Recent Research Articles from UNTHSC

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

Subscribe to Recent Research Articles from UNTHSC  feed Recent Research Articles from UNTHSC
NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 2 hours 10 min ago

Setting-based Prioritization for Birth Cohort Hepatitis C Virus Testing in the United States.

Tue, 10/06/2020 - 07:28
Related Articles

Setting-based Prioritization for Birth Cohort Hepatitis C Virus Testing in the United States.

Clin Infect Dis. 2020 01 16;70(3):543-544

Authors: MacDonald BR, Chu TC, Stewart RA, Ojha RP

PMID: 31125407 [PubMed - indexed for MEDLINE]

Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry.

Sun, 10/04/2020 - 05:13

Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry.

BMC Cancer. 2020 Oct 02;20(1):954

Authors: Pathak GA, Polimanti R, Silzer TK, Wendt FR, Chakraborty R, Phillips NR

Abstract
BACKGROUND: Proctitis is an inflammation of the rectum and may be induced by radiation treatment for cancer. The genetic heritability of developing radiotoxicity and prior role of genetic variants as being associated with side-effects of radiotherapy necessitates further investigation for underlying molecular mechanisms. In this study, we investigated gene expression regulated by genetic variants, and copy number variation in prostate cancer survivors with radiotoxicity.
METHODS: We investigated proctitis as a radiotoxic endpoint in prostate cancer patients who received radiotherapy (n = 222). We analyzed the copy number variation and genetically regulated gene expression profiles of whole-blood and prostate tissue associated with proctitis. The SNP and copy number data were genotyped on Affymetrix® Genome-wide Human SNP Array 6.0. Following QC measures, the genotypes were used to obtain gene expression by leveraging GTEx, a reference dataset for gene expression association based on genotype and RNA-seq information for prostate (n = 132) and whole-blood tissue (n = 369).
RESULTS: In prostate tissue, 62 genes were significantly associated with proctitis, and 98 genes in whole-blood tissue. Six genes - CABLES2, ATP6AP1L, IFIT5, ATRIP, TELO2, and PARD6G were common to both tissues. The copy number analysis identified seven regions associated with proctitis, one of which (ALG1L2) was also associated with proctitis based on transcriptomic profiles in the whole-blood tissue. The genes identified via transcriptomics and copy number variation association were further investigated for enriched pathways and gene ontology. Some of the enriched processes were DNA repair, mitochondrial apoptosis regulation, cell-to-cell signaling interaction processes for renal and urological system, and organismal injury.
CONCLUSIONS: We report gene expression changes based on genetic polymorphisms. Integrating gene-network information identified these genes to relate to canonical DNA repair genes and processes. This investigation highlights genes involved in DNA repair processes and mitochondrial malfunction possibly via inflammation. Therefore, it is suggested that larger studies will provide more power to infer the extent of underlying genetic contribution for an individual's susceptibility to developing radiotoxicity.

PMID: 33008348 [PubMed - as supplied by publisher]

Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis.

Sun, 10/04/2020 - 05:13

Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis.

Cells. 2020 Sep 30;9(10):

Authors: Wise RM, Harrison MAA, Sullivan BN, Al-Ghadban S, Aleman SJ, Vinluan AT, Monaco ER, Donato UM, Pursell IA, Bunnell BA

Abstract
Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4+ T helper (Th) and T regulatory (Treg) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less Th and Treg cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.

PMID: 33008073 [PubMed - as supplied by publisher]

Study protocol for a multicentre implementation trial of monotherapy anticoagulation to expedite home treatment of patients diagnosed with venous thromboembolism in the emergency department.

Sat, 10/03/2020 - 07:23

Study protocol for a multicentre implementation trial of monotherapy anticoagulation to expedite home treatment of patients diagnosed with venous thromboembolism in the emergency department.

BMJ Open. 2020 Oct 01;10(10):e038078

Authors: Kline J, Adler D, Alanis N, Bledsoe J, Courtney D, D'Etienne J, B Diercks D, Garrett J, Jones AE, MacKenzie D, Madsen T, Matuskowitz A, Mumma B, Nordenholz K, Pagenhardt J, Runyon M, Stubblefield W, Willoughby C

Abstract
INTRODUCTION: In the USA, many emergency departments (EDs) have established protocols to treat patients with newly diagnosed deep vein thrombosis (DVT) as outpatients. Similar treatment of patients with pulmonary embolism (PE) has been proposed, but no large-scale study has been published to evaluate a comprehensive, integrated protocol that employs monotherapy anticoagulation to treat patients diagnosed with DVT and PE in the ED.
METHODS AND ANALYSIS: This protocol describes the implementation of the Monotherapy Anticoagulation To expedite Home treatment of Venous ThromboEmbolism (MATH-VTE) study at 33 hospitals in the USA. The study was designed and executed to meet the requirements for the Standards for Reporting Implementation Studies guideline. The study was funded by investigator-initiated awards from industry, with Indiana University as the sponsor. The study principal investigator and study associates travelled to each site to provide on-site training. The protocol identically screens patients with both DVT or PE to determine low risk of death using either the modified Hestia criteria or physician judgement plus a negative result from the simplified PE severity index. Patients must be discharged from the ED within 24 hours of triage and treated with either apixaban or rivaroxaban. Overall effectiveness is based upon the primary efficacy and safety outcomes of recurrent VTE and bleeding requiring hospitalisation respectively. Target enrolment of 1300 patients was estimated with efficacy success defined as the upper limit of the 95% CI for the 30-day frequency of VTE recurrence below 2.0%. Thirty-three hospitals in 17 states were initiated in 2016-2017.
ETHICS AND DISSEMINATION: All sites had Institutional Review Board approval. We anticipate completion of enrolment in June 2020; study data will be available after peer-reviewed publication. MATH-VTE will provide information from a large multicentre sample of US patients about the efficacy and safety of home treatment of VTE with monotherapy anticoagulation.

PMID: 33004396 [PubMed - in process]

Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis.

Fri, 10/02/2020 - 06:24
Related Articles

Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis.

Breast Cancer Res. 2020 01 28;22(1):11

Authors: Chaudhary P, Gibbs LD, Maji S, Lewis CM, Suzuki S, Vishwanatha JK

Abstract
BACKGROUND: Limited information is available on biomarker(s) for triple-negative breast cancer (TNBC) that can address the higher incidence and aggressiveness of TNBC in African-American (AA) women. Our previous studies have demonstrated annexin A2 (AnxA2) association with exosomes which promotes angiogenesis and metastasis. Therefore, our goal was to examine the expression and function of exosomal-annexin A2 (exo-AnxA2) derived from the serum samples of breast cancer patients.
METHODS: The expression of serum exo-AnxA2 and its association with clinicopathological features of the breast cancer patients were determined. The role of serum exo-AnxA2 to promote angiogenesis was determined by an in vivo Matrigel plug assay.
RESULTS: Our results show that the expression of serum exo-AnxA2 in breast cancer patients (n = 169; 83.33 ± 2.040 ng/mL, P < 0.0001) is high compared to non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). High expression of exo-AnxA2 levels in breast cancer was significantly associated with tumor grade (P < 0.0001), poor overall survival (hazard ratio (HR) 2.802; 95% confidence intervals (CI) = 1.030-7.620; P = 0.0353), and poor disease-free survival (HR 7.934; 95% CI = 1.778-35.398; P = 0.0301). The expression of serum exo-AnxA2 levels was significantly elevated in TNBC (n = 68; 109.1 ± 2.905 ng/mL; P < 0.0001) in comparison to ER+ (n = 50; 57.35 ± 1.545 ng/mL), HER2+ (n = 59; 78.25 ± 1.146 ng/mL), and non-cancer females (n = 68; 34.21 ± 2.238 ng/mL). Exo-AnxA2 showed diagnostic values with a maximum AUC as 1.000 for TNBC, 0.8304 for ER+, and 0.9958 for HER2+ compared to non-cancer females. The expression of serum exo-AnxA2 was significantly elevated in AA women with TNBC (n = 29; 118.9 ± 4.086 ng/mL, P < 0.0001) in comparison to Caucasian-American TNBC (n = 27; 97.60 ± 3.298 ng/mL) patients. Our in vivo results suggest a role of serum exo-AnxA2 in angiogenesis and its association with aggressiveness of TNBC in AA women.
CONCLUSIONS: Our results demonstrated that the expression of serum exo-AnxA2 is high in AA women with TNBC and promotes angiogenesis. These findings suggest that exo-AnxA2 holds promise as a potential prognosticator of TNBC and may lead to an effective therapeutic option.

PMID: 31992335 [PubMed - indexed for MEDLINE]

Fluorescence anisotropy imaging in drug discovery.

Fri, 10/02/2020 - 06:24
Related Articles

Fluorescence anisotropy imaging in drug discovery.

Adv Drug Deliv Rev. 2019 Nov - Dec;151-152:262-288

Authors: Vinegoni C, Feruglio PF, Gryczynski I, Mazitschek R, Weissleder R

Abstract
Non-invasive measurement of drug-target engagement can provide critical insights in the molecular pharmacology of small molecule drugs. Fluorescence polarization/fluorescence anisotropy measurements are commonly employed in protein/cell screening assays. However, the expansion of such measurements to the in vivo setting has proven difficult until recently. With the advent of high-resolution fluorescence anisotropy microscopy it is now possible to perform kinetic measurements of intracellular drug distribution and target engagement in commonly used mouse models. In this review we discuss the background, current advances and future perspectives in intravital fluorescence anisotropy measurements to derive pharmacokinetic and pharmacodynamic measurements in single cells and whole organs.

PMID: 29410158 [PubMed - indexed for MEDLINE]

Financial performance and reimbursement of pharmacist-led chronic care management.

Thu, 10/01/2020 - 10:17

Financial performance and reimbursement of pharmacist-led chronic care management.

Am J Health Syst Pharm. 2020 Sep 30;:

Authors: Martin R, Tram K, Le L, Simmons C

Abstract
PURPOSE: The purpose of this study was to evaluate the financial performance and reimbursement of chronic care management (CCM) provided by clinical pharmacists in a primary care setting using Current Procedural Terminology codes that were added to the Medicare Physician Fee Schedule in 2017.
METHODS: A retrospective study assessing financial performance of pharmacist-led CCM was conducted for the 12-month period from May 1, 2018, through April 30, 2019, at an academic multiclinic medical practice. Pharmacist-led CCM encounters included a combination of telephone and in-clinic visits. Return on investment, a ratio of net income to financial investment, was the primary outcome. Secondary outcomes included the number of CCM encounters, time spent by pharmacists delivering CCM (ie, "time-on-task"), and third-party claim reimbursement.
RESULT: Sixty-five patients were enrolled in CCM during the 12-month study period. Pharmacists provided 236 CCM encounters, including 31 enrollment visits and 102 hours of clinical time-on-task. Gross revenue for CCM during the 12-month period was $7,433.91, and expenses totaled $6,430.36, resulting in a 15.6% return on investment. Out of 158 CCM claims, 131 (83%) were paid and 27 (17%) were unpaid or remained in adjudication at study completion.
CONCLUSION: Pharmacist-led CCM resulted in a modest positive return on investment compared to other reimbursable pharmacy services. Practitioners should evaluate opportunities to synergize CCM with other fee-for-service and quality-based reimbursement programs.

PMID: 32995845 [PubMed - as supplied by publisher]

Tat expression led to increased histone 3 tri-methylation at lysine 27 and contributed to HIV latency in astrocytes through regulation of MeCP2 and Ezh2 expression.

Thu, 10/01/2020 - 10:17
Related Articles

Tat expression led to increased histone 3 tri-methylation at lysine 27 and contributed to HIV latency in astrocytes through regulation of MeCP2 and Ezh2 expression.

J Neurovirol. 2019 08;25(4):508-519

Authors: Liu Y, Niu Y, Li L, Timani KA, He VL, Sanburns C, Xie J, He JJ

Abstract
Astrocytes are susceptible to HIV infection and potential latent HIV reservoirs. Tat is one of three abundantly expressed HIV early genes in HIV-infected astrocytes and has been shown to be a major pathogenic factor for HIV/neuroAIDS. In this study, we sought to determine if and how Tat expression would affect HIV infection and latency in astrocytes. Using the glycoprotein from vesicular stomatitis virus-pseudotyped red-green HIV (RGH) reporter viruses, we showed that HIV infection was capable of establishing HIV latency in astrocytes. We also found that Tat expression decreased the generation of latent HIV-infected cells. Activation of latent HIV-infected astrocytes showed that treatment of GSK126, a selective inhibitor of methyltransferase enhancer of zeste homolog 2 (Ezh2) that is specifically responsible for tri-methylation of histone 3 lysine 27 (H3K27me3), led to activation of significantly more latent HIV-infected Tat-expressing astrocytes. Molecular analysis showed that H3K27me3, Ezh2, MeCP2, and Tat all exhibited a similar bimodal expression kinetics in the course of HIV infection and latency in astrocytes, although H3K27me3, Ezh2, and MeCP2 were expressed higher in Tat-expressing astrocytes and their expression were peaked immediately preceding Tat expression. Subsequent studies showed that Tat expression alone was sufficient to induce H3K27me3 expression, likely through its regulation of Ezh2 and MeCP2 expression. Taken together, these results showed for the first time that Tat expression induced H3K27me3 expression and contributed to HIV latency in astrocytes and suggest a new role and novel mechanism for Tat in HIV latency.

PMID: 31020497 [PubMed - indexed for MEDLINE]

Baseline Characteristics of the 2015-2019 First Year Student Cohorts of the NIH Building Infrastructure Leading to Diversity (BUILD) Program.

Wed, 09/30/2020 - 06:15

Baseline Characteristics of the 2015-2019 First Year Student Cohorts of the NIH Building Infrastructure Leading to Diversity (BUILD) Program.

Ethn Dis. 2020;30(4):681-692

Authors: Norris KC, McCreath HE, Hueffer K, Aley SB, Chavira G, Christie CA, Crespi CM, Crespo C, D'Amour G, Eagan K, Echegoyen LE, Feig A, Foroozesh M, Guerrero LR, Johanson K, Kamangar F, Kingsford L, LaCourse W, Maccalla NM, Márquez-Magaña L, Mathur A, Maton K, Mehravaran S, Morales DX, Nakazono T, Ofili E, Okuyemi K, Ott L, Parangan-Smith A, Pfund C, Purnell D, Reynolds A, Rous PJ, Saetermoe C, Snyder K, Vishwanatha JK, Wagler A, Wallace SP, Seeman T

Abstract
Objective: The biomedical/behavioral sciences lag in the recruitment and advancement of students from historically underrepresented backgrounds. In 2014 the NIH created the Diversity Program Consortium (DPC), a prospective, multi-site study comprising 10 Building Infrastructure Leading to Diversity (BUILD) institutional grantees, the National Research Mentoring Network (NRMN) and a Coordination and Evaluation Center (CEC). This article describes baseline characteristics of four incoming, first-year student cohorts at the primary BUILD institutions who completed the Higher Education Research Institute, The Freshmen Survey between 2015-2019. These freshmen are the primary student cohorts for longitudinal analyses comparing outcomes of BUILD program participants and non-participants.
Design: Baseline description of first-year students entering college at BUILD institutions during 2015-2019.
Setting: Ten colleges/universities that each received <$7.5mil/yr in NIH Research Project Grants and have high proportions of low-income students.
Participants: First-year undergraduate students who participated in BUILD-sponsored activities and a sample of non-BUILD students at the same BUILD institutions. A total of 32,963 first-year students were enrolled in the project; 64% were female, 18% Hispanic/Latinx, 19% African American/Black, 2% American Indian/Alaska Native and Native Hawaiian/Pacific Islander, 17% Asian, and 29% White. Twenty-seven percent were from families with an income <$30,000/yr and 25% were their family's first generation in college.
Planned Outcomes: Primary student outcomes to be evaluated over time include undergraduate biomedical degree completion, entry into/completion of a graduate biomedical degree program, and evidence of excelling in biomedical research and scholarship.
Conclusions: The DPC national evaluation has identified a large, longitudinal cohort of students with many from groups historically underrepresented in the biomedical sciences that will inform institutional/national policy level initiatives to help diversify the biomedical workforce.

PMID: 32989368 [PubMed - in process]

Methods for Investigating Corneal Cell Interactions and Extracellular Vesicles In Vitro.

Tue, 09/29/2020 - 07:45
Related Articles

Methods for Investigating Corneal Cell Interactions and Extracellular Vesicles In Vitro.

Curr Protoc Cell Biol. 2020 Dec;89(1):e114

Authors: McKay TB, Guo X, Hutcheon AEK, Karamichos D, Ciolino JB

Abstract
Science and medicine have become increasingly "human-centric" over the years. A growing shift away from the use of animals in basic research has led to the development of sophisticated in vitro models of various tissues utilizing human-derived cells to study physiology and disease. The human cornea has likewise been modeled in vitro using primary cells derived from corneas obtained from cadavers or post-transplantation. By utilizing a cell's intrinsic ability to maintain its tissue phenotype in a pre-designed microenvironment containing the required growth factors, physiological temperature, and humidity, tissue-engineered corneas can be grown and maintained in culture for relatively long periods of time on the scale of weeks to months. Due to its transparency and avascularity, the cornea is an optimal tissue for studies of extracellular matrix and cell-cell interactions, toxicology and permeability of drugs, and underlying mechanisms of scarring and tissue regeneration. This paper describes methods for the cultivation of corneal keratocytes, fibroblasts, epithelial, and endothelial cells for in vitro applications. We also provide detailed, step-by-step protocols for assembling and culturing 3D constructs of the corneal stroma, epithelial- and endothelial-stromal co-cultures and isolation of extracellular vesicles. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Isolating and culturing human corneal keratocytes and fibroblasts Basic Protocol 2: Isolating and culturing human corneal epithelial cells Basic Protocol 3: Isolating and culturing human corneal endothelial cells Basic Protocol 4: 3D corneal stromal construct assembly Basic Protocol 5: 3D corneal epithelial-stromal construct assembly Basic Protocol 6: 3D corneal endothelial-stromal construct assembly Basic Protocol 7: Isolating extracellular vesicles from corneal cell conditioned medium Support Protocol: Cryopreserving human corneal fibroblasts, corneal epithelial cells, and corneal endothelial cells.

PMID: 32986311 [PubMed - as supplied by publisher]

Are low LRs reliable?

Mon, 09/28/2020 - 06:20
Related Articles

Are low LRs reliable?

Forensic Sci Int Genet. 2020 Jul 08;49:102350

Authors: Buckleton JS, Pugh SN, Bright JA, Taylor DA, Curran JM, Kruijver M, Gill P, Budowle B, Cheng K

Abstract
To answer the question "Are low likelihood ratios reliable?" requires both a definition of reliable and then a test of whether low likelihood ratios (LRs) meet that definition. We offer, from a purely statistical standpoint, that reliability can be determined by assessing whether the rate of inclusionary support for non-donors over many cases is not larger than expected from the LR value. Thus, it is not the magnitude of the LR alone that determines reliability. Turing's rule is used to inform the expected rate of non-donor inclusionary support, where the rate of non-donor inclusionary support is at most the reciprocal of the LR, i.e. Pr(LR >x|Ha) ≤1/x. There are parallel concerns about whether the value of the evidence can be communicated. We do not discuss that in depth here although it is an important consideration to be addressed with training. In this paper, we use a mixture of real and simulated data to show that the rate of non-donor inclusionary support for these data is significantly lower than the upper bound given by Turing's rule. We take this as strong evidence that low LRs are reliable.

PMID: 32979624 [PubMed - as supplied by publisher]

Biomechanical Study of Patellar Component Fixation with Varying Degrees of Bone Loss.

Mon, 09/28/2020 - 06:20
Related Articles

Biomechanical Study of Patellar Component Fixation with Varying Degrees of Bone Loss.

J Arthroplasty. 2020 Aug 25;:

Authors: Beck CM, Nwannunu BI, Teigen KJ, Wagner RA

Abstract
BACKGROUND: The decision as to whether or not to resurface the patella in revision total knee arthroplasty (TKA) is affected by the amount of patellar bone stock remaining; however, the impact of the cancellous bone status on patellar component fixation has not been studied. Therefore, we conducted a biomechanical study of patellar component fixation with varying degrees of cancellous bone loss.
METHODS: Sixty pairs of cadaveric patellae were randomly assigned between 3 groups and prepared in similar manner to a TKA with the standard 3-hole configuration. A control patella and an experimental patella were designated in each pair. To simulate bone loss in the experimental patellae, 1, 2, and 3 of the standard drill holes were uniformly enlarged to 12 mm in group 1, group 2, and group 3, respectively. Afterward, an all-polyethylene patellar component was cemented to each patella, as done intraoperatively. Patellar components were then sheared off using a materials testing system. The resulting mean offset yield force was analyzed within each group using paired t-tests.
RESULTS: The mean offset yield force for the control patellae was greater than the experimental patellae in group 1. In groups 2 and 3, the experimental patellae produced a greater mean offset yield force than the control patellae. Comparison within each group did not demonstrate a statistically significant difference.
CONCLUSION: Bone loss with enlargement of the patellar fixation holes, as is frequently seen in revision TKA, with holes up to 12 mm, does not significantly decrease patellar component fixation shear strength in this biomechanical cadaveric study.

PMID: 32978021 [PubMed - as supplied by publisher]

Understanding the Interplay Between Health Disparities and Epigenomics.

Sat, 09/26/2020 - 06:07
Related Articles

Understanding the Interplay Between Health Disparities and Epigenomics.

Front Genet. 2020;11:903

Authors: Mancilla VJ, Peeri NC, Silzer T, Basha R, Felini M, Jones HP, Phillips N, Tao MH, Thyagarajan S, Vishwanatha JK

Abstract
Social epigenomics has emerged as an integrative field of research focused on identification of socio-environmental factors, their influence on human biology through epigenomic modifications, and how they contribute to current health disparities. Several health disparities studies have been published using genetic-based approaches; however, increasing accessibility and affordability of molecular technologies have allowed for an in-depth investigation of the influence of external factors on epigenetic modifications (e.g., DNA methylation, micro-RNA expression). Currently, research is focused on epigenetic changes in response to environment, as well as targeted epigenetic therapies and environmental/social strategies for potentially minimizing certain health disparities. Here, we will review recent findings in this field pertaining to conditions and diseases over life span encompassing prenatal to adult stages.

PMID: 32973872 [PubMed]

Early phosphoproteomic changes in the retina following optic nerve crush.

Fri, 09/25/2020 - 08:00
Related Articles

Early phosphoproteomic changes in the retina following optic nerve crush.

Exp Neurol. 2020 Sep 21;:113481

Authors: Liu Y, Zhong H, Bussan EL, Pang IH

Abstract
Retinal ganglion cell (RGC) death causes irreversible blindness in adult mammals. Death of RGC occurs in diseases including glaucoma or injuries to the optic nerve (ON). To investigate mechanisms involved in RGC degeneration, we evaluated the phosphoproteomic changes in the retina induced by ON injury. Intraorbital optic nerve crush (ONC) was performed in adult C57BL/6J mice. Retinas were collected at 0, 6, and 12 h following ONC. Retinal proteins labeled with CyDye-C2 were subject to 2D-PAGE, followed by phosphoprotein staining and in-gel/cross-gel image analysis. Proteins with significant changes in phosphorylation (ratios ≥1.2) in retinas of the injured eyes compared to the control eyes were spot-picked, tryptic digested, and peptide fragments were analyzed by MALDI-TOF (MS) and TOF/TOF (tandem MS/MS). Intraorbital ONC increased phosphorylation of many retinal proteins. Among them, 29 significantly phosphorylated proteins were identified. PANTHER analysis showed that these proteins are associated with a variety of protein class, cellular component, biological process and signaling pathways. One of the identified proteins, phosphoprotein enriched in astrocytes 15 (PEA15), was further validated by western blotting and immunofluorescence staining. Function of PEA15 was determined in cultured astrocytes. PEA15 knockdown reduced astrocyte phagocytic activity but promoted cell migration. Long term PEA15 knockdown also decreased astrocyte ATP level. This study provides new insights into mechanisms of RGC degeneration after ON injury, as well as central nervous system (CNS) neurodegeneration, since the retina is an extension of the CNS. These new insights will lead to novel therapeutic targets for retinal and CNS neurodegeneration.

PMID: 32971066 [PubMed - as supplied by publisher]

Ovarian cancer: Current status and strategies for improving therapeutic outcomes.

Fri, 09/25/2020 - 08:00
Related Articles

Ovarian cancer: Current status and strategies for improving therapeutic outcomes.

Cancer Med. 2019 11;8(16):7018-7031

Authors: Chandra A, Pius C, Nabeel M, Nair M, Vishwanatha JK, Ahmad S, Basha R

Abstract
Of all the gynecologic tumors, ovarian cancer (OC) is known to be the deadliest. Advanced-stages of OC are linked with high morbidity and low survival rates despite the immense amount of research in the field. Shortage of promising screening tools for early-stage detection is one of the major challenges linked with the poor survival rate for patients with OC. In OC, therapeutic management is used with multidisciplinary approaches that includes debulking surgery, chemotherapy, and (rarely) radiotherapy. Recently, there is an increasing interest in using immunomodulation for treating OC. Relapse rates are high in this malignancy and averages around every 2-years. Further treatments after the relapse are more intense, increasing the toxicity, resistance to chemotherapy drugs, and financial burden to patients with poor quality-of-life. A procedure that has been studied to help reduce the morbidity rate involves pre-sensitizing cancer cells with standard therapy in order to produce optimal results with minimum dosage. Utilizing such an approach, platinum-based agents are effective due to their increased response to platinum-based chemotherapy in relapsed cases. These chemo-drugs also help address the issue of drug resistance. After conducting an extensive search with available literature and the resources for clinical trials, information is precisely documented on current research, biomarkers, options for treatment and clinical trials. Several schemes for enhancing the therapeutic responses for OC are discussed systematically in this review with an attempt in summarizing the recent developments in this exciting field of translational/clinical research.

PMID: 31560828 [PubMed - indexed for MEDLINE]

Circulating factors in young blood as potential therapeutic agents for age-related neurodegenerative and neurovascular diseases.

Fri, 09/25/2020 - 08:00
Related Articles

Circulating factors in young blood as potential therapeutic agents for age-related neurodegenerative and neurovascular diseases.

Brain Res Bull. 2019 11;153:15-23

Authors: Ma J, Gao B, Zhang K, Zhang Q, Jia G, Li J, Li C, Yan LJ, Cai Z

Abstract
Recent animal studies on heterochronic parabiosis (a technique combining the blood circulation of two animals) have revealed that young blood has a powerful rejuvenating effect on brain aging. Circulating factors, especially growth differentiation factor 11 (GDF11) and C-C motif chemokine 11 (CCL11), may play a key role in this effect, which inspires hope for novel approaches to treating age-related cerebral diseases in humans, such as neurodegenerative and neurovascular diseases. Recently, attempts have begun to translate these astonishing and exciting findings from mice to humans and from bench to bedside. However, increasing reports have shown contradictory data, questioning the capacity of these circulating factors to reverse age-related brain dysfunction. In this review, we summarize the current research on the role of young blood, as well as the circulating factors GDF11 and CCL11, in the aging brain and age-related cerebral diseases. We highlight recent controversies, discuss related challenges and provide a future outlook.

PMID: 31400495 [PubMed - indexed for MEDLINE]

The Perfect Storm: COVID-19 Health Disparities in US Blacks.

Thu, 09/24/2020 - 06:12
Related Articles

The Perfect Storm: COVID-19 Health Disparities in US Blacks.

J Racial Ethn Health Disparities. 2020 Sep 23;:

Authors: Phillips N, Park IW, Robinson JR, Jones HP

Abstract
Coronavirus disease 2019 (COVID-19) accounts for over 180,000 deaths in the USA. Although COVID-19 affects all racial ethnicities, non-Hispanic Blacks have the highest mortality rates. Evidence continues to emerge, linking the disproportion of contagion and mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a result of adverse social determinants of health. Yet, genetic predisposition may also play a credible role in disease transmission. SARS-CoV-2 enters cells by interaction between SARS-CoV-2 spike protein and the receptor molecule angiotensin converting enzyme 2 (ACE2) expressed on the surface of the target cells, such that polymorphisms and the expression level of ACE2 influence infectivity and consequent pathogenesis of SARS-CoV-2. Genetic polymorphisms in other multiple genes, such as acetylcholinesterase (AChE) and interleukin-6, are also closely associated with underlying diseases, such as hypertension and type 2 diabetes mellitus, which substantially raise SARS-CoV-2 mortality. However, it is unknown how these genetic polymorphisms contribute to the disparate mortality rates, with or without underlying diseases. Of particular interest is the potential that genetic polymorphisms in these genes may be influencing the disparity of COVID-19 mortality rates in Black communities. Here, we review the evidence that biological predisposition for high-risk comorbid conditions may be relevant to our ability to fully understand and therefore address health disparities of COVID-19 deaths in Blacks.

PMID: 32965660 [PubMed - as supplied by publisher]

Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity.

Thu, 09/24/2020 - 06:12
Related Articles

Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity.

J Mol Med (Berl). 2020 Sep 22;:

Authors: Daniel S, Renwick M, Chau VQ, Datta S, Maddineni P, Zode G, Wade EM, Robertson SP, Petroll WM, Hulleman JD

Abstract
Fibulin-3 (F3) is an extracellular matrix glycoprotein found in basement membranes across the body. An autosomal dominant R345W mutation in F3 causes a macular dystrophy resembling dry age-related macular degeneration (AMD), whereas genetic removal of wild-type (WT) F3 protects mice from sub-retinal pigment epithelium (RPE) deposit formation. These observations suggest that F3 is a protein which can regulate pathogenic sub-RPE deposit formation in the eye. Yet the precise role of WT F3 within the eye is still largely unknown. We found that F3 is expressed throughout the mouse eye (cornea, trabecular meshwork (TM) ring, neural retina, RPE/choroid, and optic nerve). We next performed a thorough structural and functional characterization of each of these tissues in WT and homozygous (F3-/-) knockout mice. The corneal stroma in F3-/- mice progressively thins beginning at 2 months, and the development of corneal opacity and vascularization starts at 9 months, which worsens with age. However, in all other tissues (TM, neural retina, RPE, and optic nerve), gross structural anatomy and functionality were similar across WT and F3-/- mice when evaluated using SD-OCT, histological analyses, electron microscopy, scotopic electroretinogram, optokinetic response, and axonal anterograde transport. The lack of noticeable retinal abnormalities in F3-/- mice was confirmed in a human patient with biallelic loss-of-function mutations in F3. These data suggest that (i) F3 is important for maintaining the structural integrity of the cornea, (ii) absence of F3 does not affect the structure or function of any other ocular tissue in which it is expressed, and (iii) targeted silencing of F3 in the retina and/or RPE will likely be well-tolerated, serving as a safe therapeutic strategy for reducing sub-RPE deposit formation in disease. KEY MESSAGES: • Fibulins are expressed throughout the body at varying levels. • Fibulin-3 has a tissue-specific pattern of expression within the eye. • Lack of fibulin-3 leads to structural deformities in the cornea. • The retina and RPE remain structurally and functionally healthy in the absence of fibulin-3 in both mice and humans.

PMID: 32964303 [PubMed - as supplied by publisher]

Translaminar Autonomous System Model for the Modulation of Intraocular and Intracranial Pressure in Human Donor Posterior Segments.

Thu, 09/24/2020 - 06:12
Related Articles

Translaminar Autonomous System Model for the Modulation of Intraocular and Intracranial Pressure in Human Donor Posterior Segments.

J Vis Exp. 2020 04 24;(158):

Authors: Sharma TP, Curry SM, Lohawala H, McDowell C

Abstract
There is a current unmet need for a new preclinical human model that can target disease etiology ex vivo using intracranial pressure (ICP) and intraocular pressure (IOP) which can identify various pathogenic paradigms related to the glaucoma pathogenesis. Ex vivo human anterior segment perfusion organ culture models have previously been successfully utilized and applied as effective technologies for the discovery of glaucoma pathogenesis and testing of therapeutics. Preclinical drug screening and research performed on ex vivo human organ systems can be more translatable to clinical research. This article describes in detail the generation and operation of a novel ex vivo human translaminar pressure model called the translaminar autonomous system (TAS). The TAS model can independently regulate ICP and IOP using human donor posterior segments. The model allows for studying pathogenesis in a preclinical manner. It can reduce the use of living animals in ophthalmic research. In contrast to in vitro experimental models, optic nerve head (ONH) tissue structure, complexity, and integrity can also be maintained within the ex vivo TAS model.

PMID: 32421000 [PubMed - indexed for MEDLINE]

A systematic approach to team creation and peer evaluation in a large classroom setting.

Thu, 09/24/2020 - 06:12
Related Articles

A systematic approach to team creation and peer evaluation in a large classroom setting.

Curr Pharm Teach Learn. 2019 Dec;11(12):1231-1238

Authors: Gaviola ML, Atanda A, Howard ML, Yuet WC

Abstract
INTRODUCTION: There is limited data to support a particular method for optimal team creation in pharmacy education. We aimed to implement and evaluate a systematic approach to team creation and compare the impact on team dynamics to teams created via random selection.
METHODS: Two concurrent courses were used to assess team creation methods. Student-specific variables were used for team creation in one course while another course utilized teams created via random allocation. Each course conducted similar peer evaluations to provide feedback and assess team dynamics. A matched pre- and post-course survey assessed changes in student perceptions of team creation and peer evaluation. Student-perceived team effectiveness and individual coursework performance were assessed.
RESULTS: A total of 109 students were enrolled in each of the two courses, with 98% and 93% providing evaluation of team dynamics within the intervention and control methods, respectively. Students perceived better team effectiveness in intervention-created groups in relation to decreased task (p < 0.01), relationship (p < 0.01), and process conflict (p < 0.01), along with increased task attraction (p < 0.01). There was no significant difference in student performance on individual examinations team creation methods (p = 0.17).
CONCLUSIONS: A systematic approach to team creation improved student-perceived team dynamics with no significant impact on coursework scores. A systematic approach to team creation via a web-based platform is feasible in a large classroom setting and may provide an avenue for assessment approaches related to teamwork and team dynamics.

PMID: 31836147 [PubMed - indexed for MEDLINE]

Pages