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Target engagement and drug residence time can be observed in living cells with BRET.

Recent Research Articles from UNTHSC - Tue, 05/10/2016 - 06:33
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Target engagement and drug residence time can be observed in living cells with BRET.

Nat Commun. 2015;6:10091

Authors: Robers MB, Dart ML, Woodroofe CC, Zimprich CA, Kirkland TA, Machleidt T, Kupcho KR, Levin S, Hartnett JR, Zimmerman K, Niles AL, Ohana RF, Daniels DL, Slater M, Wood MG, Cong M, Cheng YQ, Wood KV

Abstract
The therapeutic action of drugs is predicated on their physical engagement with cellular targets. Here we describe a broadly applicable method using bioluminescence resonance energy transfer (BRET) to reveal the binding characteristics of a drug with selected targets within intact cells. Cell-permeable fluorescent tracers are used in a competitive binding format to quantify drug engagement with the target proteins fused to Nanoluc luciferase. The approach enabled us to profile isozyme-specific engagement and binding kinetics for a panel of histone deacetylase (HDAC) inhibitors. Our analysis was directed particularly to the clinically approved prodrug FK228 (Istodax/Romidepsin) because of its unique and largely unexplained mechanism of sustained intracellular action. Analysis of the binding kinetics by BRET revealed remarkably long intracellular residence times for FK228 at HDAC1, explaining the protracted intracellular behaviour of this prodrug. Our results demonstrate a novel application of BRET for assessing target engagement within the complex milieu of the intracellular environment.

PMID: 26631872 [PubMed - indexed for MEDLINE]

Bars and nightclubs associated with higher HIV prevalence.

Recent Research Articles from UNTHSC - Tue, 05/10/2016 - 06:33
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Bars and nightclubs associated with higher HIV prevalence.

Drug Alcohol Depend. 2015 Oct 1;155:31-6

Authors: Rossheim ME, Thombs DL, Suzuki S

Abstract
BACKGROUND: Alcohol outlet density is positively associated with alcohol consumption and a number of related risk behaviors. However, very little is known about the effects of different types of alcohol outlets on HIV prevalence. The current cross-sectional study examines associations between the number of each type of alcohol outlet and HIV prevalence within 350 cities located in 26 U.S. metropolitan statistical areas.
METHODS: State and local health department and U.S. Census Bureau surveillance data were analyzed from 1056 ZIP codes, where an estimated 39 million people reside. Multilevel negative binomial regression models were used to examine the association between the number of each type of alcohol outlet in ZIP codes and HIV prevalence.
RESULTS: Number of on-premise alcohol outlets within a ZIP code was associated with greater HIV prevalence. In this sample, the presence of one additional on-premise outlet in a ZIP code was associated with a 1.5% increase in the HIV prevalence rate in that location.
CONCLUSION: This study extends previous research by examining the relationship between alcohol outlets and HIV prevalence in a large sample of U.S. ZIP codes. Research is needed to more closely examine the mechanisms by which on-premise alcohol outlets may affect HIV transmission. Effective policies to reduce HIV transmission may include limiting the density of on-premise alcohol establishments.

PMID: 26347407 [PubMed - indexed for MEDLINE]

Comparative molecular genetic analysis of simian and human HIV-1 integrase interactor INI1/SMARCB1/SNF5.

Recent Research Articles from UNTHSC - Sat, 05/07/2016 - 10:36
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Comparative molecular genetic analysis of simian and human HIV-1 integrase interactor INI1/SMARCB1/SNF5.

Arch Virol. 2015 Dec;160(12):3085-91

Authors: Pyeon D, Price L, Park IW

Abstract
Human integrase interactor 1 (INI1/SMARCB1/SNF5) is a chromatin-remodeling molecule that binds to HIV-1 integrase and enhances proviral DNA integration. INI1 is also known as a tumor suppressor gene and has been found to be mutated in several aggressive tumors such as rhabdoid and lymphoid tumors. To study the function of simian INI1, we screened and cloned simian INI1 cDNA from B lymphoma cells of rhesus monkeys using RT-PCR. Sequence analysis showed 23 single nucleotide differences compared to the human ortholog, which, however, did not result in amino acid changes, and the amino acid sequence is therefore 100% conserved between human and simian INI1. Two alternatively spliced isoforms, INI1a and INI1b, were also found in simian INI1. These two isoforms did not show any functional difference in HIV-1 proviral DNA integration and nuclear localization, suggesting that the specificity of simian INI1 would not be a factor preventing HIV-1 infection of a simian host. Nevertheless, INI1b is expressed only in established cancer cell lines such as Jurkat and COS-7 cells, and not in primary cells, suggesting that INIlb could be an indicator of cell transformation.

PMID: 26350979 [PubMed - indexed for MEDLINE]

Efficacy of SMS Text Message Interventions for Smoking Cessation: A Meta-Analysis.

Recent Research Articles from UNTHSC - Sat, 05/07/2016 - 10:36
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Efficacy of SMS Text Message Interventions for Smoking Cessation: A Meta-Analysis.

J Subst Abuse Treat. 2015 Sep;56:1-10

Authors: Spohr SA, Nandy R, Gandhiraj D, Vemulapalli A, Anne S, Walters ST

Abstract
BACKGROUND: Mobile technology provides new opportunities for health promotion communication. The purpose of this study was to conduct a current and extensive meta-analytic review of SMS (short message service) text message-based interventions for individual smoking cessation.
METHODS: Academic Search Complete, PsycINFO, PubMed, and Scopus were reviewed for articles meeting selection criteria: 1) randomized controlled trials, 2) measured smoking cessation, and 3) intervention primarily delivered through SMS text messaging. Three and 6month follow-up of 7-day point prevalence or continuous abstinence was considered from studies meeting criteria. All analyses were conducted with intention-to-treat. Both fixed and random effects models were used to calculate the global outcome measure and confidence intervals.
RESULTS: Thirteen studies were identified that met inclusion criteria. The studies were found to be homogeneous [Q12=12.47, p=0.14]. Odds ratios based on the random effects models suggested that interventions generally increased quit rates compared to controls, 1.36 [95% CI=1.23, 1.51]. Intervention efficacy was higher in studies with a 3month follow-up compared to 6month follow-up. Text plus programs (e.g., text messaging plus Web or in-person intervention modalities) performed only slightly better than text only programs. Pooled results also indicate message frequency schedule can affect quit rates, in which fixed schedules performed better than decreasing or variable schedules. The use of quit status assessment messages was not related to intervention efficacy.
CONCLUSION: Smoking quit rates for the text messaging intervention group were 36% higher compared to the control group quit rates. Results suggest that SMS text messaging may be a promising way to improve smoking cessation outcomes. This is significant given the relatively wide reach and low cost of text message interventions. Identifying the components that make interventions efficacious will help to increase the effectiveness of such interventions.

PMID: 25720333 [PubMed - indexed for MEDLINE]

Strategies for the Management of Postoperative Anemia in Elective Orthopedic Surgery.

Recent Research Articles from UNTHSC - Fri, 05/06/2016 - 06:37

Strategies for the Management of Postoperative Anemia in Elective Orthopedic Surgery.

Ann Pharmacother. 2016 May 4;

Authors: Steuber TD, Howard ML, Nisly SA

Abstract
OBJECTIVE: To assess the use of oral iron, intravenous (IV) iron, and erythropoiesis-stimulating agents (ESAs) for the prevention and management of perioperative anemia in elective orthopedic surgery patients, and to provide a clinical algorithm for use.
DATA SOURCES: A PubMed and MEDLINE search was conducted from 1964 through March 2016 using the following search terms alone or in combination: orthopedic, surgery, elective, anemia, blood transfusion, iron, erythropoiesis-stimulating agents, and erythropoietin.
STUDY SELECTION AND DATA EXTRACTION: All English-language prospective and retrospective human studies and meta-analyses evaluating oral iron, IV iron, or ESA alone or in combination in elective orthopedic surgery patients were evaluated, provided they reported blood transfusion outcomes.
DATA SYNTHESIS: A total of 9 prospective and retrospective studies and 1 meta-analysis were identified and included. In the preoperative setting, administration of oral iron, IV iron, or ESA alone or in combination to correct underlying anemia led to significantly reduced transfusion rates. Transfusion requirements were generally less with combination therapy (ESA + oral or IV iron). In the short-term perioperative or postoperative period, use of oral or IV iron led to conflicting results, with some reporting a statistically significant reduction in blood transfusions, whereas others reported none.
CONCLUSIONS: In elective orthopedic surgery, IV or oral iron with or without an ESA may provide benefit in prevention of postoperative anemia and results in blood transfusion reduction without significantly increasing the risk of adverse events. These agents should be considered at the lowest effective dose with emphasis on administration prior to planned surgery.

PMID: 27147703 [PubMed - as supplied by publisher]

Impact of air quality guidelines on COPD sufferers.

Recent Research Articles from UNTHSC - Thu, 05/05/2016 - 06:35

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 - in process]

Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD: A National Cross-Sectional Study.

Recent Research Articles from UNTHSC - Thu, 05/05/2016 - 06:35
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Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD: A National Cross-Sectional Study.

Medicine (Baltimore). 2015 Dec;94(51):e2175

Authors: Kuo CC, Yeh HC, Chen B, Tsai CW, Lin YS, Huang CC

Abstract
The use of metformin in chronic kidney disease (CKD) population has been intensely debated with conflicting evidence. Large population studies are needed to inform risk assessment and therapeutic decision-making. We evaluated the associations among metformin, metabolic acidosis, and CKD in a 10-year nationally representative noninstitutionalized civilian population in the United States.In this cross-sectional study, a total of 2279 diabetic adults aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012 were included and had measurements of serum bicarbonate, sodium, potassium, and chloride. The exposure was metformin use. The outcome was subclinical and severe metabolic acidosis defined by serum bicarbonate <23 mEq/L and anion gap > 16mEq/L and by serum bicarbonate < 20 mEq/L, respectively.The prevalence of metformin use decreased from 67.2% among CKD-1 and -2, 40.6% among CKD-3, to 1.3% among advanced CKD-4 and -5. Across CKD stages up to CKD-3b, we observed a tendency of lower levels of serum bicarbonate that was significant in metformin users with CKD-2 and CKD-3a and marginally significant with CKD-3b compared to nonmetformin users. The corresponding tendency of higher anion gap in metformin users with the estimated glomerular filtration rate >60 mL/min/1.73 m was also observed. In multiple linear regression analysis, metformin was significantly associated with decreased serum bicarbonate levels (β = -0.45, 95% CI: -0.73, -0.17) and increased serum anion gap levels (β = 0.40, 95% CI: 0.19, 0.61). The adjusted odds ratio of subclinical high anion gap and severe metabolic acidosis for metformin users was 1.68 (95% CI: 1.11, 2.55) and 1.31 (0.49, 3.47), respectively. The association between metformin and serum bicarbonate was significantly modified by CKD status. No interaction was found between metformin and CKD stages for serum anion gap and acidosis.Metformin is associated with subclinical metabolic acidosis but not with severe metabolic acidosis. The propensity of serum bicarbonate-lowering effect was intensified in advanced CKD; however, such tendency was not associated with the risk of clinically defined acidosis. Our findings highlight a potential of cautious expansion of metformin use among CKD-3b patients with diabetes meriting further investigations.

PMID: 26705203 [PubMed - indexed for MEDLINE]

Epidemiological and clinical profiles of respiratory syncytial virus infection in hospitalized neonates in Suzhou, China.

Recent Research Articles from UNTHSC - Thu, 05/05/2016 - 06:35
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Epidemiological and clinical profiles of respiratory syncytial virus infection in hospitalized neonates in Suzhou, China.

BMC Infect Dis. 2015;15:431

Authors: Lu L, Yan Y, Yang B, Xiao Z, Feng X, Wang Y, Ji W, Mize M, Hao C, Chen Z

Abstract
BACKGROUND: This study was designed to explore the epidemiological and clinical profiles of respiratory syncytial virus (RSV) infection in neonates from the Suzhou area of China, taking into consideration how climate factors influence disease.
METHODS: From 2010 to 2014, nasopharyngeal aspirates (NPA) collected from hospitalized neonates with lower respiratory tract infections (LRIs) were screened for seven common respiratory viruses including RSV by direct immunofluorescence assay. Human bocavirus, human metapneumovirus, and mycoplasma pneumoniae were detected by polymerase chain reaction.
RESULTS: Of the 1803 hospitalized neonates analyzed, 20.74 % were found to be infected with RSV. Interestingly, 30 subjects were identified as being coinfected with other viruses. The rate of RSV infection was highestduring thewinter and early spring seasons; however, infection was negatively associated with monthly mean temperature (rs = -0.821, P < 0.0001), total rainfall (rs = -0.406, P = 0.002), and sum of sunshine (rs = -0.386, P = 0.001). Monthly mean temperature was the only independent factor associated with RSV activity, as determined using multivariate regression analysis. Compared with non-RSV neonates, neonates with RSV infection presented more frequently with tachypnea,moist rales, and abnormal chest X-rays requiring supplemental oxygen and extended hospitalization postpartum. Neonatal admittance into the NICU was determined based on prematurity and coinfection with other viruses; two independent risk factors for RSV disease, as determined by multivariate logistic analysis.
CONCLUSIONS: Important as a major cause of LRIs in hospitalized neonate, we found that the subtropical climate of the Suzhou area was associated with RSV activity. The identified risk factors ofsevere disease in neonates with RSV infection should be taken into consideration when implementing disease health interventions.

PMID: 26470889 [PubMed - indexed for MEDLINE]

Motivational tools to improve probationer treatment outcomes.

Recent Research Articles from UNTHSC - Thu, 05/05/2016 - 06:35
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Motivational tools to improve probationer treatment outcomes.

Contemp Clin Trials. 2015 Jul;43:120-8

Authors: Taxman FS, Walters ST, Sloas LB, Lerch J, Rodriguez M

Abstract
BACKGROUND: Motivational interviewing (MI) is a promising practice to increase motivation, treatment retention, and reducing recidivism among offender populations. Computer-delivered interventions have grown in popularity as a way to change behaviors associated with drug and alcohol use.
METHODS/DESIGN: Motivational Assistance Program to Initiate Treatment (MAPIT) is a three arm, multisite, randomized controlled trial, which examines the impact of Motivational interviewing (MI), a motivational computer program (MC), and supervision as usual (SAU) on addiction treatment initiation, engagement, and retention. Secondary outcomes include drug/alcohol use, probation progress, recidivism (i.e., criminal behavior) and HIV/AIDS testing and treatment among probationers. Participant characteristics are measured at baseline, 2, and 6 months after assignment. The entire study will include 600 offenders, with each site recruiting 300 offenders (Baltimore City, Maryland and Dallas, Texas). All participants will go through standard intake procedures for probation and participate in probation requirements as usual. After standard intake, participants will be recruited and screened for eligibility.
DISCUSSION: The results of this clinical trial will fill a gap in knowledge about ways to motivate probationers to participate in addiction treatment and HIV care. This randomized clinical trial is innovative in the way it examines the use of in-person vs. technological approaches to improve probationer success.
TRIAL REGISTRATION: NCT01891656.

PMID: 26009023 [PubMed - indexed for MEDLINE]

Outcome of children with hypodiploid ALL treated with risk-directed therapy based on MRD levels.

Recent Research Articles from UNTHSC - Wed, 05/04/2016 - 06:37
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Outcome of children with hypodiploid ALL treated with risk-directed therapy based on MRD levels.

Blood. 2015 Dec 24;126(26):2896-9

Authors: Mullighan CG, Jeha S, Pei D, Payne-Turner D, Coustan-Smith E, Roberts KG, Waanders E, Choi JK, Ma X, Raimondi SC, Fan Y, Yang W, Song G, Yang JJ, Inaba H, Downing JR, Leung WH, Bowman WP, Relling MV, Evans WE, Zhang J, Campana D, Pui CH

PMID: 26527677 [PubMed - indexed for MEDLINE]

Small molecule tolfenamic acid and dietary spice curcumin treatment enhances antiproliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution.

Recent Research Articles from UNTHSC - Tue, 05/03/2016 - 06:32

Small molecule tolfenamic acid and dietary spice curcumin treatment enhances antiproliferative effect in pancreatic cancer cells via suppressing Sp1, disrupting NF-kB translocation to nucleus and cell cycle phase distribution.

J Nutr Biochem. 2016 Feb 10;31:77-87

Authors: Basha R, Connelly SF, Sankpal UT, Nagaraju GP, Patel H, Vishwanatha JK, Shelake S, Tabor-Simecka L, Shoji M, Simecka JW, El-Rayes B

Abstract
Combination of dietary/herbal spice curcumin (Cur) and COX inhibitors has been tested for improving therapeutic efficacy in pancreatic cancer (PC). The objective of this study was to identify agent with low toxicity and COX-independent mechanism to induce PC cell growth inhibition when used along with Cur. Anticancer NSAID, tolfenamic acid (TA) and Cur combination were evaluated using PC cell lines. L3.6pl and MIA PaCa-2 cells were treated with Cur (5-25μM) or TA (25-100μM) or combination of Cur (7.5μM) and TA (50μM). Cell viability was measured at 24-72h posttreatment using CellTiter-Glo kit. While both agents showed a steady/consistent effect, Cur+TA caused higher growth inhibition. Antiproliferative effect was compared with COX inhibitors, Ibuprofen and Celebrex. Cardiotoxicity was assessed using cordiomyocytes (H9C2). The expression of Sp proteins, survivin and apoptotic markers (western blot), caspase 3/7 (caspase-Glo kit), Annexin-V staining (flow cytometry), reactive oxygen species (ROS) and cell cycle phase distribution (flow cytometry) was measured. Cells were treated with TNF-α, and NF-kB translocation from cytoplasm to nucleus was evaluated (immunofluorescence). When compared to individual agents, combination of Cur+TA caused significant increase in apoptotic markers, ROS levels and inhibited NF-kB translocation to nucleus. TA caused cell cycle arrest in G0/G1, and the combination treatment showed mostly DNA synthesis phase arrest. These results suggest that combination of Cur+TA is less toxic and effectively enhance the therapeutic efficacy in PC cells via COX-independent mechanisms.

PMID: 27133426 [PubMed - as supplied by publisher]

Midcarpal Instability: A Comprehensive Review and Update.

Recent Research Articles from UNTHSC - Tue, 05/03/2016 - 06:32
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Midcarpal Instability: A Comprehensive Review and Update.

Hand Clin. 2015 Aug;31(3):487-93

Authors: Niacaris T, Ming BW, Lichtman DM

Abstract
Midcarpal instability has been well described as a clinical entity but the pathokinematics and pathologic anatomy continue to be poorly understood. This article presents a comprehensive review of the existing knowledge and literature-based evidence for the diagnosis and management of the various entities comprising midcarpal instability. It discusses the limitations of the current understanding of midcarpal instability and proposes new directions for furthering knowledge of the causes and treatment of midcarpal instability and wrist pathomechanics in general.

PMID: 26205710 [PubMed - indexed for MEDLINE]

Self-Efficacy to Drive While Intoxicated: Insights into the Persistence of Alcohol-Impaired Driving.

Recent Research Articles from UNTHSC - Tue, 05/03/2016 - 06:32
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Self-Efficacy to Drive While Intoxicated: Insights into the Persistence of Alcohol-Impaired Driving.

Alcohol Clin Exp Res. 2015 Aug;39(8):1547-54

Authors: Rossheim ME, Weiler RM, Barnett TE, Suzuki S, Walters ST, Barry AE, Cannell B, Pealer LN, Moorhouse MD, Zhang Q, Thombs DL

Abstract
BACKGROUND: Scant research has examined event-level risk factors for impaired driving in natural drinking settings. This study assessed driving self-efficacy among intoxicated individuals to better understand decision-making about alcohol-impaired driving at night after exiting on-premise drinking establishments.
METHODS: Interview and breath test data were collected from bar patrons (n = 512) exiting 2 college bar districts in Florida and Texas.
RESULTS: Results from a multivariable linear regression model indicated that self-efficacy to drive while intoxicated was more strongly associated with situational variables, that is, perceived drunkenness and self-estimated blood alcohol concentration than patron traits, that is, past-year history of drinking, risk proneness, and sex. A large proportion of bar patrons, particularly men, expressed confidence in their ability to drive, despite being highly intoxicated. Moreover, the majority of legally intoxicated patrons who were confident in their ability to drive were aware of their high level of intoxication.
CONCLUSIONS: Emphasis should be placed on the enactment and enforcement of policies and laws to prevent alcohol-impaired driving.

PMID: 26147102 [PubMed - indexed for MEDLINE]

A genetic overview of 23Y-STR markers in UAE population.

Recent Research Articles from UNTHSC - Fri, 04/29/2016 - 06:30

A genetic overview of 23Y-STR markers in UAE population.

Forensic Sci Int Genet. 2016 Apr 19;23:150-152

Authors: Nazir M, Alhaddad H, Alenizi M, Alenizi H, Taqi Z, Sanqoor S, Alrazouqi A, Hassan A, Alfalasi R, Gaur S, Al Jaber J, Ziab J, Al-Harbi E, Moura-Neto RS, Budowle B

PMID: 27124011 [PubMed - as supplied by publisher]

Reducing the burden of suicide in the U.S.: the aspirational research goals of the National Action Alliance for Suicide Prevention Research Prioritization Task Force.

Recent Research Articles from UNTHSC - Thu, 04/28/2016 - 06:32
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Reducing the burden of suicide in the U.S.: the aspirational research goals of the National Action Alliance for Suicide Prevention Research Prioritization Task Force.

Am J Prev Med. 2014 Sep;47(3):309-14

Authors: Claassen CA, Pearson JL, Khodyakov D, Satow PM, Gebbia R, Berman AL, Reidenberg DJ, Feldman S, Molock S, Carras MC, Lento RM, Sherrill J, Pringle B, Dalal S, Insel TR

Abstract
BACKGROUND: The National Action Alliance for Suicide Prevention Research Prioritization Task Force (RPTF) has created a prioritized national research agenda with the potential to rapidly and substantially reduce the suicide burden in the U.S. if fully funded and implemented.
PURPOSE: Viable, sustainable scientific research agendas addressing challenging public health issues such as suicide often need to incorporate perspectives from multiple stakeholder groups (e.g., researchers, policymakers, and other end-users of new knowledge) during an agenda-setting process. The Stakeholder Survey was a web-based survey conducted and analyzed in 2011-2012 to inform the goal-setting step in the RPTF agenda development process. The survey process, and the final list of "aspirational" research goals it produced, are presented here.
METHODS: Using a modified Delphi process, diverse constituent groups generated and evaluated candidate research goals addressing pressing suicide prevention research needs.
RESULTS: A total of 716 respondents representing 49 U.S. states and 18 foreign countries provided input that ultimately produced 12 overarching, research-informed aspirational goals aimed at reducing the U.S. suicide burden. Highest-rated goals addressed prevention of subsequent suicidal behavior after an initial attempt, strategies to retain patients in care, improved healthcare provider training, and generating care models that would ensure accessible treatment.
CONCLUSIONS: The Stakeholder Survey yielded widely valued research targets. Findings were diverse in focus, type, and current phase of research development but tended to prioritize practical solutions over theoretical advancement. Other complex public health problems requiring input from a broad-based constituency might benefit from web-based tools that facilitate such community input.

PMID: 24750971 [PubMed - indexed for MEDLINE]

Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery.

Recent Research Articles from UNTHSC - Wed, 04/27/2016 - 06:31

Rigid Residue Scan Simulations Systematically Reveal Residue Entropic Roles in Protein Allostery.

PLoS Comput Biol. 2016 Apr;12(4):e1004893

Authors: Kalescky R, Zhou H, Liu J, Tao P

Abstract
Intra-protein information is transmitted over distances via allosteric processes. This ubiquitous protein process allows for protein function changes due to ligand binding events. Understanding protein allostery is essential to understanding protein functions. In this study, allostery in the second PDZ domain (PDZ2) in the human PTP1E protein is examined as model system to advance a recently developed rigid residue scan method combining with configurational entropy calculation and principal component analysis. The contributions from individual residues to whole-protein dynamics and allostery were systematically assessed via rigid body simulations of both unbound and ligand-bound states of the protein. The entropic contributions of individual residues to whole-protein dynamics were evaluated based on covariance-based correlation analysis of all simulations. The changes of overall protein entropy when individual residues being held rigid support that the rigidity/flexibility equilibrium in protein structure is governed by the La Châtelier's principle of chemical equilibrium. Key residues of PDZ2 allostery were identified with good agreement with NMR studies of the same protein bound to the same peptide. On the other hand, the change of entropic contribution from each residue upon perturbation revealed intrinsic differences among all the residues. The quasi-harmonic and principal component analyses of simulations without rigid residue perturbation showed a coherent allosteric mode from unbound and bound states, respectively. The projection of simulations with rigid residue perturbation onto coherent allosteric modes demonstrated the intrinsic shifting of ensemble distributions supporting the population-shift theory of protein allostery. Overall, the study presented here provides a robust and systematic approach to estimate the contribution of individual residue internal motion to overall protein dynamics and allostery.

PMID: 27115535 [PubMed - as supplied by publisher]

Peripheral retinal telangiectasia and ischemia in Takayasu's arteritis.

Recent Research Articles from UNTHSC - Tue, 04/26/2016 - 06:30

Peripheral retinal telangiectasia and ischemia in Takayasu's arteritis.

Arthritis Rheumatol. 2016 Apr 25;

Authors: Batliwala SY, Perez M, Aston W, Chavala SH

PMID: 27110659 [PubMed - as supplied by publisher]

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability.

Recent Research Articles from UNTHSC - Sat, 04/23/2016 - 06:42

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability.

Int J Nanomedicine. 2016;11:1451-60

Authors: Guo S, Pham K, Li D, Penzak SR, Dong X

Abstract
PURPOSE: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability.
MATERIALS AND METHODS: In one method, we prepared ritonavir (RTV) nanoparticles (NPs) by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs). We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules.
RESULTS: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability over 2.5-fold compared to RTV solution.
CONCLUSION: We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development.

PMID: 27103803 [PubMed - in process]

Authors' Response to Letter Regarding Alcohol Sales Tax and Sexually Transmitted Infections.

Recent Research Articles from UNTHSC - Sat, 04/23/2016 - 06:42

Authors' Response to Letter Regarding Alcohol Sales Tax and Sexually Transmitted Infections.

Am J Prev Med. 2016 May;50(5):e161

Authors: Staras SA, Livingston MD, Wagenaar AC

PMID: 27102644 [PubMed - in process]

Breath-based meditation: A mechanism to restore the physiological and cognitive reserves for optimal human performance.

Recent Research Articles from UNTHSC - Fri, 04/22/2016 - 10:37
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Breath-based meditation: A mechanism to restore the physiological and cognitive reserves for optimal human performance.

World J Clin Cases. 2016 Apr 16;4(4):99-102

Authors: Carter KS, Carter Iii R

Abstract
Stress can be associated with many physiological changes resulting in significant decrements in human performance. Due to growing interests in alternative and complementary medicine by Westerners, many of the traditions and holistic yogic breathing practices today are being utilized as a measure for healthier lifestyles. These state-of-the-art practices can have a significant impact on common mental health conditions such as depression and generalized anxiety disorder. However, the potential of yogic breathing on optimizing human performance and overall well-being is not well known. Breathing techniques such as alternate nostril, Sudarshan Kriya and bhastrika utilizes rhythmic breathing to guide practitioners into a deep meditative state of relaxation and promote self-awareness. Furthermore, yogic breathing is physiologically stimulating and can be described as a natural "technological" solution to optimize human performance which can be categorized into: (1) cognitive function (i.e., mind, vigilance); and (2) physical performance (i.e., cardiorespiratory, metabolism, exercise, whole body). Based on previous studies, we postulate that daily practice of breathing meditation techniques play a significant role in preserving the compensatory mechanisms available to sustain physiological function. This preservation of physiological function may help to offset the time associated with reaching a threshold for clinical expression of chronic state (i.e., hypertension, depression, dementia) or acute state (i.e., massive hemorrhage, panic attic) of medical conditions. However, additional rigorous biomedical research is needed to evaluate the physiological mechanisms of various forms of meditation (i.e., breath-based, mantra, mindfulness) on human performance. These efforts will help to define how compensatory reserve mechanisms of cardiovascular and immune systems are modulated by breath-based meditation. While it has been suggested that breath-based meditation is easier for beginning practitioners when compared to other forms of meditation more research is needed to elucidate these observations. A breath-based meditation sequence such as Sudarshan Kriya has the potential to help develop an individual's self-awareness and support better integration of the brain (i.e., mind) with other organ systems (i.e., body) for enhanced human performance.

PMID: 27099859 [PubMed]

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