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Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells.

Recent Research Articles from UNTHSC - Thu, 01/19/2017 - 07:35
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Tolfenamic acid-induced alterations in genes and pathways in pancreatic cancer cells.

Oncotarget. 2017 Jan 14;:

Authors: Sankpal UT, Goodison S, Jones-Pauley M, Hurtado M, Zhang F, Basha R

Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are being tested extensively for their role in the treatment and prevention of several cancers. Typically NSAIDs exhibit anti-tumor activities via modulation of cyclooxygenase (COX)-dependent mechanisms, however, an anti-cancer NSAID tolfenamic acid (TA) is believed to work through COX-independent pathways. Results from our laboratory and others have demonstrated the anti-cancer activity of TA in various cancer models including pancreatic cancer. TA has been shown to modulate certain cellular processes including, apoptosis, reactive oxygen species and signaling. In this study, molecular profiling was performed to precisely understand the mode of action of TA. Three pancreatic cancer cell lines, L3.6pl, MIA PaCa-2, and Panc1 were treated with TA (50 μM for 48 h) and the changes in gene expression was evaluated using the Affymetrix GeneChip Human Gene ST Array platform. Microarray results were further validated using quantitative PCR for seven genes altered by TA treatment in all three cell lines. Functional analysis of differentially expressed genes (2 fold increase or decrease, p < 0.05) using Ingenuity Pathway Analysis software, revealed that TA treatment predominantly affected the genes involved in cell cycle, cell growth and proliferation, and cell death and survival. Promoter analysis of the differentially expressed genes revealed that they are enriched for Sp1 binding sites, suggesting that Sp1 could be a major contributor in mediating the effect of TA. The gene expression studies identified new targets involved in TA's mode of action, while supporting the hypothesis about the association of Sp1 in TA mediated effects in pancreatic cancer.

PMID: 28099934 [PubMed - as supplied by publisher]

Enhancement of Pathologist's Routine Practice: Reuse of DNA Extracted from Immunostained Formalin-fixed Paraffin-embedded (FFPE) Slides in Downstream Molecular Analysis of Cancer.

Recent Research Articles from UNTHSC - Thu, 01/19/2017 - 07:35
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Enhancement of Pathologist's Routine Practice: Reuse of DNA Extracted from Immunostained Formalin-fixed Paraffin-embedded (FFPE) Slides in Downstream Molecular Analysis of Cancer.

Cancer Genomics Proteomics. 2016 09-10;13(5):399-406

Authors: Al-Attas A, Assidi M, Al-Maghrabi J, Dallol A, Schulten HJ, Abu-Elmagd M, Chaudhary A, Abuzenadah A, Budowle B, Buhmeida A, Al-Qahtani M

Abstract
BACKGROUND/AIM: To date, the conventional formalin-fixed, paraffin-embedded (FFPE) technique is the gold-standard for preserving histomorphology. Once FFPE tissues are stained, slides are routinely archived along with their blocks at biobanks/hospitals. However, the reuse of fixed and stained biospecimens as DNA source is not a common routine practice worldwide and, thus, indicates the need of studies to investigate the feasibility of extracting DNA from already immunohistochemistry (IHC) FFPE-stained slides and its possible reuse in subsequent downstream molecular analyses.
MATERIALS AND METHODS: FFPE IHC slides from colorectal cancer (CRC) patients were prepared and stored in the CEGMR Biobank. The workflow consists of digitalization of IHC stained slide's image, removing the slide cover-slip, crude dissection and DNA extraction. Following DNA quality assessment, mutation analysis of CTNNB1 and methylation profile of CDH1 were performed.
RESULTS: High-quality DNA was obtained allowing 60% concordance between CDH1 methylation and membranous E-cadherin expression pattern. Clean CTNNB1 DNA chromatograms with evenly-spaced peaks were observed.
CONCLUSION: This study is a proof of concept to recycle and reuse DNA from IHC stained slides with suitable concentration and integrity for further downstream molecular applications. These findings will enhance the pathologists' knowledge, attitudes and practices (KAP) towards the use of these biospecimens and support the implementation of this approach in clinical pathology practice. Therefore, the scientific community will benefit from the largest comprehensive database of human fully annotated FFPE biospecimens already available at their disposal in order to demystify the complexity and the heterogeneity of many challenging diseases and foster the transition towards precision medicine.

PMID: 27566658 [PubMed - indexed for MEDLINE]

Magnetic Resonance Imaging (MRI): Operative Findings Correlation in 229 Fistula-in-Ano Patients.

Recent Research Articles from UNTHSC - Wed, 01/18/2017 - 13:37
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Magnetic Resonance Imaging (MRI): Operative Findings Correlation in 229 Fistula-in-Ano Patients.

World J Surg. 2017 Jan 17;:

Authors: Garg P, Singh P, Kaur B

Abstract
BACKGROUND: To correlate the operative findings of patients with fistula-in-ano with preoperative MRI and quantify the information added with MRI.
METHODS: All consecutive fistula-in-ano patients operated between July 2013 and May 2015 were prospectively enrolled. Preoperative MRI was done in every patient. The details of tracts, internal opening and "complex parameters" (additional tract or additional internal opening, horseshoe tract, associated abscess and supralevator extension) found at surgery were compared to the findings determined by MRI.
RESULTS: A total of 229 patients (424 tracts) with mean age-49.0 ± 11.3 years were included. M/F 198/31. James hospital classification: Type I 58, II 20, III 49, IV 86 and V 16. The sensitivity and specificity of MRI in diagnosing fistula tracts were 98.8 and 99.7%, respectively, and in identifying internal opening were 97.7 and 98.6%, respectively. MRI added significant information in 46.7% (107/229) patients which was presence of additional tracts in 71 (66.3%), horseshoe tract in 63 (58.8%), supralevator extension in 16 (14.9%), unsuspected abscess in 11 (10.3%) and multiple internal openings in one patient (1%). The proportion of simple/complex fistula (based on history and clinical examination alone) was 32.8/67.2% which changed to 21.4/78.6% after the MRI scan. MRI added significant information about unsuspecting complex parameters which were missed on history and clinical examination in more than one-third (26/75: 34.6%) of simple fistulae and more than half (81/154: 52.5%) of already known complex fistulae.
CONCLUSIONS: MRI is highly accurate in diagnosing fistula-in-ano and added significant information about unsuspected complex parameters in over one-third (34.6%) of simple and in half (52.5%) of complex fistula-in-ano.

PMID: 28097414 [PubMed - as supplied by publisher]

Prevalence and Predictors of Hypertension in the Labor Force Population in China: Results from a Cross-sectional Survey in Xinjiang Uygur Autonomous Region.

Recent Research Articles from UNTHSC - Wed, 01/18/2017 - 13:37
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Prevalence and Predictors of Hypertension in the Labor Force Population in China: Results from a Cross-sectional Survey in Xinjiang Uygur Autonomous Region.

Biomed Environ Sci. 2016 04;29(4):290-4

Authors: Xu de M, Li XF, Goan D, Yang de M, Li JM, Wang X, Huang YL, Chen YS

Abstract
The objective of this study was to examine the prevalence of hypertension and identify its contributory factors in the labor force population in Karamay. A total of 2819 adults (55.9% male adults) were interviewed and examined. The overall crude prevalence of hypertension was 32.4%. Among 914 hypertensive patients, 34.8% were aware of their diagnosis, 22.1% received treatment, and 5.6% achieved blood pressure control. Hypertension was significantly correlated with age, overweight/obesity, central obesity, diabetes, and dyslipidemia in both men and women. In addition, less education, alcohol consumption, and less walking were risk factors for men. Effective hypertension prevention and control programs are urgently needed to decrease the burden of hypertension in this region.

PMID: 27241740 [PubMed - indexed for MEDLINE]

Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target.

Recent Research Articles from UNTHSC - Tue, 01/17/2017 - 07:34
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Chemical Conditioning as an Approach to Ischemic Stroke Tolerance: Mitochondria as the Target.

Int J Mol Sci. 2016 Mar 08;17(3):351

Authors: Jin Z, Wu J, Yan LJ

Abstract
It is well established that the brain can be prepared to resist or tolerate ischemic stroke injury, and mitochondrion is a major target for this tolerance. The preparation of ischemic stroke tolerance can be achieved by three major approaches: ischemic conditioning, hypoxic conditioning and chemical conditioning. In each conditioning approach, there are often two strategies that can be used to achieve the conditioning effects, namely preconditioning (Pre-C) and postconditioning (Post-C). In this review, we focus on chemical conditioning of mitochondrial proteins as targets for neuroprotection against ischemic stroke injury. Mitochondrial targets covered include complexes I, II, IV, the ATP-sensitive potassium channel (mitoKATP), adenine dinucleotide translocase (ANT) and the mitochondrial permeability transition pore (mPTP). While numerous mitochondrial proteins have not been evaluated in the context of chemical conditioning and ischemic stroke tolerance, the paradigms and approaches reviewed in this article should provide general guidelines on testing those mitochondrial components that have not been investigated. A deep understanding of mitochondria as the target of chemical conditioning for ischemic stroke tolerance should provide valuable insights into strategies for fighting ischemic stroke, a leading cause of death in the world.

PMID: 27005615 [PubMed - indexed for MEDLINE]

People's reasons for wanting to complete probation: Use and predictive validity in an e-health intervention.

Recent Research Articles from UNTHSC - Mon, 01/16/2017 - 07:41
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People's reasons for wanting to complete probation: Use and predictive validity in an e-health intervention.

Eval Program Plann. 2017 Jan 06;61:144-149

Authors: Spohr SA, Taxman FS, Walters ST

Abstract
The criminal justice system tends to emphasize external contingencies (e.g., fees, jail time) to motivate offender compliance. However, people's reasons for desistance vary considerably. This study evaluated the acceptability, utility, and predictive validity of questions that ask about people's reasons for wanting to successfully complete probation. Substance-using probationers (N=113) participated in a web-based computer intervention that targeted substance use and treatment initiation. Questions around seven dimensions of reasons for completing probation were developed to provide tailored feedback during the web-based program. A principle components factor analysis found that survey items loaded onto two distinct factors. Factor one, "Tangible Loss" focused on external and present-focused reasons. Factor two, "Better Life" focused on internal and future-focused reasons. There was a significant negative association between Better Life scores and days of substance use after two months (β=-0.31, SE=0.13, p<0.05). There was a significant positive association with Better Life scores and days of treatment attendance (β=1.46, SE=0.26, p<0.001). Tangible Loss scores were no associated with substance use and treatment attendance. These findings may help to create more effective motivational tracks in e-health interventions, and may complement traditional motivation measures with an explicit focus on people's stated reasons for wanting to complete probation.

PMID: 28088674 [PubMed - as supplied by publisher]

Cullin Neddylation May Allosterically Tune Polyubiquitin Chain Length and Topology.

Recent Research Articles from UNTHSC - Sat, 01/14/2017 - 07:43
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Cullin Neddylation May Allosterically Tune Polyubiquitin Chain Length and Topology.

Biochem J. 2017 Jan 12;:

Authors: Onel M, Sumbul F, Liu J, Nussinov R, Haliloglu T

Abstract
Conjugation of Nedd8 (neddylation) to Cullins in Cullin-RING E3 ligases (CRL) stimulates ubiquitination and polyubiquitination of protein substrates. CRL is made up of two Cullin-flanked arms: one consists of the substrate-binding and adaptor proteins; the other of E2 and Ring-box protein (Rbx). Polyubiquitin chain length and topology determines the substrate fate. Here we ask how polyubiquitin chains are accommodated in the limited space available between the two arms and what determines the polyubiquitin linkage topology. We focus on Cullin 5 (Cul5) and Rbx1 in three states: before Cul5 neddylation (closed state), after neddylation (open state), and after deneddylation, exploiting molecular dynamics (MD) simulations and the Gaussian Network Model (GNM). We observe that regulation of substrate ubiquitination and polyubiquitination takes place through Rbx1 rotations, which are controlled by Nedd8-Rbx1 allosteric communication. Allosteric propagation proceeds from Nedd8 via Cul5 dynamic hinges and hydrogen bonds between the C-terminal domain of Cul5 (Cul5CTD) and Rbx1 (Cul5CTD residues R538/R569 and Rbx1 residue E67, or Cul5CTD E474/E478/N491 and Rbx1 K105). Importantly, at each ubiquitination step (homogeneous or heterogeneous, linear or branched), the polyubiquitin linkages fit into the distances between the two arms, and these match the inherent CRL conformational tendencies. Hinge sites may constitute drug targets.

PMID: 28082425 [PubMed - as supplied by publisher]

Losartan Reduces the Immediate and Sustained Increases in Muscle Sympathetic Nerve Activity after Hyper-Acute Intermittent Hypoxia.

Recent Research Articles from UNTHSC - Sat, 01/14/2017 - 07:43
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Losartan Reduces the Immediate and Sustained Increases in Muscle Sympathetic Nerve Activity after Hyper-Acute Intermittent Hypoxia.

J Appl Physiol (1985). 2017 Jan 12;:jap.00683.2016

Authors: Jouett NP, Moralez G, Raven PB, Smith ML

Abstract
Obstructive sleep apnea (OSA) is characterized by intermittent hypoxemia (IH), which produces elevations in sympathetic nerve activity (SNA) and associated hypertension in experimental models that persist beyond the initial exposure. We tested the hypotheses that angiotensin receptor blockade in humans using Losartan attenuates the immediate and immediately persistent increases in (a) SNA discharge and (b) mean arterial pressure (MAP) after hyper-acute intermittent hypoxia training (IHT) using a randomized, placebo controlled repeated-measures experimental design. We measured ECG and photoplethysmographic arterial pressure in 9 healthy human subjects, while muscle sympathetic nerve activity (MSNA) was recorded in 7 subjects using microneurography. Subjects were exposed to a series of hypoxic apneas in which they inhaled 2-3 breaths of nitrogen, followed by a 20-second apnea and 40 seconds of room air breathing every minute for 20 minutes. Hyper-acute IHT produced substantial and persistent elevations in MSNA burst frequency (baseline: 15.3 ± 1.8, IHT: 24 ± 1.5, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.01) and MAP (baseline: 89.2 ± 3.3, IHT: 92.62 ± 3.1, post-IHT: 93.83 ± 3.1 mm Hg mm Hg, all P < 0.02). Losartan attenuated the immediate and sustained increases in MSNA (baseline: 17.3 ± 2.5, IHT: 18.6 ± 2.2, post-IHT 20.0 ± 1.3 bursts/min, all P < 0.001) and MAP (baseline: 81.9 ± 2.6, IHT: 81.1 ± 2.8, post-IHT: 81.3 ± 3.0 mm Hg, all P >0.70). This investigation confirms the role of angiotensin II type 1a receptors in the immediate and persistent sympathoexcitatory and pressor responses to IHT.

PMID: 28082332 [PubMed - as supplied by publisher]

Impact of air quality guidelines on COPD sufferers.

Recent Research Articles from UNTHSC - Sat, 01/14/2017 - 07:43
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Impact of air quality guidelines on COPD sufferers.

Int J Chron Obstruct Pulmon Dis. 2016;11:839-72

Authors: Liu Y, Yan S, Poh K, Liu S, Iyioriobhe E, Sterling DA

Abstract
BACKGROUND: COPD is one of the leading causes of morbidity and mortality in both high- and low-income countries and a major public health burden worldwide. While cigarette smoking remains the main cause of COPD, outdoor and indoor air pollution are important risk factors to its etiology. Although studies over the last 30 years helped reduce the values, it is not very clear if the current air quality guidelines are adequately protective for COPD sufferers.
OBJECTIVE: This systematic review was to summarize the up-to-date literature on the impact of air pollution on the COPD sufferers.
METHODS: PubMed and Google Scholar were utilized to search for articles related to our study's focus. Search terms included "COPD exacerbation", "air pollution", "air quality guidelines", "air quality standards", "COPD morbidity and mortality", "chronic bronchitis", and "air pollution control" separately and in combination. We focused on articles from 1990 to 2015. We also used articles prior to 1990 if they contained relevant information. We focused on articles written in English or with an English abstract. We also used the articles in the reference lists of the identified articles.
RESULTS: Both short-term and long-term exposures to outdoor air pollution around the world are associated with the mortality and morbidity of COPD sufferers even at levels below the current air quality guidelines. Biomass cooking in low-income countries was clearly associated with COPD morbidity in adult nonsmoking females.
CONCLUSION: There is a need to continue to improve the air quality guidelines. A range of intervention measures could be selected at different levels based on countries' socioeconomic conditions to reduce the air pollution exposure and COPD burden.

PMID: 27143874 [PubMed - indexed for MEDLINE]

Increasing the reference populations for the 55 AISNP panel: the need and benefits.

Recent Research Articles from UNTHSC - Wed, 01/11/2017 - 07:33
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Increasing the reference populations for the 55 AISNP panel: the need and benefits.

Int J Legal Med. 2017 Jan 09;:

Authors: Pakstis AJ, Kang L, Liu L, Zhang Z, Jin T, Grigorenko EL, Wendt FR, Budowle B, Hadi S, Al Qahtani MS, Morling N, Mogensen HS, Themudo GE, Soundararajan U, Rajeevan H, Kidd JR, Kidd KK

Abstract
Ancestry inference for an individual can only be as good as the reference populations with allele frequency data on the SNPs being used. If the most relevant ancestral population(s) does not have data available for the SNPs studied, then analyses based on DNA evidence may indicate a quite distantly related population, albeit one among the more closely related of the existing reference populations. We have added reference population allele frequencies for 14 additional population samples (with >1100 individuals studied) to the 125 population samples previously published for the Kidd Lab 55 AISNP panel. Allele frequencies are now publicly available for all 55 SNPs in ALFRED and FROG-kb for a total of 139 population samples. This Kidd Lab panel of 55 ancestry informative SNPs has been incorporated in commercial kits by both ThermoFisher Scientific and Illumina for massively parallel sequencing. Researchers employing those kits will find the enhanced set of reference populations useful.

PMID: 28070634 [PubMed - as supplied by publisher]

DNA quality and quantity from up to 16 years old post-mortem blood stored on FTA cards.

Recent Research Articles from UNTHSC - Wed, 01/11/2017 - 07:33
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DNA quality and quantity from up to 16 years old post-mortem blood stored on FTA cards.

Forensic Sci Int. 2016 Apr;261:148-53

Authors: Rahikainen AL, Palo JU, de Leeuw W, Budowle B, Sajantila A

Abstract
Blood samples preserved on FTA cards offer unique opportunities for genetic research. DNA recovered from these cards should be stable for long periods of time. However, it is not well established as how well the DNA stored on FTA card for substantial time periods meets the demands of forensic or genomic DNA analyses and especially so for from post-mortem (PM) samples in which the quality can vary upon initial collection. The aim of this study was to evaluate the time-dependent degradation on DNA quality and quantity extracted from up to 16 years old post-mortem bloodstained FTA cards. Four random FTA samples from eight time points spanning 1998 to 2013 (n=32) were collected and extracted in triplicate. The quantity and quality of the extracted DNA samples were determined with Quantifiler(®) Human Plus (HP) Quantification kit. Internal sample and sample-to-sample variation were evaluated by comparing recovered DNA yields. The DNA from the triplicate samplings were subsequently combined and normalized for further analysis. The practical effect of degradation on DNA quality was evaluated from normalized samples both with forensic and pharmacogenetic target markers. Our results suggest that (1) a PM change, e.g. blood clotting prior to sampling, affects the recovered DNA yield, creating both internal and sample-to-sample variation; (2) a negative correlation between the FTA card storage time and DNA quantity (r=-0.836 at the 0.01 level) was observed; (3) a positive correlation (r=0.738 at the level 0.01) was found between FTA card storage time and degradation levels. However, no inhibition was observed with the method used. The effect of degradation was manifested clearly with functional applications. Although complete STR-profiles were obtained for all samples, there was evidence of degradation manifested as decreased peak heights in the larger-sized amplicons. Lower amplification success was notable with the large 5.1 kb CYP2D6 gene fragment which strongly supports degradation of the stored samples. According to our results, DNA stored on FTA cards is rather stable over a long time period. DNA extracted from this storage medium can be used as human identification purposes as the method used is sufficiently sensitive and amplicon sizes tend to be <400 bp. However, DNA integrity was affected during storage. This effect should be taken into account depending on the intended application especially if high quality DNA and long PCR amplicons are required.

PMID: 26937857 [PubMed - indexed for MEDLINE]

A Brief Report Describing the Union of Medical Training and Agricultural Health.

Recent Research Articles from UNTHSC - Wed, 01/11/2017 - 07:33
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A Brief Report Describing the Union of Medical Training and Agricultural Health.

J Agromedicine. 2016;21(1):123-6

Authors: Levin JL, Bowling J, Wickman AJ, Harris M

Abstract
This brief report describes a mutually beneficial partnership forged to extend agricultural medicine training to physicians, nurses, veterinarians, public health workers, health care professionals, medical residents, and students. Agricultural Medicine: Occupational and Environmental Health for Rural Health Professionals originated at the University of Iowa, Iowa's Center for Agricultural Safety and Health, and the Great Plains Center for Agricultural Health. Through a National Institute for Occupational Safety and Health (NIOSH)-funded Training Project Grant, The University of Texas Health Northeast worked with the University of Iowa and regional experts to adapt the agricultural medicine content for the southwestern United States. Further partnerships were developed with the Southwest Center for Agricultural Health, Injury Prevention and Education, The University of North Texas Health Science Center College of Osteopathic Medicine, and the Texas Rural Health Association to extend the reach of this training to other important stakeholders. Each of the collaborators offered unique resources to the coordination of the agricultural medicine course. Likewise, each organization benefited from extending regionally relevant agricultural medicine training to current and future health care providers. The long-term goal for the partnership is to train a broad array of health care providers with the basics of anticipation, recognition, diagnosis, treatment, and the prevention of occupational and environmental illnesses and injuries within rural and agricultural communities, customized to the Southwest Region. This brief descriptive report highlights the process by which strategic partners collaborated to conduct a regional agricultural medicine course, such that other organizations interested in offering a similar training might gain insight to best practices from our experience.

PMID: 26479683 [PubMed - indexed for MEDLINE]

A Comparison of Gene Expression Profiles between Glucocorticoid Responder and Non-Responder Bovine Trabecular Meshwork Cells Using RNA Sequencing.

Recent Research Articles from UNTHSC - Tue, 01/10/2017 - 10:35
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A Comparison of Gene Expression Profiles between Glucocorticoid Responder and Non-Responder Bovine Trabecular Meshwork Cells Using RNA Sequencing.

PLoS One. 2017;12(1):e0169671

Authors: Bermudez JY, Webber HC, Brown B, Braun TA, Clark AF, Mao W

Abstract
The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced ocular hypertension (OHT) and GC-induced glaucoma (GIG). GC-induced OHT occurs in about 40% of the general population, while the other 60% are resistant. This study aims to determine the genes and pathways involved in differential GC responsiveness in the trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), while the fellow eye was used to establish a bovine TM (BTM) cell strain. Based on maximum IOP change in the perfused eye, the BTM cell strain was identified as a DEX-responder or non-responder strain. Three responder and three non-responder BTM cell strains were cultured, treated with 0.1% ethanol or 100nM DEX for 7 days. RNA and proteins were extracted for RNA sequencing (RNAseq), qPCR, and Western immunoblotting (WB), respectively. Data were analyzed using the human and bovine genome databases as well as Tophat2 software. Genes were grouped and compared using Student's t-test. We found that DEX induced fibronectin expression in responder BTM cells but not in non-responder cells using WB. RNAseq showed between 93 and 606 differentially expressed genes in different expression groups between responder and non-responder BTM cells. The data generated by RNAseq were validated using qPCR. Pathway analyses showed 35 pathways associated with differentially expressed genes. These genes and pathways may play important roles in GC-induced OHT and will help us to better understand differential ocular responsiveness to GCs.

PMID: 28068412 [PubMed - in process]

mGlu5 negative allosteric modulators: a patent review (2013-2016).

Recent Research Articles from UNTHSC - Tue, 01/10/2017 - 10:35
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mGlu5 negative allosteric modulators: a patent review (2013-2016).

Expert Opin Ther Pat. 2017 Jan 08;:

Authors: Emmitte KA

Abstract
INTRODUCTION: The pursuit of small molecule mGlu5 NAMs as treatments for a variety of psychiatric and neurodegenerative disorders has developed into a mature field. In addition to extensive preclinical studies, multiple compounds have advanced into clinical trials with the most advanced studies occurring in patients with FXS, PD-LID, and MDD. Areas covered: This review begins with an update of the clinical activity with mGlu5 NAMs, and then moves into a summary of patent applications filed since 2013. The summaries are organized into three separate sections: (1) inventions centered on improvements to existing clinical compounds; (2) new small molecules that maintain the prototypical disubstituted alkyne chemotype found in many mGlu5 NAM compounds; and (3) new small molecules that are not from a disubstituted alkyne chemotype. Expert Opinion: It is a critical moment for mGlu5 NAM research as recent reports from clinical trials have included some significant disappointments that have blunted prior optimism. Still, research in this area remains active, and recent years have added several more attractive small molecules to this field. There is now an arsenal of diverse chemotypes available to continue to probe this target in the hopes that a drug may yet emerge.

PMID: 28067079 [PubMed - as supplied by publisher]

Social support for physical activity: Comparison of family, friends, and coworkers.

Recent Research Articles from UNTHSC - Sat, 01/07/2017 - 10:37

Social support for physical activity: Comparison of family, friends, and coworkers.

Work. 2016;55(4):893-899

Authors: Sarkar S, Taylor WC, Lai D, Shegog R, Paxton RJ

Abstract
BACKGROUND: Few studies have examined the associations among family, friend, and coworker social support for physical activity. It is important to know the sources of social support that facilitate and promote physical activity among fulltime working adults.
OBJECTIVE: We analyzed the associations among family, friend, and coworker social support for physical activity and moderate-to-vigorous physical activity among participants in a worksite study.
METHODS: This study was a cross-sectional analysis of baseline data from 144 participants from four worksites in a large, southwestern city in the United States. The intervention for the worksite study was Booster Breaks (a physical activity routine of 15 minutes) practiced daily to break-up prolonged sitting time. Descriptive statistics and multiple linear regressions were conducted using SPSS version 20.
RESULTS: Age was inversely associated (p = 0.001), and social support from friends (p = 0.04) and coworkers (p = 0.003) were positively associated with physical activity in the unadjusted model. After controlling for all the covariates (age, sex, marital status, BMI, education, and income) in the model, only coworker social support was positively (p = 0.027) associated with physical activity among participants in the workplace study.
CONCLUSIONS: Coworker social support is an important correlate of physical activity and should be incorporated in workplace health promotion programs.

PMID: 28059824 [PubMed - in process]

Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation.

Recent Research Articles from UNTHSC - Sat, 01/07/2017 - 10:37
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Corticotropin-releasing hormone improves survival in pneumococcal pneumonia by reducing pulmonary inflammation.

Physiol Rep. 2017 Jan;5(1):

Authors: Burnley B, P Jones H

Abstract
The use of glucocorticoids to reduce inflammatory responses is largely based on the knowledge of the physiological action of the endogenous glucocorticoid, cortisol. Corticotropin-releasing hormone (CRH) is a neuropeptide released from the hypothalamic-pituitary-adrenal axis of the central nervous system. This hormone serves as an important mediator of adaptive physiological responses to stress. In addition to its role in inducing downstream cortisol release that in turn regulates immune suppression, CRH has also been found to mediate inflammatory responses in peripheral tissues. Streptococcus pneumoniae is a microorganism commonly present among the commensal microflora along the upper respiratory tract. Transmission of disease stems from the resident asymptomatic pneumococcus along the nasal passages. Glucocorticoids are central mediators of immune suppression and are the primary adjuvant pharmacological treatment used to reduce inflammatory responses in patients with severe bacterial pneumonia. However, controversy exists in the effectiveness of glucocorticoid treatment in reducing mortality rates during S. pneumoniae infection. In this study, we compared the effect of the currently utilized pharmacologic glucocorticoid dexamethasone with CRH. Our results demonstrated that intranasal administration of CRH increases survival associated with a decrease in inflammatory cellular immune responses compared to dexamethasone independent of neutrophils. Thus, providing evidence of its use in the management of immune and inflammatory responses brought on by severe pneumococcal infection that could reduce mortality risks.

PMID: 28057851 [PubMed - in process]

Survival Analysis After Extracorporeal Membrane Oxygenation in Critically Ill Adults: A Nationwide Cohort Study.

Recent Research Articles from UNTHSC - Thu, 01/05/2017 - 07:38
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Survival Analysis After Extracorporeal Membrane Oxygenation in Critically Ill Adults: A Nationwide Cohort Study.

Circulation. 2016 Jun 14;133(24):2423-33

Authors: Chang CH, Chen HC, Caffrey JL, Hsu J, Lin JW, Lai MS, Chen YS

Abstract
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides circulatory and respiratory support for patients with severe acute cardiopulmonary failure. The objective of this study was to examine the survival outcomes for patients who received ECMO.
METHODS AND RESULTS: Adult patients who received ECMO from September 1, 2002, to December 31, 2012, were identified from the Taiwan National Health Insurance Database associated with coronary artery bypass graft surgery, myocardial infarction/cardiogenic shock, injury, and infection/septic shock. A Cox regression model was used to determine hazard ratios and to compare 30-day and 1-year survival rates with the myocardial infarction/cardiogenic shock group used as the reference. The mean±SD age of the 4227-patient cohort was 57±17 years, and 72% were male. The overall mortalities were 59.8% and 76.5% at 1 month and 1 year. Survival statistics deteriorated sharply when ECMO was required for >3 days. Acute (30-day) survival was more favorable in the infection/septic shock (n=1076; hazard ratio, 0.61; 95% confidence interval, 0.55-0.67), coronary artery bypass graft surgery (n=1077; hazard ratio, 0.68; 95% confidence interval, 0.61-0.75), and injury (n=369, hazard ratio, 0.82; 95% confidence interval, 0.70-0.95) groups. The extended survival rapidly approached an asymptote near 20% for the infection/septic shock, myocardial infarction/cardiogenic shock (n=1705), and coronary artery bypass graft surgery groups. The pattern of survival for the injury group was somewhat better, exceeding 30% at year-end.
CONCLUSIONS: Regardless of initial pathology, patients requiring ECMO were critically ill with similar guarded prognoses. Those in the trauma group had somewhat better outcomes. Determining the efficacy and cost-effectiveness of ECMO should be a critical future goal.

PMID: 27199466 [PubMed - indexed for MEDLINE]

A Post-Hurricane Katrina Examination of Substance Abuse Treatment Discharges with Co-Occurring Psychiatric and Substance Use Disorders.

Recent Research Articles from UNTHSC - Wed, 01/04/2017 - 07:33

A Post-Hurricane Katrina Examination of Substance Abuse Treatment Discharges with Co-Occurring Psychiatric and Substance Use Disorders.

J Dual Diagn. 2017 Jan 03;:0

Authors: Shuler M, Suzuki S, Podesta A, Qualls-Hampton R, Wallington SF

Abstract
OBJECTIVES: There is increasing literature supporting the adverse effects of disasters on substance use and psychiatric disorders. The co-occurrence of psychiatric disorders with substance use intensifies the challenge of treatment delivery. Thus the aim of this study was to examine the prevalence of substance use, treatment characteristics, and demographics of discharges from substance abuse treatment in New Orleans, post-Hurricane Katrina. Trends associated with discharges that have a co-occurring psychiatric and substance use disorder (COD) were also assessed. The secondary aim of this study was to examine the association of successful substance abuse treatment completion among those with a COD post-Hurricane Katrina.
METHODS: Substance abuse treatment discharge data (N = 16,507) from New Orleans, Louisiana, for years 2006 through 2011 was obtained from the Treatment Episode Data Set -Discharge (TEDS-D). Multiple logistic regression was employed to examine the association of discharges with a COD and completion of substance abuse treatment. Demographic, psychiatric, and treatment characteristics of discharges in 2006 were compared to characteristics in 2011. Trends of characteristics were also assessed through the study period.
RESULTS: Roughly a third (35.2%) of all discharges in New Orleans from 2006 to 2011 had a COD. After controlling for race, employment, treatment service setting at discharge, primary substance problem, and the discharge's principal source of referral, discharges with a COD were 29% less likely to complete treatment as compared to those with no COD (AOR: 0.71, 95% CI: [0.56, 0.90], p = 0.004). Treatment completion among discharges with a COD has significantly declined from 36.8% in 2006 to 18.7% in 2011 (p < .0001). Notable significant trends in homelessness, criminality, and heroin use were identified among discharges with a COD.
CONCLUSIONS: Substance abuse treatment undergoes various changes in the event of a natural disaster. These changes may increase challenges for successful treatment completion for vulnerable populations such as those with a COD. Results of this study demonstrate that discharges with a COD are less likely to complete treatment as compared to those with no COD disorder. Unmet treatment needs may also increase odds of criminalization and homelessness.

PMID: 28045601 [PubMed - as supplied by publisher]

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

Recent Research Articles from UNTHSC - Wed, 01/04/2017 - 07:33
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N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects.

Exp Physiol. 2016 Mar;101(3):387-96

Authors: Jouett NP, Moralez G, White DW, Eubank WL, Chen S, Tian J, Smith ML, Zimmerman MC, Raven PB

Abstract
NEW FINDINGS: What is the central question of this study? This study evaluated the following central question: does N-acetylcysteine (N-AC), an antioxidant that readily penetrates the blood-brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N-AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N-AC, have therapeutic potential in obstructive sleep apnoea. This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg(-1) of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

PMID: 27027616 [PubMed - indexed for MEDLINE]

Association Between Healthcare Provider Type and Intent to Breastfeed Among Expectant Mothers.

Recent Research Articles from UNTHSC - Wed, 01/04/2017 - 07:33
Related Articles

Association Between Healthcare Provider Type and Intent to Breastfeed Among Expectant Mothers.

Matern Child Health J. 2016 May;20(5):993-1000

Authors: Balyakina E, Fulda KG, Franks SF, Cardarelli KM, Hinkle K

Abstract
BACKGROUND: The primary purpose of this study was to determine the association between type of healthcare provider delivering prenatal care and intent to exclusively breastfeed.
METHODS: A self-report survey was administered to 455 expectant mothers. Logistic regression was performed to determine the association between prenatal care provider type [obstetrician; other primary care physician (family doctor/general practitioner/internist/or other physician); midwife/nurse midwife; more than one provider; and other] with intent to breastfeed (exclusive/non-exclusive).
RESULTS: Having a midwife/nurse midwife as a prenatal care provider was associated with intent to breastfeed compared to having an obstetrician (OR 2.544, 95 % CI 1.385-4.675). There was no difference in intent between women with another primary care physician and an obstetrician. Women with another type of health care provider, no prenatal care from a health professional, or no knowledge of who is providing prenatal care were less likely to intend to breastfeed (OR 0.228, CI 0.068-0.766) as compared to those with an obstetrician.
DISCUSSION/CONCLUSIONS: Provider type is associated with intent to breastfeed among pregnant women. Women's intent to breastfeed is an important predictor of breastfeeding initiation, continuation, and duration that may be assessed by healthcare providers during the prenatal period. A consideration of what features of provider care are associated with improved breastfeeding outcomes and characteristics of women seeking prenatal care with midwives may serve to formulate future prenatal care policies and education during prenatal care visits.

PMID: 26699790 [PubMed - indexed for MEDLINE]

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