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Neuroprotective and neurotoxic outcomes of androgens and estrogens in an oxidative stress environment.

Recent Research Articles from UNTHSC - Wed, 04/01/2020 - 05:38
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Neuroprotective and neurotoxic outcomes of androgens and estrogens in an oxidative stress environment.

Biol Sex Differ. 2020 Mar 29;11(1):12

Authors: Duong P, Tenkorang MAA, Trieu J, McCuiston C, Rybalchenko N, Cunningham RL

Abstract
BACKGROUND: The role of sex hormones on cellular function is unclear. Studies show androgens and estrogens are protective in the CNS, whereas other studies found no effects or damaging effects. Furthermore, sex differences have been observed in multiple oxidative stress-associated CNS disorders, such as Alzheimer's disease, depression, and Parkinson's disease. The goal of this study is to examine the relationship between sex hormones (i.e., androgens and estrogens) and oxidative stress on cell viability.
METHODS: N27 and PC12 neuronal and C6 glial phenotypic cell lines were used. N27 cells are female rat derived, whereas PC12 cells and C6 cells are male rat derived. These cells express estrogen receptors and the membrane-associated androgen receptor variant, AR45, but not the full-length androgen receptor. N27, PC12, and C6 cells were exposed to sex hormones either before or after an oxidative stressor to examine neuroprotective and neurotoxic properties, respectively. Estrogen receptor and androgen receptor inhibitors were used to determine the mechanisms mediating hormone-oxidative stress interactions on cell viability. Since the presence of AR45 in the human brain tissue was unknown, we examined the postmortem brain tissue from men and women for AR45 protein expression.
RESULTS: Neither androgens nor estrogens were protective against subsequent oxidative stress insults in glial cells. However, these hormones exhibited neuroprotective properties in neuronal N27 and PC12 cells via the estrogen receptor. Interestingly, a window of opportunity exists for sex hormone neuroprotection, wherein temporary hormone deprivation blocked neuroprotection by sex hormones. However, if sex hormones are applied following an oxidative stressor, they exacerbated oxidative stress-induced cell loss in neuronal and glial cells.
CONCLUSIONS: Sex hormone action on cell viability is dependent on the cellular environment. In healthy neuronal cells, sex hormones are protective against oxidative stress insults via the estrogen receptor, regardless of sex chromosome complement (XX, XY). However, in unhealthy (e.g., high oxidative stress) cells, sex hormones exacerbated oxidative stress-induced cell loss, regardless of cell type or sex chromosome complement. The non-genomic AR45 receptor, which is present in humans, mediated androgen's damaging effects, but it is unknown which receptor mediated estrogen's damaging effects. These differential effects of sex hormones that are dependent on the cellular environment, receptor profile, and cell type may mediate the observed sex differences in oxidative stress-associated CNS disorders.

PMID: 32223745 [PubMed - in process]

A Biomechanical Examination of Prefabricated Total Contact Cast Kits: Relevance to Patients With Diabetic Neuropathy.

Recent Research Articles from UNTHSC - Wed, 04/01/2020 - 05:38
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A Biomechanical Examination of Prefabricated Total Contact Cast Kits: Relevance to Patients With Diabetic Neuropathy.

Int J Low Extrem Wounds. 2020 Mar 29;:1534734620914440

Authors: Ersen A, Lavery LA, Monga A, Richardson M, Schwarz B, Quiben MU, Garrett AG, Flyzik M, Wukich DK, Yavuz M

Abstract
The traditional Total Contact Cast (TCC) is considered the gold standard for treating plantar diabetic ulcers. A number of prefabricated TCC kits have been introduced, which offer a user-friendly casting process for health care providers. Our objective was to evaluate pressure reduction and gait characteristics after application of a TCC kit (TCC-EZ) and traditional TCC. Fifteen individuals (9 males, 6 females; median age of 51.5 years [range = 40.5-71.2 years]) completed 30-m walking trials while fitted with TCC-EZ and TCC in a randomized order. A pair of automated wireless photogate sensors captured time to traverse the distance and pedobarographic insoles measured and recorded plantar pressures. Paired t tests were used to compare peak pressure, gait speed, and cast weights across the 2 modalities. Peak pressure and cast weight were significantly lower in the TCC-EZ arm (169.6 ± 41.3 kPa vs 214.9 ± 63.2 kPa, P = .0048; and 1.79 ± 0.17 kg vs 2.11 ± 0.25 kg, P = .0004). Contact area and gait speed were not significantly different between the 2 modalities (140.4 ± 25.8 cm2 vs 126.9 ± 37.8 cm2, P = .0228, Cohen's d = 0.40; and 0.94 ± 0.19 m/s vs 0.83 ± 0.26 m/s, P = .0532, Cohen's d = .48). TCC-EZ was found to provide more favorable pressure distributions compared with TCC. TCC-EZ is also lighter and may be a preferred treatment modality for patients. More research is necessary to reveal the clinical effectiveness of prefabricated total contact kits.

PMID: 32223354 [PubMed - as supplied by publisher]

Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama.

Recent Research Articles from UNTHSC - Tue, 03/31/2020 - 05:22
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Inflammatory Biomarkers, Depressive Symptoms and Falls Among the elderly in Panama.

Curr Aging Sci. 2019;11(4):236-241

Authors: Britton GB, O'Bryant SE, Johnson LA, Hall JR, Villarreal AE, Oviedo DC, Pérez-Lao AR, Carreira MB

Abstract
BACKGROUND: Falls are common among elderly adults, and are predictors of hospitalization, institutionalization and mortality.
OBJECTIVE: The objective of the present study was to examine the relationship between blood-based markers of inflammation and fall events in a sample of elderly Hispanic adults.
METHOD: Data were collected from 190 participants enrolled in the Panama Aging Research Initiative study who completed baseline clinical and cognitive assessments. A non-fasting blood sample was obtained. Self-reported falls were classified as no falls, single falls or recurrent (two or more) falls reported in the 12 months prior to baseline evaluations. Serum levels of C Reactive Protein (CRP), T-lymphocyte secreting protein (I-309), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 7 (IL-7) were measured. Global cognition was assessed with the Mini Mental State Examination and depressive symptoms were assessed with the Geriatric Depression Scale (GDS-30). Multinomial logistic regression was used to assess the link between inflammation and fall events.
RESULTS: Depressive symptoms, limitations in Instrumental Activities of Daily Living (IADL), IL-7 and I-309 were significantly related to fall events. Elevated levels of IL-7 increased the likelihood of single and recurrent falls, while increased levels of I-309 were associated only with recurrent falls. Greater IADL limitations and depressive symptoms were associated with an increased likelihood of recurrent falls.
CONCLUSION: There is a lack of research investigating the relationship between inflammatory biomarkers and fall events. These results provide evidence of risk factors for falls in Hispanic older adults, and could serve to guide public health professionals to establish clinical guidelines to reduce fall risks.

PMID: 30767759 [PubMed - indexed for MEDLINE]

2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) in systemic lupus erythematosus and cancer.

Recent Research Articles from UNTHSC - Tue, 03/31/2020 - 05:22
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2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) in systemic lupus erythematosus and cancer.

Clin Immunol. 2019 07;204:50-56

Authors: Malaer JD, Marrufo AM, Mathew PA

Abstract
Signaling Lymphocyte Activation Molecule (SLAM) family receptors are expressed on different types of hematopoietic cells and play important role in immune regulation in health and disease. 2B4 (CD244, SLAMF4) and CS1 (CD319, CRACC, SLAMF7) were originally identified as NK cell receptors regulating NK cell cytolytic activity. 2B4 is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Unlike other activating and inhibitory receptors, 2B4 (CD244) interaction with its ligand CD48 has been shown to mediate both activating and inhibitory functions. Defective signaling via 2B4 due to mutations in signaling adaptor SAP contributes to X-linked lymphoproliferative Disease (XLP). Expression of 2B4 and CS1 are altered in systemic lupus erythematosus (SLE). CS1 is overexpressed in multiple myeloma (MM) and anti-CS1 mab (Elotuzumab/Empliciti) has been approved by FDA as a breakthrough drug for treatment for MM patients. CAR -T cells or CAR- NK cells containing full length CS1 or the signaling domain of 2B4 with TCR-ζ have shown promising results to treat cancer and autoimmune diseases.

PMID: 30347240 [PubMed - indexed for MEDLINE]

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

Recent Research Articles from UNTHSC - Sat, 03/28/2020 - 07:30
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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 - indexed for MEDLINE]

Blood-based biomarkers for Down syndrome and Alzheimer's disease: A systematic review.

Recent Research Articles from UNTHSC - Sat, 03/28/2020 - 07:30
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Blood-based biomarkers for Down syndrome and Alzheimer's disease: A systematic review.

Dev Neurobiol. 2019 07;79(7):699-710

Authors: Petersen ME, O'Bryant SE

Abstract
Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer's disease (AD) due to increased amyloid beta (Aβ) resulting from the over-expression of the amyloid precursor protein found on chromosome 21. Diagnosis of AD among individuals with DS poses particular challenges resulting in an increased focus on alternative diagnostic methods such as blood-based biomarkers. The aim of this review was to evaluate the current state of the literature of blood-based biomarkers found in individuals with DS and particularly among those also diagnosed with AD or in prodromal stages (mild cognitive impairment [MCI]). A systematic review was conducted utilizing a comprehensive search strategy. Twenty-four references were identified, of those, 22 fulfilled inclusion criteria were selected for further analysis with restriction to only plasma-based biomarkers. Studies found Aβ to be consistently higher among individuals with DS; however, the link between Aβ peptides (Aβ1-42 and Aβ1-40) and AD among DS was inconsistent. Inflammatory-based proteins were more reliably found to be elevated leading to preliminary work focused on an algorithmic approach with predominantly inflammatory-based proteins to detect AD and MCI as well as predict risk of incidence among DS. Separate work has also shown remarkable diagnostic accuracy with the use of a single protein (NfL) as compared to combined proteomic profiles. This review serves to outline the current state of the literature and highlights the potential plasma-based biomarkers for use in detecting AD and MCI among this at-risk population.

PMID: 31389185 [PubMed - indexed for MEDLINE]

Safety and Effectiveness of CyPass Supraciliary Micro-Stent in Primary Open-Angle Glaucoma: 5-Year Results from the COMPASS XT Study.

Recent Research Articles from UNTHSC - Sat, 03/28/2020 - 07:30
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Safety and Effectiveness of CyPass Supraciliary Micro-Stent in Primary Open-Angle Glaucoma: 5-Year Results from the COMPASS XT Study.

Am J Ophthalmol. 2019 12;208:219-225

Authors: Reiss G, Clifford B, Vold S, He J, Hamilton C, Dickerson J, Lane S

Abstract
PURPOSE: To characterize the long-term (up to 5 years) safety and effectiveness of the supraciliary Micro-Stent (Alcon) implanted at the time of phacoemulsification in eyes with coexisting open-angle glaucoma (OAG) and visually significant cataract.
DESIGN: Three-year safety extension of a 2-year randomized clinical trial.
METHODS: Patients from the multicenter Study of an Implantable Device for Lowering Intraocular Pressure in Glaucoma Patients Undergoing Cataract Surgery (COMPASS) trial who underwent Micro-Stent implantation plus phacoemulsification (n = 215) or phacoemulsification alone (n = 67) were evaluated 36, 48, and 60 months postoperatively. The primary outcome measurement was the occurrence of sight-threatening ocular adverse events. Evaluations at each time point included best-corrected visual acuity (BCVA), anterior and posterior segment examinations, tonometry, gonioscopy, pachymetry, perimetry, specular microscopy, and assessment of adverse events.
RESULTS: Three sight-threatening ocular adverse events occurred, 2 in the Micro-Stent group and 1 in the control group, but none of these events was related to the Micro-Stent device. Ocular adverse events were of similar frequencies in both groups, the most common of which were BCVA loss of ≥2 lines compared with best BCVA in COMPASS and worsening of visual field mean defect (VFMD) ≥2.5 dB compared with month 24. Changes in mean BCVA from baseline, clinical examinations, pachymetry, and VFMD were similar in the 2 groups. At 60 months, a higher proportion of subjects in the Micro-Stent group (46%; 95% confidence interval [CI], 38.9%-53.2%) than in the control group (32.1%; 95% CI 19.9%-46.3%) were able to achieve a reduction of ≥20% in intraocular pressure without using hypotensive medication.
CONCLUSIONS: Few sight-threatening serious ocular adverse events occurred following Micro-Stent implantation, and clinical evidence of corneal decompensation was minimal.

PMID: 31377287 [PubMed - indexed for MEDLINE]

Corneal Endothelial Cell Loss and Morphometric Changes 5 Years after Phacoemulsification with or without CyPass Micro-Stent.

Recent Research Articles from UNTHSC - Sat, 03/28/2020 - 07:30
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Corneal Endothelial Cell Loss and Morphometric Changes 5 Years after Phacoemulsification with or without CyPass Micro-Stent.

Am J Ophthalmol. 2019 12;208:211-218

Authors: Lass JH, Benetz BA, He J, Hamilton C, Von Tress M, Dickerson J, Lane S

Abstract
PURPOSE: To characterize long-term changes in corneal endothelial cells after phacoemulsification with or without supraciliary Micro-Stent (Alcon) implantation in eyes with open-angle glaucoma (OAG) and visually significant cataract.
DESIGN: Three-year safety extension of a 2-year randomized clinical trial.
METHODS: Patients from the multicenter Study of an Implantable Device for Lowering Intraocular Pressure in Glaucoma Patients Undergoing Cataract Surgery (COMPASS) trial who underwent Micro-Stent implantation plus phacoemulsification (n = 282) or phacoemulsification alone (n = 67) were analyzed post hoc. Specular microscopy was used to assess endothelial cell loss (ECL), including changes from baseline in endothelial cell density (ECD), coefficient of variation, and percentage of hexagonal cells.
RESULTS: Preoperative ECDs in the microstent group (2,432.6 cells/mm2 [95% confidence interval [CI], 2,382.8-2,482.4 cells/mm2]) were similar to those in the control group (2,434.5 cells/mm2 [95% CI, 2,356.5-2,512.4 cells/mm2]) groups. ECL at months 48 and 60 was greater in the Micro-Stent group than in the control group. At month 60, the mean percent of changes in ECD was -20.4% (95% CI, -23.5% to -17.5%) in the Micro-Stent group and -10.1% (95% CI, -13.9% to -6.3%) in the control group. No statistically significant between-group changes from baseline in cellular morphology were observed. Nine adverse events were possibly related to ECL, including 3 eyes with transient focal corneal edema and 4 eyes that required Micro-Stent trimming due to protrusion.
CONCLUSIONS: In eyes with OAG, ECL after phacoemulsification is acute and stabilizes after 3 months, whereas ECL after phacoemulsification plus Micro-Stent implantation proceeds for at least 5 years. Clinical findings associated with ECL in these eyes were uncommon (3.3% of implanted eyes), suggesting that ECL is generally a subclinical phenomenon.

PMID: 31377278 [PubMed - indexed for MEDLINE]

Evaluation of pharmacy-based telephone interventions on medication pick-up rates: a retrospective, quality improvement study at charity outpatient clinics.

Recent Research Articles from UNTHSC - Sat, 03/28/2020 - 07:30
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Evaluation of pharmacy-based telephone interventions on medication pick-up rates: a retrospective, quality improvement study at charity outpatient clinics.

Int J Pharm Pract. 2019 Dec;27(6):510-519

Authors: Tatachar A, Cole LC, Nguyen HL, Heinrich K

Abstract
OBJECTIVES: To evaluate a live telephonic outreach intervention made by clinical pharmacists and clinical pharmacy technicians on medication pick-up rates.
METHODS: A retrospective, quality improvement study conducted at six outpatient charity clinics in Dallas-Fort Worth area between 1 January 2017 and 31 July 2017. A live telephonic call was made by a pharmacy team member if the patient did not pick-up at least one prescription item. Patients may receive more than one call if they did not pick-up medication(s) more than once during the study period. A live telephonic call resulted in three categories: contacted, left a voice message and unable to contact. Medication pick-up rates were obtained from a pharmacy claims database.
KEY FINDINGS: The study population included 1726 individual patients who failed to pick-up at least one medication from Baylor Scott & White Health pharmacy. A total of 2551 live telephonic calls were made for the study population. A total of 1175 live telephonic calls (46.1%, n = 2551) resulted in a patient picking up medication(s). Results from the generalized estimating equation logistic regression models showed that patients who received a voice message (OR: 1.37; 95% CI: 1.05 to 1.80; P < 0.021) or was contacted (OR: 1.99; 95% CI: 1.54 to 2.60; P < 0.001) were more likely to pick-up their medications as compared to the 'unable to contact' group.
CONCLUSIONS: Telephonic interventions from the pharmacy team can serve as a successful means to increase medication pick-up rates among charity clinic patients.

PMID: 31287202 [PubMed - indexed for MEDLINE]

Climatic adaptation in human inferior nasal turbinate morphology: Evidence from Arctic and equatorial populations.

Recent Research Articles from UNTHSC - Sat, 03/28/2020 - 07:30
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Climatic adaptation in human inferior nasal turbinate morphology: Evidence from Arctic and equatorial populations.

Am J Phys Anthropol. 2019 07;169(3):498-512

Authors: Marks TN, Maddux SD, Butaric LN, Franciscus RG

Abstract
OBJECTIVES: The nasal turbinates directly influence the overall size, shape, and surface area of the nasal passages, and thus contribute to intranasal heat and moisture exchange. However, unlike the encapsulating walls of the nasal cavity, ecogeographic variation in nasal turbinate morphology among humans has not yet been established. Here we investigate variation in inferior nasal turbinate morphology in two populations from climatically extreme environments.
MATERIALS AND METHODS: Twenty-three linear measurements of the inferior turbinate, nasal cavity walls, and airway passages were collected from CT scans of indigenous modern human crania from Equatorial Africa (n = 35) and the Arctic Circle (n = 35). MANOVA and ANCOVA were employed to test for predicted regional and sex differences in morphology between the samples.
RESULTS: Significant morphological differences were identified between the two regional samples, with no evidence of significant sexual dimorphism or region-sex interaction effect. Individuals from the Arctic Circle possessed superoinferiorly and mediolaterally larger inferior turbinates compared to Equatorial Africans. In conjunction with the surrounding nasal cavity walls, these differences in turbinate morphology produced airway dimensions that were both consistent with functional expectations and more regionally distinct than either skeletal component independently.
CONCLUSION: This study documents the existence of ecogeographic variation in human nasal turbinate morphology reflecting climate-mediated evolutionary demands on intranasal heat and moisture exchange. Humans adapted to cold-dry environments exhibit turbinate morphologies that enhance contact between respired air and nasal mucosa to facilitate respiratory air conditioning. Conversely, humans adapted to hot-humid environments exhibit turbinate morphologies that minimize air-to-mucosa contact, likely to minimize airflow resistance and/or facilitate expiratory heat-shedding.

PMID: 30993687 [PubMed - indexed for MEDLINE]

Differences between pharmacists' perception of counseling and practice in the era of prescription drug misuse.

Recent Research Articles from UNTHSC - Wed, 03/25/2020 - 06:24
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Differences between pharmacists' perception of counseling and practice in the era of prescription drug misuse.

Pharm Pract (Granada). 2020 Jan-Mar;18(1):1682

Authors: Thornton JD, Anyanwu P, Tata V, Al Rawwad T, Fleming ML

Abstract
Objective: This study was conducted to assess pharmacists' practices when counseling patients on their prescription medications, and their preferences for training.
Methods: Five focus group discussions of community pharmacists (n=45, with seven to eleven participants in each group) were conducted in a major metropolitan city in the southern United States. Participants were recruited via email using a list of community pharmacists provided by the Texas State Board of Pharmacy. All focus group discussions were structured using a moderator guide consisting of both discrete and open-ended questions. Qualitative analysis software was used to analyze the data with a thematic analysis approach.
Results: The participants in this study had a high self-efficacy regarding their ability to counsel on both new and opioid prescriptions. Many pharmacists experienced the same barriers to counseling and agreed on the components of counseling. However, the themes that emerged showed that the participants exhibited only a partial understanding of the components of counseling. The themes that emerged in the thematic analysis were perceived confidence and discordant counseling practices, inadequate infrastructure, lack of comprehensive counseling, inconsistent use of the Prescription Drug Monitoring Program (PDMP), and pharmacists' desired training/assistance.
Conclusions: Community pharmacists are in a unique position to help combat the opioid crisis; however, there has been very little research on the pharmacist-patient interaction in this context. With policy changes, such as the PDMP mandate, going into effect across the country, it is important to capitalize on the potential community pharmacists have in ameliorating the opioid crisis in the United States.

PMID: 32206140 [PubMed]

Global research initiatives to understand the prescription drug misuse epidemic and ways to monitor and intervene.

Recent Research Articles from UNTHSC - Tue, 03/24/2020 - 06:11
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Global research initiatives to understand the prescription drug misuse epidemic and ways to monitor and intervene.

Res Social Adm Pharm. 2019 08;15(8):907-909

Authors: Rickles NM, Fleming ML, Björnsdottir I

PMID: 31151917 [PubMed - indexed for MEDLINE]

Using the theory of planned behavior to investigate community pharmacists' beliefs regarding engaging patients about prescription drug misuse.

Recent Research Articles from UNTHSC - Tue, 03/24/2020 - 06:11
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Using the theory of planned behavior to investigate community pharmacists' beliefs regarding engaging patients about prescription drug misuse.

Res Social Adm Pharm. 2019 08;15(8):992-999

Authors: Fleming ML, Bapat SS, Varisco TJ

Abstract
INTRODUCTION: Opioid misuse causes over 50,000 deaths in America each year. Prescription drug monitoring program (PDMP) databases serve as a useful decision analysis tool in managing patients with known or potential opioid use disorder (OUD). To date, however, little research has sought to determine how pharmacists use PDMPs to engage patients with potential OUD.
OBJECTIVES: To elicit modal salient beliefs of community pharmacists regarding their willingness to engage patients (i.e., provide interventional counseling) with suspected controlled substance misuse as identified from reviewing PDMP data.
METHODS: Focus groups were conducted among Texas community pharmacists using the theory of planned behavior as a theoretical framework. Open-ended questions were used to capture behavioral beliefs, normative beliefs and control beliefs associated with pharmacists' engagement. Qualitative analysis using ATLAS.ti software was conducted to identify modal salient beliefs elicited by at least 20% of the study sample.
RESULTS: A total of 31 community pharmacists participated. Fifteen behavioral beliefs, thirteen normative beliefs and eleven control beliefs were identified as modal salient beliefs. The most prevalent behavioral belief was the disadvantage associated with patient confrontations. Pharmacists also believed that engaging patients may cause loss of customers/business but may help patients receive appropriate counseling. When asked about their normative beliefs, pharmacists identified regulatory agencies (e.g., pharmacy boards, law enforcement) and family/friends of patients as groups of individuals who influence their willingness to refer. Time required for counseling was found to be the most commonly cited control belief.
CONCLUSION: The results illustrate some of the challenges faced by community pharmacists when considering engagement of patients with misuse of prescription opioids. Addressing these barriers to patient engagement is critical to increasing pharmacists' willingness to engage patients with potential OUD.

PMID: 30442574 [PubMed - indexed for MEDLINE]

Coronaridine congeners potentiate GABAA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner.

Recent Research Articles from UNTHSC - Sat, 03/21/2020 - 05:30
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Coronaridine congeners potentiate GABAA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner.

Prog Neuropsychopharmacol Biol Psychiatry. 2020 Mar 16;:109930

Authors: Arias HR, do Rego JL, do Reg JC, Chen Z, Anouar Y, Scholze P, Gonzales EB, Huang R, Chagraoui A

Abstract
To determine whether (+)-catharanthine induces sedative- or anxiolytic/anxiogenic-like activity in male mice, proper animal paradigms were used. The results showed that (+)-catharanthine induces sedative-like activity in the 63-72 mg/Kg dose range in a flumazenil-insensitive manner, but neither this effect nor anxiolytic/anxiogenic-like activity was observed at lower doses. To determine the underlying molecular mechanism of the sedative-like activity, electrophysiological and radioligand binding experiments were performed with (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC] on GABAA (GABAARs) and glycine receptors (GlyRs). Coronaridine congeners both activated and potentiated a variety of human (h) GABAARs, except hρ1. (+)-Catharanthine-induced potentiation followed this receptor selectivity (EC50's in μM): hα1β2 (4.6 ± 0.8) > hα2β2γ2 (12.6 ± 3.8) ~ hα1β2γ2 (14.4 ± 4.6) indicating that both α1 and α2 are equally important, whereas γ2 is not necessary. (+)-Catharanthine was >2-fold more potent and efficient than (±)-18-MC at hα1β2γ2. (+)-Catharanthine also potentiated, whereas (±)-18-MC inhibited, hα1 GlyRs with very low potency. Additional [3H]-flunitrazepam competition binding experiments using rat cerebellum membranes clearly demonstrated that these ligands do not bind to the benzodiazepine site. This is supported by the observed activity at hα1β2 (lacking the BDZ site) and similar effects between α1- and α2-containing GABAARs. Our study shows, for the first time, that (+)-catharanthine induced sedative-like effects in mice, and coronaridine congeners potentiated human α1β2γ2, α1β2, and hα2β2γ2, but not ρ1, GABAARs, both in a benzodiazepine-insensitive fashion, whereas only (+)-catharanthine slightly potentiated GlyRs.

PMID: 32194202 [PubMed - as supplied by publisher]

Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV.

Recent Research Articles from UNTHSC - Sat, 03/21/2020 - 05:30
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Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV.

J Neurovirol. 2020 Mar 19;:

Authors: Swanta N, Aryal S, Nejtek V, Shenoy S, Ghorpade A, Borgmann K

Abstract
Inflammation in people living with HIV (PLWH) correlates with severity of HIV-associated neurocognitive disorders. The objective of this study is to identify blood-based markers of neurocognitive function in a demographic balanced cohort of PLWH. Seven neurocognitive domains were evaluated in 121 seropositive Black/African American, Non-Hispanic White, and White Hispanic men and women using computerized assessments. Associations among standardized neurocognitive function and HIV-related parameters, relevant sociodemographic variables, and inflammation-associated cytokines measured in plasma and cellular supernatants were examined using multivariate and univariate regression models. Outlier and covariate analyses were used to identify and normalize for education level, CD4 T cell count, viral load, CNS and drug abuse comorbidities, which could influence biomarker and neurocognitive function associations. Plasma levels of chemokine (C-C motif) ligand (CCL) 8 significantly associated with memory, complex attention, cognitive flexibility, psychomotor speed, executive function, and processing speed. Plasma tissue inhibitor of metalloproteinases 1 associated with the aforementioned domains except memory and processing speed. In addition, plasma interleukin-23 significantly associated with processing speed and executive function. Analysis of peripheral blood cell culture supernatants revealed no significant markers for neurocognitive function. In this cohort, CD4 T cell count and education level also significantly associated with neurocognitive function. All identified inflammatory biomarkers demonstrated a negative correlation to neurocognitive function. These cytokines have known connections to HIV pathophysiology and are potential biomarkers for neurocognitive function in PLWH with promising clinical applications.

PMID: 32193795 [PubMed - as supplied by publisher]

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