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How Regenerative Medicine Stakeholders Adapt to Ever-Changing Technology and Regulatory Challenges? Snapshots from the World TERMIS Industry Symposium (Sept 10, 2015, Boston, USA).

Recent Research Articles from UNTHSC - Tue, 10/25/2016 - 07:33

How Regenerative Medicine Stakeholders Adapt to Ever-Changing Technology and Regulatory Challenges? Snapshots from the World TERMIS Industry Symposium (Sept 10, 2015, Boston, USA).

Tissue Eng Part B Rev. 2016 Oct 22;

Authors: Bayon Y, van Dyke M, Buehler R, Tubo R, Bertram TA, Malfroy-Camine B, Rathman-Josserand M, Ronfard V

Abstract
Regenerative medicine, just entering the phase of maturity, is a fascinating area of research and innovation and this so even after two waves of disillusion from a commercial perspective. The huge potential of the field has been fairly under-exploited so far. Both TERMIS-AM & TERMIS-EU Industry Committees are committed to mentoring and training young entrepreneurs for more successful commercial translation of upstream research. With this objective in mind, the two entities jointly organized an Industry Symposium during the last Termis World Congress (Boston, September 8-11, 2015) and invited senior managers of the Regenerative Medicine industry for lectures and panel discussions. One of the two sessions of the symposium - How to overcome obstacles encountered when bringing products to the commercial phase? - aimed to share the inside, real experience of leaders from TEI Biosciences (an Integra Company), Vericel (formerly Aastrom; acquirer of Genzyme Regenerative Medicine assets), RegenMedTX (formerly Tengion), Mindset Rx, ViThera Pharmaceuticals, and& L'Oreal Research & Innovation. Practical The symposium provided practical recommendations were given for undertaking Regenerative Medicine product development from its very early stages, for remaining regularly reviewing advancements in critical and objective when reviewing progressways, for proposing keeping solutions simple, and the simplest solutions as possible and for remaining relevant and persistent.

PMID: 27771996 [PubMed - as supplied by publisher]

An Empirical Comparison of Competing Factor Structures for the Repeatable Battery for the Assessment of Neuropsychological Status: A Project FRONTIER Study.

Recent Research Articles from UNTHSC - Tue, 10/25/2016 - 07:33
Related Articles

An Empirical Comparison of Competing Factor Structures for the Repeatable Battery for the Assessment of Neuropsychological Status: A Project FRONTIER Study.

Arch Clin Neuropsychol. 2016 Feb;31(1):88-96

Authors: Torrence ND, John SE, Gavett BE, O'Bryant SE

Abstract
The original factor structure of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has received little empirical support, but at least eight alternative factor structures have been identified in the literature. The current study used confirmatory factor analysis to compare the original RBANS model with eight alternatives, which were adjusted to include a general factor. Participant data were obtained from Project FRONTIER, an epidemiological study of rural health, and comprised 341 adults (229 women, 112 men) with mean age of 61.2 years (SD = 12.1) and mean education of 12.4 years (SD = 3.3). A bifactor version of the model proposed by Duff and colleagues provided the best fit to the data (CFI = 0.98; root-mean-squared error of approximation = 0.07), but required further modification to produce appropriate factor loadings. The results support the inclusion of a general factor and provide partial replication of the Duff and colleagues RBANS model.

PMID: 26429558 [PubMed - indexed for MEDLINE]

The Role of Chiropractic Care in the Treatment of Dizziness or Balance Disorders: Analysis of National Health Interview Survey Data.

Recent Research Articles from UNTHSC - Tue, 10/25/2016 - 07:33
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The Role of Chiropractic Care in the Treatment of Dizziness or Balance Disorders: Analysis of National Health Interview Survey Data.

J Evid Based Complementary Altern Med. 2016 Apr;21(2):138-42

Authors: Ndetan H, Hawk C, Sekhon VK, Chiusano M

Abstract
The purpose of this study was to explore the role of chiropractic in the treatment of dizziness or balance disorders through an analysis of data from the 2008 National Health Interview Survey. Odds ratios and 95% confidence intervals (CIs) were used to assess the likelihood that respondents with dizziness or balance problems perceived that they were helped by specified practitioners. Eleven percent of respondents reported having had a balance or dizziness problem; more than 35% were aged 65 years and older. The odds ratio for perceiving being helped by a chiropractor was 4.36 (95% CI, 1.17-16.31) for respondents aged 65 years or older; 9.5 (95% CI, 7.92-11.40) for respondents reporting head or neck trauma; and 13.78 (95% CI, 5.59-33.99) for those reporting neurological or muscular conditions as the cause of their balance or dizziness.

PMID: 26362851 [PubMed - indexed for MEDLINE]

Characterization of genetic sequence variation of 58 STR loci in four major population groups.

Recent Research Articles from UNTHSC - Sun, 10/23/2016 - 07:33
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Characterization of genetic sequence variation of 58 STR loci in four major population groups.

Forensic Sci Int Genet. 2016 Nov;25:214-226

Authors: Novroski NM, King JL, Churchill JD, Seah LH, Budowle B

Abstract
Massively parallel sequencing (MPS) can identify sequence variation within short tandem repeat (STR) alleles as well as their nominal allele lengths that traditionally have been obtained by capillary electrophoresis. Using the MiSeq FGx Forensic Genomics System (Illumina), STRait Razor, and in-house excel workbooks, genetic variation was characterized within STR repeat and flanking regions of 27 autosomal, 7 X-chromosome and 24 Y-chromosome STR markers in 777 unrelated individuals from four population groups. Seven hundred and forty six autosomal, 227 X-chromosome, and 324 Y-chromosome STR alleles were identified by sequence compared with 357 autosomal, 107 X-chromosome, and 189 Y-chromosome STR alleles that were identified by length. Within the observed sequence variation, 227 autosomal, 156 X-chromosome, and 112 Y-chromosome novel alleles were identified and described. One hundred and seventy six autosomal, 123 X-chromosome, and 93 Y-chromosome sequence variants resided within STR repeat regions, and 86 autosomal, 39 X-chromosome, and 20 Y-chromosome variants were located in STR flanking regions. Three markers, D18S51, DXS10135, and DYS385a-b had 1, 4, and 1 alleles, respectively, which contained both a novel repeat region variant and a flanking sequence variant in the same nucleotide sequence. There were 50 markers that demonstrated a relative increase in diversity with the variant sequence alleles compared with those of traditional nominal length alleles. These population data illustrate the genetic variation that exists in the commonly used STR markers in the selected population samples and provide allele frequencies for statistical calculations related to STR profiling with MPS data.

PMID: 27697609 [PubMed - in process]

The Third International Genomic Medicine Conference (3rd IGMC, 2015): overall activities and outcome highlights.

Recent Research Articles from UNTHSC - Sat, 10/22/2016 - 07:32

The Third International Genomic Medicine Conference (3rd IGMC, 2015): overall activities and outcome highlights.

BMC Genomics. 2016 Oct 17;17(Suppl 9):747

Authors: Abu-Elmagd M, Assidi M, Dallol A, Buhmeida A, Pushparaj PN, Kalamegam G, Al-Hamzi E, Shay JW, Scherer SW, Agarwal A, Budowle B, Gari M, Chaudhary A, Abuzenadah A, Al-Qahtani M

Abstract
The Third International Genomic Medicine Conference (3(rd) IGMC) was organised by the Centre of Excellence in Genomic Medicine Research (CEGMR) at the King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia (KSA). This conference is a continuation of a series of meetings, which began with the first International Genomic Medicine Conference (1(st) IGMC, 2011) followed by the second International Genomic Medicine Conference (2(nd) IGMC, 2013). The 3(rd) IGMC meeting presented as a timely opportunity to bring scientists from across the world to gather, discuss, and exchange recent advances in the field of genomics and genetics in general as well as practical information on using these new technologies in different basic and clinical applications. The meeting undoubtedly inspired young male and female Saudi researchers, who attended the conference in large numbers, as evidenced by the oversubscribed oral and poster presentations. The conference also witnessed the launch of the first content for npj Genomic Medicine, a high quality new journal was established in partnership by CEGMR with Springer Nature and published as part of the Nature Partner Journal series. Here, we present a brief summary report of the 2-day meeting including highlights from the oral presentations, poster presentations, workshops, poster prize-winners and comments from the distinguished scientists.

PMID: 27766952 [PubMed - in process]

The Relationship Between Humeral Retrotorsion and Shoulder Range of Motion in Baseball Players With an Ulnar Collateral Ligament Tear.

Recent Research Articles from UNTHSC - Sat, 10/22/2016 - 07:32

The Relationship Between Humeral Retrotorsion and Shoulder Range of Motion in Baseball Players With an Ulnar Collateral Ligament Tear.

Orthop J Sports Med. 2016 Oct;4(10):2325967116667497

Authors: Lee BJ, Garrison JC, Conway JE, Pollard K, Aryal S

Abstract
BACKGROUND: Humeral retrotorsion has been investigated in relation to shoulder range of motion (ROM) in healthy baseball players. Currently, there is limited information on the osseous anatomy and development of ulnar collateral ligament (UCL) tears.
PURPOSE: To determine the relationship between humeral retrotorsion and shoulder ROM in baseball players with a UCL tear.
STUDY DESIGN: Cross-sectional study; Level of evidence, 3.
METHODS: Fifty-four baseball players (mean age, 18.5 ± 2.0 years) with a UCL tear volunteered for this study. Participants were measured bilaterally for shoulder internal (IR) and external rotation (ER) ROM and humeral retrotorsion. Differences between sides (involved to uninvolved) were used to calculate the glenohumeral internal rotation deficit (GIRD), external rotation ROM difference (ERDiff), total rotational motion difference (TRM), and humeral retrotorsion difference (HTDiff). A multivariate regression analysis was performed with GIRD, ERDiff, and TRM regressing on HTDiff. Univariate analysis was performed to further evaluate the effect of the predictors on each outcome separately. To control for the effect of age, weight, duration of symptoms, and years of experience, the variables were included as covariates. An a priori level was set at P < .05.
RESULTS: There was a statistically significant relationship between the GIRD, ERDiff, and TRM results compared with HTDiff (P = .003). Independent analysis revealed a statistically significant relationship between GIRD and HTDiff (P = .004) and between ERDiff and HTDiff (P = .003) but no significant relationship between TRM and HTDiff (P = .999). After adjusting for age, weight, duration of symptoms, years of experience, dominant arm, and position, a significant relationship was found between GIRD and HTDiff (P = .05) and between ERDiff and HTDiff (P = .01). No significant relationship was found between TRM and HTDiff (P = .54). Adjusted univariate regression analysis determined that HTDiff explains approximately 16% of the variance in GIRD (r(2) = 0.158) and approximately 24% of the variance in ERDiff (r(2) = 0.237).
CONCLUSION: In baseball players with a UCL tear, approximately 16% of the variance in GIRD and 24% of the variance in ERDiff can be attributed to differences found in humeral retrotorsion between sides. This indicates that humeral retroversion contributes significantly to GIRD and increased ER ROM in baseball players. Recognition of differences in humeral retrotorsion between the dominant and nondominant upper extremities may help explain some but not all of the changes in shoulder ROM commonly seen in baseball players.

PMID: 27766274 [PubMed - in process]

δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium.

Recent Research Articles from UNTHSC - Sat, 10/22/2016 - 07:32
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δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium.

Basic Res Cardiol. 2016 Mar;111(2):17

Authors: Estrada JA, Williams AG, Sun J, Gonzalez L, Downey HF, Caffrey JL, Mallet RT

Abstract
Intermittent, normobaric hypoxia confers robust cardioprotection against ischemia-induced myocardial infarction and lethal ventricular arrhythmias. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) have been implicated in cardioprotective phenomena, but their roles in intermittent hypoxia are unknown. This study examined the contributions of DOR and ROS in mediating intermittent hypoxia-induced cardioprotection. Mongrel dogs completed a 20 day program consisting of 5-8 daily, 5-10 min cycles of moderate, normobaric hypoxia (FIO2 0.095-0.10), with intervening 4 min room air exposures. Subsets of dogs received the DOR antagonist naltrindole (200 μg/kg, sc) or antioxidant N-acetylcysteine (250 mg/kg, po) before each hypoxia session. Twenty-four hours after the last session, the left anterior descending coronary artery was occluded for 60 min and then reperfused for 5 h. Arrhythmias detected by electrocardiography were scored according to the Lambeth II conventions. Left ventricles were sectioned and stained with 2,3,5-triphenyl-tetrazolium-chloride, and infarct sizes were expressed as percentages of the area at risk (IS/AAR). Intermittent hypoxia sharply decreased IS/AAR from 41 ± 5 % (n = 12) to 1.8 ± 0.9 % (n = 9; P < 0.001) and arrhythmia score from 4.1 ± 0.3 to 0.7 ± 0.2 (P < 0.001) vs. non-hypoxic controls. Naltrindole (n = 6) abrogated the cardioprotection with IS/AAR 35 ± 5 % and arrhythmia score 3.7 ± 0.7 (P < 0.001 vs. untreated intermittent hypoxia). N-acetylcysteine (n = 6) interfered to a similar degree, with IS/AAR 42 ± 3 % and arrhythmia score 4.7 ± 0.3 (P < 0.001 vs. untreated intermittent hypoxia). Without the intervening reoxygenations, hypoxia (n = 4) was not cardioprotective (IS/AAR 50 ± 8 %; arrhythmia score 4.5 ± 0.5; P < 0.001 vs. intermittent hypoxia). Thus DOR, ROS and cyclic reoxygenation were obligatory participants in the gradually evolving cardioprotection produced by intermittent hypoxia.

PMID: 26879900 [PubMed - indexed for MEDLINE]

Evaluating the Past, Present, and Future of Regenerative Medicine: A Global View.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43

Evaluating the Past, Present, and Future of Regenerative Medicine: A Global View.

Tissue Eng Part B Rev. 2016 Oct 20;

Authors: Ronfard V, Vertes A, May M, Dupraz A, van Dyke M, Bayon Y

Abstract
"Evaluating the Past & Present of Regenerative Medicine (RM)" was the first part of an Industry Symposium dedicated to the subject during the 2015 World TERMIS Congress in Boston. This working session presented a critical review of the current RM landscape in Europe and North America with possible projections for the future. Interestingly, the RM development cycle seems to obey the Gartner hype cycle, now at the enlightenment phase, after past exaggerated expectations and discouragements, as suggested by increasing numbers of clinical trials and recent market approvals of RM solutions in both Europe (Glybera & Holoclar® from Chiesi Pharma and Strimvelis® from GSK) and Japan (Remestemcel-L from Mesoblast® ). The successful commercial translation of RM research is governed by 5 major drivers: i) fully validated manufacturing capability for autologous or allogeneic products, ii) reimbursement for targeted clinical indications with high and demonstrable medico-economic benefits versus standard of care, iii) implication of regulatory bodies in the design and development plan of any RM solution which should be well-characterized, robust, with proven consistent efficacy and an acceptable and controlled positive benefit/ risk ratio, iv) collaborations facilitated by multi-competence hubs / consortia of excellence, v) well thought-out clinical development plans for reducing the risk of failure. Benefiting from past and present experience, the RM burgeoning industry is expected to accelerate the market release of cost-effective RM products with real curative potential for specific clinical indications with high unmet needs. This should be achieved by wisely leveraging all possible synergies of the different stakeholders, e.g. patients, clinicians, reimbursement and HTA agencies, regulatory authorities, public / private investors, academia, and companies.

PMID: 27762892 [PubMed - as supplied by publisher]

Exosomal Annexin A2 Promotes Angiogenesis and Breast Cancer Metastasis.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43

Exosomal Annexin A2 Promotes Angiogenesis and Breast Cancer Metastasis.

Mol Cancer Res. 2016 Oct 19;:

Authors: Maji S, Chaudhary P, Akopova I, Nguyen PM, Hare RJ, Gryczynski I, Vishwanatha JK

Abstract
Tumor-derived exosomes are emerging mediators of tumorigenesis and tissue-specific metastasis. Proteomic profiling has identified Annexin A2 as one of the most highly expressed proteins in exosomes; however, studies focused on the biological role of exosomal-AnnexinA2 (exo-AnxA2) are still lacking. In this study, mechanistic insight was sought regarding exo-AnxA2 and its function in angiogenesis and breast cancer metastasis. Multiple in vitro and in vivo techniques were used to study the role of exo-AnxA2 in angiogenesis. Using atomic force microscopy (AFM) and Western blotting, exo-AnxA2 expression was characterized in normal and breast cancer cells. In addition, organ specific metastatic breast cancer cells and animal models were used to define the role exo-AnxA2 in breast cancer metastasis. Results revealed that exo-AnxA2 expression is significantly higher in malignant cells than normal and pre-metastatic breast cancer cells. In vitro and in vivo studies demonstrated that exo-AnxA2 promotes tPA-dependent angiogenesis. Furthermore, in vivo analysis indicated that metastatic exosomes create a favorable microenvironment for metastasis and exo-AnxA2 plays an important role in this process, since priming with AnxA2-depleted exosomes reduces brain (~4-fold) and lung (~2-fold) metastasis. Upon delineating the mechanism it was discovered that exo-AnxA2 causes macrophage-mediated activation of the p38MAPK, NF-kappaB, and STAT3 pathways and increased secretion of IL-6 and TNF-alpha. These data demonstrate an important role for exo-AnxA2 in breast cancer pathogenesis.
IMPLICATIONS: Exosome associated Annexin A2 plays an important role in angiogenesis and breast cancer metastasis, which can be exploited as a potential biomarker as well as a therapeutic target for diagnosis and treatment of metastatic breast cancer.

PMID: 27760843 [PubMed - as supplied by publisher]

Paternity calculations in a di-spermy case.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43

Paternity calculations in a di-spermy case.

Int J Legal Med. 2016 Oct 18;

Authors: Budowle B, Capt C, Chakraborty R, Ge J

Abstract
In a criminal paternity case, which involved analysis of the product of conception, a rare circumstance was observed. The product of conception was triploidy, apparently due to an egg fertilized by two sperm. Since there is little guidance on how to calculate the probability of the DNA evidence given some basic hypotheses, the formulae were derived and are presented herein. These approaches could provide guidance for similar situations if they arise.

PMID: 27757578 [PubMed - as supplied by publisher]

Canonical Transient Receptor Potential 6 Channel: A New Target of Reactive Oxygen Species in Renal Physiology and Pathology.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43
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Canonical Transient Receptor Potential 6 Channel: A New Target of Reactive Oxygen Species in Renal Physiology and Pathology.

Antioxid Redox Signal. 2016 Nov 1;25(13):732-748

Authors: Ma R, Chaudhari S, Li W

Abstract
SIGNIFICANCE: Regulation of Ca(2+) signaling cascade by reactive oxygen species (ROS) is becoming increasingly evident and this regulation represents a key mechanism for control of many fundamental cellular functions. Canonical transient receptor potential (TRPC) 6, a member of Ca(2+)-conductive channel in the TRPC family, is widely expressed in kidney cells, including glomerular mesangial cells, podocytes, tubular epithelial cells, and vascular myocytes in renal microvasculature. Both overproduction of ROS and dysfunction of TRPC6 channel are involved in renal injury in animal models and human subjects. Although regulation of TRPC channel function by ROS has been well described in other tissues and cell types, such as vascular smooth muscle, this important cell regulatory mechanism has not been fully reviewed in kidney cells. Recent Advances: Accumulating evidence has shown that TRPC6 is a redox-sensitive channel, and modulation of TRPC6 Ca(2+) signaling by altering TRPC6 protein expression or TRPC6 channel activity in kidney cells is a downstream mechanism by which ROS induce renal damage.
CRITICAL ISSUES: This review highlights how recent studies analyzing function and expression of TRPC6 channels in the kidney and their response to ROS improve our mechanistic understanding of oxidative stress-related kidney diseases.
FUTURE DIRECTIONS: Although it is evident that ROS regulate TRPC6-mediated Ca(2+) signaling in several types of kidney cells, further study is needed to identify the underlying molecular mechanism. We hope that the newly identified ROS/TRPC6 pathway will pave the way to new, promising therapeutic strategies to target kidney diseases such as diabetic nephropathy. Antioxid. Redox Signal. 25, 732-748.

PMID: 26937558 [PubMed - in process]

Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43
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Direct Analysis in Real Time (DART) of an Organothiophosphate at Ultrahigh Resolution by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry.

Int J Mol Sci. 2016 Jan 16;17(1):

Authors: Prokai L, Stevens SM

Abstract
Direct analysis in real time (DART) is a recently developed ambient ionization technique for mass spectrometry to enable rapid and sensitive analyses with little or no sample preparation. After swab-based field sampling, the organothiophosphate malathion was analyzed using DART-Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Mass resolution was documented to be over 800,000 in full-scan MS mode and over 1,000,000 for an MS/MS product ion produced by collision-induced dissociation of the protonated analyte. Mass measurement accuracy below 1 ppm was obtained for all DART-generated ions that belonged to the test compound in the mass spectra acquired using only external mass calibration. This high mass measurement accuracy, achievable at present only through FTMS, was required for unequivocal identification of the corresponding molecular formulae.

PMID: 26784186 [PubMed - indexed for MEDLINE]

A Retrospective Study on the Protective Effects of Topical Vancomycin in Patients Undergoing Multilevel Spinal Fusion.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43
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A Retrospective Study on the Protective Effects of Topical Vancomycin in Patients Undergoing Multilevel Spinal Fusion.

Pharmacotherapy. 2016 Jan;36(1):19-25

Authors: Gaviola ML, McMillian WD, Ames SE, Endicott JA, Alston WK

Abstract
BACKGROUND: Topical vancomycin may be an effective intervention to decrease the risk of postoperative surgical site infections (SSIs). The primary objective of this study was to evaluate the impact of topical vancomycin with intravenous (IV) cefazolin compared with IV cefazolin alone on the incidence of SSI in instrumented multilevel spinal fusion (MLSF) surgery.
METHODS: This was a retrospective cohort study of patients 18 years and older who underwent instrumented MLSF surgery between January 1, 2010, and July 31, 2014. Patients who underwent anterior cervical diskectomy and fusion, had spine surgery within 3 months prior to index case, received antibiotics other than IV cefazolin prior to surgery, or had preoperative length of stay longer than 5 days were excluded. SSIs were identified using Centers for Disease Control and Prevention National Healthcare Safety Network definitions. Summary statistics were computed. Variables found to be associated with increased risk of SSI through univariate analysis were included in a multivariate analysis.
RESULTS: Among 326 patients, 29 (8.9%) developed an SSI. Univariate analysis showed a trend toward decreased SSI incidence in the cohort receiving topical vancomycin with IV cefazolin compared with IV cefazolin alone, although this was not statistically significant ([6/116] 5.2% vs [23/210] 11.0%, p = 0.08). Topical vancomycin was associated with a protective effect against SSI in the multivariate analysis (odds ratio [OR] 0.26, p = 0.02). Significant risk factors for the development of SSI included female sex (OR 3.3, p = 0.01), increasing invasiveness score (p < 0.01), and diabetes mellitus (OR 5.1, p < 0.01).
CONCLUSION: Topical vancomycin administered in addition to IV cefazolin was associated with a decreased risk of SSI in high-risk MLSF patients. Female patients and those with diabetes mellitus were at higher risk of developing postsurgical infection. Further prospective studies are needed to confirm these results and to define the most clinically effective dose of topical vancomycin in this patient population.

PMID: 26749522 [PubMed - indexed for MEDLINE]

Photophysical characterization of anticancer drug valrubicin in rHDL nanoparticles and its use as an imaging agent.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43
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Photophysical characterization of anticancer drug valrubicin in rHDL nanoparticles and its use as an imaging agent.

J Photochem Photobiol B. 2016 Feb;155:60-5

Authors: Shah S, Chib R, Raut S, Bermudez J, Sabnis N, Duggal D, Kimball JD, Lacko AG, Gryczynski Z, Gryczynski I

Abstract
Nanoparticles are target-specific drug delivery agents that are increasingly used in cancer therapy to enhance bioavailability and to reduce off target toxicity of anti-cancer agents. Valrubicin is an anti-cancer drug, currently approved only for vesicular bladder cancer treatment because of its poor water solubility. On the other hand, valrubicin carrying reconstituted high density lipoprotein (rHDL) nanoparticles appear ideally suited for extended applications, including systemic cancer chemotherapy. We determined selected fluorescence properties of the free (unencapsulated) drug vs. valrubicin incorporated into rHDL nanoparticles. We have found that upon encapsulation into rHDL nanoparticles the quantum yield of valrubicin fluorescence increased six fold while its fluorescence lifetime increased about 2 fold. Accordingly, these and potassium iodide (KI) quenching data suggest that upon incorporation, valrubicin is localized deep in the interior of the nanoparticle, inside the lipid matrix. Fluorescence anisotropy of the rHDL valrubicin nanoparticles was also found to be high along with extended rotational correlation time. The fluorescence of valrubicin could also be utilized to assess its distribution upon delivery to prostate cancer (PC3) cells. Overall the fluorescence properties of the rHDL: valrubicin complex reveal valuable novel characteristics of this drug delivery vehicle that may be particularly applicable when used in systemic (intravenous) therapy.

PMID: 26735001 [PubMed - indexed for MEDLINE]

Understanding Melanocyte Stem Cells for Disease Modeling and Regenerative Medicine Applications.

Recent Research Articles from UNTHSC - Fri, 10/21/2016 - 10:43
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Understanding Melanocyte Stem Cells for Disease Modeling and Regenerative Medicine Applications.

Int J Mol Sci. 2015 Dec 21;16(12):30458-69

Authors: Mull AN, Zolekar A, Wang YC

Abstract
Melanocytes in the skin play an indispensable role in the pigmentation of skin and its appendages. It is well known that the embryonic origin of melanocytes is neural crest cells. In adult skin, functional melanocytes are continuously repopulated by the differentiation of melanocyte stem cells (McSCs) residing in the epidermis of the skin. Many preceding studies have led to significant discoveries regarding the cellular and molecular characteristics of this unique stem cell population. The alteration of McSCs has been also implicated in several skin abnormalities and disease conditions. To date, our knowledge of McSCs largely comes from studying the stem cell niche of mouse hair follicles. Suggested by several anatomical differences between mouse and human skin, there could be distinct features associated with mouse and human McSCs as well as their niches in the skin. Recent advances in human pluripotent stem cell (hPSC) research have provided us with useful tools to potentially acquire a substantial amount of human McSCs and functional melanocytes for research and regenerative medicine applications. This review highlights recent studies and progress involved in understanding the development of cutaneous melanocytes and the regulation of McSCs.

PMID: 26703580 [PubMed - indexed for MEDLINE]

Spatial Microbial Composition Along the Gastrointestinal Tract of Captive Attwater's Prairie Chicken.

Recent Research Articles from UNTHSC - Wed, 10/19/2016 - 13:33

Spatial Microbial Composition Along the Gastrointestinal Tract of Captive Attwater's Prairie Chicken.

Microb Ecol. 2016 Oct 18;

Authors: Zhang Y, Simon SE, Johnson JA, Allen MS

Abstract
Gastrointestinal microbiota is increasingly recognized as an important component of individual health, and therefore, our ability to quantify its diversity accurately is central for exploring different ways to improve health. Non-invasive sampling methods, such as cloaca swabs, are often used to measure gastrointestinal microbiota diversity within an individual. However, few studies have addressed to what degree differences exist in microbial community composition along the gastrointestinal tract, and measures obtained from the cloaca may not actually represent the diversity present elsewhere in the gastrointestinal tract. In this study, we systematically characterized the gastrointestinal microbial community of the critically endangered Attwater's Prairie chicken (Tympanuchus cupido attwateri) by opportunistically sampling four different locations (ileum, cecum, large intestine, and cloaca) along the gastrointestinal tract of eight individuals. Spatial variation of microbial community was observed at different sampling locations within the gastrointestinal tract. The cecum harbored the most diverse and significantly different microbiota from the other locations, while the microbial α- and β-diversities were similar in the ileum, large intestine, and cloaca. The results of this study provide evidence that microbiota diversity can differ depending on sampling location and metric used to quantify diversity. As shown here, non-invasive cloacal sampling strategies may reflect microbiota diversity elsewhere in the gastrointestinal tract, yet caution is warranted when making generalizations in terms of the microbiota diversity correlations when samples are obtained from a single location within the gastrointestinal tract.

PMID: 27752719 [PubMed - as supplied by publisher]

Eyebrow restoration: the approach, considerations, and technique in follicular unit transplantation.

Recent Research Articles from UNTHSC - Wed, 10/19/2016 - 13:33
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Eyebrow restoration: the approach, considerations, and technique in follicular unit transplantation.

J Cosmet Dermatol. 2015 Dec;14(4):310-4

Authors: Tomc CM, Malouf PJ

Abstract
BACKGROUND: Eyebrows serve a key role in eye protection, communication, and self-expression. Trends in eyebrow grooming are constantly evolving, often requiring plucking, waxing, or laser hair removal to style. When combined with the natural thinning of the brow with aging, the result can be a sparse or even absent eyebrow hair over time. Follicular unit transplantation provides a means of restoring eyebrow fullness and architecture. With careful attention and augmentation of follicle transfer techniques, a natural end result is possible.

PMID: 26248542 [PubMed - indexed for MEDLINE]

Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates.

Recent Research Articles from UNTHSC - Tue, 10/18/2016 - 07:33
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Mass spectrometric analysis of carisoprodol and meprobamate in rat brain microdialysates.

J Mass Spectrom. 2016 Oct;51(10):900-907

Authors: Prokai L, Fryčák P, Nguyen V, Forster MJ

Abstract
We report the evaluation of several mass spectrometry-based methods for the determination of carisoprodol and meprobamate in samples obtained from the rat brain by in vivo intracranial microdialyis. Among the techniques that aspire to perform analyses without chromatographic separation and thereby increase throughput, chip-based nanoelectrospray ionization and the use of an atmospheric pressure solids analysis probe fell short of requirements because of insufficient detection sensitivity and hard ionization, respectively. Although direct analysis in real time provided the required soft ionization, shortcomings of a tandem mass spectrometry-based assay also included inadequate detection sensitivity and, in addition, poor quantitative reproducibility. Therefore, liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry was developed to determine carisoprodol and meprobamate from artificial cerebrospinal fluid as the medium. No desalting and/or extraction of the samples was necessary. The assay, combined with in vivo sampling via intracranial microdialyis, afforded time-resolved concentration profiles for the drug and its major metabolite from the nucleus accumbens region of the brain in rats after systemic administration of carisoprodol. Copyright © 2016 John Wiley & Sons, Ltd.

PMID: 27747995 [PubMed - in process]

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

Recent Research Articles from UNTHSC - Tue, 10/18/2016 - 07:33
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Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

J Glaucoma. 2016 Oct;25(10):e834-e842

Authors: McDonnell FS, McNally SA, Clark AF, O'Brien CJ, Wallace DM

Abstract
BACKGROUND: Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma. The purpose of this study was to compare global DNA methylation levels in primary human normal (NLC) and glaucomatous (GLC) cells, and to investigate DNA methylation in driving fibrosis through regulation of transforming growth factor β1 (TGFβ1).
MATERIALS AND METHODS: LC cells were cultured from normal and glaucomatous human donors. Global methylation was assessed by ELISA. qPCR was conducted for DNA methyltransferases (DNMTs), methyl-CpG-binding protein 2 (MeCP2), TGFβ 1 and 2, collagen 1α1 (COL1A1), and α-smooth muscle actin (αSMA). TGFβ1 and DNMT1 were examined by immunofluorescence. Methylation of the TGFβ1 promoter was determined by methylation-specific PCR (MSP).
RESULTS: Global DNA methylation demonstrated an increase in GLC compared with NLC cells (P<0.05). The previously mentioned methylation and matrix genes were increased in GLC compared with NLC cells (P<0.05). Immunofluorescence showed increased TGFβ1 and DNMT1 in GLC compared with NLC cells. MSP showed increased unmethylated DNA in the TGFβ1 promoter of GLC compared with NLC cells.
CONCLUSIONS: We found increased expression of fibrotic genes in GLC cells and demonstrated an increase in global DNA methylation and in associated enzymes in GLC cells. Furthermore, we showed decreased promoter methylation of TGFβ1 in GLC cells. Determining a role for methylation in glaucoma and in regulating TGFβ1 may provide a novel therapeutic approach.

PMID: 27300643 [PubMed - in process]

Glutaredoxins concomitant with optimal ROS activate AMPK through S-glutathionylation to improve glucose metabolism in type 2 diabetes.

Recent Research Articles from UNTHSC - Mon, 10/17/2016 - 07:35
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Glutaredoxins concomitant with optimal ROS activate AMPK through S-glutathionylation to improve glucose metabolism in type 2 diabetes.

Free Radic Biol Med. 2016 Oct 12;:

Authors: Dong K, Wu M, Liu X, Huang Y, Zhang D, Wang Y, Yan LJ, Shi D

Abstract
AMPK dysregulation contributes to the onset and development of type 2 diabetes (T2DM). AMPK is known to be activated by reactive oxygen species (ROS) and antioxidant interference. However the mechanism by which redox state mediates such contradictory result remains largely unknown. Here we used streptozotocin-high fat diet (STZ-HFD) induced-type 2 diabetic rats and cells lines (L02 and HEK 293) to explore the mechanism of redox-mediated AMPK activation. We show glutaredoxins (Grxs) concomitant with optimal ROS act as an essential mediator for AMPK activation. ROS level results in different mechanisms for AMPK activation. Under low ROS microenvironment, Grxs-mediated S-glutathionylation on AMPK-α catalytic subunit activates AMPK to improve glucose transportation and degradation while inhibiting glycogen synthesis and keeping redox balance. While, under high ROS microenvironment, AMPK is activated by an AMP-dependent mechanism, however sustained high level ROS also causes loss of AMPK protein. This finding provides evidence for a new approach to diabetes treatment by individual doses of ROS or antioxidant calibrated against the actual redox level in vivo. Moreover, the novel function of Grxs in promoting glucose metabolism may provide new target for T2DM treatment.

PMID: 27743883 [PubMed - as supplied by publisher]

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