Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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A Community-based Stress Management Program: Using Wearable Devices to Assess Whole Body Physiological Responses in Non-laboratory Settings.

Thu, 06/21/2018 - 07:33
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A Community-based Stress Management Program: Using Wearable Devices to Assess Whole Body Physiological Responses in Non-laboratory Settings.

J Vis Exp. 2018 01 22;(131):

Authors: Carter R, Carter KS, Holliday J, Holliday A, Harrison CK

Abstract
A pragmatic breath-based intervention to benefit human performance and stress management is timely and valuable to individuals seeking holistic approaches for emotional regulation and optimizing compensatory reserve mechanisms. This protocol is designed to not only teach mind-body awareness but also to provide feedback utilizing physiological data and survey results. The primary findings of this study showed that heart coherence and alpha variables were significantly correlated after four weeks of the breath-based meditation stress protocol. Meditation and rhythmic breathing produced significant increases in alpha brain activity. These brain physiological responses conformed to the Pleth Variability Index (PVI) changes, suggesting the ability of the human body to enter into a meditative state and effectively manage stress. When assessed after four weeks of daily practicing the techniques employed in the stress management protocol, based on the Five Facet Mindfulness Questionnaire, subjects improved in applying mindfulness skills. The overall mindfulness score, Pleth variability index (PVI), and perfusion index (PI) increased after the 4-week intervention period. Results from electroencephalography (brain waves) were consistent with a meditative state during the post-study follow-up session. This provides evidence that wearable devices are feasible for data collection during a breath-based stress management intervention. This protocol can be easily and efficiently implemented into any study design in which physiological data are desired in a non-laboratory-based setting.

PMID: 29443019 [PubMed - indexed for MEDLINE]

Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials.

Thu, 06/21/2018 - 07:33
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Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials.

J Exp Clin Cancer Res. 2017 Aug 11;36(1):108

Authors: Gdowski AS, Ranjan A, Vishwanatha JK

Abstract
BACKGROUND: Elucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. However, the rapid rate of progress in both the basic science literature and therapies undergoing clinical trials makes staying abreast with current developments challenging. This review seeks to provide an update on the current state of the science in bone metastasis research and give a snap shot of therapies in clinical trials for bone metastatic cancer.
MAIN BODY: Bone metastasis represents a difficult to treat clinical scenario due to pain, increased fracture risk, decreased quality of life and diminished overall survival outcomes. Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. This osteotropism was first described by Stephen Paget nearly 100 years ago as the 'seed and soil' hypothesis. Once cancer cells arrive at the bone they encounter a variety of cells native to the bone microenvironment which contribute to the establishment of bone metastatic lesions. In the first part of this review, the 'seed and soil' hypothesis is revisited while emphasizing recent developments in understanding the impact of native bone microenvironment cells on the metastatic process. Next, approved therapies for treating bone metastasis at the systemic level as well as those that target the bone microenvironment are discussed and current National Comprehensive Cancer Network (NCCN) guidelines relating to treatment of bone metastases are summarized. Finally, all open interventional clinical trials for therapies relating to treatment of bone metastasis have been complied and categorized.
CONCLUSION: Understanding the recent advancements in bone metastasis research is important for continued development of novel bone targeted therapies. The plethora of ongoing clinical trials will hopefully translate into improved treatments options for patients suffering from bone metastatic cancers.

PMID: 28800754 [PubMed - indexed for MEDLINE]

Impure but not inactive: Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis.

Tue, 06/19/2018 - 07:32
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Impure but not inactive: Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis.

J Psychopharmacol. 2018 Jun 01;:269881118780613

Authors: Dolan SB, Shetty RA, Forster MJ, Gatch MB

Abstract
BACKGROUND: Substituted piperazines comprise a substantial proportion of the novel psychoactive substance market. Among the most widely abused piperazine compounds are meta-chlorophenylpiperazine (mCPP), tri-fluoromethylphenylpiperazine (TFMPP), and, especially, benzylpiperazine (BZP), which are commonly incorporated, either alone or in combination, in illicit "party pills" or "ecstasy" formulations. Illicit synthesis of BZP often results in production of an impure by-product dibenzylpiperazine (DBZP), which frequently appears alongside BZP in these formulations; however, despite its ubiquity, little information exists regarding the abuse liability of DBZP.
AIMS: The current study aimed to evaluate the abuse-related behavioral pharmacology of DBZP.
METHODS: DBZP, mCPP, and TFMPP were tested in parallel in mice in locomotor activity and conditioned place preference assays, and in a drug discrimination assay with rats trained to discriminate either methamphetamine, cocaine, (±)-3,4-methylenedioxymethamphetamine (MDMA), or -2,5-dimethoxy-4-methylamphetamine(DOM).
RESULTS: Each of the compounds tested produced dose-dependent decreases in locomotor activity. DBZP substituted fully for methamphetamine, produced subthreshold drug-appropriate responding for cocaine and MDMA, and failed to substitute for DOM. Conversely, TFMPP and mCPP only produced subthreshold drug-appropriate responding for methamphetamine and MDMA, respectively, and both compounds failed to substitute for cocaine or DOM. None of the compounds tested produced a place preference. DBZP produced convulsions in rats at the highest dose tested.
CONCLUSIONS: These data indicate that DBZP is more similar to BZP, albeit with lower potency and efficacy, than its serotonergic piperazine counterparts, and is a behaviorally-active compound with some abuse liability and potential for adverse health effects.

PMID: 29909719 [PubMed - as supplied by publisher]

CRISPR-Cas9-based treatment of myocilin-associated glaucoma.

Tue, 06/19/2018 - 07:32
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CRISPR-Cas9-based treatment of myocilin-associated glaucoma.

Proc Natl Acad Sci U S A. 2017 10 17;114(42):11199-11204

Authors: Jain A, Zode G, Kasetti RB, Ran FA, Yan W, Sharma TP, Bugge K, Searby CC, Fingert JH, Zhang F, Clark AF, Sheffield VC

Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-of-function mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular meshwork (TM), the tissue that regulates IOP. We use CRISPR-Cas9-mediated genome editing in cultured human TM cells and in a MYOC mouse model of POAG to knock down expression of mutant MYOC, resulting in relief of ER stress. In vivo genome editing results in lower IOP and prevents further glaucomatous damage. Importantly, using an ex vivo human organ culture system, we demonstrate the feasibility of human genome editing in the eye for this important disease.

PMID: 28973933 [PubMed - indexed for MEDLINE]

Community-based participatory research to design a faith-enhanced diabetes prevention program: The Better Me Within randomized trial.

Tue, 06/19/2018 - 07:32
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Community-based participatory research to design a faith-enhanced diabetes prevention program: The Better Me Within randomized trial.

Contemp Clin Trials. 2017 Nov;62:77-90

Authors: Kitzman H, Dodgen L, Mamun A, Slater JL, King G, Slater D, King A, Mandapati S, DeHaven M

Abstract
Reducing obesity positively impacts diabetes and cardiovascular risk; however, evidence-based lifestyle programs, such as the diabetes prevention program (DPP), show reduced effectiveness in African American (AA) women. In addition to an attenuated response to lifestyle programs, AA women also demonstrate high rates of obesity, diabetes, and cardiovascular disease. To address these disparities, enhancements to evidence-based lifestyle programs for AA women need to be developed and evaluated with culturally relevant and rigorous study designs. This study describes a community-based participatory research (CBPR) approach to design a novel faith-enhancement to the DPP for AA women. A long-standing CBPR partnership designed the faith-enhancement from focus group data (N=64 AA adults) integrating five components: a brief pastor led sermon, memory verse, in class or take-home faith activity, promises to remember, and scripture and prayer integrated into participant curriculum and facilitator materials. The faith components were specifically linked to weekly DPP learning objectives to strategically emphasize behavioral skills with religious principles. Using a CBPR approach, the Better Me Within trial was able to enroll 12 churches, screen 333 AA women, and randomize 221 (Mage=48.8±11.2; MBMI=36.7±8.4; 52% technical or high school) after collection of objective eligibility measures. A prospective, randomized, nested by church, design will be used to evaluate the faith-enhanced DPP as compared to a standard DPP on weight, diabetes and cardiovascular risk, over a 16-week intervention and 10-month follow up. This study will provide essential data to guide enhancements to evidence-based lifestyle programs for AA women who are at high risk for chronic disease.

PMID: 28807739 [PubMed - indexed for MEDLINE]

New Models of Pregnancy-Associated Hypertension.

Tue, 06/19/2018 - 07:32
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New Models of Pregnancy-Associated Hypertension.

Am J Hypertens. 2017 Nov 01;30(11):1053-1062

Authors: Cushen SC, Goulopoulou S

Abstract
Pregnancy-associated hypertensive disorders are leading causes of maternal and fetal mortality. These include: pre-pregnancy hypertension that persists throughout gestation (chronic/preexisting hypertension), de novo hypertension that is diagnosed after 20 weeks of gestation and resolves after birth (gestational hypertension), de novo hypertension that is diagnosed after 20 weeks of gestation with or without proteinuria and end-organ damage (preeclampsia and eclampsia), and chronic hypertension with superimposed preeclampsia during gestation. Preeclampsia is the most severe form of these disorders. Animal models have been developed by employing surgical, genetic, and pharmacological approaches in order to recapitulate the maternal symptoms of preeclampsia and other hypertensive disorders of pregnancy. The scope of this brief review is to present an up-to-date synthesis of our knowledge of experimental models of pregnancy-associated hypertensive disorders. Novel models, defined in this review as characterized within the last 5 years, will be described and critically discussed. In this review, we will also discuss established experimental models of pregnancy-associated hypertensive disorders in the context of their contribution to new advances in our knowledge about the pathophysiology of these disorders and potential therapeutics. Emphasis will be placed on animal models of preeclampsia; however, models of other hypertensive disorders in pregnancy will also be reviewed.

PMID: 28472224 [PubMed - indexed for MEDLINE]

Cervical Sympathetic Chain Schwannoma Masquerading as a Vagus Nerve Schwannoma Complicated by Postoperative Horner's Syndrome and Facial Pain: A Case Report.

Sun, 06/17/2018 - 07:33
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Cervical Sympathetic Chain Schwannoma Masquerading as a Vagus Nerve Schwannoma Complicated by Postoperative Horner's Syndrome and Facial Pain: A Case Report.

Int J Surg Case Rep. 2018 Jun 09;49:4-7

Authors: Baker AT, Homewood TJ, Baker TR

Abstract
INTRODUCTION: Cervical Sympathetic Chain Schwannomas (CSCS) of the carotid sheath are rare neoplasms that can be misdiagnosed on imaging. The following case documents a rare incident of a misdiagnosed CSCS with unusual outcomes of permanent Horner's syndrome and facial pain.
PRESENTATION OF CASE: A 36-year-old female presented with a slow-growing neck mass. CT and MRI led to a preoperative diagnosis of vagus nerve schwannoma (VNS). However, surgical treatment revealed the mass to be involved with the cervical sympathetic chain rather than the vagus nerve. The diagnosis was corrected to CSCS and the nerve was resected with the mass. The patient presented postoperatively with Horner's syndrome and severe facial pain. These symptoms persisted despite two years of medical management.
DISCUSSION: Studies indicate that imaging trends used for distinction between VNS and CSCS show inconsistencies in making preoperative diagnoses. Recent literature reveals helpful criteria for improving diagnostic standards that assist with preoperative patient counseling. In addition, postoperative outcomes, such as temporary, asymptomatic Horner's syndrome are common in CSCS. The following case report exemplifies the difficulties in diagnosis and addresses the unique complications of facial pain and permanent Horner's syndrome.
CONCLUSION: This case report examines postoperative outcomes and improves clinician awareness of the potential for misdiagnosis of a rare neoplasm and the recently improved diagnostic measures, providing for higher quality preoperative counseling. Future research is recommended to confirm and improve diagnostic guidelines and accuracy. Additional studies may focus on evaluating the effects of incorrect preoperative diagnosis on postoperative complication rates.

PMID: 29908450 [PubMed - as supplied by publisher]

Associations between Race, Perceived Psychological Stress, and the Gut Microbiota in a Sample of Generally Healthy Black and White Women: A Pilot Study on the Role of Race and Perceived Psychological Stress.

Fri, 06/15/2018 - 07:36
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Associations between Race, Perceived Psychological Stress, and the Gut Microbiota in a Sample of Generally Healthy Black and White Women: A Pilot Study on the Role of Race and Perceived Psychological Stress.

Psychosom Med. 2018 Jun 12;:

Authors: Carson TL, Wang F, Cui X, Jackson BE, Van Der Pol WJ, Lefkowitz EJ, Morrow C, Baskin ML

Abstract
OBJECTIVE: Racial health disparities persist among black and white women for colorectal cancer. Understanding racial differences in the gut microbiota and related covariates (e.g., stress) may yield new insight into unexplained colorectal cancer disparities.
METHODS: Healthy non-Hispanic black or white females (age ≥19 years) provided survey data, anthropometrics, and stool samples. Fecal DNA was collected and isolated from a wipe. PCR was used to amplify the V4 region of the 16SrRNA gene and 250 bases were sequenced using the MiSeq platform. Microbiome data was analyzed using QIIME. OTU data were log transformed and normalized. Analyses were conducted using linear models in R Package "limma'.
RESULTS: Fecal samples were analyzed for 80 females (mean age = 39.9 (SD= 14.0) years; 47 black, 33 white). Blacks had greater average BMI (33.3 vs. 27.5 kg/m2; p<0.01) and waist circumference (98.3 vs. 86.6 cm; p=0.003) than whites. Whites reported more stressful life events (p=0.026) and greater distress (p=0.052) than Blacks. Final models accounted for these differences. There were no significant differences in dietary variables. Unadjusted comparisons revealed no racial differences in alpha diversity. Racial differences were observed in beta diversity and abundance of top-10 OTUs. Blacks had higher abundances than whites of Faecalibacterium (p=0.034) and Bacteroides (p=0.038). Stress was associated with abundances of Bifidobacterium. The association between race and Bacteroides (logFC=1.72; 0=0.020) persisted in fully adjusted models.
CONCLUSIONS: Racial differences in the gut microbiota were observed including higher Bacteroides among blacks. Efforts to cultivate an 'ideal' gut microbiota may help reduce colorectal cancer risk.

PMID: 29901485 [PubMed - as supplied by publisher]

Duty of Notification and Aviation Safety-A Study of Fatal Aviation Accidents in the United States in 2015.

Fri, 06/15/2018 - 07:36
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Duty of Notification and Aviation Safety-A Study of Fatal Aviation Accidents in the United States in 2015.

Int J Environ Res Public Health. 2018 Jun 13;15(6):

Authors: Vuorio A, Budowle B, Sajantila A, Laukkala T, Junttila I, Kravik SE, Griffiths R

Abstract
After the Germanwings accident, the French Safety Investigation Authority (BEA) recommended that the World Health Organization (WHO) and European Community (EC) develop clear rules for the duty of notification process. Aeromedical practitioners (AMEs) face a dilemma when considering the duty of notification and conflicts between pilot privacy and public and third-party safety. When balancing accountability, knowledge of the duty of notification process, legislation and the clarification of a doctor&rsquo;s own set of values should be assessed a priori. Relatively little is known of the magnitude of this problem in aviation safety. To address this, the National Transportation Safety Board (NTSB) database was searched to identify fatal accidents during 2015 in the United States in which a deceased pilot used a prescribed medication or had a disease that potentially reduced pilot performance and was not reported to the AME. Altogether, 202 finalized accident reports with toxicology were available from (the year) 2015. In 5% (10/202) of these reports, the pilot had either a medication or a disease not reported to an AME which according to the accident investigation was causal to the fatal accident. In addition, the various approaches to duty of notification in aviation in New Zealand, Finland and Norway are discussed. The process of notification of authorities without a pilot&rsquo;s express permission needs to be carried out by using a guidance protocol that works within legislation and professional responsibilities to address the pilot and the public, as well as the healthcare provider. Professional guidance defining this duty of notification is urgently needed.

PMID: 29899311 [PubMed - in process]

SDF-1/CXCR7 Chemokine Signaling is Induced in the Peri-Infarct Regions in Patients with Ischemic Stroke.

Thu, 06/14/2018 - 08:03
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SDF-1/CXCR7 Chemokine Signaling is Induced in the Peri-Infarct Regions in Patients with Ischemic Stroke.

Aging Dis. 2018 Apr;9(2):287-295

Authors: Zhang Y, Zhang H, Lin S, Chen X, Yao Y, Mao X, Shao B, Zhuge Q, Jin K

Abstract
Stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptors CXCR4 and CXCR7 play important roles in brain repair after ischemic stroke, as SDF-1/ CXCR4/CXCR7 chemokine signaling is critical for recruiting stem cells to sites of ischemic injury. Upregulation of SDF-1/CXCR4/CXCR7 chemokine signaling in the ischemic regions has been well-documented in the animal models of ischemic stroke, but not in human ischemic brain. Here, we found that protein expression of SDF-1 and CXCR7, but not CXCR4, were significantly increased in the cortical peri-infarct regions (penumbra) after ischemic stroke in human, compared with adjacent normal tissues and control subjects. Double-label fluorescence immunohistochemistry shows that SDF-1 and CXCR4 proteins were expressed in neuronal cells and astrocytes in the normal brain tissue and peri-infarct regions. CXCR7 protein was also observed in neuronal cells and astrocytes in the normal cortical regions, but predominantly in astrocytes in the penumbra of ischemic brain. Our data suggest that ischemic stroke in human leads to an increase in the expression of SDF-1 and CXCR7, but not CXCR4, in the peri-infarct cerebral cortex. Our findings suggest that chemokine SFD-1 is expressed not only in animal models of stroke, but also in the human brain after an ischemic injury. In addition, unlike animals, CXCR7 may be the primary receptor of SDF-1 in human stroke brain.

PMID: 29896417 [PubMed]

CLARITY for High-resolution Imaging and Quantification of Vasculature in the Whole Mouse Brain.

Thu, 06/14/2018 - 08:03
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CLARITY for High-resolution Imaging and Quantification of Vasculature in the Whole Mouse Brain.

Aging Dis. 2018 Apr;9(2):262-272

Authors: Zhang LY, Lin P, Pan J, Ma Y, Wei Z, Jiang L, Wang L, Song Y, Wang Y, Zhang Z, Jin K, Wang Q, Yang GY

Abstract
Elucidating the normal structure and distribution of cerebral vascular system is fundamental for understanding its function. However, studies on visualization and whole-brain quantification of vasculature with cellular resolution are limited. Here, we explored the structure of vasculature at the whole-brain level using the newly developed CLARITY technique. Adult male C57BL/6J mice undergoing transient middle cerebral artery occlusion and Tie2-RFP transgenic mice were used. Whole mouse brains were extracted for CLARITY processing. Immunostaining was performed to label vessels. Customized MATLAB code was used for image processing and quantification. Three-dimensional images were visualized using the Vaa3D software. Our results showed that whole mouse brain became transparent using the CLARITY method. Three-dimensional imaging and visualization of vasculature were achieved at the whole-brain level with a 1-μm voxel resolution. The quantitative results showed that the fractional vascular volume was 0.018 ± 0.004 mm3 per mm3, the normalized vascular length was 0.44 ± 0.04 m per mm3, and the mean diameter of the microvessels was 4.25 ± 0.08 μm. Furthermore, a decrease in the fractional vascular volume and a decrease in the normalized vascular length were found in the penumbra of ischemic mice compared to controls (p < 0.05). In conclusion, CLARITY provides a novel approach for mapping vasculature in the whole mouse brain at cellular resolution. CLARITY-optimized algorithms facilitate the assessment of structural change in vasculature after brain injury.

PMID: 29896415 [PubMed]

Antihypertensive Treatment Fails to Control Blood Pressure During Exercise.

Thu, 06/14/2018 - 08:03
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Antihypertensive Treatment Fails to Control Blood Pressure During Exercise.

Hypertension. 2018 Jun 12;:

Authors: Raven PB

PMID: 29895531 [PubMed - as supplied by publisher]

Protein kinase C-eta regulates Mcl-1 level via ERK1.

Thu, 06/14/2018 - 08:03
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Protein kinase C-eta regulates Mcl-1 level via ERK1.

Cell Signal. 2017 Dec;40:166-171

Authors: Pal D, Basu A

Abstract
Protein kinase C (PKC)-eta (PKCη) is a member of the novel category of PKC family. It is overexpressed in breast cancer and was shown to inhibit apoptosis and contribute to chemoresistance. Since 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 investigated if PKCη regulates Mcl-1 level. Silencing of PKCη decreased Mcl-1 in several breast cancer cells, including MCF-7 and T47D cells. PKCη depletion had no effect on MCL1 mRNA but the decrease in Mcl-1 by PKCη knockdown was blocked by proteasomal inhibitors, such as MG132 and lactacystin. Moreover, knockdown of Mule (Mcl-1 ubiquitin ligase) prevented Mcl-1 downregulation caused by PKCη deficiency. 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 PKCη silencing. However, knockdown of PKCη but not PKCα, -δ or -ε caused a significant decrease in ERK (extracellular signal-regulated kinase) phosphorylation. Knockdown of ERK1 but not ERK2 decreased Mcl-1 level, and the decrease in Mcl-1 caused by PKCη knockdown was restored by ERK1 overexpression. These results suggest that PKCη utilizes the ERK signaling pathway to protect against ubiquitin-mediated proteasomal degradation of Mcl-1.

PMID: 28939105 [PubMed - indexed for MEDLINE]

OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections.

Wed, 06/13/2018 - 07:38

OG716: Designing a fit-for-purpose lantibiotic for the treatment of Clostridium difficile infections.

PLoS One. 2018;13(6):e0197467

Authors: Kers JA, DeFusco AW, Park JH, Xu J, Pulse ME, Weiss WJ, Handfield M

Abstract
Lantibiotics continue to offer an untapped pipeline for the development of novel antibiotics. We report here the discovery of a novel lantibiotic for the treatment of C. difficile infection (CDI). The leads were selected from a library of over 300 multiple substitution variants of the lantibiotic Mutacin 1140 (MU1140). Top performers were selected based on testing for superior potency, solubility, manufacturability, and physicochemical and/or metabolic stability in biologically-relevant systems. The best performers in vitro were further evaluated orally in the Golden Syrian hamster model of CDAD. In vivo testing ultimately identified OG716 as the lead compound, which conferred 100% survival and no relapse at 3 weeks post infection. MU1140-derived variants are particularly attractive for further clinical development considering their novel mechanism of action.

PMID: 29894469 [PubMed - in process]

Treatment of Cosmetic Tattoos: A Review and Case Analysis.

Wed, 06/13/2018 - 07:38

Treatment of Cosmetic Tattoos: A Review and Case Analysis.

Dermatol Surg. 2018 Jun 08;:

Authors: McIlwee BE, Alster TS

Abstract
BACKGROUND: Cosmetic tattoos such as eyeliner, brow liner, and lip liner have become increasingly popular in the United States and throughout the world. For a variety of reasons, patients frequently regret their tattoos and request their removal; however, removal is often complicated by the aesthetically sensitive location of these specialized tattoos and the fact that they often contain white metallic compounds that darken on pigment-specific laser irradiation.
OBJECTIVE: To review the clinical use, effectiveness, and safety of an ablative laser technique for cosmetic tattoos.
MATERIALS AND METHODS: A thorough literature review pertaining to laser treatment of cosmetic tattoos and a discussion of illustrative patient cases showcasing the successful use of ablative carbon dioxide (CO2) laser to treat cosmetic tattoos is presented.
RESULTS: Cosmetic eyeliner and lip liner tattoos were significantly improved after CO2 laser vaporization. Side effects were limited to erythema, edema, and serosanguinous drainage. No infection, scarring, nor tattoo ink darkening was observed.
CONCLUSION: Because ablative lasers do not target specific tattoo inks, they do not pose a risk of paradoxical tattoo ink darkening and, thus, can be applied successfully in the treatment of iron oxide- or titanium dioxide-containing cosmetic tattoos.

PMID: 29894434 [PubMed - as supplied by publisher]

Characterization of the neurochemical and behavioral effects of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor.

Wed, 06/13/2018 - 07:38
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Characterization of the neurochemical and behavioral effects of solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor.

J Pharmacol Exp Ther. 2018 Jun 11;:

Authors: Baladi MG, Forster MJ, Gatch MB, Mailman RB, Hyman DL, Carter LP, Janowsky AJ

Abstract
Excessive sleepiness (ES) is associated with several sleep disorders, including narcolepsy and obstructive sleep apnea (OSA). A role for monoaminergic systems in treating these conditions is highlighted by the clinical use of United States Food and Drug Administration-approved drugs that act on these systems, such as dextroamphetamine, methylphenidate, modafinil, and armodafinil. Solriamfetol (JZP-110) is a wake-promoting agent that is currently being evaluated to treat ES in patients with narcolepsy or OSA. Clinical and preclinical data suggest that the wake-promoting effects of solriamfetol differ from medications such as modafinil and amphetamine. The goal of the current studies was to characterize the mechanism of action of solriamfetol at monoamine transporters using in vitro and in vivo assays. Results indicate that solriamfetol has dual reuptake activity at dopamine (DA; IC50=2.9 μM) and norepinephrine (NE; IC50=4.4 μM) transporters, and this activity is associated in vivo with increased extracellular concentration of DA and NE levels as measured by microdialysis. Solriamfetol has negligible functional activity at the serotonin transporter (IC50>100 μM). Moreover, the wake-promoting effects of solriamfetol are likely due to activity at DA and NE transporters rather than other neurotransmitter systems, such as histamine or orexin. The dual activity of solriamfetol at DA and NE transporters and the lack of significant monoamine-releasing properties of solriamfetol might explain the differences in the in vivo effects of solriamfetol compared with modafinil or amphetamine. Taken together, these data suggest that solriamfetol may offer an important advancement in the treatment of ES in patients with narcolepsy or OSA.

PMID: 29891587 [PubMed - as supplied by publisher]

Insulin and heparin-binding epidermal growth factor-like growth factor synergistically promote astrocyte survival and proliferation in serum-free medium.

Tue, 06/12/2018 - 07:38

Insulin and heparin-binding epidermal growth factor-like growth factor synergistically promote astrocyte survival and proliferation in serum-free medium.

J Neurosci Methods. 2018 Jun 08;:

Authors: Jia M, Shi Z, Yan X, Xu L, Dong L, Li J, Wang Y, Yang S, Yuan F

Abstract
BACKGROUND: In vitro systems allowing maintenance and experimentation on primary astrocyte cultures have been used for decades. Astrocyte cultures are most maintained in serum-containing medium which has been found to alter the morphology and gene profiles of astrocytes.
NEW METHOD: Here, we reported a new serum-free medium for astrocyte culture, which consisted of DMEM and NB media supplemented with insulin and heparin-binding epidermal growth factor-like growth factor (HB-EGF) (SF-I-H medium). Meanwhile FBS-containing (FBS) medium composed of DMEM medium containing 10% FBS were used for comparison study. Cerebral cortex was harvested from postnatal day 1 Wistar rats and brain cells were isolated and seeded to poly-L-lysine coated culture dishes after 15 min differential velocity adherence.
RESULTS: Compared with FBS medium, astrocytes in SF-I-H medium are smaller and exhibited process bearing morphologies. MTT assays showed that cell density and proliferation rate were higher in SF-I-H medium than in FBS medium all the time, and flow cytometry analysis revealed that SF-I-H medium promoted cell mitosis in a manner comparable to FBS medium. Consistently, western blot analysis further revealed that insulin and HB-EGF synergistically activated the PI3K-AKT and MAPK-ERK1/2 signaling cascades as FBS.
COMPARISON WITH EXISTING METHOD(S): Astrocytes cultured in SF-I-H medium grow faster than FBS medium.
CONCLUSION: Taken together, our results indicated that SF-I-H medium, in which cell morphology was similar with astrocytes in brain, was more effective for astrocyte survival and proliferation than FBS medium, providing a new cell model to study astrocyte functions without the interference of serum.

PMID: 29890195 [PubMed - as supplied by publisher]

Potential Audiological and MRI Markers of Tinnitus.

Tue, 06/12/2018 - 07:38
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Potential Audiological and MRI Markers of Tinnitus.

J Am Acad Audiol. 2017 Sep;28(8):742-757

Authors: Gopal KV, Thomas BP, Nandy R, Mao D, Lu H

Abstract
BACKGROUND: Subjective tinnitus, or ringing sensation in the ear, is a common disorder with no accepted objective diagnostic markers.
PURPOSE: The purpose of this study was to identify possible objective markers of tinnitus by combining audiological and imaging-based techniques.
RESEARCH DESIGN: Case-control studies.
STUDY SAMPLE: Twenty adults drawn from our audiology clinic served as participants. The tinnitus group consisted of ten participants with chronic bilateral constant tinnitus, and the control group consisted of ten participants with no history of tinnitus. Each participant with tinnitus was closely matched with a control participant on the basis of age, gender, and hearing thresholds.
DATA COLLECTION AND ANALYSES: Data acquisition focused on systematic administration and evaluation of various audiological tests, including auditory-evoked potentials (AEP) and otoacoustic emissions, and magnetic resonance imaging (MRI) tests. A total of 14 objective test measures (predictors) obtained from audiological and MRI tests were subjected to statistical analyses to identify the best predictors of tinnitus group membership. The least absolute shrinkage and selection operator technique for feature extraction, supplemented by the leave-one-out cross-validation technique, were used to extract the best predictors. This approach provided a conservative model that was highly regularized with its error within 1 standard error of the minimum.
RESULTS: The model selected increased frontal cortex (FC) functional MRI activity to pure tones matching their respective tinnitus pitch, and augmented AEP wave N₁ amplitude growth in the tinnitus group as the top two predictors of tinnitus group membership. These findings suggest that the amplified responses to acoustic signals and hyperactivity in attention regions of the brain may be a result of overattention among individuals that experience chronic tinnitus.
CONCLUSIONS: These results suggest that increased functional MRI activity in the FC to sounds and augmented N₁ amplitude growth may potentially be the objective diagnostic indicators of tinnitus. However, due to the small sample size and lack of subgroups within the tinnitus population in this study, more research is needed before generalizing these findings.

PMID: 28906245 [PubMed - indexed for MEDLINE]

Ten-Year Follow-Up of Metatarsal Head Resurfacing Implants for Treatment of Hallux Rigidus.

Tue, 06/12/2018 - 07:38
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Ten-Year Follow-Up of Metatarsal Head Resurfacing Implants for Treatment of Hallux Rigidus.

J Foot Ankle Surg. 2017 Sep - Oct;56(5):1052-1057

Authors: Hilario H, Garrett A, Motley T, Suzuki S, Carpenter B

Abstract
Controversy remains regarding the use of arthroplasty versus arthrodesis in the surgical treatment of late-stage hallux rigidus. The purpose of our retrospective study was to report the long-term follow-up results of the metatarsal head resurfacing implant used for hemiarthroplasty. The patient assessments were conducted using the American Orthopaedic Foot and Ankle Society (AOFAS) metatarsophalangeal clinical rating system and a satisfaction questionnaire. A total of 59 consecutive implantations were performed from January 2005 to December 2009 at our institution. Of the 59 patients, 2 had died and 12 were lost to follow-up, for a 76.3% follow-up rate (45 of 59 procedures) at a mean of 117.67 (range 96 to 143) months. The mean overall AOFAS scale score was 90.6 ± 7.6. The AOFAS pain scale score was 37.78 ± 4.71. One implant was removed, and all remaining patients were happy with their outcome and would repeat the procedure on their other foot, if needed. A subset of patients from a previous mid-term study at our institution showed no significant change in the AOFAS scale scores. Of these 32 patients, 30 (93.75%) were available for follow-up examination at a mean of 122.62 (range 96 to 143) months. We were able to obtain long-term results for 32 implants (30 patients), resulting in a 10-year follow-up rate of 93.7%. With the minimal resection required for this implant, salvage arthrodesis remains a viable option if revision is needed. The surgical treatment of late-stage hallux rigidus with metatarsal head resurfacing allows for low-risk and excellent outcomes at long-term follow-up point.

PMID: 28842091 [PubMed - indexed for MEDLINE]

"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

Tue, 06/12/2018 - 07:38
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"Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice".

Colloids Surf B Biointerfaces. 2017 Oct 01;158:379-386

Authors: Pieretti S, Ranjan AP, Di Giannuario A, Mukerjee A, Marzoli F, Di Giovannandrea R, Vishwanatha JK

Abstract
Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain.

PMID: 28719859 [PubMed - indexed for MEDLINE]

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