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PRECISION MEDICINE - The Golden Gate for Detection, Treatment and Prevention of Alzheimer's Disease.

Recent Research Articles from UNTHSC - Tue, 03/28/2017 - 07:35
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PRECISION MEDICINE - The Golden Gate for Detection, Treatment and Prevention of Alzheimer's Disease.

J Prev Alzheimers Dis. 2016 Dec;3(4):243-259

Authors: Hampel H, O'Bryant SE, Castrillo JI, Ritchie C, Rojkova K, Broich K, Benda N, Nisticò R, Frank RA, Dubois B, Escott-Price V, Lista S

Abstract
During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy. This approach will likely be based on the success found from more advanced research fields, such as oncology. Precision medicine will require integration and transfertilization across fragmented specialities of medicine and direct reintegration of Neuroscience, Neurology and Psychiatry into a continuum of medical sciences away from the silo approach. Precision medicine is biomarker-guided medicine on systems-levels that takes into account methodological advancements and discoveries of the comprehensive pathophysiological profiles of complex multi-factorial neurodegenerative diseases, such as late-onset sporadic AD. This will allow identifying and characterizing the disease processes at the asymptomatic preclinical stage, where pathophysiological and topographical abnormalities precede overt clinical symptoms by many years to decades. In this respect, the uncharted territory of the AD preclinical stage has become a major research challenge as the field postulates that early biomarker guided customized interventions may offer the best chance of therapeutic success. Clarification and practical operationalization is needed for comprehensive dissection and classification of interacting and converging disease mechanisms, description of genomic and epigenetic drivers, natural history trajectories through space and time, surrogate biomarkers and indicators of risk and progression, as well as considerations about the regulatory, ethical, political and societal consequences of early detection at asymptomatic stages. In this scenario, the integrated roles of genome sequencing, investigations of comprehensive fluid-based biomarkers and multimodal neuroimaging will be of key importance for the identification of distinct molecular mechanisms and signaling pathways in subsets of asymptomatic people at greatest risk for progression to clinical milestones due to those specific pathways. The precision medicine strategy facilitates a paradigm shift in Neuroscience and AD research and development away from the classical "one-size-fits-all" approach in drug discovery towards biomarker guided "molecularly" tailored therapy for truly effective treatment and prevention options. After the long and winding decade of failed therapy trials progress towards the holistic systems-based strategy of precision medicine may finally turn into the new age of scientific and medical success curbing the global AD epidemic.

PMID: 28344933 [PubMed - in process]

STRait Razor v2s: Advancing sequence-based STR allele reporting and beyond to other marker systems.

Recent Research Articles from UNTHSC - Tue, 03/28/2017 - 07:35
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STRait Razor v2s: Advancing sequence-based STR allele reporting and beyond to other marker systems.

Forensic Sci Int Genet. 2017 Mar 12;29:21-28

Authors: King JL, Wendt FR, Sun J, Budowle B

Abstract
STRait Razor has provided the forensic community a free-to-use, open-source tool for short tandem repeat (STR) analysis of massively parallel sequencing (MPS) data. STRait Razor v2s (SRv2s) allows users to capture physically phased haplotypes within the full amplicon of both commercial (ForenSeq) and "early access" panels (PowerSeq, Mixture ID). STRait Razor v2s may be run in batch mode to facilitate population-level analysis and is supported by all Unix distributions (including MAC OS). Data are reported in tables in string (haplotype), length-based (e.g., vWA allele 14), and International Society of Forensic Genetics (ISFG)-recommended (vWA [CE 14]-GRCh38-chr12:5983950-5984049 (TAGA)10 (CAGA)3 TAGA) formats. STRait Razor v2s currently contains a database of ∼2500 unique sequences. This database is used by SRv2s to match strings to the appropriate allele in ISFG-recommended format. In addition to STRs, SRv2s has configuration files necessary to capture and report haplotypes from all marker types included in these multiplexes (e.g., SNPs, InDels, and microhaplotypes). To facilitate mixture interpretation, data may be displayed from all markers in a format similar to that of electropherograms displayed by traditional forensic software. The download package for SRv2s may be found at https://www.unthsc.edu/graduate-school-of-biomedical-sciences/molecular-and-medical-genetics/laboratory-faculty-and-staff/strait-razor.

PMID: 28343097 [PubMed - as supplied by publisher]

Comparison of the Effectiveness of Interactive Didactic Lecture Versus Online Simulation-Based CME Programs Directed at Improving the Diagnostic Capabilities of Primary Care Practitioners.

Recent Research Articles from UNTHSC - Tue, 03/28/2017 - 07:35
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Comparison of the Effectiveness of Interactive Didactic Lecture Versus Online Simulation-Based CME Programs Directed at Improving the Diagnostic Capabilities of Primary Care Practitioners.

J Contin Educ Health Prof. 2016;36(1):32-7

Authors: McFadden P, Crim A

Abstract
INTRODUCTION: Diagnostic errors in primary care contribute to increased morbidity and mortality, and billions in costs each year. Improvements in the way practicing physicians are taught so as to optimally perform differential diagnosis can increase patient safety and lower the costs of care. This study represents a comparison of the effectiveness of two approaches to CME training directed at improving the primary care practitioner's diagnostic capabilities against seven common and important causes of joint pain.
METHODS: Using a convenience sampling methodology, one group of primary care practitioners was trained by a traditional live, expert-led, multimedia-based training activity supplemented with interactive practice opportunities and feedback (control group). The second group was trained online with a multimedia-based training activity supplemented with interactive practice opportunities and feedback delivered by an artificial intelligence-driven simulation/tutor (treatment group).
RESULTS: Before their respective instructional intervention, there were no significant differences in the diagnostic performance of the two groups against a battery of case vignettes presenting with joint pain. Using the same battery of case vignettes to assess postintervention diagnostic performance, there was a slight but not statistically significant improvement in the control group's diagnostic accuracy (P = .13). The treatment group, however, demonstrated a significant improvement in accuracy (P < .02; Cohen d, effect size = 0.79).
DISCUSSION: These data indicate that within the context of a CME activity, a significant improvement in diagnostic accuracy can be achieved by the use of a web-delivered, multimedia-based instructional activity supplemented by practice opportunities and feedback delivered by an artificial intelligence-driven simulation/tutor.

PMID: 26954243 [PubMed - indexed for MEDLINE]

A generalized association test based on U statistics.

Recent Research Articles from UNTHSC - Fri, 03/24/2017 - 07:33

A generalized association test based on U statistics.

Bioinformatics. 2017 Feb 17;:

Authors: Wei C, Lu Q

Abstract
Motivation: Second generation sequencing technologies are being increasingly used for genetic association studies, where the main research interest is to identify sets of genetic variants that contribute to various phenotypes. The phenotype can be univariate disease status, multivariate responses and even high-dimensional outcomes. Considering the genotype and phenotype as two complex objects, this also poses a general statistical problem of testing association between complex objects.
Results: We here proposed a similarity-based test, generalized similarity U (GSU), that can test the association between complex objects. We first studied the theoretical properties of the test in a general setting and then focused on the application of the test to sequencing association studies. Based on theoretical analysis, we proposed to use Laplacian Kernel-based similarity for GSU to boost power and enhance robustness. Through simulation, we found that GSU did have advantages over existing methods in terms of power and robustness. We further performed a whole genome sequencing (WGS) scan for Alzherimer's disease neuroimaging initiative data, identifying three genes, APOE , APOC1 and TOMM40 , associated with imaging phenotype.
Availability and Implementation: We developed a C ++ package for analysis of WGS data using GSU. The source codes can be downloaded at https://github.com/changshuaiwei/gsu .
Contact: weichangshuai@gmail.com ; qlu@epi.msu.edu.
Supplementary information: Supplementary data are available at Bioinformatics online.

PMID: 28334117 [PubMed - as supplied by publisher]

Development of novel HDL-mimicking α-tocopherol-coated nanoparticles to encapsulate nerve growth factor and evaluation of biodistribution.

Recent Research Articles from UNTHSC - Fri, 03/24/2017 - 07:33
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Development of novel HDL-mimicking α-tocopherol-coated nanoparticles to encapsulate nerve growth factor and evaluation of biodistribution.

Eur J Pharm Biopharm. 2016 Nov;108:126-135

Authors: Prathipati P, Zhu J, Dong X

Abstract
Nerve Growth Factor (NGF) is one of the members of the neurotrophin family with multifaceted functions. However, clinical application of NGF is hurdled by the challenge on formulation development. The objective of this study was to develop novel high-density lipoproteins (HDL)-mimicking nanoparticles (NPs) coated with α-tocopherol to incorporate NGF by a self-assembly approach. The NPs were prepared by an optimized self-assembly method that is simple and scalable. The composition of HDL-mimicking NPs was optimized. The prototype of the HDL-mimicking α-tocopherol-coated NPs contained phosphatidylserine (a negative charged phospholipid) and d-α-Tocopheryl polyethylene glycol succinate (a source of vitamin E) to enhance the entrapment efficiency of apolipoprotein A-I in the NPs. The entrapment efficiency of apolipoprotein A-I was about 30%. The NPs had particle size about 200nm with a relatively narrow size distribution. Finally, cationic ion-pair agents were optimized to form ion-pairs with NGF to facilitate the incorporation of NGF into the NPs. Protamine sodium salt USP formed an optimal ion-pair complex with NGF. The results showed that the novel HDL-mimicking α-tocopherol-coated NPs successfully encapsulated NGF with over 65% entrapment efficiency by using this ion-pair strategy. In vitro release studies demonstrated a slow release of NGF from NGF NPs in PBS containing 5% BSA at 37°C for 72 h. Further biodistribution studies showed that intravenously injected NGF NPs significantly increased NGF concentration in plasma and decreased the uptake in liver, spleen and kidney, compared to free NGF in mice.

PMID: 27531623 [PubMed - indexed for MEDLINE]

What's New in Musculoskeletal Infection: Update on Biofilms.

Recent Research Articles from UNTHSC - Fri, 03/24/2017 - 07:33
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What's New in Musculoskeletal Infection: Update on Biofilms.

J Bone Joint Surg Am. 2016 Jul 20;98(14):1226-34

Authors: Nana A, Nelson SB, McLaren A, Chen AF

PMID: 27440572 [PubMed - indexed for MEDLINE]

Regulation of anti-apoptotic Bcl-2 family protein Mcl-1 by S6 kinase 2.

Recent Research Articles from UNTHSC - Fri, 03/17/2017 - 16:36

Regulation of anti-apoptotic Bcl-2 family protein Mcl-1 by S6 kinase 2.

PLoS One. 2017;12(3):e0173854

Authors: Basu A, Sridharan S

Abstract
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt. Silencing of S6K2 but not S6K1 in T47D cells decreased Mcl-1 level, and potentiated apoptosis induced by TRAIL and doxorubicin. Knockdown of S6K2 also decreased the level of anti-apoptotic Bcl-xl. Depletion of the tumor suppressor protein PDCD4 (programmed cell death 4), which regulates translation of several anti-apoptotic proteins, reversed downregulation of Bcl-xl but not Mcl-1 and failed to reverse the effect of S6K2 knockdown on potentiation of doxorubicin-induced apoptosis. Downregulation of Mcl-1 by S6K2 knockdown was partly restored by the proteasome inhibitor MG132. Overexpression of catalytically-active Akt or knockdown of glycogen synthase kinase-3 (GSK3)-β, a substrate for Akt, had little effect on Mcl-1 downregulation caused by S6K2 deficiency. Silencing of S6K2 increased the level of c-Jun N-terminal kinase (JNK) and knockdown of JNK1 increased basal Mcl-1 level and partly reversed the effect of S6K2 knockdown on Mcl-1 downregulation. JNK1 knockdown also had a modest effect in attenuating the increase in doxorubicin-induced apoptosis caused by S6K2 deficiency. These results suggest that S6K2 regulates apoptosis via multiple mechanisms, and involves both Akt and JNK.

PMID: 28301598 [PubMed - in process]

Negative regulation of Smad1 pathway and collagen IV expression by store-operated Ca2+ entry in glomerular mesangial cells.

Recent Research Articles from UNTHSC - Fri, 03/17/2017 - 16:36
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Negative regulation of Smad1 pathway and collagen IV expression by store-operated Ca2+ entry in glomerular mesangial cells.

Am J Physiol Renal Physiol. 2017 Mar 15;:ajprenal.00642.2016

Authors: Wu P, Ren Y, Ma Y, Wang Y, Jiang H, Chaudhari S, Davis ME, Zuckerman JE, Ma R

Abstract
Collagen IV (Col IV) is a major component of expanded glomerular extracellular matrix in diabetic nephropathy and Smad1 is a key molecule regulating Col IV expression in mesangial cells (MCs). The present study was conducted to determine if Smad1 pathway and Col IV protein abundance were regulated by store-operated Ca2+ entry (SOCE). In cultured human MCs, pharmacological inhibition of SOCE significantly increased the total amount of Smad1 protein. Activation of SOCE blunted high glucose-increased Smad1 protein content. Treating human MCs with angiotensin II at 1 µM for 15 min, or high glucose for 3 days, or TGF-β1 at 5 ng/ml for 30 min increased the level of phosphorylated Smad1. However, the phosphorylation of Smad1 by those stimuli was significantly attenuated by activation of SOCE. Knocking down Smad1 reduced, but expressing Smad1 increased the amount of Col IV protein. Furthermore, activation of SOCE significantly attenuated high glucose-induced Col IV protein production and blockade of SOCE substantially increased the abundance of Col IV. To further verify those in vitro findings, we downregulated SOCE specifically in MCs in mice using siRNA against Orai1 (the channel protein mediating SOCE) delivered by the targeted nanoparticle delivery system. Immunohistochemical examinations showed that expression of both Smad1 and Col IV proteins were significantly greater in the glomeruli with positively-transfected Orai1 siRNA compared to the glomeruli from the mice without Orai1 siRNA treatment. Taken together, our results indicate that SOCE negatively regulates the Smad1 signaling pathway and inhibits Col IV protein production in MCs.

PMID: 28298362 [PubMed - as supplied by publisher]

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

Recent Research Articles from UNTHSC - Thu, 03/16/2017 - 10:44
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Analysis of DNA from post-blast pipe bomb fragments for identification and determination of ancestry.

Forensic Sci Int Genet. 2017 Mar 01;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 - as supplied by publisher]

Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors.

Recent Research Articles from UNTHSC - Thu, 03/16/2017 - 10:44
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Practical Strategies and Concepts in GPCR Allosteric Modulator Discovery: Recent Advances with Metabotropic Glutamate Receptors.

Chem Rev. 2016 06 08;116(11):6707-41

Authors: Lindsley CW, Emmitte KA, Hopkins CR, Bridges TM, Gregory KJ, Niswender CM, Conn PJ

Abstract
Allosteric modulation of GPCRs has initiated a new era of basic and translational discovery, filled with therapeutic promise yet fraught with caveats. Allosteric ligands stabilize unique conformations of the GPCR that afford fundamentally new receptors, capable of novel pharmacology, unprecedented subtype selectivity, and unique signal bias. This review provides a comprehensive overview of the basics of GPCR allosteric pharmacology, medicinal chemistry, drug metabolism, and validated approaches to address each of the major challenges and caveats. Then, the review narrows focus to highlight recent advances in the discovery of allosteric ligands for metabotropic glutamate receptor subtypes 1-5 and 7 (mGlu1-5,7) highlighting key concepts ("molecular switches", signal bias, heterodimers) and practical solutions to enable the development of tool compounds and clinical candidates. The review closes with a section on late-breaking new advances with allosteric ligands for other GPCRs and emerging data for endogenous allosteric modulators.

PMID: 26882314 [PubMed - indexed for MEDLINE]

The Impact of Rurality on 30-Day Preventable Readmission, Illness Severity, and Risk of Mortality for Heart Failure Medicare Home Health Beneficiaries.

Recent Research Articles from UNTHSC - Thu, 03/16/2017 - 10:44
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The Impact of Rurality on 30-Day Preventable Readmission, Illness Severity, and Risk of Mortality for Heart Failure Medicare Home Health Beneficiaries.

J Rural Health. 2016;32(2):176-87

Authors: Chen HF, Carlson E, Popoola T, Suzuki S

Abstract
PURPOSE: To examine the impact of rurality on 30-day preventable readmission, and the illness severity and risk of mortality for 30-day preventable readmissions.
METHODS: We analyzed heart failure Medicare beneficiaries who received home health services for postacute care after hospital discharge in 2009. The study was a cross-sectional design with the unit of analysis as the home health episode for postacute care. Data sources included the following: Medicare Beneficiary Summary File, Medicare Provider Analysis Review, Outcome Assessment Information Set, Home Health Agency Research Identifiable File, and Area Health Resources File. The dependent variables were 30-day preventable readmission, and the extreme/major level of illness severity and of risk of mortality for a 30-day preventable readmission. The key independent variable was rurality defined as remote rural, adjacent rural, and micropolitan areas, with urban areas in the reference group.
FINDINGS: Home health beneficiaries in remote rural areas had 27% lower 30-day preventable readmission than those in urban areas. Home health beneficiaries in adjacent rural areas were 33% less likely to have high illness severity at readmission due to a preventable condition than those in urban areas.
CONCLUSIONS: Geographical location affects preventable readmission and illness severity of preventable readmission. Patients' geographic location along with patients' risk factors should be taken into consideration in the risk adjustment model for the financial incentive program that penalizes home health agencies with high preventable readmissions.

PMID: 26348123 [PubMed - indexed for MEDLINE]

A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

Recent Research Articles from UNTHSC - Tue, 03/14/2017 - 07:39

A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

Climacteric. 2017 Apr;20(2):107-118

Authors: Hampel H, O'Bryant SE, Durrleman S, Younesi E, Rojkova K, Escott-Price V, Corvol JC, Broich K, Dubois B, Lista S, Alzheimer Precision Medicine Initiative

Abstract
After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

PMID: 28286989 [PubMed - in process]

Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.

Recent Research Articles from UNTHSC - Tue, 03/14/2017 - 07:39
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Treadmill exercise within lower body negative pressure protects leg lean tissue mass and extensor strength and endurance during bed rest.

Physiol Rep. 2016 08;4(15):

Authors: Schneider SM, Lee SM, Feiveson AH, Watenpaugh DE, Macias BR, Hargens AR

Abstract
Leg muscle mass and strength are decreased during reduced activity and non-weight-bearing conditions such as bed rest (BR) and spaceflight. Supine treadmill exercise within lower body negative pressure (LBNPEX) provides full-body weight loading during BR and may prevent muscle deconditioning. We hypothesized that a 40-min interval exercise protocol performed against LBNPEX 6 days week(-1) would attenuate losses in leg lean mass (LLM), strength, and endurance during 6° head-down tilt BR, with similar benefits for men and women. Fifteen pairs of healthy monozygous twins (8 male and 7 female pairs) completed 30 days of BR with one sibling of each twin pair assigned randomly as the non-exercise control (CON) and the other twin as the exercise subject (EX). Before and after BR, LLM and isokinetic leg strength and endurance were measured. Mean knee and ankle extensor and flexor strength and endurance and LLM decreased from pre- to post-BR in the male CON subjects (P < 0.01), but knee extensor strength and endurance, ankle extensor strength, and LLM were maintained in the male EX subjects. In contrast, no pre- to post-BR changes were significant in the female subjects, either CON or EX, likely due to their lower pre-BR values. Importantly, the LBNPEX countermeasure prevents or attenuates declines in LLM as well as extensor leg strength and endurance. Individuals who are stronger, have higher levels of muscular endurance, and/or have greater LLM are likely to experience greater losses during BR than those who are less fit.

PMID: 27495299 [PubMed - indexed for MEDLINE]

Tuberculosis hospitalization expenditures per patient from private health insurance claims data, 2010-2014.

Recent Research Articles from UNTHSC - Mon, 03/13/2017 - 07:31

Tuberculosis hospitalization expenditures per patient from private health insurance claims data, 2010-2014.

Int J Tuberc Lung Dis. 2017 Apr 01;21(4):398-404

Authors: Owusu-Edusei K, Marks SM, Miramontes R, Stockbridge EL, Winston CA

Abstract
OBJECTIVE: To determine hospitalization expenditures for tuberculosis (TB) disease among privately insured patients in the United States.
METHODS: We extracted TB hospital admissions data from the 2010-2014 MarketScan® commercial database using International Classification of Diseases version 9 codes for TB (011.0-018.96) as the principal diagnosis. We estimated adjusted average expenditures (in 2014 USD) using regression analyses controlling for patient and claim characteristics. We also estimated the total expenditure paid by enrollee and insurance, and extrapolated it to the entire US employer-based privately insured population.
RESULTS: We found 892 TB hospitalizations representing 825 unique enrollees over the 5-year period. The average hospitalization expenditure per person (including multiple hospitalizations) was US$33 085 (95%CI US$31 606- US$34 565). Expenditures for central nervous system TB (US$73 065, 95%CI US$59 572-US$86 558), bone and joint TB (US$56 842, 95%CI US$39 301-US$74 383), and miliary/disseminated TB (US$55 487, 95%CI US$46 101-US$64 873) were significantly higher than those for pulmonary TB (US$28 058, 95%CI US$26 632-US$29 484). The overall total expenditure for hospitalizations for TB disease over the period (2010-2014) was US$38.4 million; it was US$154 million when extrapolated to the entire employer-based privately insured population in the United States.
CONCLUSIONS: Hospitalization expenditures for some forms of extra-pulmonary TB were substantially higher than for pulmonary TB.

PMID: 28284254 [PubMed - in process]

Kienböck Disease: Moving Forward.

Recent Research Articles from UNTHSC - Sat, 03/11/2017 - 07:34
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Kienböck Disease: Moving Forward.

J Hand Surg Am. 2016 May;41(5):630-8

Authors: Lichtman DM, Pientka WF, Bain GI

Abstract
Over the past decade, a plethora of new information has been reported regarding etiology, natural history, classification, and treatment options for lunate osteonecrosis. New disease classifications have been described based on advanced imaging determination of lunate viability as well as a cartilage-based arthroscopic classification. Here we review the newest literature regarding Kienböck disease and present a new treatment algorithm that incorporates the traditional osseous classification system with a perfusion/viability classification and an articular cartilage-based classification.

PMID: 27055625 [PubMed - indexed for MEDLINE]

The health action process approach applied to African American breast cancer survivors.

Recent Research Articles from UNTHSC - Sat, 03/11/2017 - 07:34
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The health action process approach applied to African American breast cancer survivors.

Psychooncology. 2016 06;25(6):648-55

Authors: Paxton RJ

Abstract
BACKGROUND: The health action process approach (HAPA) is a relevant model for understanding physical activity (PA), yet it has not been examined in cancer survivors or minorities. In this study, we assessed the HAPA in African American breast cancer survivors using covariance modeling.
METHODS: A total of 304 African American breast cancer survivors (mean age = 54 years) participated in a Web-based survey assessing demographic and medical characteristics as well as constructs of the HAPA. A two-step covariance modeling approach was used to assess the structural relationships among the constructs.
RESULTS: The hypothesized measurement model fit the data; however, general severity was not significantly associated with the remaining constructs. General severity was removed, and the fit did not change significantly. The final adjusted model provided a reasonable fit to the data and accounted for significant variance in intentions (49%) and PA (42%). Action (β = 0.1, p < 0.01) and coping (β = 0.3, p < 0.01) planning mediated the relationship between intentions and behavior.
CONCLUSIONS: The HAPA appears to be a relevant model for understanding PA in African American breast cancer survivors. However, more work is needed to determine whether these relationships can be replicated in other breast cancer survivors. Copyright © 2015 John Wiley & Sons, Ltd.

PMID: 26058382 [PubMed - indexed for MEDLINE]

The factor of 10 in forensic DNA match probabilities.

Recent Research Articles from UNTHSC - Thu, 03/09/2017 - 07:34

The factor of 10 in forensic DNA match probabilities.

Forensic Sci Int Genet. 2017 Feb 16;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 - as supplied by publisher]

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

Recent Research Articles from UNTHSC - Thu, 03/09/2017 - 07:34

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

Forensic Sci Int Genet. 2017 Feb 27;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 - as supplied by publisher]

Enzymatic Debridement of Chronic Nonischemic Diabetic Foot Ulcers: Results of a Randomized, Controlled Trial.

Recent Research Articles from UNTHSC - Wed, 03/08/2017 - 07:35
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Enzymatic Debridement of Chronic Nonischemic Diabetic Foot Ulcers: Results of a Randomized, Controlled Trial.

Wounds. 2017 Feb 27;:

Authors: Jimenez JC, Agnew PS, Mayer P, Clements JR, Caporusso JM, Lange DL, Dickerson JE, Slade HB

Abstract
OBJECTIVE: The aim of this randomized, controlled multicenter trial was to evaluate the clinical outcomes associated with the use of clostridial collagenase ointment (CCO) for up to 12 weeks in 215 patients with type 1 or type 2 diabetes mellitus and a neuropathic, nonischemic diabetic foot ulcer (DFU).
MATERIALS AND METHODS: Patients were randomized into either a group receiving CCO applied once daily at a thickness of ~2 mm or a group receiving standard care (SC) consisting of a daily application of a hydrogel as needed to maintain a moist ulcer environment. All ulcers were covered with a nonadherent foam dressing that was changed once daily, and sharp debridement was allowed when the investigators deemed it medically warranted. Outcome measures included the percent change in ulcer area and the effect of baseline wound microbiota on subsequent healing. Patients with ulcers that showed no decrease in size after 4 weeks were crossed over to the other treatment group.
RESULTS: The wound area decreased relative to baseline for both the CCO group (-60%, P < .0001; -65%, P < .0001) and the control group (-50%, P = .0001; -51%, P = .0001) after 6 and 12 weeks, respectively. While the intergroup differences at 6 and 12 weeks did not reach statistical significance (P = .3801; P = .3606), mean percent reductions for the CCO group were greater than the control at all 12 time points (averages: -55%; -41%, respectively). Overall closure rate was 21% and 41% (weeks 6 and 12, P = .3705; P = .2358) with no significant differences between groups. However, the DFUs that showed no improvement at 4 weeks (N = 24, 12/group) were crossed over to the other treatment group. A numerically greater proportion of subjects who switched to CCO achieved closure (33%) than for those who switched to SC (8%). Baseline biopsy showed that despite the absence of clinical signs of infection, all ulcers were heavily colonized by 1 to 5 species of bacteria. No adverse events were assessed by the investigators as related to either treatment.
CONCLUSION: These results confirm observations from previous studies demonstrating positive outcomes associated with enzymatic debridement with CCO following 6 weeks of treatment.

PMID: 28267678 [PubMed - as supplied by publisher]

Superparamagnetic reconstituted high-density lipoprotein nanocarriers for magnetically guided drug delivery.

Recent Research Articles from UNTHSC - Tue, 03/07/2017 - 07:36
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Superparamagnetic reconstituted high-density lipoprotein nanocarriers for magnetically guided drug delivery.

Int J Nanomedicine. 2017;12:1453-1464

Authors: Sabnis S, Sabnis NA, Raut S, Lacko AG

Abstract
Current cancer chemotherapy is frequently associated with short- and long-term side effects, affecting the quality of life of cancer survivors. Because malignant cells are known to overexpress specific surface antigens, including receptors, targeted drug delivery is often utilized to reduce or overcome side effects. The current study involves a novel targeting approach using specifically designed nanoparticles, including encapsulation of the anti-cancer drug valrubicin into superparamagnetic iron oxide nanoparticle (SPION) containing reconstituted high-density lipoprotein (rHDL) nanoparticles. Specifically, rHDL-SPION-valrubicin hybrid nanoparticles were assembled and characterized with respect to their physical and chemical properties, drug entrapment efficiency and receptor-mediated release of the drug valrubicin from the nanoparticles to prostate cancer (PC-3) cells. Prussian blue staining was used to assess nanoparticle movement in a magnetic field. Measurements of cytotoxicity toward PC-3 cells showed that rHDL-SPION-valrubicin nanoparticles were up to 4.6 and 31 times more effective at the respective valrubicin concentrations of 42.4 µg/mL and 85 µg/mL than the drug valrubicin alone. These studies showed, for the first time, that lipoprotein drug delivery enhanced via magnetic targeting could be an effective chemotherapeutic strategy for prostate cancer.

PMID: 28260891 [PubMed - in process]

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