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Evaluating the Disposition of a Mixed Aldehyde Oxidase/Cytochrome P450 Substrate in Rats with Attenuated P450 Activity.

Recent Research Articles from UNTHSC - Sat, 03/05/2016 - 06:42
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Evaluating the Disposition of a Mixed Aldehyde Oxidase/Cytochrome P450 Substrate in Rats with Attenuated P450 Activity.

Drug Metab Dispos. 2016 Mar 2;

Authors: Crouch RD, Morrison RD, Byers FW, Lindsley CW, Emmitte KA, Daniels JS

Abstract
Marketed drugs cleared by aldehyde oxidase (AO) are few, with no known clinically relevant pharmacokinetic drug interactions associated with AO inhibition, while cytochrome P450 inhibition or induction mediates a number of clinical drug interactions. Little attention has been given to consequences of co-administering a P450 inhibitor with a compound metabolized by both AO and P450. Upon discovering that VU0409106 ( 1: ) was metabolized by AO (to M1) and P450 enzymes (to M4-M6), we sought to evaluate the in vivo disposition of 1: and its metabolites in rats with attenuated P450 activity. Male rats were orally pretreated with the pan-P450 inactivator, 1-aminobenzotriazole (ABT), prior to an intraperitoneal dose of 1: . Interestingly, the plasma(AUC)of M1 was increased 15-fold in ABT-treated rats, indicating a metabolic shunt towards AO resulted from the drug interaction condition. The AUC of 1: also increased 7.8-fold. Accordingly, plasma clearance of 1: decreased from 53.5 to 15.3 mL/min/kg in ABT-pretreated rats receiving an intravenous dose of 1: . Consistent with these data, M1 formation in hepatic S9 increased with NADPH-exclusion to eliminate P450 activity (50% over reactions containing NADPH). These studies reflect possible consequences of a drug interaction between P450 inhibitors and compounds cleared by both AO and P450 enzymes. Notably, increased exposure to an AO metabolite may hold clinical relevance for active metabolites or those mediating toxicity at elevated concentrations. The recent rise in clinical drug candidates metabolized by AO underscores the importance of these findings and the need for clinical studies to fully understand these risks.

PMID: 26936972 [PubMed - as supplied by publisher]

Racial disparities in reaching the renal transplant waitlist: is geography as important as race?

Recent Research Articles from UNTHSC - Sat, 03/05/2016 - 06:42
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Racial disparities in reaching the renal transplant waitlist: is geography as important as race?

Clin Transplant. 2015 Jun;29(6):531-8

Authors: Saunders MR, Lee H, Alexander GC, Tak HJ, Thistlethwaite JR, Ross LF

Abstract
BACKGROUND: In the United States, African Americans and whites differ in access to the deceased donor renal transplant waitlist. The extent to which racial disparities in waitlisting differ between United Network for Organ Sharing (UNOS) regions is understudied.
METHODS: The US Renal Data System (USRDS) was linked with US census data to examine time from dialysis initiation to waitlisting for whites (n = 188,410) and African Americans (n = 144,335) using Cox proportional hazards across 11 UNOS regions, adjusting for potentially confounding individual, neighborhood, and state characteristics.
RESULTS: Likelihood of waitlisting varies significantly by UNOS region, overall and by race. Additionally, African Americans face significantly lower likelihood of waitlisting compared to whites in all but two regions (1 and 6). Overall, 39% of African Americans with ESRD reside in Regions 3 and 4--regions with a large racial disparity and where African Americans comprise a large proportion of the ESRD population. In these regions, the African American-white disparity is an important contributor to their overall regional disparity.
CONCLUSIONS: Race remains an important factor in time to transplant waitlist in the United States. Race contributes to overall regional disparities; however, the importance of race varies by UNOS region.

PMID: 25818547 [PubMed - indexed for MEDLINE]

A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium.

Recent Research Articles from UNTHSC - Wed, 03/02/2016 - 06:34
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A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium.

Bioorg Med Chem Lett. 2015;25(10):2065-7

Authors: Mukerjee A, Iyidogan P, Castellanos-Gonzalez A, Cisneros JA, Czyzyk D, Ranjan AP, Jorgensen WL, White AC, Vishwanatha JK, Anderson KS

Abstract
Cryptosporidiosis, a gastrointestinal disease caused by protozoans of the genus Cryptosporidium, is a common cause of diarrheal diseases and often fatal in immunocompromised individuals. Bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) from Cryptosporidium hominis (C. hominis) has been a molecular target for inhibitor design. C. hominis TS-DHFR inhibitors with nM potency at a biochemical level have been developed however drug delivery to achieve comparable antiparasitic activity in Cryptosporidium infected cell culture has been a major hurdle for designing effective therapies. Previous mechanistic and structural studies have identified compound 906 as a nM C. hominis TS-DHFR inhibitor in vitro, having μM antiparasitic activity in cell culture. In this work, proof of concept studies are presented using a nanotherapy approach to improve drug delivery and the antiparasitic activity of 906 in cell culture. We utilized PLGA nanoparticles that were loaded with 906 (NP-906) and conjugated with antibodies to the Cryptosporidium specific protein, CP2, on the nanoparticle surface in order to specifically target the parasite. Our results indicate that CP2 labeled NP-906 (CP2-NP-906) reduces the level of parasites by 200-fold in cell culture, while NP-906 resulted in 4.4-fold decrease. Moreover, the anticryptosporidial potency of 906 improved 15 to 78-fold confirming the utility of the antibody conjugated nanoparticles as an effective drug delivery strategy.

PMID: 25900220 [PubMed - indexed for MEDLINE]

Discriminative and locomotor effects of five synthetic cathinones in rats and mice.

Recent Research Articles from UNTHSC - Wed, 03/02/2016 - 06:34
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Discriminative and locomotor effects of five synthetic cathinones in rats and mice.

Psychopharmacology (Berl). 2015 Apr;232(7):1197-205

Authors: Gatch MB, Rutledge MA, Forster MJ

Abstract
RATIONALE: Synthetic cathinones continue to be sold as "legal" alternatives to methamphetamine or cocaine. As these marginally legal compounds become controlled, suppliers move to other, unregulated compounds.
OBJECTIVES: The purpose of these experiments was to determine whether several temporarily controlled cathinone compounds, which are currently abused on the street, stimulate motor activity and have discriminative stimulus effects similar to cocaine and/or methamphetamine.
METHODS: Methcathinone, pentedrone, pentylone, 3-fluoromethcathinone (3-FMC), and 4-methylethcathinone (4-MEC) were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) from saline.
RESULTS: Methcathinone, pentedrone, and pentylone produced locomotor stimulant effects which lasted up to 6 h. In addition, pentylone produced convulsions and lethality at 100 mg/kg. 4-MEC produced locomotor stimulant effects which lasted up to 2 h. Methcathinone, pentedrone, pentylone, 3-FMC, and 4-MEC each produced discriminative stimulus effects similar to those of cocaine and methamphetamine.
CONCLUSIONS: All of the tested compounds produce discriminative stimulus effects similar to either those of cocaine, methamphetamine, or both, which suggests that these compounds are likely to have similar abuse liability to cocaine and/or methamphetamine. Pentylone may be more dangerous on the street, as it produced adverse effects at doses that produced maximal stimulant-like effects.

PMID: 25281225 [PubMed - indexed for MEDLINE]

Current perspectives on the link between neuroinflammation and neurogenesis.

Recent Research Articles from UNTHSC - Wed, 03/02/2016 - 06:34
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Current perspectives on the link between neuroinflammation and neurogenesis.

Metab Brain Dis. 2015 Apr;30(2):355-65

Authors: Wang B, Jin K

Abstract
The link between neuroinflammation and neurogenesis is an area of intensive research in contemporary neuroscience. The burgeoning amount of evidence accumulated over the past decade has been incredible, and now there remains the figuring out of minutia to give us a more complete picture of what individual, synergistic, and antagonistic events are occurring between neurogenesis and neuroinflammation. An intricate study of the inflammatory microenvironment influenced by the presence of the various inflammatory components like cytokines, chemokines, and immune cells is essential for: 1) understanding how neurogenesis can be affected in such a specialized niche and 2) applying the knowledge gained for the treatment of cognitive and/or motor deficits arising from inflammation-associated diseases like stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease. This review is written to provide the reader with up-to-date information explaining how these inflammatory components are effecting changes on neurogenesis.

PMID: 24623361 [PubMed - indexed for MEDLINE]

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon.

Recent Research Articles from UNTHSC - Tue, 03/01/2016 - 06:41

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon.

Primates. 2015 Dec;4(2)

Authors: Szabó CÁ, Patel M, Uteshev VV

Abstract
The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons' electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status.

PMID: 26924854 [PubMed - as supplied by publisher]

Level of Immersion in Virtual Environments Impacts the Ability to Assess and Teach Social Skills in Autism Spectrum Disorder.

Recent Research Articles from UNTHSC - Sat, 02/27/2016 - 07:18

Level of Immersion in Virtual Environments Impacts the Ability to Assess and Teach Social Skills in Autism Spectrum Disorder.

Cyberpsychol Behav Soc Netw. 2016 Feb 26;

Authors: Miller HL, Bugnariu NL

Abstract
Virtual environments (VEs) may be useful for delivering social skills interventions to individuals with autism spectrum disorder (ASD). Immersive VEs provide opportunities for individuals with ASD to learn and practice skills in a controlled replicable setting. However, not all VEs are delivered using the same technology, and the level of immersion differs across settings. We group studies into low-, moderate-, and high-immersion categories by examining five aspects of immersion. In doing so, we draw conclusions regarding the influence of this technical manipulation on the efficacy of VEs as a tool for assessing and teaching social skills. We also highlight ways in which future studies can advance our understanding of how manipulating aspects of immersion may impact intervention success.

PMID: 26919157 [PubMed - as supplied by publisher]

Empirical testing of a 23-AIMs panel of SNPs for ancestry evaluations in four major US populations.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00

Empirical testing of a 23-AIMs panel of SNPs for ancestry evaluations in four major US populations.

Int J Legal Med. 2016 Feb 25;

Authors: Zeng X, Warshauer DH, King JL, Churchill JD, Chakraborty R, Budowle B

Abstract
Ancestry informative markers (AIMs) can be used to determine population affiliation of the donors of forensic samples. In order to examine ancestry evaluations of the four major populations in the USA, 23 highly informative AIMs were identified from the International HapMap project. However, the efficacy of these 23 AIMs could not be fully evaluated in silico. In this study, these 23 SNPs were multiplexed to test their actual performance in ancestry evaluations. Genotype data were obtained from 189 individuals collected from four American populations. One SNP (rs12149261) on chromosome 16 was removed from this panel because it was duplicated on chromosome 1. The resultant 22-AIMs panel was able to empirically resolve the four major populations as in the in silico study. Eight individuals were assigned to a different group than indicated on their samples. The assignments of the 22 AIMs for these samples were consistent with AIMs results from the ForenSeq(TM) panel. No departures from Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) were detected for all 22 SNPs in four US populations (after removing the eight problematic samples). The principal component analysis (PCA) results indicated that 181 individuals from these populations were assigned to the expected groups. These 22 SNPs can contribute to the candidate AIMs pool for potential forensic identification purposes in major US populations.

PMID: 26914801 [PubMed - as supplied by publisher]

Expansion of Microbial Forensics.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00

Expansion of Microbial Forensics.

J Clin Microbiol. 2016 Feb 24;

Authors: Schmedes SE, Sajantila A, Budowle B

Abstract
Microbial forensics has been defined as the discipline of applying scientific methods to analyzing evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years technology, particularly massively parallel sequencing, and bioinformatics advances now allow characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, post-mortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to analyzing microbial evidence in criminal and civil cases for investigative purposes.

PMID: 26912746 [PubMed - as supplied by publisher]

Boosting Endogenous Resistance of Brain to Ischemia.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00
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Boosting Endogenous Resistance of Brain to Ischemia.

Mol Neurobiol. 2016 Feb 24;

Authors: Sun F, Johnson SR, Jin K, Uteshev VV

Abstract
Most survivors of ischemic stroke remain physically disabled and require prolonged rehabilitation. However, some stroke victims achieve a full neurological recovery suggesting that the human brain can defend itself against ischemic injury, but the protective mechanisms are unknown. This study used selective pharmacological agents and a rat model of cerebral ischemic stroke to detect endogenous brain protective mechanisms that require activation of α7 nicotinic acetylcholine receptors (nAChRs). This endogenous protection was found to be (1) limited to less severe injuries; (2) significantly augmented by intranasal administration of a positive allosteric modulator of α7 nAChRs, significantly reducing brain injury and neurological deficits after more severe ischemic injuries; and (3) reduced by inhibition of calcium/calmodulin-dependent kinase-II. The physiological role of α7 nAChRs remains largely unknown. The therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential.

PMID: 26910820 [PubMed - as supplied by publisher]

Rhabdomyomatous mesenchymal hamartoma of the face causing trigeminal neuralgia.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00
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Rhabdomyomatous mesenchymal hamartoma of the face causing trigeminal neuralgia.

Am J Case Rep. 2015;16:338-40

Authors: White LR, Agrawal V, Sutton L, Balbosa AC

Abstract
BACKGROUND: Rhabdomyomatous mesenchymal hamartoma (RMH) is a benign, potentially pigmented lesion that occurs in the head and neck region. It generally consists of haphazardly arranged skeletal muscle with adipose tissue, blood vessels, collagen and nerve fibers and is largely asymptomatic. Trigeminal neuralgia is pain due to compression of the trigeminal nerve. TN may be idiopathic or associated with lesion-mediated compression.
CASE REPORT: We describe the case of a 14-year-old female presenting with trigeminal neuralgia (TN) associated with RMH. On initial consultation, the patient presented with a history of right-sided lower facial swelling, numbness, and pain. Evaluation by various specialists confirmed TN. Surgical resection of the lesion resolved the condition and pathology confirmed RMH.
CONCLUSIONS: This is the first case report demonstrating RMH-mediated TN. Surgical resection of the RMH is a safe management approach for this diagnosis.

PMID: 26037964 [PubMed - indexed for MEDLINE]

Joseon funerary texts tested using ancient DNA analysis of a Korean mummy.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00
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Joseon funerary texts tested using ancient DNA analysis of a Korean mummy.

Anat Rec (Hoboken). 2015 Jun;298(6):1191-207

Authors: Oh CS, Koh BJ, Yoo DS, Park JB, Min SR, Kim YS, Lee SS, Ge J, Seo SB, Shin DH

Abstract
In Korea, ancient DNA (aDNA) analysis has been applied to investigations into the genetic affiliations of mummies found in Joseon Dynasty tombs (1392-1910 CE), becoming now indispensable tool for researches studying human remains from archaeological sites. In the course of our recent examinations on a Korean mummy of Joseon Dynasty, we discovered many teeth contained in a pouch. And in fact, the historical literature on the topic of Joseon funerals contain general accounts of pouches in which an individual's lost teeth were collected over the course of a lifetime and, after death, placed in the coffin with the body. To test the veracity of the historical texts, the present study undertook aDNA analyses and compared the results between specifically questioned (Q) samples (teeth) and known (K) samples (brain and bone) from the mummy to ensure that they came from the same individual. Although the Q-K comparison of autosomal short tandem repeat results did not show full concordance due to allelic drop-outs in some loci, our statistical calculation indicated that the teeth in the pouch are highly likely those of the mummy. Additionally, Q-K comparison of mitochondrial DNA sequence results showed 100% matches between samples. There results, in short, could not gainsay the conjecture that the teeth samples originated from the person buried in the tomb; and if so, he must have kept his teeth for a long time after their loss. As the application of aDNA analysis to Korean mummy studies develops, there will be other opportunities to test historical documents, particularly those referring to funerary rites.

PMID: 25998652 [PubMed - indexed for MEDLINE]

An overview of the Families Improving Together (FIT) for weight loss randomized controlled trial in African American families.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00
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An overview of the Families Improving Together (FIT) for weight loss randomized controlled trial in African American families.

Contemp Clin Trials. 2015 May;42:145-57

Authors: Wilson DK, Kitzman-Ulrich H, Resnicow K, Van Horn ML, St George SM, Siceloff ER, Alia KA, McDaniel T, Heatley V, Huffman L, Coulon S, Prinz R

Abstract
BACKGROUND: The Families Improving Together (FIT) randomized controlled trial tests the efficacy of integrating cultural tailoring, positive parenting, and motivational strategies into a comprehensive curriculum for weight loss in African American adolescents. The overall goal of the FIT trial is to test the effects of an integrated intervention curriculum and the added effects of a tailored web-based intervention on reducing z-BMI in overweight African American adolescents.
DESIGN AND SETTING: The FIT trial is a randomized group cohort design the will involve 520 African American families with an overweight adolescent between the ages of 11-16 years. The trial tests the efficacy of an 8-week face-to-face group randomized program comparing M + FWL (Motivational Plus Family Weight Loss) to a comprehensive health education program (CHE) and re-randomizes participants to either an 8-week on-line tailored intervention or control on-line program resulting in a 2 (M + FWL vs. CHE group) × 2 (on-line intervention vs. control on-line program) factorial design to test the effects of the intervention on reducing z-BMI at post-treatment and at 6-month follow-up.
INTERVENTION: The interventions for this trial are based on a theoretical framework that is novel and integrates elements from cultural tailoring, Family Systems Theory, Self-Determination Theory and Social Cognitive Theory. The intervention targets positive parenting skills (parenting style, monitoring, communication); cultural values; teaching parents to increase youth motivation by encouraging youth to have input and choice (autonomy-support); and provides a framework for building skills and self-efficacy through developing weight loss action plans that target goal setting, monitoring, and positive feedback.

PMID: 25835731 [PubMed - indexed for MEDLINE]

Store-Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00
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Store-Operated Ca2+ Channels in Mesangial Cells Inhibit Matrix Protein Expression.

J Am Soc Nephrol. 2015 Nov;26(11):2691-702

Authors: Wu P, Wang Y, Davis ME, Zuckerman JE, Chaudhari S, Begg M, Ma R

Abstract
Accumulation of extracellular matrix derived from glomerular mesangial cells is an early feature of diabetic nephropathy. Ca(2+) signals mediated by store-operated Ca(2+) channels regulate protein production in a variety of cell types. The aim of this study was to determine the effect of store-operated Ca(2+) channels in mesangial cells on extracellular matrix protein expression. In cultured human mesangial cells, activation of store-operated Ca(2+) channels by thapsigargin significantly decreased fibronectin protein expression and collagen IV mRNA expression in a dose-dependent manner. Conversely, inhibition of the channels by 2-aminoethyl diphenylborinate significantly increased the expression of fibronectin and collagen IV. Similarly, overexpression of stromal interacting molecule 1 reduced, but knockdown of calcium release-activated calcium channel protein 1 (Orai1) increased fibronectin protein expression. Furthermore, 2-aminoethyl diphenylborinate significantly augmented angiotensin II-induced fibronectin protein expression, whereas thapsigargin abrogated high glucose- and TGF-β1-stimulated matrix protein expression. In vivo knockdown of Orai1 in mesangial cells of mice using a targeted nanoparticle siRNA delivery system resulted in increased expression of glomerular fibronectin and collagen IV, and mice showed significant mesangial expansion compared with controls. Similarly, in vivo knockdown of stromal interacting molecule 1 in mesangial cells by recombinant adeno-associated virus-encoded shRNA markedly increased collagen IV protein expression in renal cortex and caused mesangial expansion in rats. These results suggest that store-operated Ca(2+) channels in mesangial cells negatively regulate extracellular matrix protein expression in the kidney, which may serve as an endogenous renoprotective mechanism in diabetes.

PMID: 25788524 [PubMed - indexed for MEDLINE]

An attachment-based description of the medial collateral and spring ligament complexes.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00
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An attachment-based description of the medial collateral and spring ligament complexes.

Foot Ankle Int. 2015 Jun;36(6):710-21

Authors: Cromeens BP, Kirchhoff CA, Patterson RM, Motley T, Stewart D, Fisher C, Reeves RE

Abstract
BACKGROUND: Anatomy of the medial collateral and spring ligament complexes has been the cause of confusion. The anatomic description is highly dependent on the source studied and little agreement exists between texts. In addition, inconsistent nomenclature has been used to describe the components. This study attempted to clarify confusion through the creation of a 3D ligament map using attachment-based dissection.
METHODS: Nine fresh foot and ankle specimens were observed. The medial collateral ligament and spring ligament complexes were dissected using their attachment sites as a guide to define individual components. Each component's perimeter and thickness was measured and each bony attachment was mapped using a microscribe 3D digitizer.
RESULTS: Five components were identified contributing to the ligament complexes of interest: the tibiocalcaneonavicular, superficial posterior tibiotalar, deep posterior tibiotalar, deep anterior tibiotalar, and inferoplantar longitudinal ligaments. The largest component by total attachment area was the tibiocalcaneonavicular ligament followed by the deep posterior tibiotalar ligament. The largest ligament surface area of attachment to the tibia and talus was the deep posterior tibiotalar ligament. The largest attachment to the navicular and calcaneus was the tibiocalcaneonavicular ligament, which appeared to function in holding these bones in proximity while supporting the head of the talus.
CONCLUSION: By defining complex components by their attachment sites, a novel, more functional and reproducible description of the medial collateral and spring ligament complexes was created.
CLINICAL RELEVANCE: The linear measurements and 3D maps may prove useful when attempting more anatomically accurate reconstructions.

PMID: 25712121 [PubMed - indexed for MEDLINE]

High sensitivity multiplex short tandem repeat loci analyses with massively parallel sequencing.

Recent Research Articles from UNTHSC - Fri, 02/26/2016 - 07:00
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High sensitivity multiplex short tandem repeat loci analyses with massively parallel sequencing.

Forensic Sci Int Genet. 2015 May;16:38-47

Authors: Zeng X, King JL, Stoljarova M, Warshauer DH, LaRue BL, Sajantila A, Patel J, Storts DR, Budowle B

Abstract
STR typing in forensic genetics has been performed traditionally using capillary electrophoresis (CE). However, CE-based method has some limitations: a small number of STR loci can be used; stutter products, dye artifacts and low level alleles. Massively parallel sequencing (MPS) has been considered a viable technology in recent years allowing high-throughput coverage at a relatively affordable price. Some of the CE-based limitations may be overcome with the application of MPS. In this study, a prototype multiplex STR System (Promega) was amplified and prepared using the TruSeq DNA LT Sample Preparation Kit (Illumina) in 24 samples. Results showed that the MinElute PCR Purification Kit (Qiagen) was a better size selection method compared with recommended diluted bead mixtures. The library input sensitivity study showed that a wide range of amplicon product (6-200ng) could be used for library preparation without apparent differences in the STR profile. PCR sensitivity study indicated that 62pg may be minimum input amount for generating complete profiles. Reliability study results on 24 different individuals showed that high depth of coverage (DoC) and balanced heterozygote allele coverage ratios (ACRs) could be obtained with 250pg of input DNA, and 62pg could generate complete or nearly complete profiles. These studies indicate that this STR multiplex system and the Illumina MiSeq can generate reliable STR profiles at a sensitivity level that competes with current widely used CE-based method.

PMID: 25528025 [PubMed - indexed for MEDLINE]

Effect of adenovirus-mediated RNA interference of IL-1β expression on spinal cord injury in rats.

Recent Research Articles from UNTHSC - Wed, 02/24/2016 - 07:29

Effect of adenovirus-mediated RNA interference of IL-1β expression on spinal cord injury in rats.

Spinal Cord. 2016 Feb 23;

Authors: Lin WP, Lin JH, Cai B, Shi JX, Li WJ, Choudhury GR, Wu SQ, Wu JZ, Wu HP, Ke QF

Abstract
STUDY DESIGN: We introduced an adenoviral vector expressing interleukin-1β (IL-1β) small-hairpin RNA (shRNA) into the injured spinal cords to evaluate the therapeutic potential of IL-1β downregulation in a rat model of spinal cord injury (SCI).
OBJECTIVES: The purpose of this study was to investigate the possible protective effects of the IL-1β downregulation on traumatic SCI in rats.
SETTING: Department of Orthopedic Surgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, People's Republic of China.
METHODS: An adenoviral shRNA targeting IL-1β was constructed and injected at the T12 section 7 days before SCI. The rats' motor functions were evaluated by the Basso-Beattie-Bresnahan (BBB) rating scale. Immunofluorescence, enzyme-linked immunosorbent assay, flow-cytometric analysis and western blots were also performed.
RESULTS: Animals downregulating IL-1β had significantly better recovery of locomotor function and less neuronal loss after SCI. In addition, IL-1β downregulation significantly decreased tumor necrosis factor-alpha (TNF-α) level and Bax expression, reduced the activity of caspase-3 and increased Bcl-2 expression after SCI.
CONCLUSION: This study demonstrated that the IL-1β downregulation may have potential therapeutic benefits for both reducing secondary damages and improving the outcomes after traumatic SCI.Spinal Cord advance online publication, 23 February 2016; doi:10.1038/sc.2016.20.

PMID: 26902461 [PubMed - as supplied by publisher]

Tip110: Physical properties, primary structure, and biological functions.

Recent Research Articles from UNTHSC - Sun, 02/21/2016 - 07:29

Tip110: Physical properties, primary structure, and biological functions.

Life Sci. 2016 Feb 16;

Authors: Whitmill A, Timani KA, Liu Y, He JJ

Abstract
HIV-1 Tat-interacting protein of 110kDa (Tip110), also referred to as squamous cell carcinoma antigen recognized by T cells 3 (Sart3), p110 or p110(nrb), was initially identified as a cDNA clone (KIAA0156) without annotated functions. Over the past twenty years, several functions have been attributed to this protein. The proposed biological functions include roles for Tip110 in pre-mRNA splicing, gene transcription, stem cell biology, and development. Dysregulation of Tip110 is also a contributing factor in the development of cancer and other human diseases. It is clear that our understanding of this protein is rapidly evolving. In this review, we aimed to provide a summary of all the existing literature on this gene/protein and its proposed biological functions.

PMID: 26896687 [PubMed - as supplied by publisher]

Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas.

Recent Research Articles from UNTHSC - Sun, 02/21/2016 - 07:29

Racial and Ethnic Disparities in Health and Health Care: an Assessment and Analysis of the Awareness and Perceptions of Public Health Workers Implementing a Statewide Community Transformation Grant in Texas.

J Racial Ethn Health Disparities. 2016 Mar;3(1):46-54

Authors: Akinboro O, Ottenbacher A, Martin M, Harrison R, James T, Martin E, Murdoch J, Linnear K, Cardarelli K

Abstract
INTRODUCTION: Little is known about the awareness of public health professionals regarding racial and ethnic disparities in health in the United States of America (USA). Our study objective was to assess the awareness and perceptions of a group of public health workers in Texas regarding racial health disparities and their chief contributing causes.
METHODS: We surveyed public health professionals working on a statewide grant in Texas, who were participants at health disparities' training workshops. Multivariable logistic regression was employed in examining the association between the participants' characteristics and their perceptions of the social determinants of health as principal causes of health disparities.
RESULTS: There were 106 respondents, of whom 38 and 35 % worked in health departments and non-profit organizations, respectively. The racial/ethnic groups with the highest incidence of HIV/AIDS and hypertension were correctly identified by 63 and 50 % of respondents, respectively, but only 17, and 32 % were knowledgeable regarding diabetes and cancer, respectively. Seventy-one percent of respondents perceived that health disparities are driven by the major axes of the social determinants of health. Exposure to information about racial/ethnic health disparities within the prior year was associated with a higher odds of perceiving that social determinants of health were causes of health disparities (OR 9.62; 95 % CI 2.77, 33.41).
CONCLUSION: Among public health workers, recent exposure to information regarding health disparities may be associated with their perceptions of health disparities. Further research is needed to investigate the impact of such exposure on their long-term perception of disparities, as well as the equity of services and programs they administer.

PMID: 26896104 [PubMed - in process]

WISE 2005: Aerobic and resistive countermeasures prevent paraspinal muscle deconditioning during 60-days bed rest in women.

Recent Research Articles from UNTHSC - Sat, 02/20/2016 - 07:32

WISE 2005: Aerobic and resistive countermeasures prevent paraspinal muscle deconditioning during 60-days bed rest in women.

J Appl Physiol (1985). 2016 Feb 18;:jap.00532.2015

Authors: Holt JA, Macias BR, Schneider SM, Watenpaugh DE, Lee SM, Chang DG, Hargens AR

Abstract
Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts, and may increase the risk of postflight injury. We hypothesized that a combined resistance and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60-days of bed rest in women.
METHODS: Sixteen women underwent 60-day, 6° head-down-tilt bed rest and were randomized into control and exercise groups. During bed rest, the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 d/wk and flywheel resistive exercise for 2-3 d/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after bed rest (BR). In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as mean ± SD.
RESULTS: Total lumbar paraspinal muscle CSA decreased significantly more in controls (10.9 ± 3.4%) than in exercisers (4.3 ± 3.4%; p <0.05). The erector spinae was the primary contributor (76%) to total lumbar paraspinal muscle loss. Moreover, exercise attenuated isokinetic spinal extension loss (-4.3 ± 4.5%), as compared to controls (-16.6 ± 11.2%; p <0.05).
CONCLUSIONS: LBNP treadmill and flywheel resistive exercises during simulated microgravity mitigates decrements in lumbar paraspinal muscle structure and spine function. Therefore, space flight exercise countermeasures that attempt to reproduce spinal loads experienced on Earth may mitigate spinal deconditioning during long-duration space travel.

PMID: 26893030 [PubMed - as supplied by publisher]

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