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Microphysiological Systems: Design, Fabrication, and Applications.

Recent Research Articles from UNTHSC - Fri, 11/20/2020 - 01:27
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Microphysiological Systems: Design, Fabrication, and Applications.

ACS Biomater Sci Eng. 2020 Jun 08;6(6):3231-3257

Authors: Wang K, Man K, Liu J, Liu Y, Chen Q, Zhou Y, Yang Y

Abstract
Microphysiological systems, including organoids, 3-D printed tissue constructs and organ-on-a-chips (organ chips), are physiologically relevant in vitro models and have experienced explosive growth in the past decades. Different from conventional, tissue culture plastic-based in vitro models or animal models, microphysiological systems recapitulate key microenvironmental characteristics of human organs and mimic their primary functions. The advent of microphysiological systems is attributed to evolving biomaterials, micro-/nanotechnologies and stem cell biology, which enable the precise control over the matrix properties and the interactions between cells, tissues and organs in physiological conditions. As such, microphysiological systems have been developed to model a broad spectrum of organs from microvasculature, eye, to lung and many others to understand human organ development and disease pathology and facilitate drug discovery. Multiorgans-on-a-chip systems have also been developed by integrating multiple associated organ chips in a single platform, which allows to study and employ the organ function in a systematic approach. Here we first discuss the design principles of microphysiological systems with a focus on the anatomy and physiology of organs, and then review the commonly used fabrication techniques and biomaterials for microphysiological systems. Subsequently, we discuss the recent development of microphysiological systems, and provide our perspectives on advancing microphysiological systems for preclinical investigation and drug discovery of human disease.

PMID: 33204830 [PubMed]

Developmental Validation of a MPS Workflow with a PCR-Based Short Amplicon Whole Mitochondrial Genome Panel.

Recent Research Articles from UNTHSC - Fri, 11/20/2020 - 01:27
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Developmental Validation of a MPS Workflow with a PCR-Based Short Amplicon Whole Mitochondrial Genome Panel.

Genes (Basel). 2020 Nov 13;11(11):

Authors: Cihlar JC, Amory C, Lagacé R, Roth C, Parson W, Budowle B

Abstract
For the adoption of massively parallel sequencing (MPS) systems by forensic laboratories, validation studies on specific workflows are needed to support the feasibility of implementation and the reliability of the data they produce. As such, the whole mitochondrial genome sequencing methodology-Precision ID mtDNA Whole Genome Panel, Ion Chef, Ion S5, and Converge-has been subjected to a variety of developmental validation studies. These validation studies were completed in accordance with the Scientific Working Group on DNA Analysis Methods (SWGDAM) validation guidelines and assessed reproducibility, repeatability, accuracy, sensitivity, specificity to human DNA, and ability to analyze challenging (e.g., mixed, degraded, or low quantity) samples. Intra- and inter-run replicates produced an average maximum pairwise difference in variant frequency of 1.2%. Concordance with data generated with traditional Sanger sequencing and an orthogonal MPS platform methodology was used to assess accuracy, and generation of complete and concordant haplotypes at DNA input levels as low as 37.5 pg of nuclear DNA or 187.5 mitochondrial genome copies illustrated the sensitivity of the system. Overall, data presented herein demonstrate that highly accurate and reproducible results were generated for a variety of sample qualities and quantities, supporting the reliability of this specific whole genome mitochondrial DNA MPS system for analysis of forensic biological evidence.

PMID: 33202822 [PubMed - in process]

Comment on: The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis.

Recent Research Articles from UNTHSC - Wed, 11/18/2020 - 08:12
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Comment on: The use of anakinra in the treatment of secondary hemophagocytic lymphohistiocytosis.

Pediatr Blood Cancer. 2020 Nov 16;:e28813

Authors: Vicenzi P, Jiwani Z, Guirola R, Hamby T, Ray A

PMID: 33200506 [PubMed - as supplied by publisher]

Editorial: New Insights Into Thymic Functions During Stress, Aging, and in Disease Settings.

Recent Research Articles from UNTHSC - Tue, 11/17/2020 - 16:46
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Editorial: New Insights Into Thymic Functions During Stress, Aging, and in Disease Settings.

Front Immunol. 2020;11:591936

Authors: van Oers NSC, Su DM, Chidgey AP, Dudakov J

PMID: 33193434 [PubMed - in process]

The Effect of IDO on Neural Progenitor Cell Survival Under Oxygen Glucose Deprivation.

Recent Research Articles from UNTHSC - Tue, 11/17/2020 - 16:46
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The Effect of IDO on Neural Progenitor Cell Survival Under Oxygen Glucose Deprivation.

Front Cell Neurosci. 2020;14:581861

Authors: Wang J, Wang B, Jiang L, Zhou K, Yang GY, Jin K

Abstract
Objective: Indoleamine 2,3-dioxygenase (IDO) activity plays an important role in many neurological disorders in the central nervous system, which may be associated with immunomodulation or anti-inflammatory activity. However, the action of IDO in the ischemic condition is still poorly understood. The purpose of the present study is to explore the expression and action of IDO in stem cell culture under oxygen and glucose deprivation. Methods: Neural progenitor cells were obtained from the human embryonic stem cell line BG01. These cells underwent oxygen and glucose deprivation. We examined the IDO expression at 3 and 8 h of oxygen and glucose deprivation and then examined neuronal progenitor cell viability in the normal and oxygen and glucose deprivation condition using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. In addition, we studied the effect of IDO inhibition and the expression of TNF-α, IGF-1, VEGF, IL-6, FGFβ, TGFβ, EGF, and Leptin to explore the mechanism of IDO under the oxygen and glucose deprivation. Results: IDO expression in neural progenitor cells increased under oxygen and glucose deprivation, which is closely associated with cell death (p < 0.05). Inhibiting IDO did not affect cell survival in normal neural progenitor cells. However, inhibiting IDO could attenuate cell viability under oxygen and glucose deprivation (p < 0.05). Further study demonstrated that IDO expression was closely associated to the growth factor's leptin expression. Conclusions: Our results demonstrated that an increase of IDO under oxygen and glucose deprivation was associated with cell death, suggesting that inhibiting IDO could be a target for neuroprotection.

PMID: 33192328 [PubMed]

Association of Serum Levels of Antioxidant Micronutrients with Mortality in US Adults: National Health and Nutrition Examination Survey 1999-2002.

Recent Research Articles from UNTHSC - Mon, 11/16/2020 - 21:08
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Association of Serum Levels of Antioxidant Micronutrients with Mortality in US Adults: National Health and Nutrition Examination Survey 1999-2002.

Public Health Nutr. 2020 Nov 13;:1-26

Authors: Peeri NC, Chai W, Cooney RV, Tao MH

Abstract
OBJECTIVES: To examine associations between serum antioxidant levels and mortality (all-cause, cancer, and cardiovascular disease (CVD)) among U.S. adults.
DESIGN: We examined the risk of death from all-cause and cause-specific mortality associated with serum antioxidant (vitamin E and carotenoids) and vitamin A levels using Cox regression models to estimate hazards ratios (HR) and 95% confidence intervals (CIs).
SETTING: The National Health and Nutrition Examination Survey (NHANES) 1999-2002 were follow-up through December 31, 2015.
PARTICIPANTS: The NHANES 1999-2002 cohort included 8,758 participants aged ≥20 years. Serum carotenoid levels were only assessed for the 1999-2000 cycle. Therefore, sample size for each assessed antioxidant ranged from 4,633 to 8,758.
RESULTS: Serum vitamin E level was positively associated with all-cause mortality (HR= 1.22, 95% CI: 1.04, 1.43, highest vs. lowest quartile). No other antioxidants were associated with mortality in overall analysis. In race/ethnicity-specific analyses, high vitamin E and α-tocopherol levels were associated with increased risk of all-cause mortality among non-Hispanic Whites. Among non-Hispanic Blacks, serum α-tocopherol level was associated with decreased risk of cancer mortality (HR= 0.30, 95% CI: 0.12-0.75, third vs. first quartile), and total carotenoids levels with reduced risk of CVD mortality (HR=0.26; 95% CI: 0.07, 0.97, second vs. lowest quartile). Hispanics with high β-carotene levels had reduced risk of CVD mortality.
CONCLUSIONS: Serum antioxidant levels may be related to mortality; these associations may differ by race/ethnicity and appeared to be non-linear for all-cause and cause-specific mortality. Further studies are needed to confirm our results.

PMID: 33183381 [PubMed - as supplied by publisher]

Paradoxical modulation of influenza by intranasal administration of non-replicating adenovirus particles.

Recent Research Articles from UNTHSC - Fri, 11/13/2020 - 07:48
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Paradoxical modulation of influenza by intranasal administration of non-replicating adenovirus particles.

PLoS One. 2020;15(11):e0241266

Authors: Tang DC

Abstract
Respiratory mucosal infection by airborne microbes is a common event that occurs every day. We report here that intranasal administration of non-replicating adenovirus (Ad) particles to mice could either confer rapid protection against influenza virus (IFV) challenge independent of adaptive immunity, or exacerbate influenza by triggering rapid death. The life-or-death outcome hinges on the time interval between Ad administration and IFV challenge in conjunction with specific mouse/IFV strains. Intranasal instillation of Ad particles 1-47 days prior to IFV challenge conferred rapid protection against influenza in Balb/c mice whereas exposure to Ad 39 days prior to challenge with a specific IFV strain or 1 day post-challenge with that IFV strain induced rapid death in C57BL/6 mice. Notably, consecutive administrations of Ad prior to IFV challenge conferred a synergy in triggering a potent anti-influenza state; even a detrimental Ad exposure 39 days before challenge with the deadly IFV strain was reversed to a beneficial one by subsequent Ad boosts. Results revealed an intricate relationship between infection and innate immunity that is a linchpin around which effects revolve from protective immunity to collateral damage. It is urgent to repeat the experiments with an expanded scope for characterizing the status that defines susceptibility or resistance to IFV infection and subsequently reveal the underlying mechanisms. Whether broad heterologous protective effects induced by AdE and adaptive immunity elicited by vaccination could confer synergy during mitigation of a pandemic remains to be seen.

PMID: 33180828 [PubMed - as supplied by publisher]

Wuqinxi Exercise Improves Hand Dexterity in Patients with Parkinson's Disease.

Recent Research Articles from UNTHSC - Fri, 11/13/2020 - 07:48
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Wuqinxi Exercise Improves Hand Dexterity in Patients with Parkinson's Disease.

Evid Based Complement Alternat Med. 2020;2020:8352176

Authors: Wang T, Xiao G, Li Z, Jie K, Shen M, Jiang Y, Wang Z, Shi X, Zhuang J

Abstract
Objective: This study was designed to evaluate the effect of Wuqinxi after one session and 12-week intervention on hand dexterity in patients with Parkinson's disease (PD).
Methods: Forty-six elderly participants with mild-to-moderate PD were randomly assigned to the groups trained with Wuqinxi (n = 23) or stretching (n = 23). All participants practiced 60 min session of either of these exercises, 2 sessions a week for 12 weeks in standing position. The score of Purdue Pegboard Test (PPT) and time for Soda Pop Test (SPT) were performed to assess hand dexterity and motor function along assessing the 39 items of Parkinson's Disease Questionnaire before and after 12-week interventions. In addition, the PPT scores were compared before vs. after one session of either of these two exercise modes.
Results: Single session with either Wuqinxi or stretching exercise tended to improve PPT scores in PD patients. Furthermore, the improved SPT time was significant (P < 0.01) following 12-week training interventions with Wuqinxi (-1.32 ± 0.38 sec) or stretching (-0.89 ± 0.16 sec), which showed no group difference (P=0.734). However, only the participants in Wuqinxi group significantly improved the PPT scores of the dominant hand (+0.61 ± 1.34), both hand (+1.83 ± 3.13) and assemble (+2.04 ± 3.44) performance after 12-week training intervention. In parallel with improved hand dexterity and motor function, 12-week Wuqinxi training also significantly improved the patient's emotional wellbeing.
Conclusion: The Wuqinxi intervention could be safely and effectively applied to improve hand dexterity following single-session exercise or 12-week training, which were accompanied by improved quality of life in patients with mild-to-moderate PD.

PMID: 33178323 [PubMed]

Social Determinants of Health and Health Disparities: COVID-19 Exposures and Mortality Among African American People in the United States.

Recent Research Articles from UNTHSC - Thu, 11/12/2020 - 12:49
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Social Determinants of Health and Health Disparities: COVID-19 Exposures and Mortality Among African American People in the United States.

Public Health Rep. 2020 Nov 11;:33354920969169

Authors: Maness SB, Merrell L, Thompson EL, Griner SB, Kline N, Wheldon C

PMID: 33176112 [PubMed - as supplied by publisher]

Application of Nanotechnology in Cancer Diagnosis and Therapy - A Mini-Review.

Recent Research Articles from UNTHSC - Thu, 11/12/2020 - 12:49
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Application of Nanotechnology in Cancer Diagnosis and Therapy - A Mini-Review.

Int J Med Sci. 2020;17(18):2964-2973

Authors: Jin C, Wang K, Oppong-Gyebi A, Hu J

Abstract
Cancer is a leading cause of death and poor quality of life globally. Even though several strategies are devised to reduce deaths, reduce chronic pain and improve the quality of life, there remains a shortfall in the adequacies of these cancer therapies. Among the cardinal steps towards ensuring optimal cancer treatment are early detection of cancer cells and drug application with high specificity to reduce toxicities. Due to increased systemic toxicities and refractoriness with conventional cancer diagnostic and therapeutic tools, other strategies including nanotechnology are being employed to improve diagnosis and mitigate disease severity. Over the years, immunotherapeutic agents based on nanotechnology have been used for several cancer types to reduce the invasiveness of cancerous cells while sparing healthy cells at the target site. Nanomaterials including carbon nanotubes, polymeric micelles and liposomes have been used in cancer drug design where they have shown considerable pharmacokinetic and pharmacodynamic benefits in cancer diagnosis and treatment. In this review, we outline the commonly used nanomaterials which are employed in cancer diagnosis and therapy. We have highlighted the suitability of these nanomaterials for cancer management based on their physicochemical and biological properties. We further reviewed the challenges that are associated with the various nanomaterials which limit their uses and hamper their translatability into the clinical setting in certain cancer types.

PMID: 33173417 [PubMed - in process]

β-Catenin Regulates Wound Healing and IL-6 Expression in Activated Human Astrocytes.

Recent Research Articles from UNTHSC - Thu, 11/12/2020 - 12:49
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β-Catenin Regulates Wound Healing and IL-6 Expression in Activated Human Astrocytes.

Biomedicines. 2020 Nov 06;8(11):

Authors: Edara VV, Nooka S, Proulx J, Stacy S, Ghorpade A, Borgmann K

Abstract
Reactive astrogliosis is prominent in most neurodegenerative disorders and is often associated with neuroinflammation. The molecular mechanisms regulating astrocyte-linked neuropathogenesis during injury, aging and human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) are not fully understood. In this study, we investigated the implications of the wingless type (Wnt)/β-catenin signaling pathway in regulating astrocyte function during gliosis. First, we identified that HIV-associated inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α induced mediators of the Wnt/β-catenin pathway including β-catenin and lymphoid enhancer-binding factor (LEF)-1 expression in astrocytes. Next, we investigated the regulatory role of β-catenin on primary aspects of reactive astrogliosis, including proliferation, migration and proinflammatory responses, such as IL-6. Knockdown of β-catenin impaired astrocyte proliferation and migration as shown by reduced cyclin-D1 levels, bromodeoxyuridine incorporation and wound healing. HIV-associated cytokines, IL-1β alone and in combination with TNF-α, strongly induced the expression of proinflammatory cytokines including C-C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)8 and IL-6; however, only IL-6 levels were regulated by β-catenin as demonstrated by knockdown and pharmacological stabilization. In this context, IL-6 levels were negatively regulated by β-catenin. To better understand this relationship, we examined the crossroads between β-catenin and nuclear factor (NF)-κB pathways. While NF-κB expression was significantly increased by IL-1β and TNF-α, NF-κB levels were not affected by β-catenin knockdown. IL-1β treatment significantly increased glycogen synthase kinase (GSK)-3β phosphorylation, which inhibits β-catenin degradation. Further, pharmacological inhibition of GSK-3β increased nuclear translocation of both β-catenin and NF-κB p65 into the nucleus in the absence of any other inflammatory stimuli. HIV+ human astrocytes show increased IL-6, β-catenin and NF-κB expression levels and are interconnected by regulatory associations during HAND. In summary, our study demonstrates that HIV-associated inflammation increases β-catenin pathway mediators to augment activated astrocyte responses including migration and proliferation, while mitigating IL-6 expression. These findings suggest that β-catenin plays an anti-inflammatory role in activated human astrocytes during neuroinflammatory pathologies, such as HAND.

PMID: 33171974 [PubMed]

3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro.

Recent Research Articles from UNTHSC - Thu, 11/12/2020 - 12:49
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3D Spheroids Derived from Human Lipedema ASCs Demonstrated Similar Adipogenic Differentiation Potential and ECM Remodeling to Non-Lipedema ASCs In Vitro.

Int J Mol Sci. 2020 Nov 07;21(21):

Authors: Al-Ghadban S, Pursell IA, Diaz ZT, Herbst KL, Bunnell BA

Abstract
The growth and differentiation of adipose tissue-derived stem cells (ASCs) is stimulated and regulated by the adipose tissue (AT) microenvironment. In lipedema, both inflammation and hypoxia influence the expansion and differentiation of ASCs, resulting in hypertrophic adipocytes and deposition of collagen, a primary component of the extracellular matrix (ECM). The goal of this study was to characterize the adipogenic differentiation potential and assess the levels of expression of ECM-remodeling markers in 3D spheroids derived from ASCs isolated from both lipedema and healthy individuals. The data showed an increase in the expression of the adipogenic genes (ADIPOQ, LPL, PPAR-γ and Glut4), a decrease in matrix metalloproteinases (MMP2, 9 and 11), with no significant changes in the expression of ECM markers (collagen and fibronectin), or integrin A5 in 3D differentiated lipedema spheroids as compared to healthy spheroids. In addition, no statistically significant changes in the levels of expression of inflammatory genes were detected in any of the samples. However, immunofluorescence staining showed a decrease in fibronectin and increase in laminin and Collagen VI expression in the 3D differentiated spheroids in both groups. The use of 3D ASC spheroids provide a functional model to study the cellular and molecular characteristics of lipedema AT.

PMID: 33171717 [PubMed - in process]

Elevated blood urea nitrogen is associated with recurrence of post-operative chronic subdural hematoma.

Recent Research Articles from UNTHSC - Wed, 11/11/2020 - 05:27
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Elevated blood urea nitrogen is associated with recurrence of post-operative chronic subdural hematoma.

BMC Neurol. 2020 Nov 10;20(1):411

Authors: Wang N, Hu J, Oppong-Gyebi A, Zhu X, Li Y, Yang J, Ruan L, Zhuge Q, Ye S

Abstract
BACKGROUND: Chronic subdural hematoma (CSDH) is fundamentally treatable with about a 2-31% recurrence rate. Recently, there has been renewed interest in the association between Blood Urea Nitrogen (BUN) and intracranial lesion. Therefore, this paper attempts to show the relationship between BUN and CSDH recurrence.
METHODS: A total of 653 CSDH cases with Burr-hole Irrigation (BHI) were enrolled from December 2014 to April 2019. The analyzed parameters included age, gender, comorbidities, laboratory investigations, medication use and hematoma location. The cases were divided into recurrence and non-recurrence groups while postoperative BUN concentration was further separated into quartiles (Q1 ≤ 4.0 mmol/L, 4.0 < Q2 ≤ 4.9 mmol/L, 4.9 < Q3 ≤ 6.4 mmol/L, Q4 > 6.4 mmol/L). Restricted cubic spline regressions and logistic regression models were performed to estimate the effect of BUN on CSDH recurrence.
RESULTS: CSDH recurrence was observed in 96 (14.7%) cases. Significant distinctions were found between recurrence and non-recurrence groups in postoperative BUN quartiles of cases (P = 0.003). After adjusting for the potential confounders, the odds ratio of recurrence was 3.069 (95%CI =1.488-6.330, p = 0.002) for the highest quartile of BUN compared with the lowest quartile. In multiple-adjusted spline regression, a high BUN level visually showed a significantly high OR value of recurrence risk.
CONCLUSIONS: Elevated BUN at post-operation is significantly associated with the recurrence of CSDH, and it is indicated that high levels of serum BUN after evacuation may serve as a risk factor for CSDH recurrence.

PMID: 33167883 [PubMed - in process]

At the intersection of precision medicine and population health: an implementation-effectiveness study of family health history based systematic risk assessment in primary care.

Recent Research Articles from UNTHSC - Tue, 11/10/2020 - 10:48
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At the intersection of precision medicine and population health: an implementation-effectiveness study of family health history based systematic risk assessment in primary care.

BMC Health Serv Res. 2020 Nov 07;20(1):1015

Authors: Orlando LA, Wu RR, Myers RA, Neuner J, McCarty C, Haller IV, Harry M, Fulda KG, Dimmock D, Rakhra-Burris T, Buchanan A, Ginsburg GS

Abstract
BACKGROUND: Risk assessment is a precision medicine technique that can be used to enhance population health when applied to prevention. Several barriers limit the uptake of risk assessment in health care systems; and little is known about the potential impact that adoption of systematic risk assessment for screening and prevention in the primary care population might have. Here we present results of a first of its kind multi-institutional study of a precision medicine tool for systematic risk assessment.
METHODS: We undertook an implementation-effectiveness trial of systematic risk assessment of primary care patients in 19 primary care clinics at four geographically and culturally diverse healthcare systems. All adult English or Spanish speaking patients were invited to enter personal and family health history data into MeTree, a patient-facing family health history driven risk assessment program, for 27 medical conditions. Risk assessment recommendations followed evidence-based guidelines for identifying and managing those at increased disease risk.
RESULTS: One thousand eight hundred eighty-nine participants completed MeTree, entering information on N = 25,967 individuals. Mean relatives entered = 13.7 (SD 7.9), range 7-74. N = 1443 (76.4%) participants received increased risk recommendations: 597 (31.6%) for monogenic hereditary conditions, 508 (26.9%) for familial-level risk, and 1056 (56.1%) for risk of a common chronic disease. There were 6617 recommendations given across the 1443 participants. In multivariate analysis, only the total number of relatives entered was significantly associated with receiving a recommendation.
CONCLUSIONS: A significant percentage of the general primary care population meet criteria for more intensive risk management. In particular 46% for monogenic hereditary and familial level disease risk. Adopting strategies to facilitate systematic risk assessment in primary care could have a significant impact on populations within the U.S. and even beyond.
TRIAL REGISTRATION: Clinicaltrials.gov number NCT01956773 , registered 10/8/2013.

PMID: 33160339 [PubMed - in process]

Spleen is not required for therapeutic effects of 4OH-GTS-21, a selective α7 nAChR agonist, in the sub-acute phase of ischemic stroke in rats.

Recent Research Articles from UNTHSC - Tue, 11/10/2020 - 10:48
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Spleen is not required for therapeutic effects of 4OH-GTS-21, a selective α7 nAChR agonist, in the sub-acute phase of ischemic stroke in rats.

Brain Res. 2020 Nov 04;:147196

Authors: Gaidhani N, Kem WR, Uteshev VV

Abstract
Acute ischemic stroke (AIS) causes both central and peripheral inflammation, while activation of α7 nicotinic acetylcholine receptors (nAChRs) provides both central and peripheral anti-inflammatory and anti-apoptotic effects. Here, we provide evidence that 4OH-GTS-21, a selective α7 agonist, produces its therapeutic effects via primarily central sites of action because 4OH-GTS-21 was found equally effective in splenectomized and non-spenectomized rats in the sub-acute phase of ischemic stroke (≤1 week). However, the spleen may boost the therapeutic efficacy of 4OH-GTS-21 in certain behavioral tasks as our data also indicated. In our tests, AIS was modeled by transient middle cerebral artery occlusion (tMCAO). Splenectomy was done 2 weeks before tMCAO. We determined that: 1) Daily 4OH-GTS-21 treatments for 7 days after tMCAO significantly reduced neurological deficits and brain injury in both splenectomized and non-spelenectomized rats demonstrating that the spleen is not required for therapeutic benefits of 4OH-GTS-21; 2) The effects of 4OH-GTS-21 in the adhesive sticker removal test were significantly weaker in splenectomized animals suggesting that the spleen boosts the efficacy of 4OH-GTS-21 in the first week after tMCAO; and 3) Ischemic brain injury was not significantly affected by splenectomy in both vehicle-treated and 4OH-GTS-21-treated animals. These data support the hypothesis that the therapeutic efficacy of sub-chronic (≤1 week) 4OH-GTS-21 primarily originates from central sites of action. These results validate brain availability as a critical factor for developing novel α7 ligands for AIS.

PMID: 33159972 [PubMed - as supplied by publisher]

COVID-19 and TB control in immigrant communities.

Recent Research Articles from UNTHSC - Tue, 11/10/2020 - 10:48
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COVID-19 and TB control in immigrant communities.

Int J Tuberc Lung Dis. 2020 Sep 01;24(9):975-977

Authors: Wilson FA, Miller TL, Stimpson JP

PMID: 33156769 [PubMed - in process]

Behavioral effects of four novel synthetic cathinone analogs in rodents.

Recent Research Articles from UNTHSC - Tue, 11/10/2020 - 10:48
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Behavioral effects of four novel synthetic cathinone analogs in rodents.

Addict Biol. 2020 Nov 05;:e12987

Authors: Gatch MB, Shetty RA, Sumien N, Forster MJ

Abstract
A new generation of novel cathinone compounds has been developed as stimulant substitutes to avoid drug control laws and detection of use by blood tests. Dipentylone, N-ethylhexedrone, 4-chloroethcathinone (4-CEC), and 4'-methyl-α-pyrrolidinohexiophenone (MPHP) were tested for in vivo psychostimulant-like effects to assess their abuse liability. Locomotor activity was assessed in an open-field assay using Swiss-Webster mice to screen for locomotor stimulant effects and to identify behaviorally-active dose ranges, times of peak effect, and durations of action. Discriminative stimulus effects were assessed in separate groups of Sprague-Dawley rats trained to discriminate cocaine or methamphetamine from vehicle. Dipentylone, N-ethylhexedrone, 4-CEC, and MPHP dose-dependently increased locomotor activity. Dipentylone, N-ethylhexedrone, and MPHP produced maximal stimulant effects similar to cocaine and methamphetamine. 4-CEC was less efficacious, producing peak stimulant effects of about 74% of that of methamphetamine. The compounds were less potent than methamphetamine and approximately equipotent with cocaine. The doses of cocaine, methamphetamine, dipentylone, and 4-CEC that produced peak effects lasted 2 to 3 h, the peak dose of N-ethylhexedrone lasted 4 h, and the peak dose of MPHP lasted 6 h. All four compounds fully substituted for the discriminative stimulus effects of methamphetamine and cocaine, although full substitution by 4-CEC occurred at doses that substantially decreased response rate. Only 4-CEC fully substituted for MDMA. These data provide evidence that the novel cathinone compounds dipentylone, N-ethylhexedrone, 4-CEC, and MPHP demonstrate potential for abuse as psychostimulants, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of methamphetamine and cocaine.

PMID: 33155384 [PubMed - as supplied by publisher]

ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load.

Recent Research Articles from UNTHSC - Tue, 11/10/2020 - 10:48
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ATF4 leads to glaucoma by promoting protein synthesis and ER client protein load.

Nat Commun. 2020 11 05;11(1):5594

Authors: Kasetti RB, Patel PD, Maddineni P, Patil S, Kiehlbauch C, Millar JC, Searby CC, Raghunathan V, Sheffield VC, Zode GS

Abstract
The underlying pathological mechanisms of glaucomatous trabecular meshwork (TM) damage and elevation of intraocular pressure (IOP) are poorly understood. Here, we report that the chronic endoplasmic reticulum (ER) stress-induced ATF4-CHOP-GADD34 pathway is activated in TM of human and mouse glaucoma. Expression of ATF4 in TM promotes aberrant protein synthesis and ER client protein load, leading to TM dysfunction and cell death. These events lead to IOP elevation and glaucomatous neurodegeneration. ATF4 interacts with CHOP and this interaction is essential for IOP elevation. Notably, genetic depletion or pharmacological inhibition of ATF4-CHOP-GADD34 pathway prevents TM cell death and rescues mouse models of glaucoma by reducing protein synthesis and ER client protein load in TM cells. Importantly, glaucomatous TM cells exhibit significantly increased protein synthesis along with induction of ATF4-CHOP-GADD34 pathway. These studies indicate a pathological role of ATF4-CHOP-GADD34 pathway in glaucoma and provide a possible treatment for glaucoma by targeting this pathway.

PMID: 33154371 [PubMed - in process]

Fractionation of DNA and protein from individual latent fingerprints for forensic analysis.

Recent Research Articles from UNTHSC - Fri, 11/06/2020 - 05:57
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Fractionation of DNA and protein from individual latent fingerprints for forensic analysis.

Forensic Sci Int Genet. 2020 Oct 21;50:102405

Authors: Schulte KQ, Hewitt FC, Manley TE, Reed AJ, Baniasad M, Albright NC, Powals ME, LeSassier DS, Smith AR, Zhang L, Allen LW, Ludolph BC, Weber KL, Woerner AE, Freitas MA, Gardner MW

Abstract
Human touch samples represent a significant portion of forensic DNA casework. Yet, the generally low abundance of genetic material combined with the predominantly extracellular nature of DNA in these samples makes DNA-based forensic analysis exceptionally challenging. Human proteins present in these same touch samples offer an abundant and environmentally-robust alternative. Proteogenomic methods, using protein sequence variants arising from nonsynonymous DNA mutations, have recently been applied to forensic analysis and may represent a viable option looking forward. However, DNA analysis remains the gold standard and any proteomics-based methods would need to consider how DNA could be co-extracted from samples without significant loss. Herein, we describe a simple workflow for the collection, enrichment and fractionation of DNA and protein in latent fingerprint samples. This approach ensures that DNA collected from a latent fingerprint can be analyzed by traditional DNA casework methods, while protein can be proteolytically digested and analyzed via standard liquid chromatography-tandem mass spectrometry-based proteomics methods from the same touch sample. Sample collection from non-porous surfaces (i.e., glass) is performed through the application of an anionic surfactant over the fingermark. The sample is then split into separate DNA and protein fractions following centrifugation to enrich the protein fraction by pelleting skin cells. The results indicate that this workflow permits analysis of DNA within the sample, yet highlights the challenge posed by the trace nature of DNA in touch samples and the potential for DNA to degrade over time. Protein deposited in touch samples does not appear to share this limitation, with robust protein quantities collected across multiple human donors. The quantity and quality of protein remains robust regardless of fingerprint age. The proteomic content of these samples is consistent across individual donors and fingerprint age, supporting the future application of genetically variable peptide (GVP) analysis of touch samples for forensic identification.

PMID: 33152624 [PubMed - as supplied by publisher]

A Review of Development Initiatives for Pharmacy Student and Resident Preceptors.

Recent Research Articles from UNTHSC - Fri, 11/06/2020 - 05:57
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A Review of Development Initiatives for Pharmacy Student and Resident Preceptors.

Am J Pharm Educ. 2020 Oct;84(10):ajpe7991

Authors: Howard ML, Yuet WC, Isaacs AN

Abstract
Objective. To review the published literature describing and evaluating pharmacy student and resident preceptor development. Findings. Database searches yielded 32 published articles on pharmacy preceptor development: 22 for experiential preceptors, eight for resident preceptors, and two encompassing both experiential and resident preceptors. The identified articles covered a variety of preceptor development strategies, including live, web-based, and multifaceted approaches, which were disseminated via analytical studies, needs assessment surveys, and descriptive reports. In analytical studies, the evaluation methods most commonly used were preceptor pre- and post-perception surveys. Summary. Preceptor development strategies vary among pharmacy schools and residency programs. The evaluation methods used also varied, and there is a lack of evidence-based practices related to preceptor development. Preceptor development should be tailored based on preceptor type and program needs. An opportunity exists to further evaluate which strategies are most effective for improving precepting techniques, with an ultimate goal of delineating best practices for pharmacy preceptor development.

PMID: 33149330 [PubMed - in process]

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