Recent Research Articles from UNTHSC

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

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Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats.

Wed, 12/25/2019 - 05:56
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Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats.

Drug Alcohol Depend. 2019 06 01;199:50-58

Authors: Gatch MB, Dolan SB, Forster MJ

Abstract
BACKGROUND: The development of novel synthetic psychoactive substances continues to accelerate. There are little or no data on the pharmacological mechanisms, behavioral effects, or abuse liability of many of the newer compounds, despite increasing reports of severe adverse effects in recreational users.
METHODS: The current study investigated the discriminative stimulus and locomotor stimulant effects of a group of synthetic cathinone analogs: N-ethylpentylone, dimethylone, dibutylone, clephedrone, 3',4'-tetramethylene-α-pyrrolidinovalerophenone (TH-PVP). Locomotor activity was assessed in an open-field assay using Swiss-Webster mice. Discriminative stimulus effects were assessed in Sprague-Dawley rats trained to discriminate either cocaine, methamphetamine or MDMA from vehicle.
RESULTS: N-Ethylpentylone, dimethylone, dibutylone and clephedrone increased locomotor activity. Maximal effects were similar among the test compounds. Relative potencies were: methamphetamine > N-ethylpentylone > clephedrone > dimethylone > MDMA > cocaine > dibutylone. TH-PVP dose-dependently depressed locomotor activity. N-Ethylpentylone, dimethylone, dibutylone and clephedrone substituted fully for the discriminative stimulus effects of methamphetamine. N-Ethylpentylone, dibutylone and clephedrone fully substituted for cocaine, whereas dimethylone produced a maximum of 67% drug-appropriate responding. Dimethylone, dibutylone and clephedrone fully substituted for MDMA, whereas N-ethylpentylone produced only 50% drug-appropriate responding. TH-PVP produced a maximum of 38% methamphetamine-appropriate responding, 50% cocaine-appropriate responding, and less than 1% MDMA-appropriate responding.
CONCLUSIONS: These data provide initial evidence that the novel psychoactive substances N-ethylpentylone, dimethylone, dibutylone, and clephedrone demonstrate potential for abuse as psychostimulants and/or club drugs, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of methamphetamine, cocaine and/or MDMA. TH-PVP has minimal activity in the assays tested and may have little or no abuse liability.

PMID: 30986635 [PubMed - indexed for MEDLINE]

Limited Intragenerational Mobility of Surgical Caseload of Iowa Hospitals.

Tue, 12/24/2019 - 05:41
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Limited Intragenerational Mobility of Surgical Caseload of Iowa Hospitals.

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

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

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

PMID: 31104154 [PubMed - indexed for MEDLINE]

Intracranial atherosclerotic disease.

Tue, 12/24/2019 - 05:41
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Intracranial atherosclerotic disease.

Neurobiol Dis. 2019 04;124:118-132

Authors: Wang Y, Meng R, Liu G, Cao C, Chen F, Jin K, Ji X, Cao G

Abstract
Intracranial atherosclerosis (ICAS) is a progressive pathological process that causes progressive stenosis and cerebral hypoperfusion and is a major cause of stroke occurrence and recurrence around the world. Multiple factors contribute to the development of ICAS. Angiography imaging techniques can improve the diagnosis of and the selection of appropriate treatment regimens for ICAS. Neither aggressive medication nor endovascular interventions can eradicate stroke recurrence in patients with ICAS. Non-pharmacological therapies such as remote ischemic conditioning and hypothermia are emerging. Comprehensive therapy with medication in combination with endovascular intervention and/or non-pharmacological treatment may be a potential strategy for ICAS treatment in the future. We summarized the epidemiology, pathophysiological mechanisms, risk factors, biomarkers, imaging and management of ICAS.

PMID: 30439443 [PubMed - indexed for MEDLINE]

Analogues of Arylamide Phenylpiperazine Ligands To Investigate the Factors Influencing D3 Dopamine Receptor Bitropic Binding and Receptor Subtype Selectivity.

Tue, 12/24/2019 - 05:41
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Analogues of Arylamide Phenylpiperazine Ligands To Investigate the Factors Influencing D3 Dopamine Receptor Bitropic Binding and Receptor Subtype Selectivity.

ACS Chem Neurosci. 2018 12 19;9(12):2972-2983

Authors: Hayatshahi HS, Xu K, Griffin SA, Taylor M, Mach RH, Liu J, Luedtke RR

Abstract
We have previously reported on the ability of arylamide phenylpiperazines to bind selectively to the D3 versus the D2 dopamine receptor subtype. For these studies, we used LS-3-134 as the prototypic arylamide phenylpiperazine ligand because it binds with high affinity at D3 dopamine receptor (0.17 nM) and exhibits >150-fold D3 vs D2 receptor binding selectivity. Our goal was to investigate how the composition and size of the nonaromatic ring structure at the piperazine position of substituted phenylpiperazine analogues might influence binding affinity at the human D2 and D3 dopamine receptors. Two factors were identified as being important for determining the binding affinity of bitropic arylamide phenylpiperazines at the dopamine D3 receptor subtype. One factor was the strength of the salt bridge between the highly conserved residue Asp3.32 with the protonated nitrogen of the nonaromatic ring at the piperazine position. The second factor was the configuration of the unbound ligand in an aqueous solution. These two factors were found to be related to the logarithm of the affinities using a simple correlation model, which could be useful when designing high affinity subtype selective bitropic ligands. While this model is based upon the interaction of arylamide phenylpiperazines with the D2 and D3 D2-like dopamine receptor subtypes, it provides insights into the complexity of the factors that define a bitropic mode of the binding at GPCRs.

PMID: 30010318 [PubMed - indexed for MEDLINE]

10β,17α-Dihydroxyestra-1,4-dien-3-one: A Bioprecursor Prodrug Preferentially Producing 17α-Estradiol in the Brain for Targeted Neurotherapy.

Tue, 12/24/2019 - 05:41
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10β,17α-Dihydroxyestra-1,4-dien-3-one: A Bioprecursor Prodrug Preferentially Producing 17α-Estradiol in the Brain for Targeted Neurotherapy.

ACS Chem Neurosci. 2018 11 21;9(11):2528-2533

Authors: Prokai-Tatrai K, Nguyen V, Prokai L

Abstract
Uterotrophic effect of 17α-estradiol, the C17 epimer of the main human estrogen 17β-estradiol, was shown to manifest in animal models at doses lower than those necessary for central outcome raising concerns about its potential to treat maladies of the central nervous system. We introduce here 10β,17α-dihydroxyestra-1,4-dien-3-one (α-DHED) that acts as a bioprecursor prodrug producing 17α-estradiol with remarkable selectivity to the brain and, therefore, without appreciable exposure of the periphery to the parent steroid. This distinguishing feature of α-DHED is shown by using an estrogen-responsive mouse model with complementary LC-MS/MS measurement of drug contents in target tissues. Our data warrant further research to fully establish the potential of α-DHED for a safe and efficacious 17α-estradiol-based neurotherapy.

PMID: 29843514 [PubMed - indexed for MEDLINE]

A novel autosomal recessive lipodystrophy syndrome due to homozygous LMNA variant.

Sat, 12/21/2019 - 07:36
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A novel autosomal recessive lipodystrophy syndrome due to homozygous LMNA variant.

J Med Genet. 2019 Dec 19;:

Authors: Patni N, Hatab S, Xing C, Zhou Z, Quittner C, Garg A

Abstract
BACKGROUND: Despite major advances in understanding the molecular basis of various genetic lipodystrophy syndromes, some rare patients still remain unexplained.
CASES: We report a novel autosomal recessive lipodystrophy affecting two sisters aged 17 and 19 years and characterised by early onset intellectual disability, and subsequent development of near-generalised loss of subcutaneous fat with diabetes mellitus, extreme hypertriglyceridemia, hepatic steatosis, short stature, clinodactyly, joint contractures, leiomyoma of uterus and cataracts in childhood. The lipodystrophy was more pronounced in the upper and lower extremities, and there was no associated muscular hypertrophy. Using whole exome sequencing in this consanguineous Hispanic pedigree, we report disease-causing homozygous p.Arg545His LMNA variant in the affected subjects, and confirm the lack of pathogenic variants in other known lipodystrophy genes. The mother and a younger brother were both heterozygous for p.Arg545His LMNA variant and were overweight with acanthosis nigricans without any evidence of lipodystrophy. Our patients are distinct from previously reported autosomal recessive lipodystrophy syndromes and have no overlap with other autosomal recessive laminopathies, including mandibuloacral dysplasia, Emery-Dreifuss muscular dystrophy and Charcot-Marie-Tooth neuropathy.
CONCLUSION: Our report of this unusual familial generalised lipodystrophy syndrome adds to the pleiotropy associated with biallelic autosomal recessive LMNA variants.

PMID: 31857427 [PubMed - as supplied by publisher]

Evaluation of mitogenome sequence concordance, heteroplasmy detection, and haplogrouping in a worldwide lineage study using the Precision ID mtDNA Whole Genome Panel.

Fri, 12/20/2019 - 07:21
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Evaluation of mitogenome sequence concordance, heteroplasmy detection, and haplogrouping in a worldwide lineage study using the Precision ID mtDNA Whole Genome Panel.

Forensic Sci Int Genet. 2019 09;42:244-251

Authors: Strobl C, Churchill Cihlar J, Lagacé R, Wootton S, Roth C, Huber N, Schnaller L, Zimmermann B, Huber G, Lay Hong S, Moura-Neto R, Silva R, Alshamali F, Souto L, Anslinger K, Egyed B, Jankova-Ajanovska R, Casas-Vargas A, Usaquén W, Silva D, Barletta-Carrillo C, Tineo DH, Vullo C, Würzner R, Xavier C, Gusmão L, Niederstätter H, Bodner M, Budowle B, Parson W

Abstract
The emergence of Massively Parallel Sequencing technologies enabled the analysis of full mitochondrial (mt)DNA sequences from forensically relevant samples that have, so far, only been typed in the control region or its hypervariable segments. In this study, we evaluated the performance of a commercially available multiplex-PCR-based assay, the Precision ID mtDNA Whole Genome Panel (Thermo Fisher Scientific), for the amplification and sequencing of the entire mitochondrial genome (mitogenome) from even degraded forensic specimens. For this purpose, more than 500 samples from 24 different populations were selected to cover the vast majority of established superhaplogroups. These are known to harbor different signature sequence motifs corresponding to their phylogenetic background that could have an effect on primer binding and, thus, could limit a broad application of this molecular genetic tool. The selected samples derived from various forensically relevant tissue sources and were DNA extracted using different methods. We evaluated sequence concordance and heteroplasmy detection and compared the findings to conventional Sanger sequencing as well as an orthogonal MPS platform. We discuss advantages and limitations of this approach with respect to forensic genetic workflow and analytical requirements.

PMID: 31382159 [PubMed - indexed for MEDLINE]

Massively parallel sequence data of 31 autosomal STR loci from 496 Spanish individuals revealed concordance with CE-STR technology and enhanced discrimination power.

Fri, 12/20/2019 - 07:21
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Massively parallel sequence data of 31 autosomal STR loci from 496 Spanish individuals revealed concordance with CE-STR technology and enhanced discrimination power.

Forensic Sci Int Genet. 2019 09;42:49-55

Authors: Barrio PA, Martín P, Alonso A, Müller P, Bodner M, Berger B, Parson W, Budowle B, DNASEQEX Consortium

Abstract
This study reports Short Tandem Repeat (STR) sequence-based allele data from 496 Spanish individuals across 31 autosomal STR (auSTR) loci included in the Precision ID GlobalFiler™ NGS STR Panel v2: D12S391, D13S317, D8S1179, D21S11, D3S1358, D5S818, D1S1656, D2S1338, vWA, D2S441, D5S2800, D7S820, D16S539, D6S474, D12ATA63, D4S2408, D6S1043, D19S433, D14S1434, CSF1PO, D10S1248, D18S51, D1S1677, D22S1045, D2S1776, D3S4529, FGA, Penta D, Penta E, TH01 and TPOX. The sequence of each allele was aligned to the reference sequence GRCh37 (hg19) and formatted according to the guidance of the International Society for Forensic Genetics. A subset of 221 samples was evaluated for testing concordance with allele calls derived from CE-based analysis using PowerPlex Fusion 6C, and there was 99.95% allele concordance. Twenty-five out of 31 auSTR loci showed an increased number of alleles due to repeat region sequence variation and/or single nucleotide polymorphisms (SNP) residing in the flanking regions. A total of 18 loci showed increased observed heterozygosity due to sequence variation; the loci exhibiting the greatest increase were: D13S317 (12% points), D5S818 (10% points), D8S1179 (7% points), D3S1358 (7% points), and D21S11 (6% points). The combined match probability decreased from 2.022E-24 (length-based data) to 1.042E-27 (sequence-based data) for the 20 CODIS core STR loci. The combined match probability (sequence-based data) for the 31 STR loci studied was 4.777E-40. The combined typical paternity index increased from 1.118E + 12 to 8.179E + 13 using length and sequence-based data, respectively. This Spanish population study performed in the framework of the EU-funded DNASEQEX project is expected to provide STR sequence-based allele frequencies for forensic casework and support implementation of massively parallel sequencing (MPS) technology in forensic laboratories.

PMID: 31252251 [PubMed - indexed for MEDLINE]

Photophysical properties of 2-Phenylindole in poly (vinyl alcohol) film at room temperature. Enhanced phosphorescence anisotropy with direct triplet state excitation.

Thu, 12/19/2019 - 06:32
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Photophysical properties of 2-Phenylindole in poly (vinyl alcohol) film at room temperature. Enhanced phosphorescence anisotropy with direct triplet state excitation.

Methods Appl Fluoresc. 2019 Dec 18;:

Authors: Gryczynski Z, Kimball J, Fudala R, Chavez JL, Ceresa L, Szabelski M, Borejdo J, Gryczynski I

Abstract
We report the spectral properties of 2-Phenylindole embedded in rigid poly (vinyl alcohol) film. The 2-Phenylindole-doped PVA film shows relatively strong and structured fluorescence with a maximum at 370 nm and surprisingly strong room temperature phosphorescence with an emission maximum of about 500 nm. The dye is highly immobilized in the polymer matrix, thus presenting high fluorescence anisotropy in an isotropic film of about 0.3 at room temperature. The 2-Phenylindole phosphorescence excited in the usual way through the electronic singlet state excitation (S0→S1 absorption) results in a very low, near zero anisotropy. We now report that we can directly excite the dye to the triplet state T1 and observe high phosphorescence anisotropy similar to the fluorescence anisotropy. The extinction coefficient for S0→T1 absorption in the PVA matrix is unusually high- only about 3 orders of magnitude lower than S0→S1 absorption. We consider this direct excitation to indole's triplet state a very significant finding that may lead to many practical applications. The unusually long-wavelength of excitation around 400 nm, much above typical UV absorption, results in a high phosphorescence anisotropy. This provides a new way to study rotational motion of larger biological objects in the microsecond time scale not accessible through typical fluorescence studies.

PMID: 31851960 [PubMed - as supplied by publisher]

Hybrid Compound SA-2 is Neuroprotective in Animal Models of Retinal Ganglion Cell Death.

Wed, 12/18/2019 - 06:15
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Hybrid Compound SA-2 is Neuroprotective in Animal Models of Retinal Ganglion Cell Death.

Invest Ophthalmol Vis Sci. 2019 07 01;60(8):3064-3073

Authors: Stankowska DL, Dibas A, Li L, Zhang W, Krishnamoorthy VR, Chavala SH, Nguyen TP, Yorio T, Ellis DZ, Acharya S

Abstract
Purpose: Determine the toxicity, bioavailability in the retina, and neuroprotective effects of a hybrid antioxidant-nitric oxide donor compound SA-2 against oxidative stress-induced retinal ganglion cell (RGC) death in neurodegenerative animal models.
Methods: Optic nerve crush (ONC) and ischemia reperfusion (I/R) injury models were used in 12-week-old C57BL/6J mice to mimic conditions of glaucomatous neurodegeneration. Mice were treated intravitreally with either vehicle or SA-2. Retinal thickness was measured by spectral-domain optical coherence tomography (SD-OCT). The electroretinogram and pattern ERG (PERG) were used to assess retinal function. RGC survival was determined by counting RBPMS-positive RGCs and immunohistochemical analysis of superoxide dismutase 1 (SOD1) levels was carried out in the retina sections. Concentrations of SA-2 in the retina and choroid were determined using HPLC and MS. In addition, the direct effect of SA-2 treatment on RGC survival was assessed in ex vivo rat retinal explants under hypoxic (0.5% O2) conditions.
Results: Compound SA-2 did not induce any appreciable change in retinal thickness, or in a- or b-wave amplitude in naive animals. SA-2 was found to be bioavailable in both the retina and choroid after a single intravitreal injection (2% wt/vol). An increase in SOD1 levels in the retina of mice subjected to ONC and SA-2 treatment, suggests an enhancement in antioxidant activity. SA-2 provided significant (P < 0.05) RGC protection in all three of the tested RGC injury models in rodents. PERG amplitudes were significantly higher in both I/R and ONC mouse eyes following SA-2 treatment (P ≤ 0.001) in comparison with the vehicle and control groups.
Conclusions: Compound SA-2 was effective in preventing RGC death and loss of function in three different rodent models of acute RGC injury: ONC, I/R, and hypoxia.

PMID: 31348824 [PubMed - indexed for MEDLINE]

Age- and body weight-dependent association between sleep duration and hypertension in US adults: findings from the 2014-2017 National Health Interview Survey.

Wed, 12/18/2019 - 06:15
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Age- and body weight-dependent association between sleep duration and hypertension in US adults: findings from the 2014-2017 National Health Interview Survey.

Sleep Health. 2019 10;5(5):509-513

Authors: Okunowo O, Orimoloye HT, Bakre SA, Njesada NS, Solomon A

Abstract
OBJECTIVES: Previous studies have confirmed the relationship between sleep duration and hypertension. However, there are unanswered questions on how this relationship is affected by age and body mass index (BMI). This study examined the association between sleep duration and hypertension in US adults and evaluated interaction by age and BMI.
DESIGN: Nationwide, population-based, cross-sectional survey.
SETTING: National Health Interview Survey (NHIS), 2014 to 2017.
PARTICIPANTS: Adult participants aged 18 years or older (n = 130,139).
MEASUREMENTS: Sleep duration, hypertension, age, and BMI status were assessed based on self-reported survey responses. Odds ratios (ORs) and 95% confidence intervals (CIs) for sleep duration-hypertension associations were estimated by logistic regression, adjusting for potential confounders.
RESULTS: The proportion of participants who reported sleeping less than 7 hours (short sleepers) and more than 9 hours (long sleepers) per night was 32% and 4%, respectively. In adjusted analysis, short sleepers had higher odds of hypertension (OR: 1.54, 95% CI: 1.10-2.17). Although not statistically significant, long sleepers also had higher odds of hypertension (OR: 1.28, 95% CI: 0.80-2.05). In stratified analyses by age and BMI, the association between short sleep and hypertension was especially notable in adults aged 18-44 years (OR: 1.25, 95% CI: 1.16-1.35) and adults with normal weight (OR: 1.21, 95% CI: 1.11-1.33).
CONCLUSIONS: Short sleep is associated with increased odds of hypertension among American adults and this relationship is dependent on age and BMI.

PMID: 31302069 [PubMed - indexed for MEDLINE]

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5.

Wed, 12/18/2019 - 06:15
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Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5.

Molecules. 2019 Jun 30;24(13):

Authors: Mangoni AA, Eynde JJV, Jampilek J, Hadjipavlou-Litina D, Liu H, Reynisson J, Sousa ME, Gomes PAC, Prokai-Tatrai K, Tuccinardi T, Sabatier JM, Luque FJ, Rautio J, Karaman R, Vasconcelos MH, Gemma S, Galdiero S, Hulme C, Collina S, Gütschow M, Kokotos G, Siciliano C, Capasso R, Agrofoglio LA, Ragno R, Muñoz-Torrero D

Abstract
Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes is a series of Editorials which is published on a biannual basis by the Editorial Board of the Medicinal Chemistry section of the journal Molecules [...].

PMID: 31262039 [PubMed - indexed for MEDLINE]

Improvement in mental health following total hip arthroplasty: the role of pain and function.

Wed, 12/18/2019 - 06:15
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Improvement in mental health following total hip arthroplasty: the role of pain and function.

BMC Musculoskelet Disord. 2019 Jun 29;20(1):307

Authors: Nguyen UDT, Perneger T, Franklin PD, Barea C, Hoffmeyer P, Lübbeke A

Abstract
BACKGROUND: Mental health has been shown to improve after total hip arthroplasty (THA). Little is known about the role of pain and function in this context. We assessed whether change in mental health was associated with improvement in pain and function 1 year post-surgery.
METHODS: This prospective study included patients enrolled in a THA registry from 2010 to 2014. We examined the mental component score (MCS) before and 1 year post-surgery, and 1-year change, in association with Western Ontario McMaster Universities (WOMAC) pain and function scores. All scores were normalized, ranging from 0 to 100 (larger score indicating better outcome). Analyses were adjusted for potential confounders.
RESULTS: Our study included 610 participants, of which 53% were women. Descriptive statistics are as follows: the average (SD) for age (years) was 68.5 (11.8), and for BMI was 26.9 (4.9). In addition, the MCS average (SD) at baseline was 44.7 (11.2), and at 1-year after THA was 47.5 (10.5). The average change from baseline to 1-year post-THA in MCS was 2.8 (95% CI: 1.9, 3.6), for an effect size of 0.26. As for the WOMAC pain score, the average change from baseline to 1-year post-THA was 44.2 (95%CI: 42.4, 46.0), for an effect size of 2.5. The equivalent change in WOMAC function was 38.1 (95% CI: 36.2, 40.0), for an effect size of 2.0. Results from multivariable analysis controlling for covariates showed that an improvement of 10 points in the 1-year change in pain score resulted in a 0.78 point (95%: CI 0.40, 1.26) increase in the 1-year change in MCS, whereas a 10-point improvement in the 1-year change in function was associated with a 0.94 point (95% CI: 0.56, 1.32) increase.
CONCLUSIONS: Mental health significantly improved from baseline to 1-year post-THA. Greater improvement in pain and function was associated with greater improvement in mental health 1 year post-THA.

PMID: 31253128 [PubMed - indexed for MEDLINE]

The Value of Home Health Physical Therapy.

Wed, 12/18/2019 - 06:15
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The Value of Home Health Physical Therapy.

Home Healthc Now. 2019 May/Jun;37(3):145-151

Authors: Collins TL, Yong KW, Marchetti MT, Miller KL, Booths B, Falvey JR

Abstract
The purpose of the Triple Aim is to improve population health, reduce healthcare costs, and improve the patient experience. These goals-to reduce cost while improving health outcomes and patient experiences have shifted utilization of services from other postacute care settings to the home. The purpose of this perspective article is to discuss how home healthcare services, and home physical therapy (PT) specifically, provide value to patients, caregivers, and payers to meet the goals of the Triple Aim. This article will substantiate the value of home PT and provide healthcare professionals with evidence-based information on the value of home PT.

PMID: 31058732 [PubMed - indexed for MEDLINE]

Vascular Depression and Cognition in Mexican Americans.

Wed, 12/18/2019 - 06:15
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Vascular Depression and Cognition in Mexican Americans.

Dement Geriatr Cogn Disord. 2019;47(1-2):68-78

Authors: Johnson LA, Large SE, Izurieta Munoz H, Hall JR, O'Bryant SE

Abstract
BACKGROUND: Mexican Americans are at increased risk of developing mild cognitive impairment (MCI) and Alzheimer's disease compared to non-Hispanic whites. This study sought to examine the relationship between vascular risk, depression, and cognition in Mexican American elders.
METHODS: Data from 470 (390 normal controls, 80 MCI patients) Mexican Americans enrolled in the Health and Aging Brain among Latino Elders (HABLE) study were used. The cardiovascular risk was assessed by the Framingham Risk Score. Cognition was assessed with a neuropsychological battery, and depression was assessed based on scores from the Geriatric Depression Scale (GDS). ANOVAs were utilized to determine the differences in neuropsychological scores of normal controls with and without depression and CVD risk (low vs. high). Follow-up logistic regression was conducted to determine MCI risk.
RESULTS: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance in Mexican Americans. Depressed women with high CVD risk were more likely to have executive dysfunction, language deficits, and poorer global cognition than nondepressed women with a high CVD risk. In Mexican American men, those with a high vascular risk and depression were more likely to have executive dysfunction and poorer immediate memory than the nondepressed high-risk group. Higher GDS scores (OR = 1.10; 95% CI 1.02-1.10, p = 0.001) and higher vascular risk scores (OR = 1.05; 95% CI 1.02-1.10, p = 0.001) significantly predicted MCI status in Mexican Americans.
CONCLUSION: The results of this study indicated that comorbid depression and a high CVD risk were associated with poorer cognitive performance and increased risk of MCI in Mexican Americans.

PMID: 30861514 [PubMed - indexed for MEDLINE]

NADPH Oxidase Mediates Membrane Androgen Receptor-Induced Neurodegeneration.

Wed, 12/18/2019 - 06:15
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NADPH Oxidase Mediates Membrane Androgen Receptor-Induced Neurodegeneration.

Endocrinology. 2019 04 01;160(4):947-963

Authors: Tenkorang MAA, Duong P, Cunningham RL

Abstract
Oxidative stress (OS) is a common characteristic of several neurodegenerative disorders, including Parkinson disease (PD). PD is more prevalent in men than in women, indicating the possible involvement of androgens. Androgens can have either neuroprotective or neurodamaging effects, depending on the presence of OS. Specifically, in an OS environment, androgens via a membrane-associated androgen receptor (mAR) exacerbate OS-induced damage. To investigate the role of androgens on OS signaling and neurodegeneration, the effects of testosterone and androgen receptor activation on the major OS signaling cascades, the reduced form of NAD phosphate (NADPH) oxidase (NOX)1 and NOX2 and the Gαq/inositol trisphosphate receptor (InsP3R), were examined. To create an OS environment, an immortalized neuronal cell line was exposed to H2O2 prior to cell-permeable/cell-impermeable androgens. Different inhibitors were used to examine the role of G proteins, mAR, InsP3R, and NOX1/2 on OS generation and cell viability. Both testosterone and DHT/3-O-carboxymethyloxime (DHT)-BSA increased H2O2-induced OS and cell death, indicating the involvement of an mAR. Furthermore, classical AR antagonists did not block testosterone's negative effects in an OS environment. Because there are no known antagonists specific for mARs, an AR protein degrader, ASC-J9, was used to block mAR action. ASC-J9 blocked testosterone's negative effects. To determine OS-related signaling mediated by mAR, this study examined NOX1, NOX2, Gαq. NOX1, NOX2, and the Gαq complex with mAR. Only NOX inhibition blocked testosterone-induced cell loss and OS. No effects of blocking either Gαq or G protein activation were observed on testosterone's negative effects. These results indicate that androgen-induced OS is via the mAR-NOX complex and not the mAR-Gαq complex.

PMID: 30811529 [PubMed - indexed for MEDLINE]

The shear complexity of insulin-stimulated vasodilatation.

Wed, 12/18/2019 - 06:15
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The shear complexity of insulin-stimulated vasodilatation.

J Physiol. 2019 01;597(1):11

Authors: Lalande S, Romero SA

PMID: 30447000 [PubMed - indexed for MEDLINE]

Supraciliary Microstent in Refractory Open-Angle Glaucoma: Two-Year Outcomes from the DUETTE Trial.

Wed, 12/18/2019 - 06:15
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Supraciliary Microstent in Refractory Open-Angle Glaucoma: Two-Year Outcomes from the DUETTE Trial.

J Ocul Pharmacol Ther. 2018 09;34(7):538-542

Authors: Garcìa-Feijoo J, Höh H, Uzunov R, Dickerson JE

Abstract
PURPOSE: The aim of the study was to report longer term (24-month) outcomes for primary open-angle glaucoma (POAG) patients refractory to medical therapy implanted with a supraciliary microstent (CyPass Micro-Stent, Alcon) in the DUETTE clinical study.
METHODS: Sixty-five eyes were enrolled in this multicenter single-arm trial. Enrolled patients had POAG and intraocular pressure (IOP) >21 mmHg at baseline on 1-4 ocular hypotensive medications. Microstent implantation was performed as stand-alone surgery in these phakic or pseudophakic patients through a standard clear corneal approach. IOP and the use of IOP-lowering medications were monitored in this 1-year extension beyond the 12-month primary endpoint.
RESULTS: Two-year follow-up visits were scheduled to confirm the 12-month results; safety data were obtained for 37 eyes of 35 patients. IOP at the end of the 24-month follow-up was 16.8 mmHg (n = 32), with a mean reduction of 7.7 mmHg from the baseline IOP of 24.5 mmHg (n = 65). Medication use was decreased from an average of 2.1 (baseline) to 1.5 at 24 months. The IOP and medication use at 24 months were consistent with the 12-month results (16.4 mmHg, 1.4 medications) reported previously. The adverse event profile remained as described for the first 12 months postimplantation.
CONCLUSIONS: Placement of a supraciliary microstent provides up to 24 months of effective IOP lowering for medication-refractory POAG patients while, on average, decreasing the requirement for ocular hypotensive medications.

PMID: 30074429 [PubMed - indexed for MEDLINE]

Consideration of future consequences as a moderator of the willingness-behavior relationship for young adult marijuana use and consequences.

Wed, 12/18/2019 - 06:15
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Consideration of future consequences as a moderator of the willingness-behavior relationship for young adult marijuana use and consequences.

Addict Behav. 2018 12;87:8-16

Authors: Lewis MA, Litt DM, King KM, Garcia TA, Waldron KA, Lee CM

Abstract
The Prototype Willingness Model is a dual-processing (i.e., intentional and socially reactive) health-risk behavior model. The socially reactive path includes behavioral willingness, descriptive normative perceptions, and favorable images of individuals who engage in health-risk behavior (prototype favorability) as important predictors of health behaviors. Individual differences (such as consideration of future consequences) may potentiate the effects of behavioral willingness on health-risk outcomes, such as marijuana use. Given limited research investigating marijuana use and the Prototype Willingness Model, the goals of the current study were: 1) examine consideration of future consequences and Prototype Willingness Model social reaction pathway variables in relation to behavioral willingness to use marijuana longitudinally; and 2) determine if consideration of future consequences moderated the behavioral willingness-marijuana use relation prospectively. Young adults (N = 769) from a larger longitudinal study completed baseline and 3 follow-up assessments (Months 3, 4, 5). Behavioral willingness was positively related to a higher likelihood of use, more days having used marijuana, and more consequences prospectively, over and above baseline use. Consideration of future consequences moderated the association between behavioral willingness and hours high in a typical week. These findings support the willingness-behavior association of the Prototype Willingness Model and preliminarily demonstrate consideration of future consequences' differential impact on behavioral willingness-future marijuana use relation. Intervention and prevention implications are discussed.

PMID: 29940391 [PubMed - indexed for MEDLINE]

Neutrophils Are More Effective than Monocytes at Phagosomal Containment and Killing of Listeria monocytogenes.

Sun, 12/15/2019 - 05:15
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Neutrophils Are More Effective than Monocytes at Phagosomal Containment and Killing of Listeria monocytogenes.

Immunohorizons. 2019 Dec 13;3(12):573-584

Authors: Okunnu BM, Berg RE

Abstract
Neutrophils and inflammatory monocytes are innate immune cells essential for protection during Listeria monocytogenes infection. Although certain functions have been generally assigned to each of the cells, similarities and differences in functions necessary for bacterial clearance have not previously been investigated. In the current study, phagocytosis, phagosomal containment, bacterial killing, and cytokine production by neutrophils and monocytes during L. monocytogenes infection were studied. Data obtained via in vitro studies show that neutrophils are more effective at L. monocytogenes uptake, phagosomal containment, and killing than monocytes. However, monocytes were found to be more effective at cytokine production during L. monocytogenes infection, in vivo. Additionally, the data demonstrated that neutrophils and monocytes are also capable of producing IL-1α, a cytokine that does not yet have a clearly defined role during infection with L. monocytogenes Furthermore, we were able to demonstrate a population of monocytes producing both TNF-α and IL-α, concurrently. This study highlights the multifunctional capabilities of neutrophils and monocytes, further adding to our knowledge of these innate immune cells during L. monocytogenes infection.

PMID: 31836639 [PubMed - in process]

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