Recent Research Articles from UNTHSC

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

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CRISPR based editing of SIV proviral DNA in ART treated non-human primates.

Sun, 11/29/2020 - 06:22
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CRISPR based editing of SIV proviral DNA in ART treated non-human primates.

Nat Commun. 2020 Nov 27;11(1):6065

Authors: Mancuso P, Chen C, Kaminski R, Gordon J, Liao S, Robinson JA, Smith MD, Liu H, Sariyer IK, Sariyer R, Peterson TA, Donadoni M, Williams JB, Siddiqui S, Bunnell BA, Ling B, MacLean AG, Burdo TH, Khalili K

Abstract
Elimination of HIV DNA from infected individuals remains a challenge in medicine. Here, we demonstrate that intravenous inoculation of SIV-infected macaques, a well-accepted non-human primate model of HIV infection, with adeno-associated virus 9 (AAV9)-CRISPR/Cas9 gene editing construct designed for eliminating proviral SIV DNA, leads to broad distribution of editing molecules and precise cleavage and removal of fragments of the integrated proviral DNA from the genome of infected blood cells and tissues known to be viral reservoirs including lymph nodes, spleen, bone marrow, and brain among others. Accordingly, AAV9-CRISPR treatment results in a reduction in the percent of proviral DNA in blood and tissues. These proof-of-concept observations offer a promising step toward the elimination of HIV reservoirs in the clinic.

PMID: 33247091 [PubMed - as supplied by publisher]

Knowledge, Attitudes, and Practices on Climate Change and Dengue in Lao People's Democratic Republic and Thailand.

Sat, 11/28/2020 - 07:39
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Knowledge, Attitudes, and Practices on Climate Change and Dengue in Lao People's Democratic Republic and Thailand.

Environ Res. 2020 Nov 24;:110509

Authors: Rahman MS, Overgaard HJ, Pientong C, Mayxay M, Ekalaksananan T, Aromseree S, Phanthanawiboon S, Zafar S, Shipin O, Paul RE, Phommachanh S, Pongvongsa T, Vannavong N, Haque U

Abstract
BACKGROUND: Dengue is linked with climate change in tropical and sub-tropical countries including the Lao People's Democratic Republic (Laos) and Thailand. Knowledge about these issues and preventive measures can affect the incidence and outbreak risk of dengue. Therefore, the present study was conducted to determine the knowledge, attitudes, and practices (KAP) among urban and rural communities and government officials about climate change and dengue in Laos and Thailand.
METHODS: A cross-sectional KAP survey about climate change and dengue were conducted in 360 households in Laos (180 urban and 180 rural), 359 households in Thailand (179 urban and 180 rural), and 20 government officials (10 in each country) using structured questionnaires. Data analysis was undertaken using descriptive methods, principal component analysis, Chi-square test or Fisher's exact test (as appropriate), and logistic regression.
RESULTS: Significant differences among the selected communities in both countries were found in terms of household participant's age, level of education, socioeconomic status, attitude level of climate change and KAP level of dengue (P < 0.05; 95% CI). Overall, participants' KAP about climate change and dengue were low except the attitude level for dengue in both countries. The level of awareness among government officials regarding the climatic relationship with dengue was also low. In Lao households, participants' knowledge about climate change and dengue was significantly associated with the level of education and socioeconomic status (SES) (P < 0.01). Their attitudes towards climate change and dengue were associated with educational level and internet use (P < 0.05). Householders' climate change related practices were associated with SES (P < 0.01) and dengue related practices were associated with educational level, SES, previous dengue experience and internet use (P < 0.01). In Thailand, participants' knowledge about climate change was associated with the level of education and SES (P < 0.01). Their attitudes towards climate change were associated with residence status (urban/rural) and internet use (P < 0.05); climate change related practices were associated with educational level and SES (P < 0.05). Dengue related knowledge of participants was associated with SES and previous dengue experience (P < 0.05); participants' dengue related attitudes and practices were associated with educational level (P < 0.01).
CONCLUSION: The findings call for urgently needed integrated awareness programs to increase KAP levels regarding climate change adaptation, mitigation and dengue prevention to improve the health and welfare of people in these two countries, and similar dengue-endemic countries.

PMID: 33245883 [PubMed - as supplied by publisher]

Rapid de novo evolution of lysis genes in single-stranded RNA phages.

Sat, 11/28/2020 - 07:39
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Rapid de novo evolution of lysis genes in single-stranded RNA phages.

Nat Commun. 2020 Nov 26;11(1):6009

Authors: Chamakura KR, Tran JS, O'Leary C, Lisciandro HG, Antillon SF, Garza KD, Tran E, Min L, Young R

Abstract
Leviviruses are bacteriophages with small single-stranded RNA genomes consisting of 3-4 genes, one of which (sgl) encodes a protein that induces the host to undergo autolysis and liberate progeny virions. Recent meta-transcriptomic studies have uncovered thousands of leviviral genomes, but most of these lack an annotated sgl, mainly due to the small size, lack of sequence similarity, and embedded nature of these genes. Here, we identify sgl genes in 244 leviviral genomes and functionally characterize them in Escherichia coli. We show that leviviruses readily evolve sgl genes and sometimes have more than one per genome. Moreover, these genes share little to no similarity with each other or to previously known sgl genes, thus representing a rich source for potential protein antibiotics.

PMID: 33243984 [PubMed - in process]

Use of Complementary Health Approaches for Chronic Low-Back Pain: A Pain Research Registry-Based Study.

Thu, 11/26/2020 - 07:04
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Use of Complementary Health Approaches for Chronic Low-Back Pain: A Pain Research Registry-Based Study.

J Altern Complement Med. 2020 May;26(5):369-375

Authors: Licciardone JC, Pandya V

Abstract
Objectives: To measure the use of complementary health approaches (CHAs) recommended in recent clinical practice guidelines relating to low-back pain, multivariate factors associated with their use, and clinical outcomes of CHA users and nonusers. Design: Observational cross-sectional study. Settings/Location: The Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation. Subjects: A total of 568 patients with chronic low-back pain. Interventions: Massage therapy, spinal manipulation, yoga, and acupuncture. Outcome measures: The numerical rating scale for low-back pain intensity, Roland-Morris Disability Questionnaire for back-related disability, and the Patient-Reported Outcomes Measurement Information System with 29 items for quality-of-life deficits relating to sleep disturbance, pain interference with activities, anxiety, depression, and low energy/fatigue. Results: The distribution of the number of different CHAs used by patients for low-back pain was as follows: 0, 179 (31.5%); 1, 139 (24.5%); 2, 160 (28.2%); 3, 70 (12.3%); and 4, 20 (3.5%). The numbers of patients using the specific CHAs were as follows: massage therapy, 271 (47.7%); spinal manipulation, 238 (41.9%); yoga, 144 (25.4%); and acupuncture, 96 (16.9%). Opioids had been used for low-back pain by 415 (73.1%) patients. Higher levels of education and higher pain self-efficacy scores were associated with greater use of any CHA, whereas increasing age and being Black were associated with lesser use of any CHA. Any CHA use was associated with lesser low-back pain intensity and lesser back-related disability. Patients who used massage therapy reported better clinical outcomes across all three dimensions. Patient pain self-efficacy also enhanced the effect of CHA use. Conclusions: The use of CHAs relative to opioids for low-back pain was inconsistent with recommendations from recent clinical practice guidelines despite clinical benefits with CHA use in this study. More research is needed on ways to improve the uptake of CHAs recommended for low-back pain, particularly among older and Black patients.

PMID: 32167785 [PubMed - indexed for MEDLINE]

Effect of implant formation on drug release kinetics of in situ forming implants.

Wed, 11/25/2020 - 07:37
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Effect of implant formation on drug release kinetics of in situ forming implants.

Int J Pharm. 2020 Nov 21;:120105

Authors: Sung Suh M, Kastellorizios M, Tipnis N, Zou Y, Wang Y, Choi S, Burgess DJ

Abstract
In situ forming implants are attractive long-acting implant dosage forms due to their: i) ability to control drug release; ii) simple manufacturing process; and iii) minimally invasive administration. In situ forming implants are typically made of a drug, solvent, and a biocompatible polymer that controls drug release. Once injected in the subcutaneous tissue, they form solid depots through solvent/non-solvent exchange and phase separation of the biodegradable polymer (such as poly (lactic-co-glycolic acid), PLGA and poly (lactic acid), PLA). However, the mechanism of implant formation and the changes in their microstructure that determine drug release behavior are not fully understood. Furthermore, there is no standardized in vitro release testing method for in situ forming implants due to limitations in recreating bio-relevant and reproducible implant formation in vitro with controllable implant shape, dimensions and surface-to-volume ratio. In the present study, bio-relevant implant formation was recreated in vitro by testing five different methods to determine their effect on drug release kinetics, reproducibility, and internal microstructure formation. The leuprolide acetate formulation Eligard® was used as a model in situ-forming implant, consisting of lyophilized leuprolide acetate, and PLGA dissolved in N-methyl pyrrolidone. The results revealed that the in vitro implant formation method is a crucial step in the dissolution testing process that significantly impacts the release profile of in situ forming implants. An implant formation method that utilizes dissolvable polyvinyl alcohol (PVA) films allowed for initial drug burst release control by modulating implant dimensions (i.e. surface area) and resulted in reproducible in vitro release profiles. In addition, implant formation was shown to affect the internal microstructure of in situ forming implant and was the main factor controlling the release profile which consisted of an initial release phase followed by a release plateau (lag phase) and then a second erosion-controlled release phase.

PMID: 33232755 [PubMed - as supplied by publisher]

Clinical Symptoms of Arboviruses in Mexico.

Wed, 11/25/2020 - 07:37
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Clinical Symptoms of Arboviruses in Mexico.

Pathogens. 2020 Nov 19;9(11):

Authors: Ananth S, Shrestha N, Treviño C JA, Nguyen US, Haque U, Angulo-Molina A, Lopez-Lemus UA, Lubinda J, Sharif RM, Zaki RA, Sánchez Casas RM, Cervantes D, Nandy R

Abstract
Arboviruses such as Chikungunya (CHIKV), Dengue (DENV), and Zika virus (ZIKV) have emerged as a significant public health concern in Mexico. The existing literature lacks evidence regarding the dispersion of arboviruses, thereby limiting public health policy's ability to integrate the diagnosis, management, and prevention. This study seeks to reveal the clinical symptoms of CHIK, DENV, and ZIKV by age group, region, sex, and time across Mexico. The confirmed cases of CHIKV, DENV, and ZIKV were compiled from January 2012 to March 2020. Demographic characteristics analyzed significant clinical symptoms of confirmed cases. Multinomial logistic regression was used to assess the association between clinical symptoms and geographical regions. Females and individuals aged 15 and older had higher rates of reported significant symptoms across all three arboviruses. DENV showed a temporal variation of symptoms by regions 3 and 5, whereas ZIKV presented temporal variables in regions 2 and 4. This study revealed unique and overlapping symptoms between CHIKV, DENV, and ZIKV. However, the differentiation of CHIKV, DENV, and ZIKV is difficult, and diagnostic facilities are not available in rural areas. There is a need for adequately trained healthcare staff alongside well-equipped lab facilities, including hematological tests and imaging facilities.

PMID: 33228120 [PubMed]

Possible Protective Effect of Omalizumab on Lung Function Decline in Patients Experiencing Asthma Exacerbations.

Tue, 11/24/2020 - 06:09
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Possible Protective Effect of Omalizumab on Lung Function Decline in Patients Experiencing Asthma Exacerbations.

J Allergy Clin Immunol Pract. 2020 Oct 24;:

Authors: Busse WW, Szefler SJ, Haselkorn T, Iqbal A, Ortiz B, Lanier BQ, Chipps BE

Abstract
BACKGROUND: Frequent exacerbations are associated with greater FEV1 decline in patients with asthma. The effect of omalizumab versus placebo on lung function in patients experiencing asthma exacerbations has not been previously examined.
OBJECTIVE: To evaluate the relationship between postbaseline (treatment phase) exacerbation status and lung function decline in children, adolescents, and adults treated with omalizumab versus placebo using data from 3 pediatric and adolescent/adult studies.
METHODS: Changes in percent predicted FEV1 (ppFEV1) and FEV1 by treatment (omalizumab/placebo) and postbaseline exacerbation status (exacerbators/nonexacerbators) were assessed in patients aged 6 to 11 years (IA05, n = 576) and 12 to 75 years (EXTRA/INNOVATE pooled, n = 1202). Pediatric patients were examined at treatment weeks 12, 24, 28, 40, and 52, and adolescent/adult data at weeks 4, 12, 20, and 28.
RESULTS: Omalizumab-treated patients experienced larger increases in ppFEV1 and FEV1 compared with placebo-treated patients in the pediatric and pooled adolescent/adult populations. The response was observed in pediatric exacerbators, with significantly larger increases in ppFEV1 and FEV1 at week 12 (mean difference [95% CI], 4.11% [0.93%-7.30%], P = .011 for ppFEV1; 80 [10-140] mL, P = .017 for FEV1) and week 28 (mean difference [95% CI], 3.65% [0.11%-7.19%], P = .043 for ppFEV1; 100 [30-170] mL, P = .007 for FEV1). In the adolescent/adult population, both exacerbators and nonexacerbators derived similar benefit with omalizumab compared with placebo.
CONCLUSIONS: Findings from this post hoc analysis suggest that omalizumab may confer some protection against lung function decline among patients who experienced exacerbations during treatment.

PMID: 33223095 [PubMed - as supplied by publisher]

Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

Tue, 11/24/2020 - 06:09
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Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

Sci Rep. 2020 06 10;10(1):9426

Authors: McKay TB, Serjersen H, Hjortdal J, Zieske JD, Karamichos D

Abstract
Keratoconus (KC) is classically considered a non-inflammatory condition caused by central corneal thinning that leads to astigmatism and reduced visual acuity. Previous studies have identified increased systemic levels of pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9, suggesting that KC may have an inflammatory component in at least a subset of patients. In this study, we evaluated the levels of different immunoglobulins (light and heavy chains) based on Ig α, Ig λ, Ig κ, Ig µ, and Ig heavy chain subunits in non-KC tears (n = 7 control individuals) and KC tears (n = 7 KC patients) using tandem-liquid chromatography mass spectrometry. The most abundant Ig heavy chains detected in both control individuals and KC patients were Ig α-1 and Ig α-2 likely correlating to the higher IgA levels reported in human tears. We identified significant differences in immunoglobulin κ-chain V-II levels in KC patients compared to control individuals with no significant difference in Ig κ/Ig λ ratios or heavy chain levels. Our study supports previous findings suggesting that KC possesses a systemic component that may contribute to the KC pathology. Further studies are required to define causality and establish a role for systemic immune system-dependent factors and pro-inflammatory processes in KC development or progression.

PMID: 32523038 [PubMed - indexed for MEDLINE]

Distinct Roles of mTOR Targets S6K1 and S6K2 in Breast Cancer.

Sat, 11/21/2020 - 05:56
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Distinct Roles of mTOR Targets S6K1 and S6K2 in Breast Cancer.

Int J Mol Sci. 2020 Feb 11;21(4):

Authors: Sridharan S, Basu A

Abstract
The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation, metabolism, cell growth and proliferation. It forms two complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2). mTORC1 is frequently deregulated in many cancers, including breast cancer, and is an important target for cancer therapy. The immunosuppressant drug rapamycin and its analogs that inhibit mTOR are currently being evaluated for their potential as anti-cancer agents, albeit with limited efficacy. mTORC1 mediates its function via its downstream targets 40S ribosomal S6 kinases (S6K) and eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). There are two homologs of S6K: S6K1 and S6K2. Most of the earlier studies focused on S6K1 rather than S6K2. Because of their high degree of structural homology, it was generally believed that they behave similarly. Recent studies suggest that while they may share some functions, they may also exhibit distinct or even opposite functions. Both homologs have been implicated in breast cancer, although how they contribute to breast cancer may differ. The purpose of this review article is to compare and contrast the expression, structure, regulation and function of these two S6K homologs in breast cancer.

PMID: 32054043 [PubMed - indexed for MEDLINE]

A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure.

Fri, 11/20/2020 - 08:16
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A Comparison of Protocols for Simulating Hemorrhage in Humans: Step vs. Ramp Lower Body Negative Pressure.

J Appl Physiol (1985). 2020 Nov 19;:

Authors: Rosenberg AJ, Kay VL, Anderson GK, Sprick JD, Rickards CA

Abstract
Lower body negative pressure (LBNP) elicits central hypovolemia, and has been used to simulate the cardiovascular and cerebrovascular responses to hemorrhage in humans. LBNP protocols commonly employ progressive stepwise reductions in chamber pressure for specific time periods. However, continuous ramp LBNP protocols have also been utilized to simulate the continuous nature of most bleeding injuries. The aim of this study was to compare tolerance and hemodynamic responses between these two LBNP profiles. Healthy human subjects (N=19; age, 27±4 y; 7F/12M) completed a 1) step LBNP protocol (5-min steps), and; 2) continuous ramp LBNP protocol (3 mmHg/min), both to presyncope. Heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), middle and posterior cerebral artery velocity (MCAv and PCAv), cerebral oxygen saturation (ScO2), and end-tidal CO2 (etCO2) were measured. LBNP tolerance, via the cumulative stress index (CSI, summation of chamber pressure*time at each pressure), and hemodynamic responses were compared between the two protocols. The CSI (Step: 911±97 mmHg*min vs. Ramp: 823±83 mmHg*min; P=0.12) and the magnitude of central hypovolemia (%Δ SV, Step: -54.6±2.6 % vs. Ramp: -52.1±2.8 %; P=0.32) were similar between protocols. While there were no differences between protocols for the maximal %Δ HR (P=0.88), the %Δ MAP during the step protocol was attenuated (P=0.05), and the reductions in MCAv, PCAv, ScO2,and etCO2 were greater (P≤0.08) when compared with the ramp protocol at presyncope. These results indicate that when comparing cardiovascular responses to LBNP across different laboratories, the specific pressure profile must be considered as a potential confounding factor.

PMID: 33211600 [PubMed - as supplied by publisher]

Improvements in Retention in Care and HIV Viral Suppression Among Persons with HIV and Comorbid Mental Health Conditions: Patient-Centered HIV Care Model.

Fri, 11/20/2020 - 08:16
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Improvements in Retention in Care and HIV Viral Suppression Among Persons with HIV and Comorbid Mental Health Conditions: Patient-Centered HIV Care Model.

AIDS Behav. 2020 Dec;24(12):3522-3532

Authors: Byrd KK, Hardnett F, Hou JG, Clay PG, Suzuki S, Camp NM, Shankle MD, Weidle PJ, Taitel MS, Patient-Centered HIV Care Model Team

Abstract
The Patient-centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers and required sharing of patient clinical information and collaborative therapy-related action planning. We determined the proportions of participants with HIV and mental health conditions who were retained in care and the proportion virally suppressed, pre- and post-implementation. Overall, we found a relative 13% improvement in both retention [60% to 68% (p = 0.009)] and viral suppression [79% to 90% (p < 0.001)]. Notable improvements were seen among persons triply diagnosed with HIV, mental illness and substance use [+ 36% (50% to 68%, p = 0.036) and + 32% (66% to 86%, p = 0.001) in retention and viral suppression, respectively]. There were no differences in the proportions of persons adherent to psychiatric medications, pre- to post-implementation, nor were there differences in the proportions of persons retained in care or virally suppressed by psychiatric medication adherence, post-implementation. PCHCM demonstrated that collaborations between community-based pharmacists and medical providers can improve HIV care continuum outcomes among persons with mental health conditions.

PMID: 32415615 [PubMed - indexed for MEDLINE]

Microphysiological Systems: Design, Fabrication, and Applications.

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.

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.

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.

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.

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.

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.

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.

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.

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]

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