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The effects of state rules on opioid prescribing in Indiana.

Recent Research Articles from UNTHSC - Sat, 01/20/2018 - 07:40

The effects of state rules on opioid prescribing in Indiana.

BMC Health Serv Res. 2018 Jan 18;18(1):29

Authors: Al Achkar M, Grannis S, Revere D, MacKie P, Howard M, Gupta S

Abstract
BACKGROUND: Prescription opioids have been linked to over half of the 28,000 opioid overdose deaths in 2014. High rates of prescription opioid non-medical use have continued despite nearly all states implementing large-scale prescription drug monitoring programs (PDMP), which points to the need to examine the impact of state PDMP's on curbing inappropriate opioid prescribing. In the short-term, PDMPs have been associated with short-term prescribing declines. Yet little is known about how such policies differentially impact patient subgroups or are interpreted by prescribing providers. Our objective was to compare volumes of prescribed opioids before and after Indiana implemented opioid prescribing emergency rules and stratify the changes in opioid prescribing by patient and provider subgroups.
METHODS: An interrupted time series analysis was conducted using data obtained from the Indiana PDMP. Prescription level data was merged with census data to characterize patient socioeconomic status. Analyses were stratified by patients' gender, age, opioid dosage, and payer. The primary outcome indicator was the total morphine equivalent dose (MED) of dispensed opioids per day in the state of Indiana. Also considered were number of unique patients, unique providers, and prescriptions; MED per transaction and per day; and number of days supplied.
RESULTS: After controlling for time trends, we found that total MED for opioids decreased after implementing the new emergency rules, differing by patient gender, age, and payer. The effect was larger for males than females and almost 10 times larger for 0-20 year olds as compared to the 60+ age range. Medicare and Medicaid patients experienced more decline in prescribing than patients with private insurance. Patients with prescriptions paid for by workers' comp experienced the most significant decline. The emergency rules were associated with decline in both the number of prescribers and the number of day supply.
CONCLUSIONS: Although the Indiana opioid prescribing emergency rules impacted statewide prescribing behavior across all individual patient and provider characteristics, the emergency rules' effect was not consistent across patient characteristics. Further studies are needed to assess how individual patient characteristics influence the interpretation and application of state policies on opioid prescribing.

PMID: 29347984 [PubMed - in process]

Feeling No Buzz or a Slight Buzz Is Common When Legally Drunk.

Recent Research Articles from UNTHSC - Sat, 01/20/2018 - 07:40
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Feeling No Buzz or a Slight Buzz Is Common When Legally Drunk.

Am J Public Health. 2016 Oct;106(10):1761-2

Authors: Rossheim ME, Thombs DL, Gonzalez-Pons KM, Killion JA, Clapp JD, Reed MB, Croff JM, Ruderman DE, Weiler RM

PMID: 27626346 [PubMed - indexed for MEDLINE]

A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats.

Recent Research Articles from UNTHSC - Fri, 01/19/2018 - 07:34
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A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats.

Behav Brain Res. 2016 Nov 01;314:199-214

Authors: Jung ME, Metzger DB

Abstract
Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy drinking, and provokes oxidative brain damage. Here, we investigated whether the cerebellum and hippocampus of female rats are less affected by prooxidant EW than male rats due to the antioxidant effect of 17β-estradiol (E2). Female and male rats received a four-week ethanol diet and three-week withdrawal per cycle for two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus (water-maze)-related behaviors, oxidative markers (O2(-), malondialdehyde, protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were subjected to ethanol-exposure and withdrawal for two cycles to assess the effect of a CcO inhibitor on E2's protection for mitochondrial respiration and cell viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative markers in cerebellum and hippocampus than male rats, and E2 treatment decreased the oxidative markers. Compared to male counterparts, ethanol-withdrawn female rats showed better Rotarod but poorer water-maze performance, accompanied by more severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or antioxidant treatment improved Rotarod but not water-maze performance. In the presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial respiration and cell viability from EW. These data suggest that antioxidant E2 contributes to smaller oxidative stress in ethanol-withdrawn female than male rats. They also suggest that EW-induced severe mitochondrial damage in hippocampus may blunt E2's antioxidant protection for hippocampus-related behavior.

PMID: 27503149 [PubMed - indexed for MEDLINE]

MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics.

Recent Research Articles from UNTHSC - Fri, 01/19/2018 - 07:34
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MIEN1 drives breast tumor cell migration by regulating cytoskeletal-focal adhesion dynamics.

Oncotarget. 2016 Aug 23;7(34):54913-54924

Authors: Kpetemey M, Chaudhary P, Van Treuren T, Vishwanatha JK

Abstract
Migration and invasion enhancer 1 (MIEN1) is an important regulator of cell migration and invasion. MIEN1 overexpression represents an oncogenic event that promotes tumor cell dissemination and metastasis. The underlying mechanism by which MIEN1 regulates migration and invasion has yet to be deciphered. Here, we demonstrate that MIEN1 acts as a cytoskeletal-signaling adapter protein to drive breast cancer cell migration. MIEN1 localization is concentrated underneath the actin-enriched protrusive structures of the migrating breast cancer cells. Depletion of MIEN1 led to the loss of actin-protrusive structures whereas the over-expression of MIEN1 resulted in rich and thick membrane extensions. Knockdown of MIEN1 also decreased the cell-substratum adhesion, suggesting a role for MIEN1 in actin cytoskeletal dynamics. Our results show that MIEN1 supports the transition of G-actin to F-actin polymerization and stabilizes F-actin polymers. Additionally, MIEN1 promotes cellular adhesion and actin dynamics by inducing phosphorylation of FAK at Tyr-925 and reducing phosphorylation of cofilin at Ser-3, which results in breast cancer cell migration. Collectively, our data show that MIEN1 plays an essential role in maintaining the plasticity of the dynamic membrane-associated actin cytoskeleton, which leads to an increase in cell motility. Hence, targeting MIEN1 might represent a promising means to prevent breast tumor metastasis.

PMID: 27462783 [PubMed - indexed for MEDLINE]

Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension in mice.

Recent Research Articles from UNTHSC - Thu, 01/18/2018 - 07:48

Glucocorticoid receptor GRβ regulates glucocorticoid-induced ocular hypertension in mice.

Sci Rep. 2018 Jan 16;8(1):862

Authors: Patel GC, Liu Y, Millar JC, Clark AF

Abstract
Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent vision loss. The alternatively spliced isoform of glucocorticoid receptor GRβ acts as dominant negative regulator of GR activity, and it has been shown that overexpressing GRβ in trabecular meshwork (TM) cells inhibits GC-induced glaucomatous damage in TM cells. The purpose of this study was to use viral vectors to selectively overexpress the GRβ isoform in the TM of mouse eyes treated with GCs, to precisely dissect the role of GRβ in regulating steroid responsiveness. We show that overexpression of GRβ inhibits GC effects on MTM cells in vitro and GC-induced OHT in mouse eyes in vivo. Ad5 mediated GRβ overexpression reduced the GC induction of fibronectin, collagen 1, and myocilin in TM of mouse eyes both in vitro and in vivo. GRβ also reversed DEX-Ac induced IOP elevation, which correlated with increased conventional aqueous humor outflow facility. Thus, GRβ overexpression reduces effects caused by GCs and makes cells more resistant to GC treatment. In conclusion, our current work provides the first evidence of the in vivo physiological role of GRβ in regulating GC-OHT and GC-mediated gene expression in the TM.

PMID: 29339763 [PubMed - in process]

Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations.

Recent Research Articles from UNTHSC - Thu, 01/18/2018 - 07:48
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Cas9-catalyzed DNA Cleavage Generates Staggered Ends: Evidence from Molecular Dynamics Simulations.

Sci Rep. 2016 11 22;5:37584

Authors: Zuo Z, Liu J

Abstract
The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (spCas9) along with a single guide RNA (sgRNA) has emerged as a versatile toolbox for genome editing. Despite recent advances in the mechanism studies on spCas9-sgRNA-mediated double-stranded DNA (dsDNA) recognition and cleavage, it is still unclear how the catalytic Mg2+ ions induce the conformation changes toward the catalytic active state. It also remains controversial whether Cas9 generates blunt-ended or staggered-ended breaks with overhangs in the DNA. To investigate these issues, here we performed the first all-atom molecular dynamics simulations of the spCas9-sgRNA-dsDNA system with and without Mg2+ bound. The simulation results showed that binding of two Mg2+ ions at the RuvC domain active site could lead to structurally and energetically favorable coordination ready for the non-target DNA strand cleavage. Importantly, we demonstrated with our simulations that Cas9-catalyzed DNA cleavage produces 1-bp staggered ends rather than generally assumed blunt ends.

PMID: 27874072 [PubMed - indexed for MEDLINE]

People's reasons for wanting to complete probation: Use and predictive validity in an e-health intervention.

Recent Research Articles from UNTHSC - Wed, 01/17/2018 - 16:45
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People's reasons for wanting to complete probation: Use and predictive validity in an e-health intervention.

Eval Program Plann. 2017 Apr;61:144-149

Authors: Spohr SA, Taxman FS, Walters ST

Abstract
The criminal justice system tends to emphasize external contingencies (e.g., fees, jail time) to motivate offender compliance. However, people's reasons for desistance vary considerably. This study evaluated the acceptability, utility, and predictive validity of questions that ask about people's reasons for wanting to successfully complete probation. Substance-using probationers (N=113) participated in a web-based computer intervention that targeted substance use and treatment initiation. Questions around seven dimensions of reasons for completing probation were developed to provide tailored feedback during the web-based program. A principle components factor analysis found that survey items loaded onto two distinct factors. Factor one, "Tangible Loss" focused on external and present-focused reasons. Factor two, "Better Life" focused on internal and future-focused reasons. There was a significant negative association between Better Life scores and days of substance use after two months (β=-0.31, SE=0.13, p<0.05). There was a significant positive association with Better Life scores and days of treatment attendance (β=1.46, SE=0.26, p<0.001). Tangible Loss scores were no associated with substance use and treatment attendance. These findings may help to create more effective motivational tracks in e-health interventions, and may complement traditional motivation measures with an explicit focus on people's stated reasons for wanting to complete probation.

PMID: 28088674 [PubMed - in process]

Preparation and Characterization of Novel HDL-mimicking Nanoparticles for Nerve Growth Factor Encapsulation.

Recent Research Articles from UNTHSC - Tue, 01/16/2018 - 07:33
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Preparation and Characterization of Novel HDL-mimicking Nanoparticles for Nerve Growth Factor Encapsulation.

J Vis Exp. 2017 May 22;(123):

Authors: Zhu J, Dong X

Abstract
The objective of this article is to introduce preparation and characterization methods for nerve growth factor (NGF)-loaded, high-density, lipoprotein (HDL)-mimicking nanoparticles (NPs). HDLs are endogenous NPs and have been explored as vehicles for the delivery of therapeutic agents. Various methods have been developed to prepare HDL-mimicking NPs. However, they are generally complicated, time consuming, and difficult for industrial scale-up. In this study, one-step homogenization was used to mix the excipients and form the prototype NPs. NGF is a water-soluble protein of 26 kDa. To facilitate the encapsulation of NGF into the lipid environment of HDL-mimicking NPs, protamine USP was used to form an ion-pair complex with NGF to neutralize the charges on the NGF surface. The NGF/protamine complex was then introduced into the prototype NPs. Apolipoprotein A-I was finally coated on the surface of the NPs. NGF HDL-mimicking NPs showed preferable properties in terms of particle size, size distribution, entrapment efficiency, in vitro release, bioactivity, and biodistribution. With the careful design and exploration of homogenization in HDL-mimicking NPs, the procedure was greatly simplified, and the NPs were made scalable. Moreover, various challenges, such as separating unloaded NGF from the NPs, conducting reliable in vitro release studies, and measuring the bioactivity of the NPs, were overcome.

PMID: 28570541 [PubMed - indexed for MEDLINE]

Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.

Recent Research Articles from UNTHSC - Tue, 01/16/2018 - 07:33
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Contra-directional Coupling of Nur77 and Nurr1 in Neurodegeneration: A Novel Mechanism for Memantine-Induced Anti-inflammation and Anti-mitochondrial Impairment.

Mol Neurobiol. 2016 Nov;53(9):5876-5892

Authors: Wei X, Gao H, Zou J, Liu X, Chen D, Liao J, Xu Y, Ma L, Tang B, Zhang Z, Cai X, Jin K, Xia Y, Wang Q

Abstract
Recent evidence suggests that nerve growth factor IB (Nur77) and nuclear receptor related1 (Nurr1) are differentially involved in dopaminergic neurodegeneration. Since memantine has shown clinically relevant efficacy in Parkinson's disease (PD) and displayed a potent protective effect on dopaminergic neurons in experimental PD models, we asked if it exerts its neuroprotection by regulating Nur77 and Nurr1 signaling. We adopted a well-established in vitro PD model, 6-hydroxydopamine (OHDA)-lesioned PC12 cells, to test our hypothesis. Different concentrations of memantine were incubated with 6-OHDA-lesioned PC12 cells, and Nur77/Nurr1 and their related signaling molecules were examined by Western blot and immunocytochemistry. Nur77-deficient PC12 cells were used to verify the influences of Nur77 on neurodegeneration and memantine-mediated neuroprotection. We found that memantine reversed Nur77 upregulation and restored Nurr1 downregulation in 6-OHDA-lesioned PC12 cells. 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and induced co-localization of Cyt c/HSP60/Nur77 in the cytosol. Memantine strongly reduced the sub-cellular translocations of Nur77/Cyt c/HSP60 under 6-OHDA-induced oxidative condition. Knockdown of Nur77 enhanced the viability of PC12 cells exposed to 6-OHDA, while memantine-induced neuroprotection was much less in the cells with Nur77 knockdown than in those without it. We conclude that Nur77 plays a crucial role in modulating mitochondrial impairment and contributes to neurodegeneration under the experimental PD condition. Memantine effectively suppresses such Nur77-mediated neurodegeneration and promotes survival signaling through post-translational modification of Nurr1. Nur77 and Nurr1 present a contra-directionally coupling interaction in memantine-mediated neuroprotection.

PMID: 26497037 [PubMed - indexed for MEDLINE]

Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

Recent Research Articles from UNTHSC - Tue, 01/16/2018 - 07:33
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Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

Mol Vis. 2016;22:1048-61

Authors: Phatak NR, Stankowska DL, Krishnamoorthy RR

Abstract
PURPOSE: Brn3b is a class IV POU domain transcription factor that plays an important role in the development of retinal ganglion cells (RGCs), RGC survival, and particularly axon growth and pathfinding. Our previous study demonstrated that recombinant adenoassociated virus serotype 2 (rAAV-2)-mediated overexpression of Brn3b in RGCs promoted neuroprotection in a rodent model of glaucoma. However, the mechanisms underlying neuroprotection of RGCs in rats overexpressing Brn3b in animal models of glaucoma remain largely unknown. The goal of this study was to understand some of the mechanisms underlying the neuroprotection of RGCs overexpressing Brn3b during intraocular pressure (IOP) elevation in Brown Norway rats.
METHODS: One eye of Brown Norway rats (Rattus norvegicus) was injected with an AAV construct encoding either green fluorescent protein (GFP; recombinant adenoassociated virus-green fluorescent protein, rAAV-hSyn-GFP) or Brn3b (rAAV-hSyn-Brn3b). Expression of antiapoptotic proteins, including B cell lymphoma/leukemia-2 (Bcl-2) family proteins (Bcl-2 and Bcl-xL), and p-AKT, was observed following immunostaining of rat retinas that overexpress Brn3b. In a different set of experiments, intraocular pressure was elevated in one eye of Brown Norway rats, which was followed by intravitreal injection with AAV constructs encoding either GFP (rAAV-CMV-GFP) or Brn3b (rAAV-CMV-Brn3b). Retinal sections were stained for prosurvival factors, including Bcl-2, Bcl-XL, and p-AKT.
RESULTS: AAV-mediated expression of transcription factor Brn3b promoted statistically significant upregulation of the Bcl-2 protein and increased expression of p-AKT in RGCs of Brown Norway rats. In addition, following IOP elevation, AAV-mediated Brn3b expression also statistically significantly increased levels of Bcl-2 in the RGC layer in Brown Norway rats.
CONCLUSIONS: Adenoassociated virus-mediated Brn3b protein overexpression may promote neuroprotection by upregulating key antiapoptotic proteins, including Bcl-2, Bcl-xL, and p-AKT, in animal models of glaucoma.

PMID: 27587945 [PubMed - indexed for MEDLINE]

Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in Parkinson's progression: Evidence from clinical studies and neurotoxin models.

Recent Research Articles from UNTHSC - Mon, 01/15/2018 - 07:32

Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in Parkinson's progression: Evidence from clinical studies and neurotoxin models.

Prog Neurobiol. 2018 Jan 10;:

Authors: Johnson ME, Salvatore MF, Maiolo SA, Bobrovskaya L

Abstract
Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While the typical motor symptoms of PD are well known, the lesser known non-motor symptoms can also greatly impact the patient's quality of life. These symptoms often appear before motor impairment, therefore identifying biomarkers that may predict PD risk or pathology has been a major and challenging endeavour. Given that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH) occurs in PD, the expression and accompanying post-translational changes in TH during PD progression could yield insight into the disruption of cellular signalling occurring in the CNS, and also in peripheral tissues wherein catecholamine function plays a role. Furthermore, changes in expression and phosphorylation of TH in the brain and periphery can potentially reveal how TH stability and function are compromised in PD. As such, these changes can reveal how catecholamine synthesis capacity is gradually compromised and how changes in cellular signalling may govern the functional status of remaining catecholaminergic neurons. This review summarises the findings of clinical PD and neurotoxin models of PD that assessed TH expression or phosphorylation in catecholaminergic pathways in the brain and relevant peripheral tissues. We propose that establishing similar changes in TH expression and function in the CNS and periphery of established neurotoxin models can be a potential reference for comparison to changes in TH in human peripheral tissues. These changes in TH expression and phosphorylation may have predictive validity to estimate risk of PD progression before motor impairment is evident.

PMID: 29331395 [PubMed - as supplied by publisher]

Ligandomics: a paradigm shift in biological drug discovery.

Recent Research Articles from UNTHSC - Sat, 01/13/2018 - 07:42
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Ligandomics: a paradigm shift in biological drug discovery.

Drug Discov Today. 2018 Jan 08;:

Authors: Li W, Pang IH, Pacheco MTF, Tian H

Abstract
As productivity of pharmaceutical research and development (R&D) for small-molecule drugs declines, the trend in drug discovery strategies is shifting towards biologics, which predominantly target secreted or cell surface proteins. Receptors and ligands are the most-valuable drug targets. In contrast to conventional approaches of discovering one ligand at a time, the emerging technology of ligandomics can systematically map disease-selective cellular ligands in the absence of molecular probes. Biologics targeting these ligands with disease selectivity have the advantages of high efficacy, minimal adverse effects, wide therapeutic indices, and low safety-related attrition rates. Therefore, ligandomics represents a paradigm shift to address the bottleneck of target discovery for biologics development.

PMID: 29326083 [PubMed - as supplied by publisher]

An approach to understanding sleep and depressed mood in adolescents: person-centred sleep classification.

Recent Research Articles from UNTHSC - Sat, 01/13/2018 - 07:42
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An approach to understanding sleep and depressed mood in adolescents: person-centred sleep classification.

J Sleep Res. 2017 Dec;26(6):709-717

Authors: Shochat T, Barker DH, Sharkey KM, Van Reen E, Roane BM, Carskadon MA

Abstract
Depressive mood in youth has been associated with distinct sleep dimensions, such as timing, duration and quality. To identify discrete sleep phenotypes, we applied person-centred analysis (latent class mixture models) based on self-reported sleep patterns and quality, and examined associations between phenotypes and mood in high-school seniors. Students (n = 1451; mean age = 18.4 ± 0.3 years; 648 M) completed a survey near the end of high-school. Indicators used for classification included school night bed- and rise-times, differences between non-school night and school night bed- and rise-times, sleep-onset latency, number of awakenings, naps, and sleep quality and disturbance. Mood was measured using the total score on the Center for Epidemiologic Studies-Depression Scale. One-way anova tested differences between phenotype for mood. Fit indexes were split between 3-, 4- and 5-phenotype solutions. For all solutions, between phenotype differences were shown for all indicators: bedtime showed the largest difference; thus, classes were labelled from earliest to latest bedtime as 'A' (n = 751), 'B' (n = 428) and 'C' (n = 272) in the 3-class solution. Class B showed the lowest sleep disturbances and remained stable, whereas classes C and A each split in the 4- and 5-class solutions, respectively. Associations with mood were consistent, albeit small, with class B showing the lowest scores. Person-centred analysis identified sleep phenotypes that differed in mood, such that those with the fewest depressive symptoms had moderate sleep timing, shorter sleep-onset latencies and fewer arousals. Sleep characteristics in these groups may add to our understanding of how sleep and depressed mood associate in teens.

PMID: 28573658 [PubMed - indexed for MEDLINE]

Sex-specific and genotype-specific differences in vocalization development in FMR1 knockout mice.

Recent Research Articles from UNTHSC - Thu, 01/11/2018 - 07:37
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Sex-specific and genotype-specific differences in vocalization development in FMR1 knockout mice.

Neuroreport. 2016 Dec 14;27(18):1331-1335

Authors: Reynolds CD, Nolan SO, Jefferson T, Lugo JN

Abstract
Fragile X syndrome is a neurodevelopmental disorder caused by a trinucleotide (CGG) hyperexpansion in the FMR1 gene, functionally silencing transcription of the fragile X mental retardation protein (FMRP). This disorder is characterized by impaired cognition, communication, and social behavior. The aim of this study was to investigate the development of ultrasonic vocalization (USV) behavior in a Fmr1-deficient mouse model. On postnatal days (PD) 9-14, separate cohorts of FVB/NJ pups were removed from their homecage and isolation-induced USVs were recorded. There were significant genotype-dependent and sex-dependent differences in USV behavior across the different testing days. Fmr1 knockout (KO) mice showed a significant reduction in vocalizations across all days. There was also a significant difference in vocalizations between male and female mice. We found a significant decrease in the total number of calls for KO males on PD9 and PD13 as well as an increase in the total number of calls for KO males on PD12. The KO males also showed a significant increase in the total call duration on PD12 and a reduction on PD13. The KO female showed a significant decrease in the total number of calls on PD9 and PD10. They also showed a significant decrease in the total call duration on PD9 and a marginal decrease in the total call duration on PD10. These results provide additional evidence for communication deficits in Fmr1 deficient mice and provide new insight suggesting sexually dimorphic vocalizations during the neonatal period.

PMID: 27824730 [PubMed - indexed for MEDLINE]

Adequate dietary fiber supplement and TONE can help avoid surgery in most patients with advanced hemorrhoids.

Recent Research Articles from UNTHSC - Tue, 01/09/2018 - 07:36
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Adequate dietary fiber supplement and TONE can help avoid surgery in most patients with advanced hemorrhoids.

Minerva Gastroenterol Dietol. 2017 Jun;63(2):92-96

Authors: Garg P, Singh P

Abstract
BACKGROUND: The root cause of hemorrhoids resides in three deranged defecation habits (DDH), namely increased straining, prolonged defecation-time, and frequent bowel-motions. These DDH are responsible for the development of new hemorrhoids, progression of existing one and hemorrhoidal rupture (bleeding). DDH can be corrected with the help of the "TONE" mnemonic. TONE entails specifying exact treatment goals: T, three minutes at defecation; O, once-a-day defecation frequency; N, no straining during passing motions; E, enough fiber. TONE can be implemented by proper counseling and by prescribing fiber supplement appropriately (5-6 teaspoonfuls of psyllium husk with 600 mL of water daily. Corrected DDH would prevent the progression of hemorrhoids and bleeding episodes. An office procedure may be done to further downgrade the hemorrhoids.
METHODS: Patients with advanced hemorrhoids (grades III and IV) who were referred for surgery were prescribed fiber supplement and were counseled to follow TONE. The outcome parameters evaluated were improvement in prolapse, bleeding episodes, satisfaction levels.
RESULTS: A total of 102 patients (75 males and 10 females, mean age 46.0±13.5 years, 17 lost to follow-up) with advanced hemorrhoids (41 with early grade III, 38 with late grade III, and 6 with grade IV) were included in the study. All patients had symptoms of prolapsed hemorrhoids and bleeding episodes were present in 71.8% (61/85) of patients. After the follow-up of 40 (12-96) months, 68.2% (58/85) patients were highly satisfied, 12.9% (11/85) were moderately satisfied and 18.9% (16/85) were not satisfied with treatment. Prolapse improved in 56.5% (48/85), did not progress over time in 25.9 (22/85) and continued to progress in 4.7% (4/85) patients. 12.9% (11/85) underwent operation for hemorrhoids. Bleeding episodes decreased from 71.8% (61/85) to 29.4% (25/85) (P<0.0001).
CONCLUSIONS: Adequate fiber supplement combined with the TONE method can correct DDH, thus stopping the progression of hemorrhoids and bleeding, and preventing surgery in most patients with advanced hemorrhoids.

PMID: 28150480 [PubMed - indexed for MEDLINE]

Effects of low-dose aspirin on maternal blood pressure and vascular function in an experimental model of gestational hypertension.

Recent Research Articles from UNTHSC - Sat, 01/06/2018 - 07:46
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Effects of low-dose aspirin on maternal blood pressure and vascular function in an experimental model of gestational hypertension.

Pharmacol Res. 2017 Jun;120:267-278

Authors: Osikoya O, Jaini PA, Nguyen A, Valdes M, Goulopoulou S

Abstract
Daily intake of low-dose aspirin after 12weeks of gestation is currently recommended as a preventative intervention in pregnancies in high risk of developing preeclampsia. This recommendation is based on epidemiological evidence, whereas experimental studies investigating the exact mechanisms of aspirin action during pregnancy are lacking. We previously showed that treating pregnant rats with a synthetic mimetic of unmethylated CpG DNA (bacterial DNA) caused preeclampsia-like characteristics such as maternal hypertension and increased cyclooxygenase (COX) expression and activity. In this study, we tested the hypothesis that daily maternal treatment with low-dose aspirin would prevent the development of maternal hypertension, reduce COX activity and thromboxane A2 (TxA2) production, and improve maternal vascular function in pregnant rats exposed to CpG ODN during gestation. Pregnant rats were treated with ODN2395 (synthetic CpG DNA) or saline (vehicle) on gestational days (GD) 14, 16, 18. Daily low-dose aspirin treatment (1.5mg/kgBW) started on GD10 and continued throughout gestation. Pregnant rats treated with ODN2395 had greater systolic blood pressure compared to controls (120±4mmHg vs. 100±5mmHg, p=0.03) and aspirin did not prevent this increase (p=0.86). Aspirin prevented ODN2395-induced increases of TxB2 (TxA2 metabolite) in serum and mesenteric arteries. ODN2395 increased expression of COX-1 and COX-2 in mesenteric and uterine arteries and aspirin abolished these effects. Aspirin reduced contractile responses to phenylephrine and U46619 (TxA2 mimetic) in mesenteric arteries from control rats but not from ODN2395-treated rats. In conclusion, treatment with low-dose aspirin reduced systemic and vascular COX expression and activity but did not prevent the development of maternal hypertension induced by exposure to unmethylated CpG DNA (bacterial DNA).

PMID: 28412461 [PubMed - indexed for MEDLINE]

Motivational Interviewing Fidelity in a Community Corrections Setting: Treatment Initiation and Subsequent Drug Use.

Recent Research Articles from UNTHSC - Sat, 01/06/2018 - 07:46
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Motivational Interviewing Fidelity in a Community Corrections Setting: Treatment Initiation and Subsequent Drug Use.

J Subst Abuse Treat. 2016 Jun;65:20-5

Authors: Spohr SA, Taxman FS, Rodriguez M, Walters ST

Abstract
INTRODUCTION: Although substance use is common among people in the U.S. criminal justice system, treatment initiation remains an ongoing problem. This study assessed the reliability and predictive validity of the Motivational Interviewing Treatment Integrity 3.1.1. (MITI) coding instrument in a community corrections sample.
METHODS: We used data from 80 substance-using clients who were participating in a clinical trial of MI in a probation setting. We analyzed 124 MI counseling sessions using the MITI, a coding system for documenting MI fidelity. Bivariate associations and logistic regression modeling were used to determine if MI-consistent behaviors predicted substance use or treatment initiation at a 2-month follow-up.
RESULTS: We found a high level of agreement between coders on behavioral utterance counts. Counselors met at least beginning proficiency on most MITI summary scores. Probationers who initiated treatment at 2-month follow-up had significantly higher ratings of clinician empathy and MI spirit than clients who did not initiate treatment. Other MITI summary scores were not significantly different between clients who had initiated treatment and those who did not. MI spirit and empathy ratings were entered into a forward logistic regression in which MI spirit significantly predicted 2-month treatment initiation (χ(2) (1)=4.10, p<.05, R(2)=.05) but counselor empathy did not. MITI summary scores did not predict substance use at 2-month follow-up.
CONCLUSIONS: Counselor MI-consistent relational skills were an important predictor of client treatment initiation. Counselor behaviors such as empathy and MI spirit may be important for developing client rapport with people in a probation setting.

PMID: 26365536 [PubMed - indexed for MEDLINE]

Dyslipidemia, weight gain, and decreased growth velocity in a 14-year-old male.

Recent Research Articles from UNTHSC - Tue, 01/02/2018 - 07:47
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Dyslipidemia, weight gain, and decreased growth velocity in a 14-year-old male.

J Clin Lipidol. 2017 Mar - Apr;11(2):562-566

Authors: Wilson DP, Hamilton L, Prakash S, Castro-Silva FJ, Friedman J

Abstract
A 14-year-old male was referred for dyslipidemia. His findings were consistent with metabolic syndrome. Although he lacked the typical physical appearance, his accelerated weight gain combined with a decreased linear growth velocity suggested Cushing syndrome. He was subsequently found to have adrenocorticotropic hormone-independent Cushing syndrome secondary to primary pigmented nodular adrenal disease without Carney Complex. After bilateral adrenalectomy, his lipid profile returned to normal. In this article, we discuss the role of glucocorticoids on lipid and lipoprotein metabolism.

PMID: 28502514 [PubMed - indexed for MEDLINE]

American College of Foot and Ankle Surgeons Clinical Consensus Statement: Diagnosis and Treatment of Adult Acquired Infracalcaneal Heel Pain.

Recent Research Articles from UNTHSC - Sat, 12/30/2017 - 10:41
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American College of Foot and Ankle Surgeons Clinical Consensus Statement: Diagnosis and Treatment of Adult Acquired Infracalcaneal Heel Pain.

J Foot Ankle Surg. 2017 Dec 25;:

Authors: Schneider HP, Baca J, Carpenter B, Dayton P, Fleischer AE, Sachs BD

Abstract
Adult acquired inferior calcaneal heel pain is a common pathology seen in a foot and ankle practice. A literature review and expert panel discussion of the most common findings and treatment options are presented. Various diagnostic and treatment modalities are available to the practitioner. It is prudent to combine appropriate history and physical examination findings with patient-specific treatment modalities for optimum success. We present the most common diagnostic tools and treatment options, followed by a discussion of the appropriateness of each based on the published data and experience of the expert panel.

PMID: 29284574 [PubMed - as supplied by publisher]

Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores.

Recent Research Articles from UNTHSC - Sat, 12/30/2017 - 10:41
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Highly Selective Dopamine D3 Receptor Antagonists with Arylated Diazaspiro Alkane Cores.

J Med Chem. 2017 Dec 14;60(23):9905-9910

Authors: Reilly SW, Griffin S, Taylor M, Sahlholm K, Weng CC, Xu K, Jacome DA, Luedtke RR, Mach RH

Abstract
A series of potent and selective D3 receptor (D3R) analogues with diazaspiro alkane cores were synthesized. Radioligand binding of compounds 11, 14, 15a, and 15c revealed favorable D3R affinity (Ki = 12-25.6 nM) and were highly selective for D3R vs D3R (ranging from 264- to 905-fold). Variation of these novel ligand architectures can be achieved using our previously reported 10-20 min benchtop C-N cross-coupling methodology, affording a broad range of arylated diazaspiro precursors.

PMID: 29125762 [PubMed - indexed for MEDLINE]

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