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Adherence and Viral Suppression Among Participants of the Patient-centered Human Immunodeficiency Virus (HIV) Care Model Project: A Collaboration Between Community-based Pharmacists and HIV Clinical Providers.

Recent Research Articles from UNTHSC - Thu, 01/07/2021 - 10:33
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Adherence and Viral Suppression Among Participants of the Patient-centered Human Immunodeficiency Virus (HIV) Care Model Project: A Collaboration Between Community-based Pharmacists and HIV Clinical Providers.

Clin Infect Dis. 2020 02 14;70(5):789-797

Authors: Byrd KK, Hou JG, Bush T, Hazen R, Kirkham H, Delpino A, Weidle PJ, Shankle MD, Camp NM, Suzuki S, Clay PG, Patient-centered HIV Care Model Team

Abstract
BACKGROUND: Human immunodeficiency virus (HIV) viral suppression (VS) decreases morbidity, mortality, and transmission risk.
METHODS: The Patient-centered HIV Care Model integrated community-based pharmacists with HIV medical providers and required them to share patient clinical information, identify therapy-related problems, and develop therapy-related action plans.Proportions adherent to antiretroviral therapy (proportion of days covered [PDC] ≥90%) and virally suppressed (HIV RNA <200 copies/mL), before and after model implementation, were compared. Factors associated with postimplementation VS were determined using multivariable logistic regression; participant demographics, baseline viral load, and PDC were explanatory variables. PDC was modified to account for time to last viral load in the year postimplementation, and stratified as <50%, 50% to <80%, 80% to <90%, and ≥90%.
RESULTS: The 765 enrolled participants were 43% non-Hispanic black, 73% male, with a median age of 48 years; 421 and 649 were included in the adherence and VS analyses, respectively. Overall, proportions adherent to therapy remained unchanged. However, VS improved a relative 15% (75% to 86%, P < .001). Higher PDC (adjusted odds ratio [AOR], 1.74 per 1-level increase in PDC category [95% confidence interval {CI}, 1.30-2.34]) and baseline VS (AOR, 7.69 [95% CI, 3.96-15.7]) were associated with postimplementation VS. Although non-Hispanic black persons (AOR, 0.29 [95% CI, .12-.62]) had lower odds of suppression, VS improved a relative 23% (63% to 78%, P < .001).
CONCLUSIONS: Integrated care models between community-based pharmacists and primary medical providers may identify and address HIV therapy-related problems and improve VS among persons with HIV.

PMID: 30953062 [PubMed - indexed for MEDLINE]

Comparison of two escalated enoxaparin dosing regimens for venous thromboembolism prophylaxis in obese hospitalized patients.

Recent Research Articles from UNTHSC - Wed, 01/06/2021 - 06:30
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Comparison of two escalated enoxaparin dosing regimens for venous thromboembolism prophylaxis in obese hospitalized patients.

J Thromb Thrombolysis. 2021 Jan 05;:

Authors: Gibson CM, Hall C, Davis S, Schillig JM

Abstract
Standard fixed-dose enoxaparin dosing regimens may not provide adequate prophylaxis against venous thromboembolism among obese hospitalized patients. While several escalated doses have been shown to result in more frequent attainment of target anti-factor Xa levels than standard doses, few studies compare escalated doses to each other. In this prospective, multi-center trial, enoxaparin 0.5 mg/kg daily (weight-based dosing) and enoxaparin 40 mg twice daily were compared to determine if either dose resulted in more frequent attainment of anti-factor Xa levels within the goal range of 0.2-0.5 IU/mL. Eighty patients with a BMI ≥ 40 kg/m2 were enrolled. There was no difference in the percent of patients achieving goal anti-factor Xa levels (72.5% vs. 70.0%, respectively; p = 0.72). Patients were more likely to attain anti-factor Xa levels below goal range than above. No bleeding or thrombotic events occurred. Either weight-based or twice-daily escalated enoxaparin dosing regimens appear effective at achieving target anti-factor Xa levels among hospitalized patients, and no safety events were noted. Future studies are needed to determine the clinical significance of this result.

PMID: 33400099 [PubMed - as supplied by publisher]

A novel approach for visualization and localization of small amounts of DNA on swabs to improve DNA collection and recovery process.

Recent Research Articles from UNTHSC - Tue, 01/05/2021 - 06:07
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A novel approach for visualization and localization of small amounts of DNA on swabs to improve DNA collection and recovery process.

Analyst. 2021 Jan 04;:

Authors: Kitchner E, Chavez J, Ceresa L, Bus MM, Budowle B, Gryczynski Z

Abstract
In this report, a simple and practical procedure is proposed for DNA localization on a solid matrix e.g., a collection swab. The approach is straightforward and employs spectrum decomposition using a model DNA intercalator Ethidium Bromide (EtBr). The proposed approach can detect picograms of DNA in solution and nanograms of DNA on solid surfaces (swabs) without the need for PCR amplification. The proposed technology offers the possibility for developing an inexpensive, sensitive, rapid, and practical method for localizing and recovering DNA deposited on collection swabs during routine DNA screening. Improved detection of low DNA concentrations is needed and, if feasible, will allow for better decision making in clinical medicine, biological and environmental research, and human identification in forensic investigations.

PMID: 33393553 [PubMed - as supplied by publisher]

Effect of lidocaine iontophoresis combined with exercise intervention on gait and spasticity in children with spastic hemiplegic cerebral palsy: A randomized controlled trial.

Recent Research Articles from UNTHSC - Tue, 01/05/2021 - 06:07
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Effect of lidocaine iontophoresis combined with exercise intervention on gait and spasticity in children with spastic hemiplegic cerebral palsy: A randomized controlled trial.

NeuroRehabilitation. 2020;47(2):133-141

Authors: Hegazy FA, Aboelnasr EA, Salem YT

Abstract
BACKGROUND: Gait deviations and spasticity are common impairments seen in children with cerebral palsy (CP) and may interfere with functional performance and effective walking pattern. Lidocaine iontophoresis is effective for reducing muscle spasticity in adults.
PURPOSE: To investigate the effect of lidocaine epinephrine iontophoresis combined with exercises on gait and spasticity in children with spastic hemiplegic cerebral palsy (HCP).
METHODS: Thirty children with spastic HCP aged 4-6 (5.20±0.32) years were randomly assigned to the experimental group (n = 15) and control group (n = 15). Children in both groups received one hour of exercises, three times a week for three months. Children in the experimental group received 2% lidocaine iontophoresis immediately before the exercises. The lidocaine iontophoresis was delivered for 20 minutes (1mA/min). Spatio-temporal gait parameters were assessed within one week before and after the intervention using 3D motion analysis. Surface electromyography was used to assess muscle tone using H/M ratio of the soleus muscle. ANOVA was used to investigate the differences between experimental and control groups. Statistical significance was set at P value less than 0.05.
RESULTS: There was no difference between groups at baseline. Post-intervention, the experimental group showed significant improvements when compared to the control group for gait speed (p = 0.03), stride length (p = 0.04), cadence (p = 0.0001), cycle time (p = 0.0001), and H/M ratio (p = 0.02).
CONCLUSION: Lidocaine iontophoresis combined with exercises was effective in improving gait spatiotemporal parameters and reducing spasticity in children with CP.

PMID: 32716326 [PubMed - indexed for MEDLINE]

Instructional and Assessment Redesign of a Sterile Compounding Course Using Immersive Simulation.

Recent Research Articles from UNTHSC - Tue, 01/05/2021 - 06:07
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Instructional and Assessment Redesign of a Sterile Compounding Course Using Immersive Simulation.

Am J Pharm Educ. 2020 02;84(2):7473

Authors: Monestime S, Thomas D, Hooper CD, Day T, Suzuki S, Martin RD

Abstract
Objective. To revise a traditional sterile compounding course to include content, competencies, and immersive simulations relevant to the current practice of sterile compounding pharmacy. Methods. Faculty and staff at the University of North Texas System College of Pharmacy made significant revisions to an existing sterile compounding course. Instruction was provided in didactic and laboratory sessions and delivered in three modules: fundamental skills, integration of skills and knowledge, and exceptions and specialty topics. Integration laboratory sessions consisted primarily of repetitive but increasingly difficult simulations that included both technician and pharmacist activities. Assessment methods included checkpoint assessments, a mock objective structured clinical examination (OSCE), a written examination, and a final comprehensive OSCE. Effectiveness of the course redesign was assessed by comparing student performance on assessments, overall course performance, and student perceptions extracted from the student course evaluation. Results. Of the 364 students enrolled in the sterile compounding course across four terms, 156 were in the pre-implementation cohort (cohort 1) and 208 were in the post-implementation cohort (cohort 2). Two hundred twenty-eight students completed the course evaluation. Course evaluations significantly demonstrated students' improved perceptions related to seven of 11 survey elements, most notably, critical thinking, integration of concepts, and students feeling challenged. Student performance on laboratory summative assessments also improved. However, written examination scores did not change. Conclusion. This novel sterile compounding course provided a practice-oriented blueprint for instruction and assessment of sterile compounding.

PMID: 32226068 [PubMed - indexed for MEDLINE]

Effects of mesencephalic astrocyte-derived neurotrophic factor on cerebral angiogenesis in a rat model of cerebral ischemia.

Recent Research Articles from UNTHSC - Tue, 01/05/2021 - 06:07
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Effects of mesencephalic astrocyte-derived neurotrophic factor on cerebral angiogenesis in a rat model of cerebral ischemia.

Neurosci Lett. 2020 01 10;715:134657

Authors: Gao B, Deng J, Zhang X, Sun H, Jia G, Li J, Zhang K, Wan C, Wang L, Yan LJ, Cai Z, Ma J

Abstract
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum stress-related protein that exhibits neuroprotective effects. Recent studies have shown that MANF promotes poststroke functional recovery in rats. However, the underlying mechanisms have not yet been fully understood. Here, we examined the effects of MANF on cerebral angiogenesis in a permanent middle cerebral artery occlusion model in rats. Recombinant human MANF was administered intracerebroventricularly 24 h after stroke. We performed neurobehavioral tests and assessed microvessel density, functional microvessels, and regional cerebral blood flow (rCBF), as well as detected angiogenic factors in the peri-infarct cerebral cortex. Results showed that MANF ameliorated neurobehavioral scores, promoted rCBF, upregulated the expression of CD34, as well as the total vessel surface area and the number of microvessel branch points, and activated the vascular endothelial growth factor (VEGF) pathway. In conclusion, our findings provide insight into the mechanisms of MANF in promoting functional recovery from ischemic stroke. Our results suggest that MANF improves neurobehavioral recovery from cerebral ischemic injury, and that this effect is mediated partly by its proangiogenic effects and augmentation of rCBF, which are possibly associated with VEGF.

PMID: 31785307 [PubMed - indexed for MEDLINE]

A genome-wide association study of tramadol metabolism from post-mortem samples.

Recent Research Articles from UNTHSC - Tue, 01/05/2021 - 06:07
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A genome-wide association study of tramadol metabolism from post-mortem samples.

Pharmacogenomics J. 2020 02;20(1):94-103

Authors: Wendt FR, Rahikainen AL, King JL, Sajantila A, Budowle B

Abstract
Phase I tramadol metabolism requires cytochrome p450 family 2, subfamily D, polypeptide 6 (CYP2D6) to form O-desmethyltramadol (M1). CYP2D6 genetic variants may infer metabolizer phenotype; however, drug ADME (absorption, distribution, metabolism, and excretion) and response depend on protein pathway(s), not CYP2D6 alone. There is a paucity of data regarding the contribution of trans-acting proteins to idiosyncratic phenotypes following drug exposure. A genome-wide association study identified five markers (rs79983226/kgp11274252, rs9384825, rs62435418/kgp10370907, rs72732317/kgp3743668, and rs184199168/exm1592932) associated with the conversion of tramadol to M1 (M1:T). These SNPs reside within five genes previously implicated with adverse reactions. Analysis of accompanying toxicological meta-data revealed a significant positive linear relationship between M1:T and degree of sample polypharmacy. Taken together, these data identify candidate loci for potential clinical inferences of phenotype following exposure to tramadol and highlight sample polypharmacy as a possible diagnostic covariate in post-mortem genetic studies.

PMID: 30971809 [PubMed - indexed for MEDLINE]

Exploring college students' sexual and reproductive health literacy.

Recent Research Articles from UNTHSC - Tue, 01/05/2021 - 06:07
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Exploring college students' sexual and reproductive health literacy.

J Am Coll Health. 2020 01;68(1):79-88

Authors: Vamos CA, Thompson EL, Logan RG, Griner SB, Perrin KM, Merrell LK, Daley EM

Abstract
Objective: To assess college students' sexual and reproductive health (SRH) literacy experiences, specific to contraception use and STI prevention. Participants: In Spring 2015, participants (n = 43) from a large institution participated in six focus groups (two male and four females groups). Methods: Focus groups were guided by the health literacy domains (access; understand; appraise; apply); data were analyzed in MaxQDA using the constant comparative method. Results: The Internet was the most commonly accessed source for SRH information. Participants discussed facilitators (eg, use of visuals) and barriers (eg, medical jargon) to understanding information; and personal lifestyle, advice from family/friends, symptoms, and sexual partners as appraisal factors. Participants applied information by communicating with friends/providers and seeking healthcare. However, findings were not linear nor mutually exclusive, representing the interaction of health literacy skills. Conclusion: Findings suggest that a patient-centered intervention capitalizing on technology and trusted individuals (providers/peer educators) may facilitate college students' SRH literacy.

PMID: 30388946 [PubMed - indexed for MEDLINE]

Colorectal Cancer: An Emphasis on Factors Influencing Racial/Ethnic Disparities.

Recent Research Articles from UNTHSC - Mon, 01/04/2021 - 05:16
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Colorectal Cancer: An Emphasis on Factors Influencing Racial/Ethnic Disparities.

Crit Rev Oncog. 2020;25(2):151-160

Authors: Sharma I, Kim S, Sridhar S, Basha R

Abstract
Current statistics related to cancer incidence and cancer-related death rates clearly show that specific racial/ethnic minorities are more likely to be diagnosed and/or die with cancer. Colorectal cancer (CRC) is one of the leading causes of cancer deaths in the United States and it disproportionately affects the non-Hispanic Black or African American (AA) population. When compared to the non-Hispanic White (nHW) population, incidence and death rates in AAs are 28% and 60% higher, respectively. Hispanics have an overall lower CRC incidence rate than nHWs (Hispanics: 35.5 per 100,000 population; nHWs: 40.2 per 100,000 population), but their incidence continues to rise, unlike nHWs, who are experiencing a decline. This disparity between Hispanics and nHWs is further highlighted in the younger Hispanic population. While the cause of the disparities is associated with CRC-related genetic and environmental factors, the role of specific genes/mutations in each population are still not fully unraveled. However, because CRC is a slowly progressing disease, routine screening and/or early intervention are key to achieving better outcomes in CRC patients and ultimately in closing the disparity gap among different populations. This review discusses the major factors influencing the disparities in CRC and also focuses on factors such as treatment response, family history, and screening that potentially contribute to the racial/ethnic disparities in CRC.

PMID: 33389864 [PubMed - as supplied by publisher]

Cone of economy classification: evolution, concept of stability, severity level, and correlation to patient-reported outcome scores.

Recent Research Articles from UNTHSC - Mon, 01/04/2021 - 05:16
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Cone of economy classification: evolution, concept of stability, severity level, and correlation to patient-reported outcome scores.

Eur Spine J. 2021 Jan 03;:

Authors: Haddas R, Sambhariya V, Kosztowski T, Block A, Lieberman I

Abstract
STUDY DESIGN: A prospective cohort study OBJECTIVE: To determine a classification system for cone of economy (CoE) measurements that defines clinically significant changes in altered balance and to assess if the CoE measurements directly impacts patients reported outcome measures (PROMs). Preoperative functional data is a crucial component of determining patient disability and prognosis. The CoE has been theorized to be the foundation of biomechanical changes that leads to increased energy expenditure and disability in spine patients. PROMs have been developed to quantify the level of debilitation in spine patients but have various limitations.
METHODS: A total of 423 symptomatic adult patients with spine pathology completed a series of PROMs preoperatively including VAS, ODI, Tampa Scale for Kinesiophobia (TSK), Fear and Avoidance Beliefs Questionnaire (FABQ), and Demoralization (DS). Functional balance was tested in this group using a full-body reflective marker set to measure head and center of mass (CoM) sway.
RESULTS: PROMs scores were correlated with the magnitude of the CoE measurements. Patients were separated by the following proposed classification: CoM coronal sway > 1.5 cm, CoM sagittal sway > 3.0 cm, CoM total sway > 30.0 cm, head coronal sway > 3.0 cm, head sagittal sway > 6.0 cm, and head total sway > 60.0 cm. Significant differences were noted in the ODI (< 0.001), FABQ physical activity (< 0.001-0.009), DS (< 0.001-0.023), and TSK (< 0.001-0.032) across almost all planes of motion for both CoM and head sway. The ODI was most sensitive to the difference between groups across CoM and head sway planes with a mean ODI of 47.5-49.5 (p < 0.001) in the severe group versus 36.6-39.3 (p < 0.001) in the moderate group.
CONCLUSIONS: By classifying CoE measurements by the cutoffs proposed, clinically significant alterations in balance can be quantified. Furthermore, this study demonstrates that across spinal pathology, higher magnitude CoE and range of sway measurements correlate with worsening PROMs. The Haddas' CoE classification system in this study helps to identify patients that may benefit from surgery and guide their postoperative prognosis.

PMID: 33389136 [PubMed - as supplied by publisher]

COVID-19 in SOT vs. non-SOT.

Recent Research Articles from UNTHSC - Sun, 01/03/2021 - 06:46
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COVID-19 in SOT vs. non-SOT.

Am J Transplant. 2021 Jan 02;:

Authors: Allam SR, Fisher AM, Schlauch D

Abstract
We read with great interest "Inpatient COVID-19 Outcomes in Solid Organ Transplant Recipients Compared to Non-Solid Organ Transplant Patients: A Retrospective Cohort" by Avery et al 1 . Authors compared outcomes of 45 solid organ transplant recipients with 2427 non-transplant patients admitted with COVID-19 at Johns Hopkins medical system with finding of no differences in outcomes between the groups and concluded that SOT status does not portend adverse outcome from COVID-19.

PMID: 33387393 [PubMed - as supplied by publisher]

Shared Features or Co-occurrence? Evaluating Symptoms of Developmental Coordination Disorder in Children and Adolescents with Autism Spectrum Disorder.

Recent Research Articles from UNTHSC - Sun, 01/03/2021 - 06:46
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Shared Features or Co-occurrence? Evaluating Symptoms of Developmental Coordination Disorder in Children and Adolescents with Autism Spectrum Disorder.

J Autism Dev Disord. 2021 Jan 02;:

Authors: Miller HL, Sherrod GM, Mauk JE, Fears NE, Hynan LS, Tamplain PM

Abstract
Motor differences are common in Autism Spectrum Disorder (ASD), but rarely evaluated against diagnostic criteria for Developmental Coordination Disorder (DCD). We aimed to determine whether motor problems in ASD represent the possible co-occurrence of DCD. We retrospectively reviewed standardized assessments and parent-reports to evaluate motor ability in 43 individuals with ASD against diagnostic criteria for DCD, and compared to 18 individuals with DCD. Over 97% of cases in the ASD group scored below the 16th percentile in motor ability, with most below the 5th percentile. Over 90% of cases in the ASD group met criteria for co-occurring DCD. Motor challenges are a clinically-significant problem in ASD; systematically assessing the prevalence of co-occurring ASD + DCD is necessary to optimize assessment and intervention.

PMID: 33387238 [PubMed - as supplied by publisher]

HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol.

Recent Research Articles from UNTHSC - Sat, 01/02/2021 - 08:38
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HOXA5 Expression Is Elevated in Breast Cancer and Is Transcriptionally Regulated by Estradiol.

Front Genet. 2020;11:592436

Authors: Hussain I, Deb P, Chini A, Obaid M, Bhan A, Ansari KI, Mishra BP, Bobzean SA, Udden SMN, Alluri PG, Das HK, Brothers RM, Perrotti LI, Mandal SS

Abstract
HOXA5 is a homeobox-containing gene associated with the development of the lung, gastrointestinal tract, and vertebrae. Here, we investigate potential roles and the gene regulatory mechanism in HOXA5 in breast cancer cells. Our studies demonstrate that HOXA5 expression is elevated in breast cancer tissues and in estrogen receptor (ER)-positive breast cancer cells. HOXA5 expression is critical for breast cancer cell viability. Biochemical studies show that estradiol (E2) regulates HOXA5 gene expression in cultured breast cancer cells in vitro. HOXA5 expression is also upregulated in vivo in the mammary tissues of ovariectomized female rats. E2-induced HOXA5 expression is coordinated by ERs. Knockdown of either ERα or ERβ downregulated E2-induced HOXA5 expression. Additionally, ER co-regulators, including CBP/p300 (histone acetylases) and MLL-histone methylases (MLL2, MLL3), histone acetylation-, and H3K4 trimethylation levels are enriched at the HOXA5 promoter in present E2. In summary, our studies demonstrate that HOXA5 is overexpressed in breast cancer and is transcriptionally regulated via estradiol in breast cancer cells.

PMID: 33384715 [PubMed]

Astrocyte HIV-1 Tat Differentially Modulates Behavior and Brain MMP/TIMP Balance During Short and Prolonged Induction in Transgenic Mice.

Recent Research Articles from UNTHSC - Sat, 01/02/2021 - 08:38
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Astrocyte HIV-1 Tat Differentially Modulates Behavior and Brain MMP/TIMP Balance During Short and Prolonged Induction in Transgenic Mice.

Front Neurol. 2020;11:593188

Authors: Joshi CR, Stacy S, Sumien N, Ghorpade A, Borgmann K

Abstract
Despite effective antiretroviral therapy (ART), mild forms of HIV-associated neurocognitive disorders (HAND) continue to afflict approximately half of all people living with HIV (PLWH). As PLWH age, HIV-associated inflammation perturbs the balance between brain matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs), likely contributing to neuropathogenesis. The MMP/TIMP balance is associated with cognition, learning, and memory, with TIMPs eliciting neuroprotective effects. Dysregulation of the MMP/TIMP balance was evident in the brains of PLWH where levels of TIMP-1, the inducible family member, were significantly lower than non-infected controls, and MMPs were elevated. Here, we evaluated the MMP/TIMP levels in the doxycycline (DOX)-induced glial fibrillary acidic protein promoter-driven HIV-1 transactivator of transcription (Tat) transgenic mouse model. The HIV-1 protein Tat is constitutively expressed by most infected cells, even during ART suppression of viral replication. Many studies have demonstrated indirect and direct mechanisms of short-term Tat-associated neurodegeneration, including gliosis, blood-brain barrier disruption, elevated inflammatory mediators and neurotoxicity. However, the effects of acute vs. prolonged exposure on Tat-induced dysregulation remain to be seen. This is especially relevant for TIMP-1 as expression was previously shown to be differentially regulated in human astrocytes during acute vs. chronic inflammation. In this context, acute Tat expression was induced with DOX intraperitoneal injections over 3 weeks, while DOX-containing diet was used to achieve long-term Tat expression over 6 months. First, a series of behavior tests evaluating arousal, ambulation, anxiety, and cognition was performed to examine impairments analogous to those observed in HAND. Next, gene expression of components of the MMP/TIMP axis and known HAND-relevant inflammatory mediators were assessed. Altered anxiety-like, motor and/or cognitive behaviors were observed in Tat-induced (iTat) mice. Gene expression of MMPs and TIMPs was altered depending on the duration of Tat expression, which was independent of the HIV-associated neuroinflammation typically implicated in MMP/TIMP regulation. Collectively, we infer that HIV-1 Tat-mediated dysregulation of MMP/TIMP axis and behavioral changes are dependent on duration of exposure. Further, prolonged Tat expression demonstrates a phenotype comparable to asymptomatic to mild HAND manifestation in patients.

PMID: 33384653 [PubMed]

Acceleration of Anxiety, Depression, and Suicide: Secondary Effects of Economic Disruption Related to COVID-19.

Recent Research Articles from UNTHSC - Sat, 01/02/2021 - 08:38
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Acceleration of Anxiety, Depression, and Suicide: Secondary Effects of Economic Disruption Related to COVID-19.

Front Psychiatry. 2020;11:592467

Authors: Brenner MH, Bhugra D

Abstract
The SARS-CoV-2 (COVID-19) pandemic has contributed to increasing levels of anxiety, depression and other symptoms of stress around the globe. Reasons for this increase are understandable in the context of individual level factors such as self-isolation, lockdown, grief, survivor guilt, and other factors but also broader social and economic factors such as unemployment, insecure employment and resulting poverty, especially as the impacts of 2008 recession are still being felt in many countries further accompanied by social isolation. For those who are actively employed a fear of job and income loss and those who have actually become ill and recovered or those who have lost family and friends to illness, it is not surprising that they are stressed and feeling the psychological impact. Furthermore, multiple uncertainties contribute to this sense of anxiety. These fears and losses are major immediate stresses and undoubtedly can have long-term implications on mental health. Economic uncertainty combined with a sense of feeling trapped and resulting lack of control can contribute to helplessness and hopelessness where people may see suicide as a way out. Taking a macro view, we present a statistical model of the impact of unemployment, and national income declines, on suicide, separately for males and females over the life cycle in developed countries. This impact may reflect a potent combination of social changes and economic factors resulting in anomie. The governments and policymakers have a moral and ethical obligation to ensure the physical health and well-being of their populations. While setting in place preventive measures to avoid infections and then subsequent mortality, the focus on economic and social recovery is crucial. A global pandemic requires a global response with a clear inter-linked strategy for health as well as economic solutions. The models we have constructed represent predictions of suicide rates among the 38 highly industrialized OECD countries over a period of 18 years (2000-2017). Unemployment has a major effect on increasing suicide, especially in middle-aged groups. However, the impact of economic decline through losses of national income (GDP per capita) are substantially greater than those of unemployment and influence suicide throughout the life course, especially at the oldest ages.

PMID: 33384627 [PubMed]

Genetic assessment reveals no population substructure and divergent regional and sex-specific histories in the Chachapoyas from northeast Peru.

Recent Research Articles from UNTHSC - Fri, 01/01/2021 - 09:21
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Genetic assessment reveals no population substructure and divergent regional and sex-specific histories in the Chachapoyas from northeast Peru.

PLoS One. 2020;15(12):e0244497

Authors: Guevara EK, Palo JU, Översti S, King JL, Seidel M, Stoljarova M, Wendt FR, Bus MM, Guengerich A, Church WB, Guillén S, Roewer L, Budowle B, Sajantila A

Abstract
Many native populations in South America have been severely impacted by two relatively recent historical events, the Inca and the Spanish conquest. However decisive these disruptive events may have been, the populations and their gene pools have been shaped markedly also by the history prior to the conquests. This study focuses mainly on the Chachapoya peoples that inhabit the montane forests on the eastern slopes of the northern Peruvian Andes, but also includes three distinct neighboring populations (the Jívaro, the Huancas and the Cajamarca). By assessing mitochondrial, Y-chromosomal and autosomal diversity in the region, we explore questions that have emerged from archaeological and historical studies of the regional culture (s). These studies have shown, among others, that Chachapoyas was a crossroads for Coast-Andes-Amazon interactions since very early times. In this study, we examine the following questions: 1) was there pre-Hispanic genetic population substructure in the Chachapoyas sample? 2) did the Spanish conquest cause a more severe population decline on Chachapoyan males than on females? 3) can we detect different patterns of European gene flow in the Chachapoyas region? and, 4) did the demographic history in the Chachapoyas resemble the one from the Andean area? Despite cultural differences within the Chachapoyas region as shown by archaeological and ethnohistorical research, genetic markers show no significant evidence for past or current population substructure, although an Amazonian gene flow dynamic in the northern part of this territory is suggested. The data also indicates a bottleneck c. 25 generations ago that was more severe among males than females, as well as divergent population histories for populations in the Andean and Amazonian regions. In line with previous studies, we observe high genetic diversity in the Chachapoyas, despite the documented dramatic population declines. The diverse topography and great biodiversity of the northeastern Peruvian montane forests are potential contributing agents in shaping and maintaining the high genetic diversity in the Chachapoyas region.

PMID: 33382772 [PubMed - as supplied by publisher]

A Machine Learning Approach to Identify Predictors of Potentially Inappropriate Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Use in Older Adults with Osteoarthritis.

Recent Research Articles from UNTHSC - Fri, 01/01/2021 - 09:21
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A Machine Learning Approach to Identify Predictors of Potentially Inappropriate Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Use in Older Adults with Osteoarthritis.

Int J Environ Res Public Health. 2020 Dec 28;18(1):

Authors: Patel J, Ladani A, Sambamoorthi N, LeMasters T, Dwibedi N, Sambamoorthi U

Abstract
Evidence from some studies suggest that osteoarthritis (OA) patients are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) that are not in accordance with their cardiovascular (CV) or gastrointestinal (GI) risk profiles. However, no such study has been carried out in the United States. Therefore, we sought to examine the prevalence and predictors of potentially inappropriate NSAIDs use in older adults (age > 65) with OA using machine learning with real-world data from Optum De-identified Clinformatics® Data Mart. We identified a retrospective cohort of eligible individuals using data from 2015 (baseline) and 2016 (follow-up). Potentially inappropriate NSAIDs use was identified using the type (COX-2 selective vs. non-selective) and length of NSAIDs use and an individual's CV and GI risk. Predictors of potentially inappropriate NSAIDs use were identified using eXtreme Gradient Boosting. Our study cohort comprised of 44,990 individuals (mean age 75.9 years). We found that 12.8% individuals had potentially inappropriate NSAIDs use, but the rate was disproportionately higher (44.5%) in individuals at low CV/high GI risk. Longer duration of NSAIDs use during baseline (AOR 1.02; 95% CI:1.02-1.02 for both non-selective and selective NSAIDs) was associated with a higher risk of potentially inappropriate NSAIDs use. Additionally, individuals with low CV/high GI (AOR 1.34; 95% CI:1.20-1.50) and high CV/low GI risk (AOR 1.61; 95% CI:1.34-1.93) were also more likely to have potentially inappropriate NSAIDs use. Heightened surveillance of older adults with OA requiring NSAIDs is warranted.

PMID: 33379288 [PubMed - in process]

Safety and Efficacy of Cannabis in Autism Spectrum Disorder.

Recent Research Articles from UNTHSC - Thu, 12/31/2020 - 08:01
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Safety and Efficacy of Cannabis in Autism Spectrum Disorder.

Pediatr Neurol Briefs. 2020 Dec 24;34:25

Authors: Ganesh A, Shareef S

Abstract
Investigators from the Soroka University Medical Centre, The Hebrew University of Jerusalem, and Tikun Olam Ltd. in Israel studied the safety and efficacy of medical cannabis treatment on 188 patients with autism spectrum disorder (ASD) for six months.

PMID: 33376294 [PubMed]

Adipose-Derived Stem Cells from Obese Donors Polarize Macrophages and Microglia toward a Pro-Inflammatory Phenotype.

Recent Research Articles from UNTHSC - Thu, 12/31/2020 - 08:01
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Adipose-Derived Stem Cells from Obese Donors Polarize Macrophages and Microglia toward a Pro-Inflammatory Phenotype.

Cells. 2020 Dec 25;10(1):

Authors: Harrison MAA, Wise RM, Benjamin BP, Hochreiner EM, Mohiuddin OA, Bunnell BA

Abstract
Macrophages and microglia represent the primary phagocytes and first line of defense in the peripheral and central immune systems. They activate and polarize into a spectrum of pro- and anti-inflammatory phenotypes in response to various stimuli. This activation is tightly regulated to balance the appropriate immune response with tissue repair and homeostasis. Disruption of this balance results in inflammatory disease states and tissue damage. Adipose stem cells (ASCs) have great therapeutic potential because of the potent immunomodulatory capabilities which induce the polarization of microglia and macrophages to the anti-inflammatory, M2, phenotype. In this study, we examined the effects of donor heterogeneity on ASC function. Specifically, we investigated the impact of donor obesity on ASC stemness and immunomodulatory abilities. Our findings revealed that ASCs from obese donors (ObASCs) exhibited reduced stem cell characteristics when compared to ASCs from lean donors (LnASCs). We also found that ObASCs promote a pro-inflammatory phenotype in murine macrophage and microglial cells, as indicated by the upregulated expression of pro-inflammatory genes, increased nitric oxide pathway activity, and impaired phagocytosis and migration. These findings highlight the importance of considering individual donor characteristics such as obesity when selecting donors and cells for use in ASC therapeutic applications and regenerative medicine.

PMID: 33375695 [PubMed - in process]

Comparative Proteomics Analysis Reveals Unique Early Signaling Response of Saccharomyces cerevisiae to Oxidants with Different Mechanism of Action.

Recent Research Articles from UNTHSC - Thu, 12/31/2020 - 08:01
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Comparative Proteomics Analysis Reveals Unique Early Signaling Response of Saccharomyces cerevisiae to Oxidants with Different Mechanism of Action.

Int J Mol Sci. 2020 Dec 26;22(1):

Authors: Pandey P, Zaman K, Prokai L, Shulaev V

Abstract
The early signaling events involved in oxidant recognition and triggering of oxidant-specific defense mechanisms to counteract oxidative stress still remain largely elusive. Our discovery driven comparative proteomics analysis revealed unique early signaling response of the yeast Saccharomyces cerevisiae on the proteome level to oxidants with a different mechanism of action as early as 3 min after treatment with four oxidants, namely H2O2, cumene hydroperoxide (CHP), and menadione and diamide, when protein abundances were compared using label-free quantification relying on a high-resolution mass analyzer (Orbitrap). We identified significant regulation of 196 proteins in response to H2O2, 569 proteins in response to CHP, 369 proteins in response to menadione and 207 proteins in response to diamide. Only 17 proteins were common across all treatments, but several more proteins were shared between two or three oxidants. Pathway analyses revealed that each oxidant triggered a unique signaling mechanism associated with cell survival and repair. Signaling pathways mostly regulated by oxidants were Ran, TOR, Rho, and eIF2. Furthermore, each oxidant regulated these pathways in a unique way indicating specificity of response to oxidants having different modes of action. We hypothesize that interplay of these signaling pathways may be important in recognizing different oxidants to trigger different downstream MAPK signaling cascades and to induce specific responses.

PMID: 33375274 [PubMed - in process]

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