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Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas.

Recent Research Articles from UNTHSC - Fri, 07/14/2017 - 07:36
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Dopamine agonist resistance-related endocan promotes angiogenesis and cells viability of prolactinomas.

Endocrine. 2016 Jun;52(3):641-51

Authors: Cai L, Leng ZG, Guo YH, Lin SJ, Wu ZR, Su ZP, Lu JL, Wei LF, Zhuge QC, Jin K, Wu ZB

Abstract
Dopamine agonists (DAs) are the first-line treatment of prolactinomas. They function through the dopamine 2 receptor (D2R) in the tumor cells. Endocan, also called endothelial cell-specific molecule-1 (ESM1), has been described as a marker of neoangiogenesis. However, whether ESM1 promotes the resistance of prolactinomas to DA therapy is largely unknown. In our study, 25 patients with prolactinomas were divided into resistant- and sensitive- groups according to the clinical response to bromocriptine. We found that ESM1-microvessel density of resistant prolactinomas was significantly higher than that of sensitive prolactinomas (47.9 ± 11.6, n = 8, vs 13.1 ± 2.8, n = 17, p = 0.0006), indicating that ESM1 was a DA resistance-related gene. Immunostaining showed that ESM1 was expressed in tumor vessels and sporadic tumor cells, and ESM1 was overlapped with the Smooth Muscle Actin (SMA) and von Willebrand Factor (VWF) in the tumor vessels. Silencing of ESM1 markedly suppressed the viability of GH3 and MMQ cells in vitro, and furthermore, significantly increased the sensitivity of GH3 and MMQ cells to DA treatment. Additionally, silencing of ESM1 down-regulated the angiogenesis-associated genes, such as VEGFR2, FGF2, CD34, CD31, VWF, and EGFR. Knockdown of ESM1 decreased endothelial tube formation of HUVECs, and significantly increased the sensitivity of HUVECs to Avastin treatment. Therefore, we first demonstrate that DA resistance-related ESM1 promotes the angiogenesis and tumor cells growth of prolactinomas, suggesting that ESM1 may be a novel therapeutic target for prolactinomas.

PMID: 26662185 [PubMed - indexed for MEDLINE]

Energetic redistribution in allostery to execute protein function.

Recent Research Articles from UNTHSC - Wed, 07/12/2017 - 07:35
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Energetic redistribution in allostery to execute protein function.

Proc Natl Acad Sci U S A. 2017 Jul 10;:

Authors: Liu J, Nussinov R

PMID: 28696318 [PubMed - as supplied by publisher]

Potassium as a pluripotency-associated element identified through inorganic element profiling in human pluripotent stem cells.

Recent Research Articles from UNTHSC - Wed, 07/12/2017 - 07:35
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Potassium as a pluripotency-associated element identified through inorganic element profiling in human pluripotent stem cells.

Sci Rep. 2017 Jul 10;7(1):5005

Authors: Lin VJT, Zolekar A, Shi Y, Koneru B, Dimitrijevich S, Di Pasqua AJ, Wang YC

Abstract
Despite their well-known function in maintaining normal cell physiology, how inorganic elements are relevant to cellular pluripotency and differentiation in human pluripotent stem cells (hPSCs) has yet to be systematically explored. Using total reflection X-ray fluorescence (TXRF) spectrometry and inductively coupled plasma mass spectrometry (ICP-MS), we analyzed the inorganic components of human cells with isogenic backgrounds in distinct states of cellular pluripotency. The elemental profiles revealed that the potassium content of human cells significantly differs when their cellular pluripotency changes. Pharmacological treatment that alters cell membrane permeability to potassium affected the maintenance and establishment of cellular pluripotency via multiple mechanisms in bona fide hPSCs and reprogrammed cells. Collectively, we report that potassium is a pluripotency-associated inorganic element in human cells and provide novel insights into the manipulation of cellular pluripotency in hPSCs by regulating intracellular potassium.

PMID: 28694442 [PubMed - in process]

Adiponectin: Its role in obesity-associated colon and prostate cancers.

Recent Research Articles from UNTHSC - Wed, 07/12/2017 - 07:35
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Adiponectin: Its role in obesity-associated colon and prostate cancers.

Crit Rev Oncol Hematol. 2017 Aug;116:125-133

Authors: Muppala S, Konduru SKP, Merchant N, Ramsoondar J, Rampersad CK, Rajitha B, Mukund V, Kancherla J, Hammond A, Barik TK, Mannarapu M, Alam A, Basha R, Bramhachari PV, Verma D, Sushma PS, Pattnaik S, Nagaraju GP

Abstract
Adipose tissue synthesizes many proteins and hormones collectively called adipokines, which are linked to a number of diseases, including cancer. Low levels of adiponectin are reported to be a risk factor for obesity-related cancers including colorectal and prostate cancers. Accordingly, obesity/lifestyle-related diseases, including certain cancers, may be treated by developing drugs that act specifically on adiponectin levels in circulation. Adiponectin may also serve as a clinical biomarker in obesity-related diseases. Adiponectin-based therapies are known to inhibit cancer advancement and thus may provide a therapeutic approach to delay cancer progression. Better understanding of the function of adiponectin is of great significance in the fight against cancer. This timely review is concentrated on the role of adiponectin and the impact of obesity on the development of cancers, especially colorectal and prostate cancers.

PMID: 28693794 [PubMed - in process]

Optimal Measurement Interval for Emergency Department Crowding Estimation Tools.

Recent Research Articles from UNTHSC - Mon, 07/10/2017 - 07:35

Optimal Measurement Interval for Emergency Department Crowding Estimation Tools.

Ann Emerg Med. 2017 Jul 06;:

Authors: Wang H, Ojha RP, Robinson RD, Jackson BE, Shaikh SA, Cowden CD, Shyamanand R, Leuck J, Schrader CD, Zenarosa NR

Abstract
STUDY OBJECTIVE: Emergency department (ED) crowding is a barrier to timely care. Several crowding estimation tools have been developed to facilitate early identification of and intervention for crowding. Nevertheless, the ideal frequency is unclear for measuring ED crowding by using these tools. Short intervals may be resource intensive, whereas long ones may not be suitable for early identification. Therefore, we aim to assess whether outcomes vary by measurement interval for 4 crowding estimation tools.
METHODS: Our eligible population included all patients between July 1, 2015, and June 30, 2016, who were admitted to the JPS Health Network ED, which serves an urban population. We generated 1-, 2-, 3-, and 4-hour ED crowding scores for each patient, using 4 crowding estimation tools (National Emergency Department Overcrowding Scale [NEDOCS], Severely Overcrowded, Overcrowded, and Not Overcrowded Estimation Tool [SONET], Emergency Department Work Index [EDWIN], and ED Occupancy Rate). Our outcomes of interest included ED length of stay (minutes) and left without being seen or eloped within 4 hours. We used accelerated failure time models to estimate interval-specific time ratios and corresponding 95% confidence limits for length of stay, in which the 1-hour interval was the reference. In addition, we used binomial regression with a log link to estimate risk ratios (RRs) and corresponding confidence limit for left without being seen.
RESULTS: Our study population comprised 117,442 patients. The time ratios for length of stay were similar across intervals for each crowding estimation tool (time ratio=1.37 to 1.30 for NEDOCS, 1.44 to 1.37 for SONET, 1.32 to 1.27 for EDWIN, and 1.28 to 1.23 for ED Occupancy Rate). The RRs of left without being seen differences were also similar across intervals for each tool (RR=2.92 to 2.56 for NEDOCS, 3.61 to 3.36 for SONET, 2.65 to 2.40 for EDWIN, and 2.44 to 2.14 for ED Occupancy Rate).
CONCLUSION: Our findings suggest limited variation in length of stay or left without being seen between intervals (1 to 4 hours) regardless of which of the 4 crowding estimation tools were used. Consequently, 4 hours may be a reasonable interval for assessing crowding with these tools, which could substantially reduce the burden on ED personnel by requiring less frequent assessment of crowding.

PMID: 28688771 [PubMed - as supplied by publisher]

Measurement of drug-target engagement in live cells by two-photon fluorescence anisotropy imaging.

Recent Research Articles from UNTHSC - Sat, 07/08/2017 - 07:36

Measurement of drug-target engagement in live cells by two-photon fluorescence anisotropy imaging.

Nat Protoc. 2017 Jul;12(7):1472-1497

Authors: Vinegoni C, Fumene Feruglio P, Brand C, Lee S, Nibbs AE, Stapleton S, Shah S, Gryczynski I, Reiner T, Mazitschek R, Weissleder R

Abstract
The ability to directly image and quantify drug-target engagement and drug distribution with subcellular resolution in live cells and whole organisms is a prerequisite to establishing accurate models of the kinetics and dynamics of drug action. Such methods would thus have far-reaching applications in drug development and molecular pharmacology. We recently presented one such technique based on fluorescence anisotropy, a spectroscopic method based on polarization light analysis and capable of measuring the binding interaction between molecules. Our technique allows the direct characterization of target engagement of fluorescently labeled drugs, using fluorophores with a fluorescence lifetime larger than the rotational correlation of the bound complex. Here we describe an optimized protocol for simultaneous dual-channel two-photon fluorescence anisotropy microscopy acquisition to perform drug-target measurements. We also provide the necessary software to implement stream processing to visualize images and to calculate quantitative parameters. The assembly and characterization part of the protocol can be implemented in 1 d. Sample preparation, characterization and imaging of drug binding can be completed in 2 d. Although currently adapted to an Olympus FV1000MPE microscope, the protocol can be extended to other commercial or custom-built microscopes.

PMID: 28686582 [PubMed - in process]

Analysis of DNA from post-blast pipe bomb fragments for identification and determination of ancestry.

Recent Research Articles from UNTHSC - Sat, 07/08/2017 - 07:36
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Analysis of DNA from post-blast pipe bomb fragments for identification and determination of ancestry.

Forensic Sci Int Genet. 2017 May;28:195-202

Authors: Tasker E, LaRue B, Beherec C, Gangitano D, Hughes-Stamm S

Abstract
Improvised explosive devices (IEDs) such as pipe bombs are weapons used to detrimentally affect people and communities. A readily accessible brand of exploding targets called Tannerite® has been identified as a potential material for abuse as an explosive in pipe bombs. The ability to recover and genotype DNA from such weapons may be vital in the effort to identify suspects associated with these devices. While it is possible to recover DNA from post-blast fragments using short tandem repeat markers (STRs), genotyping success can be negatively affected by low quantities of DNA, degradation, and/or PCR inhibitors. Alternative markers such as insertion/null (INNULs) and single nucleotide polymorphisms (SNPs) are bi-allelic genetic markers that are shorter genomic targets than STRs for amplification, which are more likely to resist degradation. In this study, we constructed pipe bombs that were spiked with known amounts of biological material to: 1) recover "touch" DNA from the surface of the device, and 2) recover traces of blood from the ends of wires (simulated finger prick). The bombs were detonated with the binary explosive Tannerite® using double-base smokeless powder to initiate the reaction. DNA extracted from the post-blast fragments was quantified with the Quantifiler® Trio DNA Quantification Kit. STR analysis was conducted using the GlobalFiler® Amplification Kit, INNULs were amplified using an early-access version of the InnoTyper™ 21 Kit, and SNP analysis via massively parallel sequencing (MPS) was performed using the HID-Ion Ampliseq™ Identity and Ancestry panels using the Ion Chef and Ion PGM sequencing system. The results of this study showed that INNUL markers resulted in the most complete genetic profiles when compared to STR and SNP profiles. The random match probabilities calculated for samples using INNULs were lower than with STRs when less than 14 STR alleles were reported. These results suggest that INNUL analysis may be well suited for low-template and/or degraded DNA samples, and may be used to supplement incomplete or failed STR analysis. Human identification using SNP analysis via MPS showed variable success with low-level post-blast samples in this study (<150pg). While neat DNA samples (6μL input as recommended) resulted in <50% of SNP calls, samples that were concentrated from 15μL to 6μL (15μL was added for STR and INNUL typing) resulted in more complete SNP profiles. Five out of six blood samples recovered from the wires attached to the pipe-bombs resulted in the correct ancestry predictions.

PMID: 28292727 [PubMed - indexed for MEDLINE]

The factor of 10 in forensic DNA match probabilities.

Recent Research Articles from UNTHSC - Sat, 07/08/2017 - 07:36
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The factor of 10 in forensic DNA match probabilities.

Forensic Sci Int Genet. 2017 May;28:178-187

Authors: Gittelson S, Moretti TR, Onorato AJ, Budowle B, Weir BS, Buckleton J

Abstract
An update was performed of the classic experiments that led to the view that profile probability assignments are usually within a factor of 10 of each other. The data used in this study consist of 15 Identifiler loci collected from a wide range of forensic populations. Following Budowle et al. [1], the terms cognate and non-cognate are used. The cognate database is the database from which the profiles are simulated. The profile probability assignment was usually larger in the cognate database. In 44%-65% of the cases, the profile probability for 15 loci in the non-cognate database was within a factor of 10 of the profile probability in the cognate database. This proportion was between 60% and 80% when the FBI and NIST data were used as the non-cognate databases. A second experiment compared the match probability assignment using a generalised database and recommendation 4.2 from NRC II (the 4.2 assignment) with a proxy for the matching proportion developed using subpopulation allele frequencies and the product rule. The findings support that the 4.2 assignment has a large conservative bias. These results are in agreement with previous research results.

PMID: 28273509 [PubMed - indexed for MEDLINE]

Flanking region variation of ForenSeq™ DNA Signature Prep Kit STR and SNP loci in Yavapai Native Americans.

Recent Research Articles from UNTHSC - Sat, 07/08/2017 - 07:36
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Flanking region variation of ForenSeq™ DNA Signature Prep Kit STR and SNP loci in Yavapai Native Americans.

Forensic Sci Int Genet. 2017 May;28:146-154

Authors: Wendt FR, King JL, Novroski NM, Churchill JD, Ng J, Oldt RF, McCulloh KL, Weise JA, Smith DG, Kanthaswamy S, Budowle B

Abstract
Massively parallel sequencing (MPS) offers advantages over current capillary electrophoresis-based analysis of short tandem repeat (STR) loci for human identification testing. In particular STR repeat motif sequence information can be obtained, thereby increasing the discrimination power of some loci. While sequence variation within the repeat region is observed relatively frequently in some of the commonly used STRs, there is an additional degree of variation found in the flanking regions adjacent to the repeat motif. Repeat motif and flanking region sequence variation have been described for major population groups, however, not for more isolated populations. Flanking region sequence variation in STR and single nucleotide polymorphism (SNP) loci in the Yavapai population was analyzed using the ForenSeq™ DNA Signature Prep Kit and STRait Razor v2s. Seven and 14 autosomal STRs and identity-informative single nucleotide polymorphisms (iiSNPs), respectively, had some degree of flanking region variation. Three and four of these identity-informative loci, respectively, showed ≥5% increase in expected heterozygosity. The combined length- and sequence-based random match probabilities (RMPs) for 27 autosomal STRs were 6.11×10(-26) and 2.79×10(-29), respectively. When combined with 94 iiSNPs (a subset of which became microhaplotypes) the combined RMP was 5.49×10(-63). Analysis of length-based and sequence-based autosomal STRs in STRUCTURE indicated that the Yavapai are most similar to the Hispanic population. While producing minimal increase in X- and Y-STR discrimination potential, access to flanking region data enabled identification of one novel X-STR and three Y-STR alleles relative to previous reports. Five ancestry-informative SNPs (aiSNPs) and two phenotype-informative SNPs (piSNPs) exhibited notable flanking region variation.

PMID: 28273507 [PubMed - indexed for MEDLINE]

Factors Associated with Self-Estimated Breath Alcohol Concentration Among Bar Patrons.

Recent Research Articles from UNTHSC - Fri, 07/07/2017 - 07:34
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Factors Associated with Self-Estimated Breath Alcohol Concentration Among Bar Patrons.

Alcohol Clin Exp Res. 2017 Jul 06;:

Authors: Rossheim ME, Barry AE, Thombs DL, Weiler RM, Krall JR, Stephenson CJ, Walters ST, Reed MB, Clapp JD, Suzuki S, Barnett TE, Cannell MB

Abstract
BACKGROUND: Few studies have examined the context in which drinkers underestimate their breath alcohol concentration (BrAC) in natural drinking environments. This study examined factors associated with bar patrons' self-estimated BrAC in high-risk college town settings.
METHODS: Guided interview and BrAC data were collected from 510 participants recruited as they exited bars located close to large universities: 1 in Florida and 1 in Texas.
RESULTS: Participants with the highest measured BrACs underestimated their BrAC levels the most. Findings from multivariable linear regression analysis indicated that BrAC (std β = 0.014, p < 0.001), number of alcoholic drinks consumed (std β = 0.006, p < 0.01), and perceived drunkenness (std β = 0.024, p < 0.001) had significant positive associations with BrAC self-estimates, where the regression coefficients were scaled by values approximately equal to each variable's interquartile range. Among the 321 participants with BrAC levels ≥ 0.08 g/dl, 21.2% believed their BrAC was below the legal per se driving limit of 0.08 g/dl. Results from a logistic regression analysis indicated that higher levels of perceived drunkenness were associated with better self-recognition that one's BrAC level exceeded the legal driving threshold (OR = 3.312, p < 0.001). Further, participants under 26 years of age had reduced odds of recognizing that their BrAC was greater than 0.079 g/dl (OR = 0.245, p < 0.05).
CONCLUSIONS: These findings highlight the inaccuracy of self-estimated BrAC when drinking, particularly among younger drinkers. Adjusting for BrAC, situational factors were strongly associated with self-estimated BrAC. Future research is needed to better understand how altering drinking environments may improve accuracy of BrAC self-estimates and deter driving after drinking.

PMID: 28683518 [PubMed - as supplied by publisher]

A Comparison and Integration of MiSeq and MinION Platforms for Sequencing Single Source and Mixed Mitochondrial Genomes.

Recent Research Articles from UNTHSC - Fri, 07/07/2017 - 07:34
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A Comparison and Integration of MiSeq and MinION Platforms for Sequencing Single Source and Mixed Mitochondrial Genomes.

PLoS One. 2016;11(12):e0167600

Authors: Lindberg MR, Schmedes SE, Hewitt FC, Haas JL, Ternus KL, Kadavy DR, Budowle B

Abstract
Single source and multiple donor (mixed) samples of human mitochondrial DNA were analyzed and compared using the MinION and the MiSeq platforms. A generalized variant detection strategy was employed to provide a cursory framework for evaluating the reliability and accuracy of mitochondrial sequences produced by the MinION. The feasibility of long-read phasing was investigated to establish its efficacy in quantitatively distinguishing and deconvolving individuals in a mixture. Finally, a proof-of-concept was demonstrated by integrating both platforms in a hybrid assembly that leverages solely mixture data to accurately reconstruct full mitochondrial genomes.

PMID: 27936026 [PubMed - indexed for MEDLINE]

Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms.

Recent Research Articles from UNTHSC - Thu, 07/06/2017 - 07:36

Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms.

Cell Mol Neurobiol. 2017 Jul 04;:

Authors: Lazuko SS, Kuzhel OP, Belyaeva LE, Manukhina EB, Fred Downey H, Tseilikman OB, Komelkova MV, Tseilikman VE

Abstract
Posttraumatic stress disorder (PTSD) is associated with myocardial injury, but changes in coronary regulatory mechanisms in PTSD have not been investigated. This study evaluated the effect of PTSD-inducing stress on coronary tone and its regulation by nitric oxide (NO) and voltage-gated K(+) channels. PTSD was induced by exposing rats to predator stress, 15 min daily for 10 days, followed by 14 stress-free days. Presence of PTSD was confirmed by the elevated plus-maze test. Coronary tone was evaluated from changes in coronary perfusion pressure of Langendorff isolated hearts. Predator stress induced significant decreases in coronary tone of isolated hearts and in blood pressure of intact rats. L-NAME, a non-selective NO synthase (NOS) inhibitor, but not S-MT, a selective iNOS inhibitor, and increased coronary tone of control rats. In PTSD rats, both L-NAME and S-MT increased coronary tone. Therefore, the stress-induced coronary vasodilation resulted from NO overproduction by both iNOS and eNOS. NOS induction was apparently due to systemic inflammation as evidenced by increased serum interleukin-1β and C-reactive protein in PTSD rats. Decreased corticosterone in PTSD rats may have contributed to inflammation and its effect on coronary tone. PTSD was also associated with voltage-gated K(+) channel dysfunction, which would have also reduced coronary tone.

PMID: 28676988 [PubMed - as supplied by publisher]

Calcium plus vitamin D supplementation and lung cancer incidence among postmenopausal women in the Women's Health Initiative.

Recent Research Articles from UNTHSC - Thu, 07/06/2017 - 07:36

Calcium plus vitamin D supplementation and lung cancer incidence among postmenopausal women in the Women's Health Initiative.

Lung Cancer. 2017 Aug;110:42-47

Authors: Tao MH, Dai Q, Chen S, Freudenheim JL, Rohan T, Wakelee H, Datta M, Wactawski-Wende J

Abstract
BACKGROUND: Magnesium and calcium are antagonistic in many physiologic processes. However, few studies have investigated the associations of supplemental calcium with lung cancer risk taking this antagonism into account. We evaluated the effect of calcium and vitamin D supplementation on lung cancer incidence and explored whether the ratio of baseline calcium to magnesium (Ca:Mg) intake modifies the association in the Women's Health Initiative (WHI) calcium plus vitamin D supplementation (CaD) trial.
METHODS: The intervention phase of the WHI CaD was a double-blinded, randomized, placebo-controlled trial in 36,382 postmenopausal women aged 50-79 years, recruited at 40U.S. centers. Post-intervention follow-up continued among 29,862 (86%) of the surviving participants. Risk of lung cancer in association with CaD supplementation was evaluated using proportional hazard regression models.
RESULTS: After 11 years' cumulative follow-up, there were 207 lung cancers (incidence 0.11% per year) in the supplement arm and 241 (0.12%) in the placebo arm (hazard ratio (HR) for the intervention, 0.91; 95% confidence interval (CI), 0.71-1.17). Subgroup analyses suggested that the HR for lung cancer varied by baseline Ca:Mg intake ratio among women who were current smokers at enrollment (p=0.04 for interaction).
CONCLUSIONS: Over the entire follow-up period, calcium and vitamin D supplementation did not reduce lung cancer incidence among postmenopausal women. In exploratory analyses, an interaction was found for the baseline Ca:Mg intake ratio on lung cancer among current smokers at the trial entry. This findings need to be further studied for the role of calcium with magnesium in lung carcinogenesis in current smokers.

PMID: 28676217 [PubMed - in process]

Associations Between Self-Reported Physical Activity and Physical Performance Measures Over Time in Postmenopausal Women: The Women's Health Initiative.

Recent Research Articles from UNTHSC - Wed, 07/05/2017 - 07:38

Associations Between Self-Reported Physical Activity and Physical Performance Measures Over Time in Postmenopausal Women: The Women's Health Initiative.

J Am Geriatr Soc. 2017 Jul 04;:

Authors: Laddu DR, Wertheim BC, Garcia DO, Brunner R, Groessl E, Shadyab AH, Going SB, LaMonte MJ, Cannell B, LeBoff MS, Cauley JA, Thomson CA, Stefanick ML

Abstract
OBJECTIVES: To examine prospective associations between changes in physical activity (PA) and changes in physical performance measures (PPMs) over 6 years in older women.
DESIGN: Prospective cohort study.
SETTING: Forty clinical centers in the United States.
PARTICIPANTS: Women aged 65 and older (mean age 69.8) enrolled in the Women's Health Initiative Clinical Trials with gait speed, timed chair stand, grip strength, and self-reported recreational PA data assessed at baseline (1993-98) and follow-up Years 1, 3, and 6 (N = 5,092).
MEASUREMENTS: Mixed-effects linear regression models were used to determine the association between time-varying PA and change in each PPM. Potential interactions between time-varying PA and age (<70, ≥70) were also tested.
RESULTS: Significan, dose-response associations between PA and improvements in all PPMs were observed over the 6 years of follow-up after adjusting for important covariates. High PA groups (≥1,200 metabolic equivalent (MET)-min/wk) had stronger grip strength (0.48 kg greater; P < .01), more chair stands (0.35 more; P < .001), and faster gait speeds (0.06 m/s faster; P < .001) than sedentary women (<100 MET-min/wk). Higher PA levels were associated with a greater increase in chair stands over time in women aged 70 and older (P < .001) than in those younger than 70 (Pinteraction for age  = .01).
CONCLUSION: In postmenopausal women, maintaining high PA levels over time is associated with better lower extremity function. These data support the view that regular PA plays an important role in maintaining functional status during aging in older women.

PMID: 28675421 [PubMed - as supplied by publisher]

SR-B1-targeted nanodelivery of anti-cancer agents: a promising new approach to treat triple-negative breast cancer.

Recent Research Articles from UNTHSC - Tue, 07/04/2017 - 07:37

SR-B1-targeted nanodelivery of anti-cancer agents: a promising new approach to treat triple-negative breast cancer.

Breast Cancer (Dove Med Press). 2017;9:383-392

Authors: Johnson R, Sabnis N, Sun X, Ahluwalia R, Lacko AG

Abstract
Patients with triple-negative breast cancer (TNBC) have a considerably less favorable prognosis than those with hormone-positive breast cancers. TNBC patients do not respond to current endocrine treatment and have a 5-year survival prognosis of <30%. The research presented here is intended to fill a void toward the much needed development of improved treatment strategies for metastatic TNBC. The overall goal of this research was to evaluate the effectiveness of reconstituted high-density lipoprotein (rHDL) nanoparticles (NPs) as delivery agents for anti-TNBC drugs. Using lapatinib and valrubicin as components of the rHDL/drug complexes resulted in a significantly better performance of the NP-transported drugs compared with their free (unencapsulated) counterparts. The enhancement of the therapeutic effect and the protection of normal cells (cardiomyocytes) achieved via the rHDL NPs were likely due to the overexpression of the high-density lipoprotein (HDL) (scavenger receptor class B type 1 [SR-B1]) receptor by the TNBC cells.

PMID: 28670138 [PubMed]

Resistance training for activity limitations in older adults with skeletal muscle function deficits: a systematic review.

Recent Research Articles from UNTHSC - Tue, 07/04/2017 - 07:37

Resistance training for activity limitations in older adults with skeletal muscle function deficits: a systematic review.

Clin Interv Aging. 2017;12:955-961

Authors: Papa EV, Dong X, Hassan M

Abstract
Human aging results in a variety of changes to skeletal muscle. Sarcopenia is the age-associated loss of muscle mass and is one of the main contributors to musculoskeletal impairments in the elderly. Previous research has demonstrated that resistance training can attenuate skeletal muscle function deficits in older adults, however few articles have focused on the effects of resistance training on functional mobility. The purpose of this systematic review was to 1) present the current state of literature regarding the effects of resistance training on functional mobility outcomes for older adults with skeletal muscle function deficits and 2) provide clinicians with practical guidelines that can be used with seniors during resistance training, or to encourage exercise. We set forth evidence that resistance training can attenuate age-related changes in functional mobility, including improvements in gait speed, static and dynamic balance, and fall risk reduction. Older adults should be encouraged to participate in progressive resistance training activities, and should be admonished to move along a continuum of exercise from immobility, toward the recommended daily amounts of activity.

PMID: 28670114 [PubMed - in process]

The Risks to Patient Privacy from Publishing Data from Clinical Anesthesia Studies.

Recent Research Articles from UNTHSC - Tue, 07/04/2017 - 07:37
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The Risks to Patient Privacy from Publishing Data from Clinical Anesthesia Studies.

Anesth Analg. 2016 Jun;122(6):2017-27

Authors: O'Neill L, Dexter F, Zhang N

Abstract
In this article, we consider the privacy implications of posting data from small, randomized trials, observational studies, or case series in anesthesia from a few (e.g., 1-3) hospitals. Prior to publishing such data as supplemental digital content, the authors remove attributes that could be used to re-identify individuals, a process known as "anonymization." Posting health information that has been properly "de-identified" is assumed to pose no risks to patient privacy. Yet, computer scientists have demonstrated that this assumption is flawed. We consider various realistic scenarios of how the publication of such data could lead to breaches of patient privacy. Several examples of successful privacy attacks are reviewed, as well as the methods used. We survey the latest models and methods from computer science for protecting health information and their application to posting data from small anesthesia studies. To illustrate the vulnerability of such published data, we calculate the "population uniqueness" for patients undergoing one or more surgical procedures using data from the State of Texas. For a patient selected uniformly at random, the probability that an adversary could match this patient's record to a unique record in the state external database was 42.8% (SE < 0.1%). Despite the 42.8% being an unacceptably high level of risk, it underestimates the risk for patients from smaller states or provinces. We propose an editorial policy that greatly reduces the likelihood of a privacy breach, while supporting the goal of transparency of the research process.

PMID: 27172145 [PubMed - indexed for MEDLINE]

Clinical predictors of recurrent stenosis and need for re-intervention in the cephalic arch in patients with brachiocephalic AV fistulas.

Recent Research Articles from UNTHSC - Sat, 07/01/2017 - 07:39

Clinical predictors of recurrent stenosis and need for re-intervention in the cephalic arch in patients with brachiocephalic AV fistulas.

J Vasc Access. 2017 Jun 23;:0

Authors: Balamuthusamy S, Reddi AL, Madhrira MH, Sankarapandian B, Nguyen P, Vallurupalli A, Gabbard W, Jalandhara N, Yurvati A

Abstract
INTRODUCTION: Cephalic arch stenosis is one of the most common reasons for repeated endovascular intervention and eventual abandonment of access in hemodialysis patients. There is no prediction model to identify risk factors for recurrent cephalic arch stenosis. We have developed a mathematical model to predict the need for reintervention in brachiocephalic (BC) fistulas with recurrent cephalic arch stenosis.
METHODS: Single-center retrospective analysis of 143 patients with a BC fistula referred to the vascular clinic for access dysfunction who underwent cephalic arch angioplasty were included for the analysis. Twelve-month post-index angioplasty data were analyzed using parametric, non-parametric and multiple regression models using SPSS software.
RESULTS: The mean need for re-intervention in 1 year since first index visit was 2.46 ± 1.404. Statistically significant correlation (p≤0.001) for re-intervention was observed with the severity of stenosis at index visit, access flow, vessel wall diameter proximal to the stenosis, average venous pressure >50% of the delivered blood flow rate and prolonged bleeding for >30 minutes as a reason for referral. Three equations have been derived for calculating the need for re-intervention based on the diameter of the vessel wall proximal to the stenosis.
CONCLUSIONS: Risk stratification of BC fistulas utilizing the above parameters could enable clinicians to identify accesses that are at risk for multiple re-interventions. Early identification of accesses that are at high risk for re-interventions at the cephalic arch might prolong access survival and reduce the cost for intervention by utilizing alternate strategies.

PMID: 28665461 [PubMed - as supplied by publisher]

Comparative exploration of the structure-activity space of cloned α-like octopamine receptors from a marine and a terrestrial arthropod.

Recent Research Articles from UNTHSC - Sat, 07/01/2017 - 07:39

Comparative exploration of the structure-activity space of cloned α-like octopamine receptors from a marine and a terrestrial arthropod.

Mol Pharmacol. 2017 Jun 29;:

Authors: Dalwadi DA, Schetz JA

Abstract
The α-like octopamine receptors are believed to be the evolutionary precursor to the vertebrate α2-adrenergic receptors (α2-ARs) based upon sequence similarity and the ability to interact with norepinephrine and a number of compounds that bind with high affinity to α2-ARs. Barnacles and fruit flies are two prominent model marine and terrestrial representatives of the Arthropoda phylum, and while α-like OctRs have been cloned from Balanus improvisus (BiOctR) and Drosophila melanogaster (DmOctR), little is known about the structure-activity space for these important species. A diverse panel of twenty-two probes spanning different structural classes were employed to interrogate the structure-activity of the BiOctR and DmOctR. While BiOctR and DmOctR exhibited similar functional profiles for mammalian biogenic amine GPCR agonists and antagonists, some ligands had dramatically different mechanisms of action. For instance, significant differences in the efficacy for some agonists was observed, including that vertebrate biogenic amines structurally related to octopamine acted as super agonists at the fly receptor but partial agonists at the BiOctR, and the two species diverged in their sensitivities to the α2-AR antagonist [3H]rauwolscine. Further, sodium enhanced [3H]rauwolscine's interactions with the BiOctR, but not at a vertebrate α2-AR. Molecular mechanistic studies indicate that rauwolscine interacts with the BiOctR, DmOctR and α2C-AR at an allosteric site. Further, compounds that acted as agonists at a cloned α-like BiOctR also induced a hyperactivity response in Balanus cyprids mediated by the α-like OctR suggesting that the receptor may serve as a higher throughput proxy for discovering compounds with potential cyprid deterrent properties.

PMID: 28663279 [PubMed - as supplied by publisher]

Common Lung Microbiome Identified among Mechanically Ventilated Surgical Patients.

Recent Research Articles from UNTHSC - Sat, 07/01/2017 - 07:39
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Common Lung Microbiome Identified among Mechanically Ventilated Surgical Patients.

PLoS One. 2016;11(11):e0166313

Authors: Smith AD, Zhang Y, Barber RC, Minshall CT, Huebinger RM, Allen MS

Abstract
The examination of the pulmonary microbiome in patients with non-chronic disease states has not been extensively examined. Traditional culture based screening methods are often unable to identify bacteria from bronchoalveolar lavage samples. The advancement of next-generation sequencing technologies allows for a culture-independent molecular based analysis to determine the microbial composition in the lung of this patient population. For this study, the Ion Torrent PGM system was used to assess the microbial complexity of culture negative bronchoalveolar lavage samples. A group of samples were identified that all displayed high diversity and similar relative abundance of bacteria. This group consisted of Hydrogenophaga, unclassified Bacteroidetes, Pedobacter, Thauera, and Acinetobacter. These bacteria may be representative of a common non-pathogenic pulmonary microbiome associated within this population of patients.

PMID: 27898681 [PubMed - indexed for MEDLINE]

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