just met and embarrassment compared to the group who used neither substance. No associations were found for condom use or emotional difficulties.
CONCLUSIONS: Preventative interventions may need to address both alcohol and marijuana to more effectively reduce risky behaviors.

PMID: 29510295 [PubMed - as supplied by publisher]

Calpain: A Novel Mediator of MPO (Myeloperoxidase)-Induced Endothelial Dysfunction.

Wed, 03/07/2018 - 07:38
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Calpain: A Novel Mediator of MPO (Myeloperoxidase)-Induced Endothelial Dysfunction.

Hypertension. 2018 Mar 05;:

Authors: Goulopoulou S

PMID: 29507102 [PubMed - as supplied by publisher]

Cystatin C as a potential therapeutic mediator against Parkinson's disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units.

Wed, 03/07/2018 - 07:38
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Cystatin C as a potential therapeutic mediator against Parkinson's disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units.

Cell Death Dis. 2017 Jun 01;8(6):e2854

Authors: Zou J, Chen Z, Wei X, Chen Z, Fu Y, Yang X, Chen D, Wang R, Jenner P, Lu JH, Li M, Zhang Z, Tang B, Jin K, Wang Q

Abstract
Cystatin C (CYS C, Cst3) is an endogenous cysteine protease inhibitor that plays neuroprotective roles in neurodegenerative diseases. We aimed to explore the association of CYS C with Parkinson's disease (PD) models and investigate its involvement in the role of neurovascular units (NVUs) in PD neuro-pathogenesis. We used A53T α-synuclein (SNCA) transgenic mice and 6-hydroxydopamine-lesioned DAergic PC12 cells as experimental PD models to investigate the mechanisms behind this association. The injections of CYS C were administered to the right substantia nigra (SN) of A53T SNCA transgenic mice to measure the effects of CYS C in transgenic A53T SNCA mice. To explore the angiogenesis in vivo and in vitro, we used the chick embryo chorioallantoic membrane (CAM) assay and tube formation (TF) assay. We found that CYS C has a neuroprotective effect in this in vivo PD model. We observed increased VEGF, NURR1 and autophagy markers LC3B and decreased SNCA and apoptosis marker cleaved CASP3 in different brain regions of CYS C-treated A53T SNCA transgenic mice. In vitro, we observed that CYS C-induced VEGF, a secreted protein, attenuated 6-OHDA-lesioned DAergic PC12 cell degeneration by regulating p-PKC-α/p-ERK1/2-Nurr1 signaling and inducing autophagy. VEGF-mediated angiogenesis was markedly enhanced in the conditioned media of 6-OHDA-lesioned PC12 cells with CYS C-overexpression, whereas blockage of autophagy in CYS C-overexpressing PC12 cells significantly downregulated VEGF expression and the associated angiogenesis. Our data indicate that CYS C displays dual neuronal-vascular functions, promoting PC12 cell survival and angiogenesis via regulating the level of secreted VEGF in NVUs. Our study provides evidence that may aid in the development of an alternative approach for the treatment of PD through modulation of CYS C-mediated neuronal-vascular pathways.

PMID: 28569795 [PubMed - indexed for MEDLINE]

Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

Tue, 03/06/2018 - 07:46
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Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

Methods Mol Biol. 2017;1598:101-115

Authors: Lista S, Zetterberg H, O'Bryant SE, Blennow K, Hampel H

Abstract
Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD.

PMID: 28508359 [PubMed - indexed for MEDLINE]

Rapid-eye-movement sleep-predominant central sleep apnea relieved by positive airway pressure: a case report.

Tue, 03/06/2018 - 07:46
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Rapid-eye-movement sleep-predominant central sleep apnea relieved by positive airway pressure: a case report.

Physiol Rep. 2017 May;5(9):

Authors: Jouett NP, Smith ML, Watenpaugh DE, Siddiqui M, Ahmad M, Siddiqui F

Abstract
Central Sleep Apnea (CSA) is characterized by intermittent apneas and hypopneas during sleep that result from absent central respiratory drive. CSA occurs almost exclusively during non-rapid-eye-movement (NREM) sleep due to enhanced neuronal ventilatory drive during REM sleep that makes central apneas highly unlikely to form. A 45-year-old obese African American female presented with co-existing Obstructive Sleep Apnea (OSA) and CSA, not in the form of mixed or complex sleep apnea. Peculiarly, her CSA occurred only during rapid-eye-movement (REM) sleep, which is exceedingly rare. The patient's CSA was resolved when appropriate positive airway pressure (PAP) was prescribed. Our patient remains stable and has reported significant benefit from PAP usage. We offer possible neuro-physiological mechanisms herein, including enhanced loop gain and/or malfunction or malformation of the pre-Botzinger nucleus or other neurological process, that could explain the unique findings of this case.

PMID: 28483860 [PubMed - indexed for MEDLINE]

Chronic intermittent hypoxia induces oxidative stress and inflammation in brain regions associated with early-stage neurodegeneration.

Tue, 03/06/2018 - 07:46
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Chronic intermittent hypoxia induces oxidative stress and inflammation in brain regions associated with early-stage neurodegeneration.

Physiol Rep. 2017 May;5(9):

Authors: Snyder B, Shell B, Cunningham JT, Cunningham RL

Abstract
Sleep apnea is a common comorbidity of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Previous studies have shown an association between elevated oxidative stress and inflammation with severe sleep apnea. Elevated oxidative stress and inflammation are also hallmarks of neurodegenerative diseases. We show increased oxidative stress and inflammation in a manner consistent with early stages of neurodegenerative disease in an animal model of mild sleep apnea. Male rats were exposed to 7 days chronic intermittent hypoxia (CIH) for 8 h/day during the light period. Following CIH, plasma was collected and tested for circulating oxidative stress and inflammatory markers associated with proinflammatory M1 or anti-inflammatory M2 profiles. Tissue punches from brain regions associated with different stages of neurodegenerative diseases (early stage: substantia nigra and entorhinal cortex; intermediate: hippocampus; late stage: rostral ventrolateral medulla and solitary tract nucleus) were also assayed for inflammatory markers. A subset of the samples was examined for 8-hydroxydeoxyguanosine (8-OHdG) expression, a marker of oxidative stress-induced DNA damage. Our results showed increased circulating oxidative stress and inflammation. Furthermore, brain regions associated with early-stage (but not late-stage) AD and PD expressed oxidative stress and inflammatory profiles consistent with reported observations in preclinical neurodegenerative disease populations. These results suggest mild CIH induces key features that are characteristic of early-stage neurodegenerative diseases and may be an effective model to investigate mechanisms contributing to oxidative stress and inflammation in those brain regions.

PMID: 28473320 [PubMed - indexed for MEDLINE]

A home-based exercise program for children with congenital heart disease following interventional cardiac catheterization: study protocol for a randomized controlled trial.

Tue, 03/06/2018 - 07:46
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A home-based exercise program for children with congenital heart disease following interventional cardiac catheterization: study protocol for a randomized controlled trial.

Trials. 2017 Jan 23;18(1):38

Authors: Du Q, Salem Y, Liu HH, Zhou X, Chen S, Chen N, Yang X, Liang J, Sun K

Abstract
BACKGROUND: Cardiac catheterization has opened an innovative treatment field for cardiac disease; this treatment is becoming the most popular approach for pediatric congenital heart disease (CHD) and has led to a significant growth in the number of children with cardiac catheterization. Unfortunately, based on evidence, it has been demonstrated that the majority of children with CHD are at an increased risk of "non-cardiac" problems. Effective exercise therapy could improve their functional status significantly. As studies identifying the efficacy of exercise therapy are rare in this field, the aims of this study are to (1) identify the efficacy of a home-based exercise program to improve the motor function of children with CHD with cardiac catheterization, (2) reduce parental anxiety and parenting burden, and (3) improve the quality of life for parents whose children are diagnosed with CHD with cardiac catheterization through the program.
METHODS/DESIGN: A total of 300 children who will perform a cardiac catheterization will be randomly assigned to two groups: a home-based intervention group and a control group. The home-based intervention group will carry out a home-based exercise program, and the control group will receive only home-based exercise education. Assessments will be undertaken before catheterization and at 1, 3, and 6 months after catheterization. Motor ability quotients will be assessed as the primary outcomes. The modified Ross score, cardiac function, speed of sound at the tibia, functional independence of the children, anxiety, quality of life, and caregiver burden of their parents or the main caregivers will be the secondary outcome measurements.
DISCUSSION: The proposed prospective randomized controlled trial will evaluate the efficiency of a home-based exercise program for children with CHD with cardiac catheterization. We anticipate that the home-based exercise program may represent a valuable and efficient intervention for children with CHD and their families.
TRIAL REGISTRATION: http://www.chictr.org.cn/ on: ChiCTR-IOR-16007762 . Registered on 13 January 2016.

PMID: 28115007 [PubMed - indexed for MEDLINE]

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