Recent Research Articles from UNTHSC

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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: 39 min 40 sec ago

Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

Tue, 10/27/2015 - 07:29
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Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

Dement Geriatr Cogn Disord. 2014;38(5-6):300-9

Authors: Hall JR, Wiechmann AR, Johnson LA, Edwards M, Barber RC, Cunningham R, Singh M, O'Bryant SE

Abstract
BACKGROUND: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD.
METHODS: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed.
RESULTS: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC.
CONCLUSION: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.

PMID: 25011444 [PubMed - indexed for MEDLINE]

The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

Sat, 10/24/2015 - 07:33
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The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

Disabil Health J. 2015 Sep 25;

Authors: Cannell MB, Bouldin ED, Teigen K, Akhtar WZ, Andresen EM

Abstract
BACKGROUND: Research has demonstrated a clear association between cognitive decline and non-cognitive disability; however, all of these studies focus on disability as a correlate or result of some level of cognitive impairment or dysfunction. The relationship between disability and cognition is likely a complex one, that is currently incompletely described in the literature.
OBJECTIVES: Our objective was to estimate the prevalence of long-term, non-cognitive disability using a population-representative sample of adults aged 18 and older, and then estimate the association between long-term, non-cognitive disability and self-reported worsening memory.
METHODS: Using the 2009 Florida Behavioral Risk Factor Surveillance System (BRFSS), we measured the relationship between non-cognitive disability and worsening memory using multivariable logistic regression analysis weighted to account for the complex sampling design of the BRFSS. We also estimated the adjusted odds of worsening memory by disability severity, classified according to the types of assistance needed.
RESULTS: Approximately 18% (95% confidence interval = (16%, 19%)) of Floridians were living with a long-term, non-cognitive disability in 2009. Among adults with no disability during or prior to the last year, only 5% reported worsening memory. The proportion of Floridians reporting worsening memory increases with increasing severity of disability-related limitations. In a multivariable logistic regression model, odds of worsening memory increased significantly with severity of disability-related limitations.
CONCLUSIONS: These results highlight the association between non-cognitive disability and subsequent increased odds of worsening memory, independent of several other known risk factors, and a dose-response association with disability-related limitations.

PMID: 26493638 [PubMed - as supplied by publisher]

Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.

Sat, 10/24/2015 - 07:33
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Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.

J Neurophysiol. 2015 Feb 15;113(4):1165-74

Authors: Xu H, Boychuk JA, Boychuk CR, Uteshev VV, Smith BN

Abstract
The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study used transgenic mice that express enhanced green fluorescent protein (EGFP) under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brain stem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments.

PMID: 25429117 [PubMed - indexed for MEDLINE]

Y BALANCE TEST™ ANTERIOR REACH SYMMETRY AT THREE MONTHS IS RELATED TO SINGLE LEG FUNCTIONAL PERFORMANCE AT TIME OF RETURN TO SPORTS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.

Fri, 10/23/2015 - 07:29

Y BALANCE TEST™ ANTERIOR REACH SYMMETRY AT THREE MONTHS IS RELATED TO SINGLE LEG FUNCTIONAL PERFORMANCE AT TIME OF RETURN TO SPORTS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.

Int J Sports Phys Ther. 2015 Oct;10(5):602-11

Authors: Garrison JC, Bothwell JM, Wolf G, Aryal S, Thigpen CA

Abstract
BACKGROUND: Restoration of symmetrical strength, balance, and power following anterior cruciate ligament reconstruction (ACL-R) are thought to be important factors for successful return to sports. Little information is available regarding early rehabilitation outcomes and achieving suggested limb indices of 90% on functional performance measures at the time of return to sports (RTS).
HYPOTHESIS/PURPOSE: To examine the relationship between symmetry of the anterior reach of the Y Balance Test™ at 12 weeks and functional performance measures at time of return to sports after anterior cruciate ligament (ACL) reconstruction.
STUDY DESIGN: Retrospective Cohort.
METHODS: Forty subjects (mean ± SD age, 17.2 ± 3.8 years) who were in the process of rehabilitation following ACL reconstruction. Each subject volunteered and was enrolled in the study during physical therapy following ACL-R. Participants averaged two visits per week in physical therapy until the time of testing for RTS. The Y Balance Test™ was assessed at 12 weeks. Participants completed a battery of tests at RTS (6.4 ± 1.1 months) including triple hop distance (THD), single hop distance (SHD), isometric knee extension strength (KE), and the Vail Sport Test™. Side to side difference was calculated for the Y Balance Test™ anterior reach and limb symmetry indices (LSI) were computed for THD, SHD, and KE. Multiple regression models were used to study the relationship between variables at 12 weeks and RTS while controlling for age, gender, type of graft, and pain score. In addition, subjects were dichotomized based on a side-to-side Y Balance anterior reach difference into high risk (>4 cm) or low risk (≤4 cm) categories. A receiver operating characteristic (ROC) curve was used to identify individuals at 12 weeks who do not achieve 90% limb symmetry indices at time of RTS testing. .
RESULTS: A statistically significant association was seen between Y Balance ANT at 12 weeks and SHD at RTS (β = -1.46, p = 0.0005, R(2) = 0.395), THD at RTS (β = -1.08, p = 0.0011, R(2) = 0.354) and KE at RTS (β = -1.00, p = 0.0025, R(2) = 0.279) after adjusting for age, gender, type of graft and pain score at week 12. There was no significant association between Y Balance ANT at 12 weeks and Vail Sport Test at RTS (p = 0.273). ROC curves indicated that the Y Balance ANT at 12 weeks identified participants who did not achieve 90% LSI for the SHD (AUC = 0.82 p = 0.02) and THD (AUC=0.85, p = 0.01) at RTS with a sensitivity of 0.96 (SHD) and 0.92 (THD) respectively.
CONCLUSIONS: Participants following ACL-R who demonstrated > 4 cm Y Balance ANT deficits at 12 weeks on their involved limb did not tend to achieve 90% LSI for the SHD and THD at time of return to sports. The Y Balance ANT at 12 weeks and Vail Sport Test™ appear to measure different constructs following ACL-R.
LEVELS OF EVIDENCE: Level 3.

PMID: 26491610 [PubMed]

The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations.

Tue, 10/20/2015 - 07:29
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The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations.

J Prev Alzheimers Dis. 2014 Dec;1(3):181-202

Authors: Cavedo E, Lista S, Khachaturian Z, Aisen P, Amouyel P, Herholz K, Jack CR, Sperling R, Cummings J, Blennow K, O'Bryant S, Frisoni GB, Khachaturian A, Kivipelto M, Klunk W, Broich K, Andrieu S, de Schotten MT, Mangin JF, Lammertsma AA, Johnson K, Teipel S, Drzezga A, Bokde A, Colliot O, Bakardjian H, Zetterberg H, Dubois B, Vellas B, Schneider LS, Hampel H

Abstract
Alzheimer's disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group's revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard ("core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for "prodromal AD" and "mild cognitive impairment due to AD" include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in regions of interest, such as the hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) and advanced tractography as well as resting-state functional MRI provide useful additionally useful measures indicating the degree of fiber tract and neural network disintegration (structural, effective and functional connectivity) that may substantially contribute to early detection and the mapping of progression. These modalities require further standardization and validation. The use of molecular in vivo amyloid imaging agents (the fifth validated biomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection of early AD pathological processes and associated neurodegeneration. How to use, interpret, and disclose biomarker results drives the need for optimized standardization. Multimodal AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping fashion. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. AD biomarkers can be combined to increase accuracy or risk. A list of genetic risk factors is increasingly included in secondary prevention trials to stratify and select individuals at genetic risk of AD. Although most of these biomarker candidates are not yet qualified and approved by regulatory authorities for their intended use in drug trials, they are nonetheless applied in ongoing clinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patient stratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety. Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic, electrophysiological, and neuroimaging markers for use in clinical trials are being developed. The current state-of-the-art and future perspectives on both biological and neuroimaging derived biomarker discovery and development as well as the intended application in prevention trials is outlined in the present publication.

PMID: 26478889 [PubMed - as supplied by publisher]

Effect of Posterior Tibial Slope on Flexion and Anterior-Posterior Tibial Translation in Posterior Cruciate-Retaining Total Knee Arthroplasty.

Tue, 10/20/2015 - 07:29
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Effect of Posterior Tibial Slope on Flexion and Anterior-Posterior Tibial Translation in Posterior Cruciate-Retaining Total Knee Arthroplasty.

J Arthroplasty. 2015 Aug 29;

Authors: Chambers AW, Wood AR, Kosmopoulos V, Sanchez HB, Wagner RA

Abstract
Reduced posterior tibial slope (PTS) and posterior tibiofemoral translation (PTFT) in posterior cruciate-retaining (PCR) total knee arthroplasty (TKA) may result in suboptimal flexion. We evaluated the relationship between PTS, PTFT, and total knee flexion after PCR TKA in a cadaveric model. We performed a balanced PCR TKA using 9 transfemoral cadaver specimens and changed postoperative PTS in 1° increments. We measured maximal flexion and relative PTFT at maximal flexion. We determined significant changes in flexion and PTFT as a function of PTS. Findings showed an average increase in flexion of 2.3° and average PTFT increase of 1mm per degree of PTS increase when increasing PTS from 1° to 4° (P<.05). Small initial increases in PTS appear to significantly increase knee flexion and PTFT.

PMID: 26476469 [PubMed - as supplied by publisher]

The structural basis of an NADP⁺-independent dithiol oxidase in FK228 biosynthesis.

Tue, 10/20/2015 - 07:29
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The structural basis of an NADP⁺-independent dithiol oxidase in FK228 biosynthesis.

Sci Rep. 2014;4:4145

Authors: Li J, Wang C, Zhang ZM, Cheng YQ, Zhou J

Abstract
The disulfide bond is unusual in natural products and critical for thermal stability, cell permeability and bioactivity. DepH from Chromobacterium violaceum No. 968 is an FAD-dependent enzyme responsible for catalyzing the disulfide bond formation of FK228, an anticancer prodrug approved for the treatment of cutaneous T-cell lymphoma. Here we report the crystal structures of DepH and DepH complexed with a substrate analogue S,S'-dimethyl FK228 at 1.82 Å and 2.00 Å, respectively. Structural and biochemical analyses revealed that DepH, in contrast to the well characterized low molecular weight thioredoxin reductases (LMW TrxRs), is an NADP(+)-independent dithiol oxidase. DepH not only lacks a conserved GGGDXAXE motif necessary for NADP(+) binding in the canonical LMW TrxRs, but also contains a 11-residue sequence which physically impedes the binding of NADP(+). These observations explain the difference between NADP(+)-independent small molecule dithiol oxidases and NADP(+)-dependent thioredoxin reductases and provide insights for understanding the catalytic mechanism of dithiol oxidases involved in natural product biosynthesis.

PMID: 24553401 [PubMed - indexed for MEDLINE]

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