Recent Research Articles from UNTHSC

Functional connectome biotypes of chemotherapy-related cognitive impairment.

Wed, 12/16/2020 - 07:47
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Functional connectome biotypes of chemotherapy-related cognitive impairment.

J Cancer Surviv. 2020 08;14(4):483-493

Authors: Kesler SR, Petersen ML, Rao V, Harrison RA, Palesh O

Abstract
PURPOSE: Cancer-related cognitive impairment (CRCI) is a common neurotoxicity among patients with breast and other cancers. Neuroimaging studies have demonstrated measurable biomarkers of CRCI but have largely neglected the potential heterogeneity of the syndrome.
METHODS: We used retrospective functional MRI data from 80 chemotherapy-treated breast cancer survivors to examine neurophysiologic subtypes or "biotypes" of CRCI. The breast cancer group consisted of training (N = 57) and validation (N = 23) samples.
RESULTS: An unsupervised clustering approach using connectomes from the training sample identified three distinct biotypes. Cognitive performance (p < 0.05, corrected) and regional connectome organization (p < 0.001, corrected) differed significantly between the biotypes and also from 103 healthy female controls. We then built a random forest classifier using connectome features to distinguish between the biotypes (accuracy = 91%) and applied this to the validation sample to predict biotype assignment. Cognitive performance (p < 0.05, corrected) and regional connectome organization (p < 0.005, corrected) differed significantly between the predicted biotypes and healthy controls. Biotypes were also characterized by divergent clinical and demographic factors as well as patient reported outcomes.
CONCLUSIONS: Neurophysiologic biotypes may help characterize the heterogeneity associated with CRCI in a data-driven manner based on neuroimaging biomarkers.
IMPLICATIONS FOR CANCER SURVIVORS: Our novel findings provide a foundation for detecting potential risk and resilience factors that warrant further study. With further investigation, biotypes might be used to personalize assessments of and interventions for CRCI.

PMID: 32157609 [PubMed - indexed for MEDLINE]

Canaloplasty and Trabeculotomy ab interno with the OMNI System Combined with Cataract Surgery in Open-Angle Glaucoma: 12-month Outcomes from the ROMEO Study.

Tue, 12/15/2020 - 09:31
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Canaloplasty and Trabeculotomy ab interno with the OMNI System Combined with Cataract Surgery in Open-Angle Glaucoma: 12-month Outcomes from the ROMEO Study.

J Cataract Refract Surg. 2020 Dec 09;:

Authors: Hirsch L, Cotliar J, Vold S, Selvadurai D, Campbell AG, Ferreira G, Aminlari A, Cho A, Heersink S, Hochman M, Gallardo M, Williamson B, Phan R, Nelson C, Dickerson JE

Abstract
PURPOSE: Provide safety and effectiveness outcomes 12 months post-surgically for sequential canaloplasty and trabeculotomy with the OMNI system combined with cataract surgery in mild-to-moderate open-angle glaucoma (OAG).
SETTING: Eleven ophthalmology practices and surgery centers located in eight states (AL, AR, CA, KS, LA, MO, NY, TX).
DESIGN: Retrospective, multicenter, single arm METHODS:: IRB approved. Twelve surgeons contributed 81 patients meeting eligibility criteria: OAG, 12-month follow-up, medicated intraocular pressure (IOP) ≤36 mmHg on ≤ 4 medications preoperatively. Analysis stratified by baseline (BL) IOP; >18 mmHg (group 1), ≤ 18 mmHg (Group 2). Success defined as proportion with ≥ 20% reduction in IOP OR IOP between 6 and 18 mmHg (inclusive) AND on the same or fewer medications without secondary surgical intervention (SSI). Other endpoints included mean IOP and medications at 12 months. Safety included best corrected visual acuity (BCVA) and adverse events (AE).
RESULTS: Primary success was met by 79% (Group 1) and 81% (Group 2). Mean IOP was reduced in Group 1 (21.9 to 15.1 mmHg, p < 0.0001), and remained controlled in Group 2 (14.1 to 13.4 mmHg, p = 0.3177). Medications went from 2.0 ± 1.3 to 1.1 ± 1.1 (Group 1) and from 1.6 ± 1.3 to 0.9 ± 1.2 (Group 2). AE were typical for cataract or angle surgery. Mild inflammation (11%), IOP spikes (5%), hyphema (4%). 4 patients (5%) required an SSI.
CONCLUSIONS: The OMNI system provides effective IOP reduction, sustained IOP control, and meaningful medication reduction for up to 12 months postoperative.

PMID: 33315733 [PubMed - as supplied by publisher]

Dental visits in Medicaid-enrolled youth with mental illness: an analysis of administrative claims data.

Tue, 12/15/2020 - 09:31
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Dental visits in Medicaid-enrolled youth with mental illness: an analysis of administrative claims data.

BMC Health Serv Res. 2020 Dec 11;20(1):1138

Authors: Stockbridge EL, Dhakal E, Griner SB, Loethen AD, West JF, Vera JW, Nandy K

Abstract
BACKGROUND: State Medicaid plans across the United States provide dental insurance coverage to millions of young persons with mental illness (MI), including those with attention deficit hyperactivity disorder (ADHD), depression, anxiety, bipolar disorder, and schizophrenia. There are significant oral health challenges associated with MI, and providing dental care to persons with MI while they are young provides a foundation for future oral health. However, little is known about the factors associated with the receipt of dental care in young Medicaid enrollees with MI. We aimed to identify mental and physical health and sociodemographic characteristics associated with dental visits among this population.
METHODS: We retrospectively analyzed administrative claims data from a Medicaid specialty health plan (September 2014 to December 2015). All enrollees in the plan had MI and were ≥ 7 years of age; data for enrollees aged 7 to 20 years were analyzed. We used two-level, mixed effects regression models to explore the relationships between enrollee characteristics and dental visits during 2015.
RESULTS: Of 6564 Medicaid-enrolled youth with MI, 29.0% (95% CI, 27.9, 30.1%) had one or more visits with a dentist or dental hygienist. Within youth with MI, neither anxiety (Adjusted odds ratio [AOR] = 1.15, p = 0.111), post-traumatic stress disorder (AOR = 1.31, p = 0.075), depression (AOR = 1.02, p = 0.831), bipolar disorder (AOR = 0.97, p = 0.759), nor schizophrenia (AOR = 0.83, p = 0.199) was associated with dental visits in adjusted analyses, although having ADHD was significantly associated with higher odds of dental visits relative to not having this condition (AOR = 1.34, p < 0.001). Age, sex, race/ethnicity, language, and education were also significantly associated with visits (p < 0.05 for all).
CONCLUSIONS: Dental utilization as measured by annual dental visits was lower in Medicaid-enrolled youth with MI relative to the general population of Medicaid-enrolled youth. However, utilization varied within the population of Medicaid-enrolled youth with MI, and we identified a number of characteristics significantly associated with the receipt of dental services. By identifying these variations in dental service use this study facilitates the development of targeted strategies to increase the use of dental care in - and consequently improve the current and long-term wellbeing of - the vulnerable population of Medicaid-enrolled youth with MI.

PMID: 33308226 [PubMed - in process]

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

Tue, 12/15/2020 - 09:31
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CRISPR based editing of SIV proviral DNA in ART treated non-human primates.

Nat Commun. 2020 11 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 - indexed for MEDLINE]

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

Tue, 12/15/2020 - 09:31
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Rapid de novo evolution of lysis genes in single-stranded RNA phages.

Nat Commun. 2020 11 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 - indexed for MEDLINE]

Fibronectin extra domain A (FN-EDA) elevates intraocular pressure through Toll-like receptor 4 signaling.

Tue, 12/15/2020 - 09:31
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Fibronectin extra domain A (FN-EDA) elevates intraocular pressure through Toll-like receptor 4 signaling.

Sci Rep. 2020 06 17;10(1):9815

Authors: Roberts AL, Mavlyutov TA, Perlmutter TE, Curry SM, Harris SL, Chauhan AK, McDowell CM

Abstract
Elevated intraocular pressure (IOP) is a major risk factor for the development and progression of primary open angle glaucoma and is due to trabecular meshwork (TM) damage, which leads to impaired aqueous humor outflow. Here, we explore a novel molecular mechanism involved in glaucomatous TM damage. We investigated the role of an endogenous Toll-like receptor 4 (TLR4) ligand, fibronectin-EDA (FN-EDA), in TGFβ2-induced ocular hypertension in mice. We utilized transgenic mouse strains that either constitutively express only FN containing the EDA isoform or contain an EDA-null allele and express only FN lacking EDA, with or without a mutation in Tlr4, in our inducible mouse model of ocular hypertension by injection of Ad5.TGFβ2. IOP was measured over time and eyes accessed by immunohistochemistry for total FN and FN-EDA expression. Constitutively active EDA caused elevated IOP starting at 14 weeks of age. Ad5.TGFβ2 induced ocular hypertension in wildtype C57BL/6J mice and further amplified the IOP in constitutively active EDA mice. TLR4 null and EDA null mice blocked Ad5.TGFβ-induced ocular hypertension. Total FN and FN-EDA isoform expression increased in response to Ad5.TGFβ2. These data suggest that both TLR4 and FN-EDA contribute to TGFβ2 induced ocular hypertension.

PMID: 32555351 [PubMed - indexed for MEDLINE]

Differentiation of Hispanic biogeographic ancestry with 80 ancestry informative markers.

Tue, 12/15/2020 - 09:31
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Differentiation of Hispanic biogeographic ancestry with 80 ancestry informative markers.

Sci Rep. 2020 05 08;10(1):7745

Authors: Setser CH, Planz JV, Barber RC, Phillips NR, Chakraborty R, Cross DS

Abstract
Ancestry informative single nucleotide polymorphisms (SNPs) can identify biogeographic ancestry (BGA); however, population substructure and relatively recent admixture can make differentiation difficult in heterogeneous Hispanic populations. Utilizing unrelated individuals from the Genomic Origins and Admixture in Latinos dataset (GOAL, n = 160), we designed an 80 SNP panel (Setser80) that accurately depicts BGA through STRUCTURE and PCA. We compared our Setser80 to the Seldin and Kidd panels via resampling simulations, which models data based on allele frequencies. We incorporated Admixed American 1000 Genomes populations (1000 G, n = 347), into a combined populations dataset to determine robustness. Using multinomial logistic regression (MLR), we compared the 3 panels on the combined dataset and found overall MLR classification accuracies: 93.2% Setser80, 87.9% Seldin panel, 71.4% Kidd panel. Naïve Bayesian classification had similar results on the combined dataset: 91.5% Setser80, 84.7% Seldin panel, 71.1% Kidd panel. Although Peru and Mexico were absent from panel design, we achieved high classification accuracy on the combined populations for Peru (MLR = 100%, naïve Bayes = 98%), and Mexico (MLR = 90%, naïve Bayes = 83.4%) as evidence of the portability of the Setser80. Our results indicate the Setser80 SNP panel can reliably classify BGA for individuals of presumed Hispanic origin.

PMID: 32385290 [PubMed - indexed for MEDLINE]

Peripheral Circulating Exosomal miRNAs Potentially Contribute to the Regulation of Molecular Signaling Networks in Aging.

Tue, 12/15/2020 - 09:31
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Peripheral Circulating Exosomal miRNAs Potentially Contribute to the Regulation of Molecular Signaling Networks in Aging.

Int J Mol Sci. 2020 Mar 11;21(6):

Authors: Zhang H, Jin K

Abstract
People are living longer than ever. Consequently, they have a greater chance for developing a functional impairment or aging-related disease, such as a neurodegenerative disease, later in life. Thus, it is important to identify and understand mechanisms underlying aging as well as the potential for rejuvenation. Therefore, we used next-generation sequencing to identify differentially expressed microRNAs (miRNAs) in serum exosomes isolated from young (three-month-old) and old (22-month-old) rats and then used bioinformatics to explore candidate genes and aging-related pathways. We identified 2844 mRNAs and 68 miRNAs that were differentially expressed with age. TargetScan revealed that 19 of these miRNAs are predicated to target the 766 mRNAs. Pathways analysis revealed signaling components targeted by these miRNAs: mTOR, AMPK, eNOS, IGF, PTEN, p53, integrins, and growth hormone. In addition, the most frequently predicted target genes regulated by these miRNAs were EIF4EBP1, insulin receptor, PDK1, PTEN, paxillin, and IGF-1 receptor. These signaling pathways and target genes may play critical roles in regulating aging and lifespan, thereby validating our analysis. Understanding the causes of aging and the underlying mechanisms may lead to interventions that could reverse certain aging processes and slow development of aging-related diseases.

PMID: 32168775 [PubMed - indexed for MEDLINE]

Endothelin-1 Mediated Decrease in Mitochondrial Gene Expression and Bioenergetics Contribute to Neurodegeneration of Retinal Ganglion Cells.

Tue, 12/15/2020 - 09:31
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Endothelin-1 Mediated Decrease in Mitochondrial Gene Expression and Bioenergetics Contribute to Neurodegeneration of Retinal Ganglion Cells.

Sci Rep. 2020 02 27;10(1):3571

Authors: Chaphalkar RM, Stankowska DL, He S, Kodati B, Phillips N, Prah J, Yang S, Krishnamoorthy RR

Abstract
Endothelin-1 (ET-1) is a vasoactive peptide that is elevated in aqueous humor as well as circulation of primary open angle glaucoma (POAG) patients. ET-1 has been shown to promote degeneration of optic nerve axons and apoptosis of retinal ganglion cells (RGCs), however, the precise mechanisms are still largely unknown. In this study, RNA-seq analysis was used to assess changes in ET-1 mediated gene expression in primary RGCs, which revealed that 23 out of 156 differentially expressed genes (DEGs) had known or predicted mitochondrial function, of which oxidative phosphorylation emerged as the top-most enriched pathway. ET-1 treatment significantly decreased protein expression of key mitochondrial genes including cytochrome C oxidase copper chaperone (COX17) and ATP Synthase, H+ transporting, Mitochondrial Fo Complex (ATP5H) in primary RGCs and in vivo following intravitreal ET-1 injection in rats. A Seahorse ATP rate assay revealed a significant decrease in the rate of mitochondrial ATP production following ET-1 treatment. IOP elevation in Brown Norway rats showed a trend towards decreased expression of ATP5H. Our results demonstrate that ET-1 produced a decrease in expression of vital components of mitochondrial electron transport chain, which compromise bioenergetics and suggest a mechanism by which ET-1 promotes neurodegeneration of RGCs in glaucoma.

PMID: 32107448 [PubMed - indexed for MEDLINE]

Intermittent Hypoxia Training for Treating Mild Cognitive Impairment: A Pilot Study.

Tue, 12/15/2020 - 09:31
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Intermittent Hypoxia Training for Treating Mild Cognitive Impairment: A Pilot Study.

Am J Alzheimers Dis Other Demen. 2020 Jan-Dec;35:1533317519896725

Authors: Wang H, Shi X, Schenck H, Hall JR, Ross SE, Kline GP, Chen S, Mallet RT, Chen P

Abstract
Although intermittent hypoxia training (IHT) has proven effective against various clinical disorders, its impact on mild cognitive impairment (MCI) is unknown. This pilot study examined IHT's safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI). Seven patients with aMCI (age 69 ± 3 years) alternately breathed 10% O2 and room-air, each 5 minutes, for 8 cycles/session, 3 sessions/wk for 8 weeks. The patients' resting arterial pressures fell by 5 to 7 mm Hg (P < .05) and cerebral tissue oxygenation increased (P < .05) following IHT. Intermittent hypoxia training enhanced hypoxemia-induced cerebral vasodilation (P < .05) and improved mini-mental state examination and digit span scores from 25.7 ± 0.4 to 27.7 ± 0.6 (P = .038) and from 24.7 ± 1.2 to 26.1 ± 1.3 (P = .047), respectively. California verbal learning test score tended to increase (P = .102), but trail making test-B and controlled oral word association test scores were unchanged. Adaptation to moderate IHT may enhance cerebral oxygenation and hypoxia-induced cerebrovasodilation while improving short-term memory and attention in elderly patients with aMCI.

PMID: 31902230 [PubMed - indexed for MEDLINE]

Dengue Seroprevalence and Seroconversion in Urban and Rural Populations in Northeastern Thailand and Southern Laos.

Fri, 12/11/2020 - 14:18

Dengue Seroprevalence and Seroconversion in Urban and Rural Populations in Northeastern Thailand and Southern Laos.

Int J Environ Res Public Health. 2020 Dec 07;17(23):

Authors: Doum D, Overgaard HJ, Mayxay M, Suttiprapa S, Saichua P, Ekalaksananan T, Tongchai P, Rahman MS, Haque U, Phommachanh S, Pongvongsa T, Rocklöv J, Paul R, Pientong C

Abstract
Dengue is the most rapidly spreading mosquito-borne viral disease in the world. The detection of clinical cases enables us to measure the incidence of dengue infection, whereas serological surveys give insights into the prevalence of infection. This study aimed to determine dengue seroprevalence and seroconversion rates in northeastern Thailand and southern Laos and to assess any association of mosquito control methods and socioeconomic factors with dengue virus (DENV) infection. Cross-sectional seroprevalence surveys were performed in May and November 2019 on the same individuals. Blood samples were collected from one adult and one child, when possible, in each of 720 randomly selected households from two urban and two rural sites in both northeastern Thailand and southern Laos. IgG antibodies against DENV were detected in serum using a commercial enzyme-linked immunosorbent assay (ELISA) kit. Overall, 1071 individuals participated in the study. The seroprevalence rate was high (91.5%) across all 8 study sites. Only age and province were associated with seroprevalence rates. There were 33 seroconversions during the period from May to November, of which seven reported fever. More than half of the seroconversions occurred in the rural areas and in Laos. Dengue seroconversion was significantly associated with young age (<15 years old), female gender, province, and duration of living in the current residence. No socioeconomic factors or mosquito control methods were found to be associated with seroprevalence or seroconversion. Notably, however, the province with most seroconversions had lower diurnal temperature ranges than elsewhere. In conclusion, our study has highlighted the homogeneity of dengue exposure across a wide range of settings and most notably those from rural and urban areas. Dengue can no longer be considered to be solely an urban disease nor necessarily one linked to poverty.

PMID: 33297445 [PubMed - in process]

Role of LLT1 and PCNA as Natural Killer Cell Immune Evasion Strategies of HCT 116 Cells.

Wed, 12/09/2020 - 13:56

Role of LLT1 and PCNA as Natural Killer Cell Immune Evasion Strategies of HCT 116 Cells.

Anticancer Res. 2020 Dec;40(12):6613-6621

Authors: Malaer JD, Mathew PA

Abstract
BACKGROUND/AIM: Cancer stem cells (CSCs) are a subpopulation of cells that retain self-renewal and pluripotency capabilities, are resistant to chemotherapy, and are thought to facilitate metastasis. Target cell expression of proliferating cell nuclear antigen (PCNA) or lectin-like transcript 1 (LLT1) inhibits natural killer (NK) cell functions. The purpose of this study was to characterize the expression of LLT1 or PCNA as NK cell evasion strategies of HCT 116, a colorectal cancer cell line.
MATERIALS AND METHODS: Protein expression was determined by flow cytometry and/or confocal microscopy. Stem-like cells were sorted and characterized, and NK cell effector functions measured by interferon-γ secretion and cytotoxicity assay.
RESULTS: PCNA expressing cells are potential CSCs, blocking PCNA alters interferon-γ secretion, and blocking PCNA or LLT1 increases cytotoxicity.
CONCLUSION: PCNA is a potential biomarker of stem-like colon cancer cells. Based on the results of this study, PCNA and LLT1 should be further explored as in vivo immunotherapeutic targets for NK cell-mediated killing.

PMID: 33288556 [PubMed - in process]

Cystatin C is a Potential Predictor of Unfavorable Outcomes for Cerebral Ischemia with IV-tPA Treatment: A Multicenter Prospective Nested Case-Control Study.

Mon, 12/07/2020 - 11:20
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Cystatin C is a Potential Predictor of Unfavorable Outcomes for Cerebral Ischemia with IV-tPA Treatment: A Multicenter Prospective Nested Case-Control Study.

Eur J Neurol. 2020 Dec 04;:

Authors: Chang Z, Zou H, Xie Z, Deng B, Que R, Huang Z, Weng G, Wu Z, Pan Y, Wang Y, Li M, Xie H, Zhu S, Xiong L, Mok VC, Jin K, Yenari MA, Wei X, Wang Q

Abstract
BACKGROUND: This study is to explore whether Cystatin C could be used as a potential predictor of the clinical outcomes in acute ischemic stroke patients treated by intravenous tissue plasminogen activator.
METHODS: We performed an observational study with a retrospective analysis of data from 125 acute ischemic stroke patients with intravenous thrombolysis. General linear models were applied to assess Cystatin C levels between groups with different outcomes; logistic regression analysis and receiver operating characteristic curves were adopted to identify the association between Cystatin C and the therapeutic effects.
RESULTS: Compared with the Good&Sustained Benefit group (≥4 reduction in National Institutes of Health Stroke Scale or a score of 0-1 at 24 hours and 7 days) and the Good Functional Outcome group (modified Rankin Scale 0-2 at 90 days), serum Cystatin C baseline levels were increased in the non-Good&Sustained Benefit and non-Good Functional Outcome groups. Logistic regression analysis found that Cystatin C was an independent negative prognostic factor for Good&Sustained Benefit (odds ratio = 0.010, p = 0.005) and Good Functional Outcome (odds ratio = 0.011, p = 0.021) after adjustment for potential influencing factors. Receiver operating characteristic curves showed the Cystatin C-involved combined models provided credible efficacy for predicting post-90-day favorable clinical outcomes (area under the curve = 0.86, p < 0.001).
CONCLUSIONS: Elevated serum Cystatin C is independently associated with unfavorable clinical outcomes after intravenous tissue plasminogen activator therapy in acute ischemic stroke. Our findings provide new insights into discovering potential mediators for neuropathological process or treatment in stroke.

PMID: 33277774 [PubMed - as supplied by publisher]

Use of a Health Advocacy Model for Survivors of Interpersonal Violence.

Mon, 12/07/2020 - 11:20
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Use of a Health Advocacy Model for Survivors of Interpersonal Violence.

Int J Environ Res Public Health. 2020 Dec 02;17(23):

Authors: Grace J, Walters ST, Gallegos I, Thompson EL, Spence EE

Abstract
This article examines the implementation of a health advocacy model designed for survivors of interpersonal violence (IPV) in a metropolitan area of North Texas. Using a framework influenced by motivational interviewing, solution-focused therapy, and trauma-informed care, this program engaged IPV survivors in creating health and safety goals. Goal attainment scaling was used to track progress after each health advocacy encounter. Clients could set their own goals for healthcare, self-care, and safety. The program served 419 clients and 648 goals were set by clients at the first visit. Among all goals, 89% selected goals focused on healthcare, with 47% of those selecting obtaining health insurance or coverage as a need. These results demonstrate the need for an enhanced healthcare response for this population. The remaining goals selected were self-care (7%) and safety (3%). The design of the health advocacy intervention shows promise towards filling the gaps between IPV and healthcare service delivery systems.

PMID: 33276649 [PubMed - as supplied by publisher]

Host antibacterial defense of 6-10 Gy γ-irradiated mice subjected to lentiviral vector-based Gas5 gene therapy.

Thu, 12/03/2020 - 11:45
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Host antibacterial defense of 6-10 Gy γ-irradiated mice subjected to lentiviral vector-based Gas5 gene therapy.

Gene Ther. 2020 Dec 01;:

Authors: Ito I, Loucas BD, Suzuki S, Kobayashi M, Suzuki F

Abstract
Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, all mice exposed to 8 Gy of whole body γ-irradiation (8 Gy GIARS-mice) died by sepsis stemming from bacterial translocation. M1Mϕ located in the bacterial translocation site (i.e., the mesenteric lymph nodes, MLNs) have been characterized as major antibacterial effector cells. However, M2bMϕ, inhibitor cells for M1Mϕ polarization, predominated in the MLNs of these mice. The reduced expression of long noncoding RNA Gas5 was associated with M2bMϕ polarization. In this study, we tried to reduce the mortality rate of 8 Gy GIARS-mice through Gas5 gene transduction using lentivirus (Gas5 lentivirus). After Gas5 lentivirus injection, Gas5 RNA was overexpressed in MLN-F4/80+ cells of 8 Gy GIARS-mice, and these cells were identified as non-M2bMϕ. All of the 8 Gy GIARS-mice injected with Gas5 lentivirus survived 30 days or more after irradiation, and bacterial translocation and subsequent sepsis were shown to be minimal in these mice. These results indicate that the antibacterial resistance of 8 Gy GIASR-mice can be restored through the modulation of M2bMϕ located in the bacterial translocation site by Gas5 transduction.

PMID: 33262512 [PubMed - as supplied by publisher]

Age, gender, and racial/ethnic differences in the association of triclocarban with adulthood obesity using NHANES 2013-2016.

Wed, 12/02/2020 - 09:48
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Age, gender, and racial/ethnic differences in the association of triclocarban with adulthood obesity using NHANES 2013-2016.

Arch Environ Occup Health. 2020 Dec 01;:1-8

Authors: Uche UI, King CC

Abstract
This study examined the association between triclocarban and obesity among US adults and compared the pattern of this association across age, gender, and racial/ethnic groups. Study found triclocarban to be associated with obesity (OR: OR:1.123 95% CI: 1.046, 1.205) and this association remained among women (OR:1.14 95% CI: 1.031, 1.261). Study participants aged 60 years and older were more likely to be overweight (OR:1.131 95% CI: 1.022 1.251) and obese (OR:1.192 95% CI: 1.079, 1.317) when compared to other age groups. Likewise, non-Hispanic whites (OR:1.126 95% CI: 1.003, 1.263) and "other race including multi-racial" (OR:1.431 95% CI: 1.219, 1.679) were more likely to be obese when compared to other racial/ethnic groups. In conclusion, triclocarban is associated with obesity among US adults and there is evidence of gender, age, and racial/ethnicity differences in the association.

PMID: 33256559 [PubMed - as supplied by publisher]

Kupffer Cells: Inflammation Pathways and Cell-Cell Interactions in Alcohol-Associated Liver Disease.

Wed, 12/02/2020 - 09:48
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Kupffer Cells: Inflammation Pathways and Cell-Cell Interactions in Alcohol-Associated Liver Disease.

Am J Pathol. 2020 11;190(11):2185-2193

Authors: Slevin E, Baiocchi L, Wu N, Ekser B, Sato K, Lin E, Ceci L, Chen L, Lorenzo SR, Xu W, Kyritsi K, Meadows V, Zhou T, Kundu D, Han Y, Kennedy L, Glaser S, Francis H, Alpini G, Meng F

Abstract
Chronic alcohol consumption is linked to the development of alcohol-associated liver disease (ALD). This disease is characterized by a clinical spectrum ranging from steatosis to hepatocellular carcinoma. Several cell types are involved in ALD progression, including hepatic macrophages. Kupffer cells (KCs) are the resident macrophages of the liver involved in the progression of ALD by activating pathways that lead to the production of cytokines and chemokines. In addition, KCs are involved in the production of reactive oxygen species. Reactive oxygen species are linked to the induction of oxidative stress and inflammation in the liver. These events are activated by the bacterial endotoxin, lipopolysaccharide, that is released from the gastrointestinal tract through the portal vein to the liver. Lipopolysaccharide is recognized by receptors on KCs that are responsible for triggering several pathways that activate proinflammatory cytokines involved in alcohol-induced liver injury. In addition, KCs activate hepatic stellate cells that are involved in liver fibrosis. Novel strategies to treat ALD aim at targeting Kupffer cells. These interventions modulate Kupffer cell activation or macrophage polarization. Evidence from mouse models and early clinical studies in patients with ALD injury supports the notion that pathogenic macrophage subsets can be successfully translated into novel treatment options for patients with this disease.

PMID: 32919978 [PubMed - indexed for MEDLINE]

Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

Wed, 12/02/2020 - 09:48
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Kynurenic Acid Protects Against Ischemia/Reperfusion-Induced Retinal Ganglion Cell Death in Mice.

Int J Mol Sci. 2020 Mar 05;21(5):

Authors: Nahomi RB, Nam MH, Rankenberg J, Rakete S, Houck JA, Johnson GC, Stankowska DL, Pantcheva MB, MacLean PS, Nagaraj RH

Abstract
BACKGROUND: Glaucoma is an optic neuropathy and involves the progressive degeneration of retinal ganglion cells (RGCs), which leads to blindness in patients. We investigated the role of the neuroprotective kynurenic acid (KYNA) in RGC death against retinal ischemia/reperfusion (I/R) injury.
METHODS: We injected KYNA intravenously or intravitreally to mice. We generated a knockout mouse strain of kynurenine 3-monooxygenase (KMO), an enzyme in the kynurenine pathway that produces neurotoxic 3-hydroxykynurenine. To test the effect of mild hyperglycemia on RGC protection, we used streptozotocin (STZ) induced diabetic mice. Retinal I/R injury was induced by increasing intraocular pressure for 60 min followed by reperfusion and RGC numbers were counted in the retinal flat mounts.
RESULTS: Intravenous or intravitreal administration of KYNA protected RGCs against I/R injury. The I/R injury caused a greater loss of RGCs in wild type than in KMO knockout mice. KMO knockout mice had mildly higher levels of fasting blood glucose than wild type mice. Diabetic mice showed significantly lower loss of RGCs when compared with non-diabetic mice subjected to I/R injury.
CONCLUSION: Together, our study suggests that the absence of KMO protects RGCs against I/R injury, through mechanisms that likely involve higher levels of KYNA and glucose.

PMID: 32151061 [PubMed - indexed for MEDLINE]

Recent changes in cervical cancer screening guidelines: U.S. women's willingness for HPV testing instead of Pap testing.

Wed, 12/02/2020 - 09:48
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Recent changes in cervical cancer screening guidelines: U.S. women's willingness for HPV testing instead of Pap testing.

Prev Med. 2020 01;130:105928

Authors: Thompson EL, Galvin AM, Daley EM, Tatar O, Zimet GD, Rosberger Z

Abstract
Cervical cancer screening guidelines in the United States were revised in 2018 to include the option of primary human papillomavirus (HPV) testing. The transition to this screening method may face difficulties as Pap testing has been the primary screening modality in the United States. The objective of this study is to assess information, motivation, and behavioral skills associated with willingness to receive an HPV test instead of a Pap test among women. The sample included U.S. 812 women, ages 30 to 65 years. Participants completed an online survey in 2018. The Information, Motivation, and Behavioral Skills (IMB) model was used to measure predictors of willingness for HPV testing. The outcome variables were willingness to receive the HPV test instead of the Pap test, with and without time interval details. Logistic regression modeling was used with SAS 9.4. Over half of the sample (55%) were willing to receive the HPV test. For the information domain, HPV knowledge was significantly associated with willingness for HPV testing (OR = 1.08, 95%CI 1.04-1.13). Significant motivating factors included: positive attitudes, social norms, perceived benefits, worry about cervical cancer, and worry about abnormal HPV tests. For behavioral skills, women were significantly more willing to get the HPV test if a provider recommended it (OR = 2.43, 95%CI 1.53-3.87) and currently up-to-date on cervical cancer screening guidelines (OR = 1.52, 95%CI 1.52-2.26). Addressing barriers and facilitators to willingness to transition to primary HPV testing over Pap testing is needed as the United States has updated guidelines for cervical cancer screening.

PMID: 31756351 [PubMed - indexed for MEDLINE]

Store-operated calcium entry: Pivotal roles in renal physiology and pathophysiology.

Tue, 12/01/2020 - 09:29
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Store-operated calcium entry: Pivotal roles in renal physiology and pathophysiology.

Exp Biol Med (Maywood). 2020 Nov 29;:1535370220975207

Authors: Chaudhari S, Mallet RT, Shotorbani PY, Tao Y, Ma R

Abstract
Research conducted over the last two decades has dramatically advanced the understanding of store-operated calcium channels (SOCC) and their impact on renal function. Kidneys contain many types of cells, including those specialized for glomerular filtration (fenestrated capillary endothelium, podocytes), water and solute transport (tubular epithelium), and regulation of glomerular filtration and renal blood flow (vascular smooth muscle cells, mesangial cells). The highly integrated function of these myriad cells effects renal control of blood pressure, extracellular fluid volume and osmolality, electrolyte balance, and acid-base homeostasis. Many of these cells are regulated by Ca2+ signaling. Recent evidence demonstrates that SOCCs are major Ca2+ entry portals in several renal cell types. SOCC is activated by depletion of Ca2+ stores in the sarco/endoplasmic reticulum, which communicates with plasma membrane SOCC via the Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Orai1 is recognized as the main pore-forming subunit of SOCC in the plasma membrane. Orai proteins alone can form highly Ca2+ selective SOCC channels. Also, members of the Transient Receptor Potential Canonical (TRPC) channel family are proposed to form heteromeric complexes with Orai1 subunits, forming SOCC with low Ca2+ selectivity. Recently, Ca2+ entry through SOCC, known as store-operated Ca2+ entry (SOCE), was identified in glomerular mesangial cells, tubular epithelium, and renovascular smooth muscle cells. The physiological and pathological relevance and the characterization of SOCC complexes in those cells are still unclear. In this review, we summarize the current knowledge of SOCC and their roles in renal glomerular, tubular and vascular cells, including studies from our laboratory, emphasizing SOCE regulation of fibrotic protein deposition. Understanding the diverse roles of SOCE in different renal cell types is essential, as SOCC and its signaling pathways are emerging targets for treatment of SOCE-related diseases.

PMID: 33249888 [PubMed - as supplied by publisher]

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