Recent Research Articles from UNTHSC

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

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Updated: 2 hours 26 min ago

Diagnostic capability of dynamic ultrasound evaluation of supination-external rotation ankle injuries: a cadaveric study.

Fri, 11/01/2019 - 15:22
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Diagnostic capability of dynamic ultrasound evaluation of supination-external rotation ankle injuries: a cadaveric study.

BMC Musculoskelet Disord. 2019 Oct 30;20(1):502

Authors: Fisher CL, Rabbani T, Johnson K, Reeves R, Wood A

Abstract
BACKGROUND: Ankle syndesmosis injuries are common and range in severity from subclinical to grossly unstable. Definitive diagnosis of these injuries can be made with plain film radiographs, but are often missed when severity or image quality is low. Computed tomography (CT) and magnetic resonance imaging (MRI) can provide definitive diagnosis, but are costly and introduce the patient to radiation when CT is used. Ultrasonography may circumvent many of these disadvantages by being inexpensive, efficient, and able to detect injuries without radiation exposure. The purpose of this study was to evaluate the ability of ultrasonography to detect early stage supination-external rotation (SER) ankle syndesmosis injuries with a dynamic external rotational stress test.
METHODS: Nine, all male, fresh frozen specimens were secured to an ankle rig and stress tested to 10 Nm of external rotational torque with ultrasonography at the tibiofibular clear space. The ankles were subjected to syndesmosis ligament sectioning and repeat stress measurements of the tibiofibular clear space at peak torque. Stress tests and measurements were repeated three times and averaged and analyzed using a repeated one-way analysis of variance (ANOVA). There were six ankle injury states examined including: Intact State, 75% of AITFL Cut, 100% of AITFL Cut, Fibula FX - Cut 8 cm proximal, 75% PITFL Cut, and 100% PITFL Cut.
RESULTS: Dynamic external rotation stress evaluation using ultrasonography was able to detect a significant difference between the uninjured ankle with a tibiofibular clear space of 4.5 mm and the stage 1 complete injured ankle with a clear space of 6.0 mm (P < .02). Additionally, this method was able to detect significant differences between the uninjured ankle and the stage 2-4 injury states.
CONCLUSION: Dynamic external rotational stress evaluation using ultrasonography was able to detect stage 1 Lauge-Hansen SER injuries with statistical significance and corroborates criteria for diagnosing a syndesmosis injury at ≥6.0 mm of tibiofibular clear space widening.

PMID: 31666051 [PubMed - in process]

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

Fri, 11/01/2019 - 15:22
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Impure but not inactive: Behavioral pharmacology of dibenzylpiperazine, a common by-product of benzylpiperazine synthesis.

J Psychopharmacol. 2018 07;32(7):802-810

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 - indexed for MEDLINE]

The impact of comorbid depression-diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment.

Wed, 10/30/2019 - 06:05
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The impact of comorbid depression-diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment.

Int Psychogeriatr. 2019 Oct 29;:1-7

Authors: Johnson LA, Zhang F, Large S, Hall J, O'Bryant SE

Abstract
BACKGROUND: Mexican Americans suffer from a disproportionate burden of modifiable risk factors, which may contribute to the health disparities in mild cognitive impairment (MCI) and Alzheimer's disease (AD).
OBJECTIVE: The purpose of this study was to elucidate the impact of comorbid depression and diabetes on proteomic outcomes among community-dwelling Mexican American adults and elders.
METHODS: Data from participants enrolled in the Health and Aging Brain among Latino Elders study was utilized. Participants were 50 or older and identified as Mexican American (N = 514). Cognition was assessed via neuropsychological test battery and diagnoses of MCI and AD adjudicated by consensus review. The sample was stratified into four groups: Depression only, Neither depression nor diabetes, Diabetes only, and Comorbid depression and diabetes. Proteomic profiles were created via support vector machine analyses.
RESULTS: In Mexican Americans, the proteomic profile of MCI may change based upon the presence of diabetes. The profile has a strong inflammatory component and diabetes increases metabolic markers in the profile.
CONCLUSION: Medical comorbidities may impact the proteomics of MCI and AD, which lend support for a precision medicine approach to treating this disease.

PMID: 31658917 [PubMed - as supplied by publisher]

Organellar stress intersects the astrocyte endoplasmic reticulum, mitochondria and nucleolus in HIV associated neurodegeneration.

Wed, 10/30/2019 - 06:05
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Organellar stress intersects the astrocyte endoplasmic reticulum, mitochondria and nucleolus in HIV associated neurodegeneration.

Cell Death Dis. 2018 02 22;9(3):317

Authors: Nooka S, Ghorpade A

PMID: 29472528 [PubMed - indexed for MEDLINE]

Establishing a Multidisciplinary Framework to Study Drug-Drug Interactions of Hormonal Contraceptives: An Invitation to Collaborate.

Tue, 10/29/2019 - 12:00
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Establishing a Multidisciplinary Framework to Study Drug-Drug Interactions of Hormonal Contraceptives: An Invitation to Collaborate.

CPT Pharmacometrics Syst Pharmacol. 2018 11;7(11):706-708

Authors: Lesko LJ, Vozmediano V, Brown JD, Winterstein A, Zhao P, Lippert J, Höchel J, Chaturvedula A, White A, Schmidt S

Abstract
Hormonal contraceptive agents (HCAs) are widely used throughout the world, and women taking HCAs are likely to take other medications. However, little is known about the clinical effect of most drug-drug interactions (DDIs) associated with HCAs. A team of interdisciplinary outcomes and pharmacometric researchers from academia and industry jointly engage in a research project to (i) quantitatively elucidate DDI impacts on unintended pregnancies and breakthrough bleeding, and (ii) establish a DDI-prediction framework to inform optimal use of HCAs.

PMID: 30260082 [PubMed - indexed for MEDLINE]

The language of change among criminal justice clients: Counselor language, client language, and client substance use outcomes.

Tue, 10/29/2019 - 12:00
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The language of change among criminal justice clients: Counselor language, client language, and client substance use outcomes.

J Clin Psychol. 2018 04;74(4):626-636

Authors: Rodriguez M, Walters ST, Houck JM, Ortiz JA, Taxman FS

Abstract
OBJECTIVE: Counselor and client language have been identified as mechanisms of change in motivational interviewing (MI) counseling sessions. This study evaluated whether language patterns exhibited during MI sessions with substance users in the community would also be found during MI sessions with substance users in the criminal justice system.
METHOD: Forty audio recordings of MI sessions with substance-using probationers were coded and analyzed sequentially using the Motivational Interviewing Skills Code (MISC) 2.5. Analyses examined the relationship between counselor and client language, and the relationship between client language and client substance use after 2 months.
RESULTS: Counselor MI inconsistent language was associated with decreased change talk (lnOR = - 0.76, p < .05) though not with increased sustain talk. Both sustain talk (b = - 4.591, t = - 18.634 p < .001) and MI inconsistent language MIIN (b = - 4.419, t = - 19.886, p < .001) were positively associated with substance use at 2 months. Sustain talk early in the session (i.e., during deciles 1 and 2) was significantly greater among clients who reported using substances at 2 months, compared to clients who did not use substances.
CONCLUSION: These findings are broadly consistent with previous literature documenting the association between counselor language, client language, and client outcome.

PMID: 28940435 [PubMed - indexed for MEDLINE]

Targets of Neuroprotection in Glaucoma.

Tue, 10/29/2019 - 12:00
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Targets of Neuroprotection in Glaucoma.

J Ocul Pharmacol Ther. 2018 Jan/Feb;34(1-2):85-106

Authors: He S, Stankowska DL, Ellis DZ, Krishnamoorthy RR, Yorio T

Abstract
Progressive neurodegeneration of the optic nerve and the loss of retinal ganglion cells is a hallmark of glaucoma, the leading cause of irreversible blindness worldwide, with primary open-angle glaucoma (POAG) being the most frequent form of glaucoma in the Western world. While some genetic mutations have been identified for some glaucomas, those associated with POAG are limited and for most POAG patients, the etiology is still unclear. Unfortunately, treatment of this neurodegenerative disease and other retinal degenerative diseases is lacking. For POAG, most of the treatments focus on reducing aqueous humor formation, enhancing uveoscleral or conventional outflow, or lowering intraocular pressure through surgical means. These efforts, in some cases, do not always lead to a prevention of vision loss and therefore other strategies are needed to reduce or reverse the progressive neurodegeneration. In this review, we will highlight some of the ocular pharmacological approaches that are being tested to reduce neurodegeneration and provide some form of neuroprotection.

PMID: 28820649 [PubMed - indexed for MEDLINE]

NT3P75-2 gene-modified bone mesenchymal stem cells improve neurological function recovery in mouse TBI model.

Mon, 10/28/2019 - 14:50
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NT3P75-2 gene-modified bone mesenchymal stem cells improve neurological function recovery in mouse TBI model.

Stem Cell Res Ther. 2019 Oct 24;10(1):311

Authors: Wu K, Huang D, Zhu C, Kasanga EA, Zhang Y, Yu E, Zhang H, Ni Z, Ye S, Zhang C, Hu J, Zhuge Q, Yang J

Abstract
BACKGROUND: The attainment of extensive neurological function recovery remains the key challenge for the treatment of traumatic brain injury (TBI). Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has been shown to improve neurological function recovery after TBI. However, the survival of BMSCs after transplantation in early-stage TBI is limited, and much is unknown about the mechanisms mediating this neurological function recovery. Secretion of neurotrophic factors, including neurotrophin 3 (NT3), is one of the critical factors mediating BMSC neurological function recovery. Gene mutation of NT3 (NT3P75-2) has been shown to enhance the biological function of NT3 via the reduction of the activation of the P75 signal pathway. Thus, we investigated whether NT3P75-2 gene-modified BMSCs could enhance the survival of BMSCs and further improve neurological function recovery after TBI.
METHODS: The ability of NT3P75-2 induction to improve cell growth rate of NSC-34 and PC12 cells in vitro was first determined. BMSCs were then infected with three different lentiviruses (green fluorescent protein (GFP), GFP-NT3, or GFP-NT3P75-2), which stably express GFP, GFP-NT3, or GFP-NT3P75-2. At 24 h post-TBI induction in mice, GFP-labeled BMSCs were locally transplanted into the lesion site. Immunofluorescence and histopathology were performed at 1, 3, and/or 7 days after transplantation to evaluate the survival of BMSCs as well as the lesion volume. A modified neurological severity scoring system and the rotarod test were chosen to evaluate the functional recovery of the mice. Cell growth rate, glial activation, and signaling pathway analyses were performed to determine the potential mechanisms of NT3P75-2 in functional recovery after TBI.
RESULTS: Overall, NT3P75-2 improved cell growth rate of NSC-34 and PC12 cells in vitro. In addition, NT3P75-2 significantly improved the survival of transplanted BMSCs and neurological function recovery after TBI. Overexpression of NT3P75-2 led to a significant reduction in the activation of glial cells, brain water content, and brain lesion volume after TBI. This was associated with a reduced activation of the p75 neurotrophin receptor (P75NTR) and the c-Jun N-terminal kinase (JNK) signal pathway due to the low affinity of NT3P75-2 for the receptor.
CONCLUSIONS: Taken together, our results demonstrate that administration of NT3P75-2 gene-modified BMSCs dramatically improves neurological function recovery after TBI by increasing the survival of BMSCs and ameliorating the inflammatory environment, providing a new promising treatment strategy for TBI.

PMID: 31651375 [PubMed - in process]

Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.

Thu, 10/24/2019 - 05:07
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Genome-Wide Methylation of Mild Cognitive Impairment in Mexican Americans Highlights Genes Involved in Synaptic Transport, Alzheimer's Disease-Precursor Phenotypes, and Metabolic Morbidities.

J Alzheimers Dis. 2019 Oct 18;:

Authors: Pathak GA, Silzer TK, Sun J, Zhou Z, Daniel AA, Johnson L, O'Bryant S, Phillips NR, Barber RC

Abstract
The Mexican American population is among the fastest growing aging population and has a younger onset of cognitive decline. This group is also heavily burdened with metabolic conditions such as hypertension, diabetes, and obesity. Unfortunately, limited research has been conducted in this group. Understanding methylation alterations, which are influenced by both genetic and lifestyle factors, is key to identifying and addressing the root cause for mild cognitive impairment, a clinical precursor for dementia. We conducted an epigenome-wide association study on a community-based Mexican American population using the Illumina EPIC array. Following rigorous quality control measures, we identified 10 CpG sites to be differentially methylated between normal controls and individuals with mild cognitive impairment annotated to PKIB, KLHL29, SEPT9, OR2C3, CPLX3, BCL2L2-PABPN1, and CCNY. We found four regions to be differentially methylated in TMEM232, SLC17A8, ALOX12, and SEPT8. Functional gene-set analysis identified four gene-sets, RIN3, SPEG, CTSG, and UBE2L3, as significant. The gene ontology and pathway analyses point to neuronal cell death, metabolic dysfunction, and inflammatory processes. We found 1,450 processes to be enriched using empirical Bayes gene-set enrichment. In conclusion, the functional overlap of differentially methylated genes associated with cognitive impairment in Mexican Americans implies cross-talk between metabolically-instigated systemic inflammation and disruption of synaptic vesicular transport.

PMID: 31640099 [PubMed - as supplied by publisher]

DAV131A protects hamsters from lethal Clostridioides difficile infection induced by fluoroquinolones.

Wed, 10/23/2019 - 07:58
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DAV131A protects hamsters from lethal Clostridioides difficile infection induced by fluoroquinolones.

Antimicrob Agents Chemother. 2019 Oct 21;:

Authors: Saint-Lu N, Burdet C, Sablier-Gallis F, Corbel T, Nevière A, Sayah-Jeanne S, Pulse M, Weiss W, Ferreira S, Andremont A, Mentré F, de Gunzburg J

Abstract
Fluoroquinolone treatments induce dysbiosis of the intestinal microbiota resulting in loss of resistance to colonization by exogenous bacteria such as Clostridioides difficile that may cause severe diarrhea in humans, and lethal infection in hamsters. We show here that DAV131A, a charcoal-based adsorbent, decreases intestinal levels of the fluoroquinolone antibiotics levofloxacin and ciprofloxacin in hamsters, protects their intestinal microbiota and prevents lethal infection by C. difficile.

PMID: 31636067 [PubMed - as supplied by publisher]

Mortality association between obesity and pneumonia using a dual restricted cohort model.

Wed, 10/23/2019 - 07:58
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Mortality association between obesity and pneumonia using a dual restricted cohort model.

Obes Res Clin Pract. 2019 Oct 18;:

Authors: Wang H, Lee CC, Chou EH, Hsu WT, Robinson RD, Su KY, Kirby JJ, Hassani D

Abstract
BACKGROUND: An obesity survival paradox has been reported among obese patients with pneumonia.
AIMS: To determine the impact of obesity on pneumonia outcomes and analyze the correlation between in-hospital all-cause mortality and obesity among patients with pneumonia.
METHODS: The United States Nationwide Readmissions Database (NRD) was retrospectively analyzed for patients with pneumonia from 2013 to 2014. We used a step-wise restricted and propensity score matching cohort model (dual model) to compare mortality rates and other outcomes among pneumonia patients based on BMI. Mortality was calculated by a Cox proportional hazard model, adjusted for potential confounders with propensity score matched analysis.
RESULTS: A total of 70,886,775 patients were registered in NRD during the study period. Of these, 7,786,913 patients (11.0%) were considered obese and 1,652,456 patients (2.3%) were admitted to the hospital with pneumonia. Based on the step-wise restricted cohort model, the hazard ratio comparing the mortality rates among obese pneumonia patients to mortality rates among normal BMI pneumonia patients was 0.75 (95% CI 0.60-0.94). The propensity score matched analysis estimated a hazard rate of 0.84 (95% CI 0.79-0.90) and the hazard ratio estimated from the dual model was 0.82 (95% CI 0.63-1.07).
CONCLUSIONS: With the application of a dual model, there appears to be no significant difference in mortality of obese patients with pneumonia compared to normal BMI patients with pneumonia.

PMID: 31635969 [PubMed - as supplied by publisher]

Community-Engaged Lifestyle Medicine: Building Health Equity Through Preventive Medicine Residency Training.

Wed, 10/23/2019 - 07:58
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Community-Engaged Lifestyle Medicine: Building Health Equity Through Preventive Medicine Residency Training.

Am J Prev Med. 2018 09;55(3):412-421

Authors: Krishnaswami J, Jaini PA, Howard R, Ghaddar S

Abstract
Vulnerable populations in the U.S. experience persistent disparities in chronic disease and associated lifestyle-based risk factors. Because of environmental, cultural, and health systems barriers affecting vulnerable populations, lifestyle medicine interventions may miss those at highest risk for chronic disease. Numerous reports suggest that graduate medical education (GME) inadequately prepares physicians to promote healthy lifestyles and health equity in vulnerable groups. General Preventive Medicine/Public Health (GPM/PH), the medical specialty dedicated to health promotion and disease prevention in populations, can fill this gap. However, virtually no published reports describe health equity-oriented GPM/PH residency programs. The authors describe implementation of the novel Community-Engaged Lifestyle Medicine at the University of Texas Rio Grande Valley GPM/PH residency program between 2017 and 2018. Community-Engaged Lifestyle Medicine applies community engagement principles to lifestyle medicine practice, training residents in multilevel, intersectoral approaches promoting behavior change and health equity. Community-Engaged Lifestyle Medicine is described in the context of health equity and the local border community, along with associated curricular objectives and experiences. In 2017, the authors assessed first-year Community-Engaged Lifestyle Medicine process outcomes, fidelity to health equity mechanisms, and feasibility in a GPM/PH residency, by mapping Community-Engaged Lifestyle Medicine activities to American Council of Graduate Medical Education and the American College of Lifestyle Medicine competencies. The Community-Engaged Lifestyle Medicine framework was successfully implemented in 2017, meets all American Council of Graduate Medical Education competency domains, and demonstrates fidelity to mechanisms of community engagement, health equity, and the practice of lifestyle medicine. Community-Engaged Lifestyle Medicine represents a feasible and valid framework to promote health equity via GPM/PH and GME training and practice.

PMID: 29954645 [PubMed - indexed for MEDLINE]

Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise-induced increases in muscle sympathetic nerve activity.

Wed, 10/23/2019 - 07:58
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Effect of centrally acting angiotensin converting enzyme inhibitor on the exercise-induced increases in muscle sympathetic nerve activity.

J Physiol. 2018 06;596(12):2315-2332

Authors: Moralez G, Jouett NP, Tian J, Zimmerman MC, Bhella P, Raven PB

Abstract
KEY POINTS: The arterial baroreflex's operating point pressure is reset upwards and rightwards from rest in direct relation to the increases in dynamic exercise intensity. The intraneural pathways and signalling mechanisms that lead to upwards and rightwards resetting of the operating point pressure, and hence the increases in central sympathetic outflow during exercise, remain to be identified. We tested the hypothesis that the central production of angiotensin II during dynamic exercise mediates the increases in sympathetic outflow and, therefore, the arterial baroreflex operating point pressure resetting during acute and prolonged dynamic exercise. The results identify that perindopril, a centrally acting angiotensin converting enzyme inhibitor, markedly attenuates the central sympathetic outflow during acute and prolonged dynamic exercise.
ABSTRACT: We tested the hypothesis that the signalling mechanisms associated with the dynamic exercise intensity related increases in muscle sympathetic nerve activity (MSNA) and arterial baroreflex resetting during exercise are located within the central nervous system. Participants performed three randomly ordered trials of 70° upright back-supported dynamic leg cycling after ingestion of placebo and two different lipid soluble angiotensin converting enzyme inhibitors (ACEi): perindopril (high lipid solubility), captopril (low lipid solubility). Repeated measurements of whole venous blood (n = 8), MSNA (n = 7) and arterial blood pressures (n = 14) were obtained at rest and during an acute (SS1) and prolonged (SS2) bout of steady state dynamic exercise. Arterial baroreflex function curves were modelled at rest and during exercise. Peripheral venous superoxide concentrations measured by electron spin resonance spectroscopy were elevated during exercise and were not altered by ACEi at rest (P ≥ 0.4) or during exercise (P ≥ 0.3). Baseline MSNA and mean arterial pressure were unchanged at rest (P ≥ 0.1; P ≥ 0.8, respectively). However, during both SS1 and SS2, the centrally acting ACEi perindopril attenuated MSNA compared to captopril and the placebo (P < 0.05). Arterial pressures at the operating point and threshold pressures were decreased with perindopril from baseline to SS1 with no further changes in the operating point pressure during SS2 under all three conditions. These data suggest that centrally acting ACEi is significantly more effective at attenuating the increase in the acute and prolonged exercise-induced increases in MSNA.

PMID: 29635787 [PubMed - indexed for MEDLINE]

Cost and cost-effectiveness of computerized vs. in-person motivational interventions in the criminal justice system.

Wed, 10/23/2019 - 07:58
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Cost and cost-effectiveness of computerized vs. in-person motivational interventions in the criminal justice system.

J Subst Abuse Treat. 2018 04;87:42-49

Authors: Cowell AJ, Zarkin GA, Wedehase BJ, Lerch J, Walters ST, Taxman FS

Abstract
INTRODUCTION: Although substance use is common among probationers in the United States, treatment initiation remains an ongoing problem. Among the explanations for low treatment initiation are that probationers are insufficiently motivated to seek treatment, and that probation staff have insufficient training and resources to use evidence-based strategies such as motivational interviewing. A web-based intervention based on motivational enhancement principles may address some of the challenges of initiating treatment but has not been tested to date in probation settings. The current study evaluated the cost-effectiveness of a computerized intervention, Motivational Assessment Program to Initiate Treatment (MAPIT), relative to face-to-face Motivational Interviewing (MI) and supervision as usual (SAU), delivered at the outset of probation.
METHODS: The intervention took place in probation departments in two U.S. cities. The baseline sample comprised 316 participants (MAPIT = 104, MI = 103, and SAU = 109), 90% (n = 285) of whom completed the 6-month follow-up. Costs were estimated from study records and time logs kept by interventionists. The effectiveness outcome was self-reported initiation into any treatment (formal or informal) within 2 and 6 months of the baseline interview. The cost-effectiveness analysis involved assessing dominance and computing incremental cost-effectiveness ratios and cost-effectiveness acceptability curves. Implementation costs were used in the base case of the cost-effectiveness analysis, which excludes both a hypothetical license fee to recoup development costs and startup costs. An intent-to-treat approach was taken.
RESULTS: MAPIT cost $79.37 per participant, which was ~$55 lower than the MI cost of $134.27 per participant. Appointment reminders comprised a large proportion of the cost of the MAPIT and MI intervention arms. In the base case, relative to SAU, MAPIT cost $6.70 per percentage point increase in the probability of initiating treatment. If a decision-maker is willing to pay $15 or more to improve the probability of initiating treatment by 1%, estimates suggest she can be 70% confident that MAPIT is good value relative to SAU at the 2-month follow-up and 90% confident that MAPIT is good value at the 6-month follow-up.
CONCLUSIONS: Web-based MAPIT may be good value compared to in-person delivered alternatives. This conclusion is qualified because the results are not robust to narrowing the outcome to initiating formal treatment only. Further work should explore ways to improve access to efficacious treatment in probation settings.

PMID: 29471925 [PubMed - indexed for MEDLINE]

Implementation of The Steps Toward Academic Research (STAR) Fellowship Program to Promote Underrepresented Minority Faculty into Health Disparity Research.

Wed, 10/23/2019 - 07:58
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Implementation of The Steps Toward Academic Research (STAR) Fellowship Program to Promote Underrepresented Minority Faculty into Health Disparity Research.

Ethn Dis. 2018;28(1):3-10

Authors: Vishwanatha JK, Jones HP

Abstract
Eliminating disparities in health can benefit from the inclusion of diverse populations pursuing health disparity research careers. A goal of the Texas Center for Health Disparities (TCHD) is to provide opportunities for underrepresented minority faculty to become successful health disparity researchers. The TCHD created the Steps Toward Academic Research (STAR) fellowship program to provide faculty and community partners a yearlong face-to-face and online hybrid curriculum focused on acquiring fundamental concepts in biomedical and behavioral health disparity research, basics in grantsmanship as well as professional development skills. In total, this training approach is envisioned to provide mutually beneficial co-learning experiences that will increase the number of under-represented minorities (URMs) entering translational research focused on the elimination of health disparities.

PMID: 29467560 [PubMed - indexed for MEDLINE]

Knee Loading After ACL-R Is Related to Quadriceps Strength and Knee Extension Differences Across the Continuum of Care.

Tue, 10/22/2019 - 07:49
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Knee Loading After ACL-R Is Related to Quadriceps Strength and Knee Extension Differences Across the Continuum of Care.

Orthop J Sports Med. 2019 Oct;7(10):2325967119870155

Authors: Garrison JC, Hannon J, Goto S, Kosmopoulos V, Aryal S, Bush C, Bothwell JM, Singleton SB

Abstract
Background: Quadriceps strength and knee extension are believed to be important in the ability to effectively load the knee after anterior cruciate ligament (ACL) reconstruction (ACL-R).
Purpose: To compare quadriceps strength (QUADS), side-to-side knee extension difference (ExtDiff), and knee energy absorption contribution (EAC) in patients preoperatively, 12 weeks postoperatively, and at return to sport (RTS). A secondary aim was to determine how the factors of QUADS and ExtDiff contributed to the ability to load the knee (knee EAC) at each of the 3 time points.
Study Design: Case series; Level of evidence, 4.
Methods: Overall, 41 individuals (mean ± SD age, 15.95 ± 1.63 years) were enrolled in this study. QUADS, ExtDiff, and knee EAC during a double-limb squat were collected preoperatively, 12 weeks postoperatively, and at RTS. Isokinetic QUADS was collected at 60 deg/s, normalized to body mass, and averaged across 5 trials. Knee extension was measured with a goniometer, and ExtDiff was calculated for analyses. Knee EAC was measured during double-limb squat descent and was calculated as a percentage of total energy absorption for the limb. Observations were obtained from both the surgical and nonsurgical limbs at the 3 time points. A mixed regression model with random intercept to compare change over the 3 time points was used, and a model selection was conducted with Akaike information criteria. Significance was set at P < .05.
Results: Surgical limb QUADS was significantly lower preoperatively (mean ± SD, 1.37 ± 0.49 N·m/kg; P = .0023) and at 12 weeks (1.11 ± 0.38 N·m/kg; P < .0001) than at RTS (1.58 ± 0.47 N·m/kg). Nonsurgical limb QUADS was also significantly lower preoperatively (2.01 ± 0.54 N·m/kg; P < .0256) and at 12 weeks (2.03 ± 0.48 N·m/kg; P < .0233) than at RTS (2.18 ± 0.54 N·m/kg). Knee EAC for the surgical limb was significantly lower at 12 weeks than at RTS (40.98% ± 13.73% vs 47.50% ± 12.04%; P < .0032), and ExtDiff was significantly greater preoperatively than at RTS (-2.68° ± 3.19° vs -0.63° ± 1.43°; P < .0001). Preoperatively, QUADS for both the surgical (P < .0003) and nonsurgical (P = .0023) limbs was a significant predictor of surgical limb knee EAC, explaining 33.99% of the variance. At 12 weeks, surgical limb QUADS was a significant predictor (P < .0051) of surgical limb knee EAC, explaining 18.83% of the variance. At RTS, ExtDiff was a significant predictor (P = .0201) of surgical limb knee EAC, explaining 12.92% of the variance.
Conclusion: The ability to load the knee after ACL injury changes across the continuum of care and is related to QUADS and ExtDiff. These results provide clinicians with insight into potential contributing factors that may limit knee loading during the rehabilitation process.

PMID: 31632992 [PubMed]

Effects of dietary 5-methoxyindole-2-carboxylic acid on brain functional recovery after ischemic stroke.

Mon, 10/21/2019 - 07:38
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Effects of dietary 5-methoxyindole-2-carboxylic acid on brain functional recovery after ischemic stroke.

Behav Brain Res. 2019 Oct 17;:112278

Authors: Sumien N, Huang R, Chen Z, Vann PH, Wong JM, Li W, Yang S, Forster M, Yan LJ

Abstract
Stroke leads to devastating outcomes including impairments of sensorimotor and cognitive function that may be long lasting. New intervention strategies are needed to overcome the long-lasting effects of ischemic injury. Previous studies determined that treatment with 5-methoxyindole-2-carboxylic acid (MICA) conferred chemical preconditioning and neuroprotection against stroke. The purpose of the current study was to determine whether the preconditioning can lead to functional improvements after stroke (done by transient middle cerebral artery occlusion). After 4 weeks of MICA feeding, half the rats underwent ischemic injury, while the other half remained intact. After one week recovery, all the rats were tested for motor and cognitive function (rotorod and water maze). At the time of euthanasia, measurements of long-term potentiation (LTP) were performed. While stroke injury led to motor and cognitive dysfunction, MICA supplementation did not reverse these impairments. However, MICA supplementation did improve stroke-related impairments in hippocampal LTP. The dichotomy of the outcomes suggest that more studies are needed to determine optimum duration and dosage for MICA to lead to substantial motor and cognitive improvements, along with LTP change and neuroprotection.

PMID: 31629836 [PubMed - as supplied by publisher]

Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment.

Mon, 10/21/2019 - 07:38
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Overexpression of somatostatin receptor type 2 in neuroendocrine tumors for improved Ga68-DOTATATE imaging and treatment.

Surgery. 2019 Oct 16;:

Authors: Guenter R, Aweda T, Carmona Matos DM, Jang S, Whitt J, Cheng YQ, Liu XM, Chen H, Lapi SE, Jaskula-Sztul R

Abstract
BACKGROUND: Neuroendocrine tumors are found throughout the body, including the pancreas. These tumors are phenotypically and genetically heterogeneous and can be difficult to accurately image using current imaging standards. However, positron emission tomography/computed tomography with radiolabeled somatostatin analogs has shown clinical success because many neuroendocrine tumors overexpress somatostatin receptor subtype 2. Unfortunately, patients with poorly differentiated neuroendocrine tumors often have a diminished level of somatostatin receptor subtype 2. We found that histone deacetylase inhibitors can upregulate the functional expression of somatostatin receptor subtype 2.
METHODS: We evaluated the effect of histone deacetylase inhibitors on somatostatin receptor subtype 2 expression at the mRNA and protein level in neuroendocrine tumor cell lines. The effect of histone deacetylase inhibitors on surface somatostatin receptor subtype 2 was also investigated by fluorescence-activated cell sorting analysis. Changes in somatostatin receptor subtype 2 expression in neuroendocrine tumor xenografts after treatment were imaged using Ga68-DOTATATE positron emission tomography/computed tomography.
RESULTS: The functional increase of somatostatin receptor subtype 2 in neuroendocrine tumors after histone deacetylase inhibitor treatment was confirmed through in vitro experiments and small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging. Histone deacetylase inhibitors increased somatostatin receptor subtype 2 transcription and protein expression in neuroendocrine tumor cell lines. Small animal Ga68-DOTATATE positron emission tomography/computed tomography imaging confirmed the enhancement of radiopeptide uptake after histone deacetylase inhibitor administration.
CONCLUSION: This study demonstrates a new method to potentially improve imaging and treatments that target somatostatin receptor subtype 2 in neuroendocrine tumors.

PMID: 31629542 [PubMed - as supplied by publisher]

Promoting Independent Sleep Onset in Young Children: Examination of the Excuse Me Drill.

Fri, 10/18/2019 - 07:16
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Promoting Independent Sleep Onset in Young Children: Examination of the Excuse Me Drill.

Behav Sleep Med. 2019 Oct 17;:1-16

Authors: Kuhn BR, LaBrot ZC, Ford R, Roane BM

Abstract
Background: There is compelling evidence to support behavioral interventions as the first-line approach for bedtime resistance in young children. Among the behavioral treatment options, extinction ("cry it out") has the most extensive empirical support and tends to produce the most rapid gains. There are well known problems with the use of extinction, however, including side effects (extinction burst, spontaneous recovery) and poor acceptance, not to mention that extinction fails to teach children appropriate replacement behaviors (what "to do"). This study introduces a new behavioral sleep intervention, the Excuse Me Drill, designed to address some of the limitations of extinction. The EMD was formally evaluated for the first time using a multiple-baseline research design across four participants with sleep disturbance.Participants: Participants included four children who were clinically referred to outpatient pediatric psychology clinics for the treatment of behavioral insomnia of childhood, and included one 2-year-old female, two 7-year-old females, and one 7-year-old male. All participants had a history of dependent sleep onset at bedtime (i.e., parents remained in the child's bedroom upon sleep onset). Methods: A non-concurrent multiple baseline design across participants was used to experimentally evaluate the effectiveness of the EMD. During baseline, parents collected data on independent sleep onset and disruptive bedtime behaviors, but conducted the bedtime routine as usual. Immediately following baseline, parents implemented the EMD protocol until data indicated that children were consistently initiating sleep independently. Follow-up data were collected to determine the extent to which children continued to initiate sleep independently at bedtime in absence of the EMD. Results: Outcomes were promising as the EMD successfully taught all four children to initiate sleep independently and produced notable decreases in disruptive bedtime behavior. Results were maintained at follow-up for three of four participants. In addition, parents rated the EMD to be a socially acceptable procedure for their children. Conclusions: Results of this study indicate that the EMD was effective in promoting independent sleep onset and reducing disruptive bedtime behavior that maintained over time. The EMD should be considered to be a viable alternative to traditional extinction procedures for pediatric sleep disturbance. Implications for practice, limitations, and direction for future research are discussed.

PMID: 31621416 [PubMed - as supplied by publisher]

Modeling SNP array ascertainment with Approximate Bayesian Computation for demographic inference.

Fri, 10/18/2019 - 07:16
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Modeling SNP array ascertainment with Approximate Bayesian Computation for demographic inference.

Sci Rep. 2018 07 05;8(1):10209

Authors: Quinto-Cortés CD, Woerner AE, Watkins JC, Hammer MF

Abstract
Single nucleotide polymorphisms (SNPs) in commercial arrays have often been discovered in a small number of samples from selected populations. This ascertainment skews patterns of nucleotide diversity and affects population genetic inferences. We propose a demographic inference pipeline that explicitly models the SNP discovery protocol in an Approximate Bayesian Computation (ABC) framework. We simulated genomic regions according to a demographic model incorporating parameters for the divergence of three well-characterized HapMap populations and recreated the SNP distribution of a commercial array by varying the number of haploid samples and the allele frequency cut-off in the given regions. We then calculated summary statistics obtained from both the ascertained and genomic data and inferred ascertainment and demographic parameters. We implemented our pipeline to study the admixture process that gave rise to the present-day Mexican population. Our estimate of the time of admixture is closer to the historical dates than those in previous works which did not consider ascertainment bias. Although the use of whole genome sequences for demographic inference is becoming the norm, there are still underrepresented areas of the world from where only SNP array data are available. Our inference framework is applicable to those cases and will help with the demographic inference.

PMID: 29977040 [PubMed - indexed for MEDLINE]

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