Recent Research Articles from UNTHSC

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

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 1 hour 51 min ago

Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.

Sun, 10/16/2016 - 07:31
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Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.

Oncotarget. 2016 Oct 11;:

Authors: Coder B, Wang W, Wang L, Wu Z, Zhuge Q, Su DM

Abstract
The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process. Cellular immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution - sources of chronic inflammation in the elderly (termed inflammaging), potentially induces an acceleration of brain aging and memory loss. In turn, aging of the brain via neuro-endocrine-immune network drives total body systemic aging, including that of the immune system. Therefore, immunotherapeutics including vaccination and "protective autoimmunity" provide promising means to rejuvenate neuro-inflammatory disorders and repair CNS acute injury and chronic neuro-degeneration. We review the current understanding and recent discoveries linking the aging immune system with CNS injury and neuro-degeneration. Additionally, we discuss potential recovery and rejuvenation strategies, focusing on targeting the aging T cell immune system in an effort to alleviate acute brain injury and chronic neuro-degeneration during aging, via the "thymus-inflammaging-neurodegeneration axis".

PMID: 27738345 [PubMed - as supplied by publisher]

A two-stage approach to genetic risk assessment in primary care.

Sun, 10/16/2016 - 07:31
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A two-stage approach to genetic risk assessment in primary care.

Breast Cancer Res Treat. 2016 Jan;155(2):375-83

Authors: Biswas S, Atienza P, Chipman J, Blackford AL, Arun B, Hughes K, Parmigiani G

Abstract
Genetic risk prediction models such as BRCAPRO are used routinely in genetic counseling for identification of potential BRCA1 and BRCA2 mutation carriers. They require extensive information on the counselee and her family history, and thus are not practical for primary care. To address this gap, we develop and test a two-stage approach to genetic risk assessment by balancing the tradeoff between the amount of information used and accuracy achieved. The first stage is intended for primary care wherein limited information is collected and analyzed using a simplified version of BRCAPRO. If the assessed risk is sufficiently high, more extensive information is collected and the full BRCAPRO is used (stage two: intended for genetic counseling). We consider three first-stage tools: BRCAPROLYTE, BRCAPROLYTE-Plus, and BRCAPROLYTE-Simple. We evaluate the two-stage approach on independent clinical data on probands with family history of breast and ovarian cancers, and BRCA genetic test results. These include population-based data on 1344 probands from Newton-Wellesley Hospital and mostly high-risk family data on 2713 probands from Cancer Genetics Network and MD Anderson Cancer Center. We use discrimination and calibration measures, appropriately modified to evaluate the overall performance of a two-stage approach. We find that the proposed two-stage approach has very limited loss of discrimination and comparable calibration as BRCAPRO. It identifies a similar number of carriers without requiring a full family history evaluation on all probands. We conclude that the two-stage approach allows for practical large-scale genetic risk assessment in primary care.

PMID: 26786860 [PubMed - indexed for MEDLINE]

Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway.

Sun, 10/16/2016 - 07:31
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Danshensu protects against ischemia/reperfusion injury and inhibits the apoptosis of H9c2 cells by reducing the calcium overload through the p-JNK-NF-κB-TRPC6 pathway.

Int J Mol Med. 2016 Jan;37(1):258-66

Authors: Meng Y, Li WZ, Shi YW, Zhou BF, Ma R, Li WP

Abstract
Ischemia-reperfusion (I/R) plays an important role in myocardial injury. In the present study, we aimed to examine the protective effects of Danshensu (DSS) against I/R injury and to elucidate the underlying mechanisms. For this purpose, H9c2 cells were cultured in hypoxic solution in a hypoxic incubator for 2 h, and then cultured in a high oxygen incubator for various periods of time and pre-treated with or without DSS, ammonium pyrrolidine dithiocarbamate (PDTC) or SP600125 [a c-Jun N-terminal kinase (JNK) inhibitor]. Cell apoptosis and cytosolic free Ca2+ ([Ca2+]i) levels were analyzed by flow cytometry. The protein expression levels of JNK, phosphorylated (p-)JNK, nuclear factor-κB (NF-κB) and transient receptor potential cation channel, subfamily C, member 6 (TRPC6) were measured by western blot analysis. The mRNA expression levels of JNK were measured by RT-qPCR. The results revealed that TRPC6 protein expression, the cell apoptotic rate and the [Ca2+]i levels increased in a time-dependent manner in the H9c2 cells following the induction of I/R injury. The apoptotic rate and TRPC6 protein expression decreased when the cells were treated with DSS prior to the induction of I/R injury. The knockdown of JNK expression by siRNA decreased the p-JNK and TRPC6 protein expression levels in the H9c2 cells subjected to I/R injury. The protein expression levels of p-JNK and NF-κB in the nucleus increased significantly when the H9c2 cells were subjected to I/R injury, whereas NF-κB expression in the cytoplasm decreased in a time‑dependent manner. However, p-JNK, NF-κB and TRPC6 protein expression, the [Ca2+]i level and cell apoptosis decreased when the H9c2 cells were pre-treated with DSS or SP600125. Therefore, our data suggest that DSS prevents myocardial I/R injury by inhibiting p-JNK activation and NF-κB translocation, which potentially upregulate TRPC6 expression, increase the [Ca2+]i level, and result in the apoptosis of H9c2 cells.

PMID: 26718129 [PubMed - indexed for MEDLINE]

Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas.

Fri, 10/14/2016 - 07:45
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Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas.

J Racial Ethn Health Disparities. 2016 Mar;3(1):46-54

Authors: Akinboro O, Ottenbacher A, Martin M, Harrison R, James T, Martin E, Murdoch J, Linnear K, Cardarelli K

Abstract
INTRODUCTION: Little is known about the awareness of public health professionals regarding racial and ethnic disparities in health in the United States of America (USA). Our study objective was to assess the awareness and perceptions of a group of public health workers in Texas regarding racial health disparities and their chief contributing causes.
METHODS: We surveyed public health professionals working on a statewide grant in Texas, who were participants at health disparities' training workshops. Multivariable logistic regression was employed in examining the association between the participants' characteristics and their perceptions of the social determinants of health as principal causes of health disparities.
RESULTS: There were 106 respondents, of whom 38 and 35 % worked in health departments and non-profit organizations, respectively. The racial/ethnic groups with the highest incidence of HIV/AIDS and hypertension were correctly identified by 63 and 50 % of respondents, respectively, but only 17, and 32 % were knowledgeable regarding diabetes and cancer, respectively. Seventy-one percent of respondents perceived that health disparities are driven by the major axes of the social determinants of health. Exposure to information about racial/ethnic health disparities within the prior year was associated with a higher odds of perceiving that social determinants of health were causes of health disparities (OR 9.62; 95 % CI 2.77, 33.41).
CONCLUSION: Among public health workers, recent exposure to information regarding health disparities may be associated with their perceptions of health disparities. Further research is needed to investigate the impact of such exposure on their long-term perception of disparities, as well as the equity of services and programs they administer.

PMID: 26896104 [PubMed - indexed for MEDLINE]

Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

Fri, 10/14/2016 - 07:45
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Systolic pressure response to voluntary apnea predicts sympathetic tone in obstructive sleep apnea as a clinically useful index.

Auton Neurosci. 2016 Jan;194:38-45

Authors: Jouett NP, Hardisty JM, Mason JR, Niv D, Romano JJ, Watenpaugh DE, Burk JR, Smith ML

Abstract
The present investigation tested the hypotheses that systolic arterial pressure (SAP) responses to voluntary apnea (a) serve as a surrogate of sympathetic nerve activity (SNA), (b) can distinguish Obstructive Sleep Apnea (OSA) patients from control subjects and (c) can document autonomic effects of treatment. 9 OSA and 10 control subjects were recruited in a laboratory study; 44 OSA subjects and 78 control subjects were recruited in a clinical study; and 21 untreated OSA subjects and 14 well-treated OSA subjects were recruited into a treatment study. Each subject performed hypoxic and room air voluntary apneas in triplicate. Muscle SNA (MSNA) and continuous AP were measured during each apnea in the laboratory study, while systolic arterial pressure (SAP) responses were measured continuously and by standard auscultation in the clinical and treatment studies. OSA subjects exhibited increased mean arterial pressure (MAP), SAP and MSNA responses to hypoxic apnea (all P<0.01) and the SAP response highly correlated with the MSNA response (R(2)=0.72, P<0.001). Clinical assessment confirmed that OSA subjects exhibited markedly elevated SAP responses (P<0.01), while treated OSA subjects had a decreased SAP response to apnea (P<0.04) compared to poorly treated subjects. These data indicate that (a) OSA subjects exhibit increased pressor and MSNA responses to apnea, and that (b) voluntary apnea may be a clinically useful assessment tool of autonomic dysregulation and treatment efficacy in OSA.

PMID: 26774324 [PubMed - indexed for MEDLINE]

Comparison of Hallux Interphalangeal Joint Arthrodesis Fixation Techniques: A Retrospective Multicenter Study.

Fri, 10/14/2016 - 07:45
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Comparison of Hallux Interphalangeal Joint Arthrodesis Fixation Techniques: A Retrospective Multicenter Study.

J Foot Ankle Surg. 2016 Jan-Feb;55(1):22-7

Authors: Thorud JC, Jolley T, Shibuya N, Lew E, Britt M, Butterfield T, Boike A, Hardy M, Brancheau SP, Motley T, Jupiter DC

Abstract
Few studies have investigated the complications that occur after hallux interphalangeal joint arthrodesis. The present study evaluated complications in 152 patients aged 18 to 80 years from 2005 to 2012 from 4 different academic institutions after hallux interphalangeal joint arthrodesis. Overall, 65.8% of the patients had ≥1 complication. Infections occurred in 16.5%, dehiscence in 12.5%, and reoperations in 27.0%. The clinical nonunion rate was ≥17.8%, and the radiographic nonunion rate was ≥13.8%. After logistic regression analysis, only the study site and peripheral neuropathy were associated with having ≥1 complication (p < .01 and p < .05, respectively). Single screw fixation compared with other fixation did not have a statistically significant influence on the postoperative complications. However, when fixation was expanded to 4 categories, single screw fixation had lower infection and reoperation rates than either crossed Kirschner wires or other fixation category but not compared with crossed screws on multivariate logistic regression analysis. Although additional studies are warranted, the findings from the present study might aid in both the prognosis of complications and the support of the use of a single screw over crossed Kirchner wire fixation in hallux interphalangeal joint arthrodesis.

PMID: 25960055 [PubMed - indexed for MEDLINE]

Principles of Ocular Pharmacology.

Thu, 10/13/2016 - 07:32
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Principles of Ocular Pharmacology.

Handb Exp Pharmacol. 2016 Oct 12;

Authors: Park Y, Ellis D, Mueller B, Stankowska D, Yorio T

Abstract
Recently, in a poll by Research America, a significant number of individuals placed losing their eyesight as having the greatest impact on their lives more so than other conditions, such as limb loss or memory loss. When they were also asked to rank which is the worst disease that could happen to them, blindness was ranked first by African-Americans and second by Caucasians, Hispanics, and Asians. Therefore, understanding the mechanisms of disease progression in the eye is extremely important if we want to make a difference in people's lives. In addition, developing treatment programs for these various diseases that could affect our eyesight is also critical. One of the most effective treatments we have is in the development of specific drugs that can be used to target various components of the mechanisms that lead to ocular disease. Understanding basic principles of the pharmacology of the eye is important if one seeks to develop effective treatments. As our population ages, the incidence of devastating eye diseases increases. It has been estimated that more than 65 million people suffer from glaucoma worldwide (Quigley and Broman. Br J Ophthalmol 90:262-267, 2006). Add to this the debilitating eye diseases of age-related macular degeneration, diabetic retinopathy, and cataract, the number of people effected exceeds 100 million. This chapter focuses on ocular pharmacology with specific emphasis on basic principles and outlining where in the various ocular sites are drug targets currently in use with effective drugs but also on future drug targets.

PMID: 27730396 [PubMed - as supplied by publisher]

Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.

Thu, 10/13/2016 - 07:32
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Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology.

Cancer Res. 2016 Oct 11;

Authors: Langevin HM, Keely P, Mao J, Hodge LM, Schleip R, Deng G, Hinz B, Swartz MA, de Valois BA, Zick S, Findley T

Abstract
Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 1-4. ©2016 AACR.

PMID: 27729327 [PubMed - as supplied by publisher]

Whole mitochondrial genome genetic diversity in an Estonian population sample.

Thu, 10/13/2016 - 07:32
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Whole mitochondrial genome genetic diversity in an Estonian population sample.

Int J Legal Med. 2016 Jan;130(1):67-71

Authors: Stoljarova M, King JL, Takahashi M, Aaspõllu A, Budowle B

Abstract
Mitochondrial DNA is a useful marker for population studies, human identification, and forensic analysis. Commonly used hypervariable regions I and II (HVI/HVII) were reported to contain as little as 25% of mitochondrial DNA variants and therefore the majority of power of discrimination of mitochondrial DNA resides in the coding region. Massively parallel sequencing technology enables entire mitochondrial genome sequencing. In this study, buccal swabs were collected from 114 unrelated Estonians and whole mitochondrial genome sequences were generated using the Illumina MiSeq system. The results are concordant with previous mtDNA control region reports of high haplogroup HV and U frequencies (47.4 and 23.7% in this study, respectively) in the Estonian population. One sample with the Northern Asian haplogroup D was detected. The genetic diversity of the Estonian population sample was estimated to be 99.67 and 95.85%, for mtGenome and HVI/HVII data, respectively. The random match probability for mtGenome data was 1.20 versus 4.99% for HVI/HVII. The nucleotide mean pairwise difference was 27 ± 11 for mtGenome and 7 ± 3 for HVI/HVII data. These data describe the genetic diversity of the Estonian population sample and emphasize the power of discrimination of the entire mitochondrial genome over the hypervariable regions.

PMID: 26289416 [PubMed - indexed for MEDLINE]

Roles of disease severity and post-discharge outpatient visits as predictors of hospital readmissions.

Wed, 10/12/2016 - 13:41

Roles of disease severity and post-discharge outpatient visits as predictors of hospital readmissions.

BMC Health Serv Res. 2016 Oct 10;16(1):564

Authors: Wang H, Johnson C, Robinson RD, Nejtek VA, Schrader CD, Leuck J, Umejiego J, Trop A, Delaney KA, Zenarosa NR

Abstract
BACKGROUND: Risks prediction models of 30-day all-cause hospital readmissions are multi-factorial. Severity of illness (SOI) and risk of mortality (ROM) categorized by All Patient Refined Diagnosis Related Groups (APR-DRG) seem to predict hospital readmission but lack large sample validation. Effects of risk reduction interventions including providing post-discharge outpatient visits remain uncertain. We aim to determine the accuracy of using SOI and ROM to predict readmission and further investigate the role of outpatient visits in association with hospital readmission.
METHODS: Hospital readmission data were reviewed retrospectively from September 2012 through June 2015. Patient demographics and clinical variables including insurance type, homeless status, substance abuse, psychiatric problems, length of stay, SOI, ROM, ICD-10 diagnoses and medications prescribed at discharge, and prescription ratio at discharge (number of medications prescribed divided by number of ICD-10 diagnoses) were analyzed using logistic regression. Relationships among SOI, type of hospital visits, time between hospital visits, and readmissions were also investigated.
RESULTS: A total of 6011 readmissions occurred from 55,532 index admissions. The adjusted odds ratios of SOI and ROM predicting readmissions were 1.31 (SOI: 95 % CI 1.25-1.38) and 1.09 (ROM: 95 % CI 1.05-1.14) separately. Ninety percent (5381/6011) of patients were readmitted from the Emergency Department (ED) or Urgent Care Center (UCC). Average time interval from index discharge date to ED/UCC visit was 9 days in both the no readmission and readmission groups (p > 0.05). Similar hospital readmission rates were noted during the first 10 days from index discharge regardless of whether post-index discharge patient clinic visits occurred when time-to-event analysis was performed.
CONCLUSIONS: SOI and ROM significantly predict hospital readmission risk in general. Most readmissions occurred among patients presenting for ED/UCC visits after index discharge. Simply providing early post-discharge follow-up clinic visits does not seem to prevent hospital readmissions.

PMID: 27724889 [PubMed - in process]

Evaluation of the Illumina(®) Beta Version ForenSeq™ DNA Signature Prep Kit for use in genetic profiling.

Wed, 10/12/2016 - 13:41
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Evaluation of the Illumina(®) Beta Version ForenSeq™ DNA Signature Prep Kit for use in genetic profiling.

Forensic Sci Int Genet. 2016 Jan;20:20-9

Authors: Churchill JD, Schmedes SE, King JL, Budowle B

Abstract
While capillary electrophoresis-based technologies have been the mainstay for human identity typing applications, there are limitations with this methodology's resolution, scalability, and throughput. Massively parallel sequencing (MPS) offers the capability to multiplex multiple types of forensically-relevant markers and multiple samples together in one run all at an overall lower cost per nucleotide than traditional capillary electrophoresis-based methods; thus, addressing some of these limitations. MPS also is poised to expand forensic typing capabilities by providing new strategies for mixture deconvolution with the identification of intra-STR allele sequence variants and the potential to generate new types of investigative leads with an increase in the overall number and types of genetic markers being analyzed. The beta version of the Illumina ForenSeq DNA Signature Prep Kit is a MPS library preparation method with a streamlined workflow that allows for targeted amplification and sequencing of 63 STRs and 95 identity SNPs, with the option to include an additional 56 ancestry SNPs and 22 phenotypic SNPs depending on the primer mix chosen for amplification, on the MiSeq desktop sequencer (Illumina). This study was divided into a series of experiments that evaluated reliability, sensitivity of detection, mixture analysis, concordance, and the ability to analyze challenged samples. Genotype accuracy, depth of coverage, and allele balance were used as informative metrics for the quality of the data produced. The ForenSeq DNA Signature Prep Kit produced reliable, reproducible results and obtained full profiles with DNA input amounts of 1ng. Data were found to be concordant with current capillary electrophoresis methods, and mixtures at a 1:19 ratio were resolved accurately. Data from the challenged samples showed concordant results with current DNA typing methods with markers in common and minimal allele drop out from the large number of markers typed on these samples. This set of experiments indicates the beta version of the ForenSeq DNA Signature Prep Kit is a valid tool for forensic DNA typing and warrants full validation studies of this MPS technology.

PMID: 26433485 [PubMed - indexed for MEDLINE]

Heat Shock Protein 47 Promotes Glioma Angiogenesis.

Wed, 10/12/2016 - 13:41
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Heat Shock Protein 47 Promotes Glioma Angiogenesis.

Brain Pathol. 2016 Jan;26(1):31-42

Authors: Wu ZB, Cai L, Lin SJ, Leng ZG, Guo YH, Yang WL, Chu YW, Yang SH, Zhao WG

Abstract
Heat shock protein 47 (HSP47) is a collagen-binding protein, which has been recently found to express in glioma vessels. However, the expression profile of HSP47 in glioma patients and the underlying mechanisms of HSP47 on glioma angiogenesis are not fully explored. In the current study, we found that expression of HSP47 in glioma vessels was correlated with the grades of gliomas. HSP47 knockdown by siRNAs significantly decreased cell viability in vitro and tumor volume in vivo; moreover, it reduced the microvessel density (MVD) by CD31 immunohistochemistry in vivo. HSP47 knockdown significantly inhibited tube formation, invasion and proliferation of human umbilical vein endothelial cells (HUVECs). Furthermore, conditional medium derived from HSP47 knockdown cells significantly inhibited HUVECs tube formation and migration, while it increased chemosensitivity of HUVECs cells to Avastin. Silencing of HSP47 decreased VEGF expression in glioma cells consistently, and reduced glioma vasculature. Furthermore, HSP47 promoted glioma angiogenesis through HIF1α-VEGFR2 signaling. The present study demonstrates that HSP47 promotes glioma angiogenesis and highlights the importance of HSP47 as an attractive therapeutic target of GBM.

PMID: 25758142 [PubMed - indexed for MEDLINE]

Pathways between physical activity and quality of life in African-American breast cancer survivors.

Fri, 10/07/2016 - 07:38
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Pathways between physical activity and quality of life in African-American breast cancer survivors.

Support Care Cancer. 2016 Oct 5;:

Authors: Meadows R, Bonner T, Dobhal M, Borra S, Killion JA, Paxton R

Abstract
INTRODUCTION: Several studies have indicated that the relationship between physical activity and quality of life is not directed but mediated through various pathways. The purpose of this study was to assess the role of cancer-related fatigue, disability, and functional status as potential mediators in African-American breast cancer survivors.
METHODS: African-American breast cancer survivors (N = 135, mean age = 63) aged 55 years and older participated in a web-based survey consisting of measures assessing physical activity, functional status, cancer-related fatigue, disability, quality of life, and sociodemographic and medical characteristics. Structural equation modeling was used to assess the structural relationships among the constructs.
RESULTS: The initial structural model fit the data and revealed a significant relationship between physical activity and quality of life (β = 0.34, P < 0.01). Subsequent structural models with proposed complementary and mediating paths of fatigue, function, and disability fit the data. The adjusted model indicated that physical activity was no longer associated with quality of life (β = 0.11, P > 0.05) and mediated through pathways of functional status and fatigue (total β = 0.16, P < 0.01). The final adjusted model accounted for 32 % of the variance in quality of life.
CONCLUSION: Our data suggest that physical activity may be indirectly related to quality of life through pathways consisting of fatigue and functional status. Further longitudinal studies are needed to test the pathways through which varying levels of physical activity influence cancer-related and quality of life outcomes in minority cancer survivors.

PMID: 27709312 [PubMed - as supplied by publisher]

Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Fri, 10/07/2016 - 07:38
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Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy.

Bioorg Med Chem Lett. 2016 Mar 1;26(5):1490-4

Authors: Acharya S, Rogers P, Krishnamoorthy RR, Stankowska DL, Dias HV, Yorio T

Abstract
Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy.

PMID: 26832784 [PubMed - indexed for MEDLINE]

CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

Fri, 10/07/2016 - 07:38
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CXCL8 as a Potential Therapeutic Target for HIV-Associated Neurocognitive Disorders.

Curr Drug Targets. 2016;17(1):111-21

Authors: Mamik MK, Ghorpade A

Abstract
Chemokine CXCL8 is a low molecular weight neutrophil chemoattractant implicated in various neurodegenerative disorders including Alzheimer's disease and stroke. Increased expression of CXCL8 has been reported in serum, plasma and brain of human immunodeficiency virus (HIV)-1 infected individuals with neurocognitive impairment, indicating its role in neuroinflammation associated with HIV-1 infection of the brain. Since chemokines are critical in eliciting immune responses in the central nervous system (CNS), CXCL8 is of particular importance for being one of the first chemokines described in the brain. Activation of astrocytes and microglia by HIV-1 and virus associated proteins results in production of this chemokine in the brain microenvironment. Consequently, CXCL8 exerts its effect on target cells via Gprotein coupled receptors CXCR1 and CXCR2. Neutrophils are the main target cells for CXCL8; however, microglia and neurons also express CXCR1/CXCR2 and therefore are important targets for CXCL8-mediated crosstalk. The objective of this review is to focus on CXCL8 production, signaling and regulation in neuronal and glial cells in response to HIV-1 infection. We highlight the role of HIV-1 secreted proteins such as trans-activator of transcription, envelope glycoprotein, negative regulatory factor and viral protein r in the regulation of CXCL8. We discuss dual role of CXCL8 in neurodegeneration as well as neuroprotection in the CNS. Thus, targeting CXCL8 through the development of CXCR1/CXCR2-based therapeutic strategies to either selectively agonize or antagonize receptors may be able to selectively promote neuroprotective and anti-inflammatory outcomes, leading to significant clinical applications in many neuroinflammatory CNS diseases, including HIV-associated neurocognitive disorders.

PMID: 26112047 [PubMed - indexed for MEDLINE]

Racial and ethnic differences in health behaviors among cancer survivors.

Fri, 10/07/2016 - 07:38
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Racial and ethnic differences in health behaviors among cancer survivors.

Am J Prev Med. 2015 Jun;48(6):729-36

Authors: Nayak P, Paxton RJ, Holmes H, Thanh Nguyen H, Elting LS

Abstract
INTRODUCTION: Previous studies of health behaviors of adult cancer survivors have not adequately examined racial and ethnic differences because of small sample sizes. A national data set was used to examine differences in health behaviors between cancer survivors and controls and between racial and ethnic groups among survivors.
METHODS: The study analyzed 2009 Behavioral Risk Factor Surveillance System survey data in 2012-2014. Descriptive statistics were used to examine differences in health behaviors between cancer survivors and controls aged 20-64 years. Multivariable analysis was conducted to examine associations between race/ethnicity (white, African American, Hispanic, Asian, or Native American) and health behaviors (BMI, fruit and vegetable consumption, physical activity, and smoking status) while adjusting for demographic and medical characteristics. Significance was set at p<0.01.
RESULTS: Compared with controls (n=245,283), cancer survivors (n=17,158) had higher prevalence rates for overweight/obese status (67% vs 65%); not meeting physical activity recommendations (53% vs 49%); and current smoking status (22% vs 20%). In the multivariable model, diet and smoking behavior differed across cancer status. African American (AOR=1.95) and Hispanic (AOR=2.06) survivors were more likely to have higher BMI than white survivors. African American survivors (AOR=1.6) were less likely to meet physical activity guidelines. Native American (AOR=3.08) and multiracial (AOR=1.74) survivors were more likely to be current smokers than non-Hispanic white survivors.
CONCLUSIONS: This study suggests that racial and ethnic differences exist in the adoption of recommended health behaviors; future research should identify factors to reduce these differences.

PMID: 25998923 [PubMed - indexed for MEDLINE]

Clinical response and relapse in patients with chronic low back pain following osteopathic manual treatment: results from the OSTEOPATHIC Trial.

Fri, 10/07/2016 - 07:38
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Clinical response and relapse in patients with chronic low back pain following osteopathic manual treatment: results from the OSTEOPATHIC Trial.

Man Ther. 2014 Dec;19(6):541-8

Authors: Licciardone JC, Aryal S

Abstract
Clinical response and relapse following a regimen of osteopathic manual treatment (OMT) were assessed in patients with chronic low back pain (LBP) within the OSTEOPATHIC Trial, a randomized, double-blind, sham-controlled study. Initial clinical response and subsequent stability of response, including final response and relapse status at week 12, were determined in 186 patients with high baseline pain severity (≥50 mm on a 100-mm visual analogue scale). Substantial improvement in LBP, defined as 50% or greater pain reduction relative to baseline, was used to assess clinical response at weeks 1, 2, 4, 6, 8, and 12. Sixty-two (65%) patients in the OMT group attained an initial clinical response vs. 41 (45%) patients in the sham OMT group (risk ratio [RR], 1.45; 95% confidence interval [CI], 1.11-1.90). The median time to initial clinical response to OMT in these patients was 4 weeks. Among patients with an initial clinical response prior to week 12, 13 (24%) patients in the OMT group vs. 18 (51%) patients in the sham OMT group relapsed (RR, 0.47; 95% CI, 0.26-0.83). Overall, 49 (52%) patients in the OMT group attained or maintained a clinical response at week 12 vs. 23 (25%) patients in the sham OMT group (RR, 2.04; 95% CI, 1.36-3.05). The large effect size for short-term efficacy of OMT was driven by stable responders who did not relapse.

PMID: 24965494 [PubMed - indexed for MEDLINE]

Alcohol Sales to Youth: Data from Rural Communities Within the Cherokee Nation.

Sat, 10/01/2016 - 07:37
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Alcohol Sales to Youth: Data from Rural Communities Within the Cherokee Nation.

Prev Sci. 2016 Jan;17(1):32-9

Authors: Lynne-Landsman SD, Kominsky TK, Livingston MD, Wagenaar AC, Komro KA

Abstract
Access to alcohol among individuals under 21 years of age continues to be a public health concern with approximately 5000 youth deaths attributable to alcohol each year (US Department of Health and Human Services 2007). To date, there is no research on youth access to alcohol from commercial sources within rural communities with large populations of Native American families. We evaluated commercial access to alcohol by underage-appearing female confederates in 4 rural towns within the Cherokee Nation, a non-reservation tribal jurisdiction that includes a high proportion of Native Americans embedded within a predominately White population. Alcohol purchase attempts were conducted approximately every 4 weeks on 10 occasions for a total of 997 alcohol purchase attempts. In addition to purchase attempt outcome, we collected data on characteristics of the outlets and clerks. Alcohol was sold to confederates without use of age identification on 23 % of all purchase attempts. Across repeated attempts, 76 % of outlets sold alcohol to a confederate at least once. Males and younger clerks were more likely to sell alcohol to the confederates. Grocery stores and gas stations were more likely to sell alcohol to the confederate than liquor stores, but this effect was no longer significant once seller age was accounted for in a multivariable model. Three out of 4 outlets sold alcohol to young-appearing buyers at least once across repeated attempts. Results reinforce the continuing need for regular enforcement of laws against selling alcohol to minors.

PMID: 26228479 [PubMed - indexed for MEDLINE]

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

Fri, 09/30/2016 - 07:32

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

Forensic Sci Int Genet. 2016 Sep 20;25:198-209

Authors: Wendt FR, Warshauer DH, Zeng X, Churchill JD, Novroski NM, Song B, King JL, LaRue BL, Budowle B

Abstract
Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The Nextera™ Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well-characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome.

PMID: 27685342 [PubMed - as supplied by publisher]

Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress.

Fri, 09/30/2016 - 07:32

Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress.

Sci Rep. 2016;6:34403

Authors: Gao H, Chen Z, Fu Y, Yang X, Weng R, Wang R, Lu J, Pan M, Jin K, McElroy C, Tang B, Xia Y, Wang Q

Abstract
The nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77. Nur77 activation further decreased cell viability, aggravated intracellular LDH release, intracellular Ca(2+), ROS levels, apoptosis, ER tress and, mitochondrial transmembrane potential (ΔΨm) decline. In addition, Nur77 activation significantly enhanced the efficiency of autophagy as indicated by an up-regulation of Beclin-1/LC-3 and downregulation of p62, and aggravated mitochondrial dysfunctions and ER stress as shown by increased HSP60/Cytochrome C (Cyt C) and CHOP-ATF3 levels respectively. These changes could be partially reversed by Nur77 knockdown. Moreover, Nur77 activation upregulated PINK1 and downregulated Parkin levels. We conclude that Nur77 exacerbates PC12 cell death at least partially by aggravating the mitochondrial impairment and ER stress and enhancing autophagy. We propose that Nur77 is likely a critical target in the PD therapy.

PMID: 27679973 [PubMed - as supplied by publisher]

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