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Retina-Targeted Delivery of 17β-Estradiol by the Topically Applied DHED Prodrug.

Recent Research Articles from UNTHSC - Thu, 05/21/2020 - 05:26

Retina-Targeted Delivery of 17β-Estradiol by the Topically Applied DHED Prodrug.

Pharmaceutics. 2020 May 16;12(5):

Authors: Prokai-Tatrai K, Nguyen V, De La Cruz DL, Guerra R, Zaman K, Rahlouni F, Prokai L

Abstract
The purpose of this study was to explore retina-targeted delivery of 17β-estradiol (E2), a powerful neuroprotectant, by its bioprecursor prodrug 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) administered as eye drops in animal models. Compared to the parent hormone, DHED displayed increased transcorneal flux ex vivo both with and without the presence of 2-hydroxypropyl-β-cyclodextrin used as a penetration-enhancing excipient in rat, rabbit, and pig. In vitro, the prodrug also showed facile bioactivation to E2 in the retina but not in the cornea. After topical administration to rats and rabbits, peak DHED-derived E2 concentrations reached 13 ± 5 ng/g and 18 ± 7 ng/g in the retina of female rats and rabbits, respectively. However, the prodrug remained inert in the rest of the body and, therefore, did not cause increase in circulating hormone concentration, as well as wet uterine and anterior pituitary weights as typical markers of E2's endocrine impact. Altogether, our studies presented here have demonstrated the premise of topical retina-selective estrogen therapy by the DHED prodrug approach for the first time and provide compelling support for further investigation into the full potential of DHED for an efficacious and safe ocular neurotherapy.

PMID: 32429388 [PubMed]

Tenofovir Plasma Concentration from Preexposure Prophylaxis at the Time of Potential HIV Exposure: a Population Pharmacokinetic Modeling and Simulation Study Involving Serodiscordant Couples in East Africa.

Recent Research Articles from UNTHSC - Thu, 05/21/2020 - 05:26
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Tenofovir Plasma Concentration from Preexposure Prophylaxis at the Time of Potential HIV Exposure: a Population Pharmacokinetic Modeling and Simulation Study Involving Serodiscordant Couples in East Africa.

Antimicrob Agents Chemother. 2019 08;63(8):

Authors: Mallayasamy S, Chaturvedula A, Fossler MJ, Sale M, Goti V, Bumpus NN, Marzinke MA, Hendrix CW, Haberer JE, Partners Demonstration Project Team

Abstract
The Partners Demonstration Project was a prospective, open-label, implementation science-driven study of preexposure prophylaxis (PrEP) among heterosexual HIV serodiscordant couples in Kenya and Uganda. Adherence data were collected using the Medication Event Monitoring System (MEMS), and time of sexual activity was collected using the mobile phone short message service (SMS). Two plasma samples were collected at a single study visit. We integrated adherence, pharmacokinetics, and SMS data using a population pharmacokinetic (PopPK) model to simulate tenofovir plasma concentrations from PrEP at the time of sexual activity. In the first stage of this analysis, we used data from the current study to update a prior PopPK model of tenofovir (TFV) developed with data from the Partners PrEP Study (a phase III clinical trial). The second stage involved simulating plasma concentrations at the time of sexual activity using empirical Bayes estimates (EBEs) derived from the final model. In addition, EBEs from a previously published parent metabolite model of TFV (MTN-001, an open-label 3-way crossover study in healthy women) was used to simulate tenofovir diphosphate (TFV-DP) concentrations. We estimated percent PrEP "coverage" as the number of reported sexual events during which simulated concentrations were above an a priori threshold concentrations associated with a high degree of protection from HIV infection: plasma TFV of >40 ng/ml and peripheral blood mononuclear cell (PBMC) TFV-DP concentration of >36 fmol/million cells. The levels of coverage were 72% for TFV and 81% for TFV-DP. These levels are consistent with a high degree of protection against HIV acquisition in this study of a pragmatic delivery model for antiretroviral-based HIV prevention.

PMID: 31182536 [PubMed - indexed for MEDLINE]

On the Origin and Correction for Inner Filter Effects in Fluorescence. Part I: Primary Inner Filter Effect -The Proper Approach for Sample Absorbance Correction.

Recent Research Articles from UNTHSC - Wed, 05/20/2020 - 08:14

On the Origin and Correction for Inner Filter Effects in Fluorescence. Part I: Primary Inner Filter Effect -The Proper Approach for Sample Absorbance Correction.

Methods Appl Fluoresc. 2020 May 19;:

Authors: Kimball J, Chavez JL, Ceresa L, Kitchner E, Nurekeyev Z, Doan H, Szabelski M, Borejdo J, Gryczynski I, Gryczynski Z

Abstract
Fluorescence technologies have been the preferred method for detection, analytical sensing, medical diagnostics, biotechnology, imaging, and gene expression for many years. Fluorescence becomes essential for studying molecular processes with high specificity and sensitivity through a variety of biological processes. A significant problem for practical fluorescence applications is the apparent non-linearity of the fluorescence intensity resulting from inner-filter effects, sample scattering, and absorption of intrinsic components of biological samples. Sample absorption can lead to the primary inner filter effect (Type I inner filter effect) and is the first factor that should be considered. This is a relatively simple factor to be controlled in any fluorescence experiment. However, many previous approaches have given only approximate experimental methods for correcting the deviation from expected results. In this part we are discussing the origin of the primary inner filter effect and presenting a universal approach for correcting the fluorescence intensity signal in the full absorption range. Importantly, we present direct experimental results of how the correction works. One considers problems emerging from varying absorption across its absorption spectrum for all fluorophores. We use Rhodamine 800 and demonstrate how to properly correct the excitation spectra in a broad wavelength range. Second is the effect of an inert absorber that attenuates the intensity of the excitation beam as it travels through the cuvette, which leads to a significant deviation of observed results. As an example, we are presenting fluorescence quenching of a tryptophan analog, NATA, by acrylamide and we show how properly corrected results compare to the initial erroneous results. The procedure is generic and applies to many other applications like quantum yield determination, tissue/blood absorption, or acceptor absorption in FRET experiments.

PMID: 32428893 [PubMed - as supplied by publisher]

Thymic Function Associated With Cancer Development, Relapse, and Antitumor Immunity - A Mini-Review.

Recent Research Articles from UNTHSC - Wed, 05/20/2020 - 08:14

Thymic Function Associated With Cancer Development, Relapse, and Antitumor Immunity - A Mini-Review.

Front Immunol. 2020;11:773

Authors: Wang W, Thomas R, Sizova O, Su DM

Abstract
The thymus is the central lymphoid organ for T cell development, a cradle of T cells, and for central tolerance establishment, an educator of T cells, maintaining homeostatic cellular immunity. T cell immunity is critical to control cancer occurrence, relapse, and antitumor immunity. Evidence on how aberrant thymic function influences cancer remains largely insufficient, however, there has been recent progress. For example, the involuted thymus results in reduced output of naïve T cells and a restricted T cell receptor (TCR) repertoire, inducing immunosenescence and potentially dampening immune surveillance of neoplasia. In addition, the involuted thymus relatively enhances regulatory T (Treg) cell generation. This coupled with age-related accumulation of Treg cells in the periphery, potentially provides a supportive microenvironment for tumors to escape T cell-mediated antitumor responses. Furthermore, acute thymic involution from chemotherapy can create a tumor reservoir, resulting from an inflammatory microenvironment in the thymus, which is suitable for disseminated tumor cells to hide, survive chemotherapy, and become dormant. This may eventually result in cancer metastatic relapse. On the other hand, if thymic involution is wisely taken advantage of, it may be potentially beneficial to antitumor immunity, since the involuted thymus increases output of self-reactive T cells, which may recognize certain tumor-associated self-antigens and enhance antitumor immunity, as demonstrated through depletion of autoimmune regulator (AIRE) gene in the thymus. Herein, we briefly review recent research progression regarding how altered thymic function modifies T cell immunity against tumors.

PMID: 32425946 [PubMed - in process]

A pilot study on the design and validation of a hybrid exoskeleton robotic device for hand rehabilitation.

Recent Research Articles from UNTHSC - Wed, 05/20/2020 - 08:14
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A pilot study on the design and validation of a hybrid exoskeleton robotic device for hand rehabilitation.

J Hand Ther. 2020 May 16;:

Authors: Haghshenas-Jaryani M, Patterson RM, Bugnariu N, Wijesundara MBJ

Abstract
STUDY DESIGN: An iterative design process was used to obtain design parameters that satisfy both kinematic and dynamic requirements for the hand exoskeleton. This design was validated through experimental studies.
INTRODUCTION: The success of hand rehabilitation after impairments depends on the timing, intensity, repetition, and frequency, as well as task-specific training. Considering the continuing constraints placed on therapist-led rehabilitation and need for better outcomes, robot-assisted rehabilitation has been explored. Soft robotic approaches have been implemented for a hand rehabilitation exoskeleton as they have more tolerance for alignment with biological joints than those of hard exoskeletons.
PURPOSE OF THE STUDY: The purpose of the study was to design, develop, and validate a soft robotic exoskeleton for hand rehabilitation.
METHODS: A motion capture system validated the kinematics of the soft robotic digit attached on top of a human index finger. A pneumatic control system and algorithms were developed to operate the exoskeleton based on three therapeutic modes: continuous passive, active assistive, and active resistive motion. Pilot studies were carried out on one healthy and one poststroke participant using continuous passive motion and bilateral/bimanual therapy modes.
RESULTS: The soft robotic digits were able to produce required range of motion and accommodate for dorsal lengthening, with trajectories of the center of rotation of the soft robotic joints in close agreement with the center of rotation of the human finger joints.
DISCUSSION: The exoskeleton showed the robust performance of the robot in applying continuous passive motion and bilateral/bimanual therapy.
CONCLUSIONS: This soft robotic exoskeleton is promising for assisting in the rehabilitation of the hand.

PMID: 32423846 [PubMed - as supplied by publisher]

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

Recent Research Articles from UNTHSC - Tue, 05/19/2020 - 05:00
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Translaminar Autonomous System Model for the Modulation of Intraocular and Intracranial Pressure in Human Donor Posterior Segments.

J Vis Exp. 2020 Apr 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 - as supplied by publisher]

Osteopathic Manipulative Treatment Alters Gastric Myoelectric Activity in Healthy Subjects.

Recent Research Articles from UNTHSC - Tue, 05/19/2020 - 05:00
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Osteopathic Manipulative Treatment Alters Gastric Myoelectric Activity in Healthy Subjects.

J Altern Complement Med. 2018 Dec;24(12):1176-1180

Authors: Shadiack E, Jouett N, van den Raadt A, Liganor R, Watters J, Hensel K, Smith M

Abstract
Objectives: It is unclear whether osteopathic manipulative treatment (OMT) affects gastric myoelectric activity (GMA), an index of gastric motility. We hypothesized that OMT significantly alters power spectral density (PSD) analyses of electrogastrography (EGG) recordings, an index of GMA, compared with time control OMT. Design: GMA data were obtained from nine subjects before and after OMT and time control on separate days in a cross-over design. Fifteen-minute EGG recordings were obtained before and after each intervention and after a water challenge (WC). Percent power in the normogastric range (PPN) was estimated from PSD analyses. Absolute percent change of PPN and dominant frequency (DF) from baseline to postintervention and baseline to post-WC was computed and compared using two-way repeated-measures ANOVA. Results: OMT altered PPN versus time control (time control: 5.3% ± 1.2%; OMT: 24.5% ± 4.5%; p = 0.015). WC altered PPN compared with time control (post-time control ΔPPN: 5.3% ± 1.2%; post-drink ΔPPN: 30.3% ± 7.2%; p < 0.01). However, WC did not alter PPN with prior OMT treatment (post-OMT ΔPPN: 24.5% ± 4.5%; post-WC ΔPPN: 19.4% ± 5.6%; p = 0.47). Nevertheless, OMT reduced the rate of change for DF compared with time control (WC post-time control: 37.9% ± 7.4%; WC post-OMT: 20.0% ± 5.9%; p = 0.02). Conclusions: We conclude that (1) OMT significantly alters GMA compared with time control and that (2) OMT reduces the rate of change in the frequency response to WC within the normal frequency range of 2-4 cycles per minute, indicating a physiological effect.

PMID: 30376351 [PubMed - indexed for MEDLINE]

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

Recent Research Articles from UNTHSC - Sun, 05/17/2020 - 16:29
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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 May 15;:

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 - as supplied by publisher]

Broader Implications of Modeling and Simulation (M&S) Tools in Pharmacotherapeutic Decisions: A Cautionary Optimism.

Recent Research Articles from UNTHSC - Sat, 05/16/2020 - 07:15

Broader Implications of Modeling and Simulation (M&S) Tools in Pharmacotherapeutic Decisions: A Cautionary Optimism.

Front Pharmacol. 2020;11:571

Authors: Chaturvedula A, Palasik BN, Cho HJ, Goyal N

PMID: 32411002 [PubMed]

Approaches to Whole Mitochondrial Genome Sequencing on the Oxford Nanopore MinION.

Recent Research Articles from UNTHSC - Sat, 05/16/2020 - 07:15
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Approaches to Whole Mitochondrial Genome Sequencing on the Oxford Nanopore MinION.

Curr Protoc Hum Genet. 2019 12;104(1):e94

Authors: Zascavage RR, Hall CL, Thorson K, Mahmoud M, Sedlazeck FJ, Planz JV

Abstract
Traditional approaches for interrogating the mitochondrial genome often involve laborious extraction and enrichment protocols followed by Sanger sequencing. Although preparation techniques are still demanding, the advent of next-generation or massively parallel sequencing has made it possible to routinely obtain nucleotide-level data with relative ease. These short-read sequencing platforms offer deep coverage with unparalleled read accuracy in high-complexity genomic regions but encounter numerous difficulties in the low-complexity homopolymeric sequences characteristic of the mitochondrial genome. The inability to discern identical units within monomeric repeats and resolve copy-number variations for heteroplasmy detection results in suboptimal genome assemblies that ultimately complicate downstream data analysis and interpretation of biological significance. Oxford Nanopore Technologies offers the ability to generate long-read sequencing data on a pocket-sized device known as the MinION. Nanopore-based sequencing is scalable, portable, and theoretically capable of sequencing the entire mitochondrial genome in a single contig. Furthermore, the recent development of a nanopore protein with dual reader heads allows for clear identification of nucleotides within homopolymeric stretches, significantly increasing resolution throughout these regions. The unrestricted read lengths, superior homopolymeric resolution, and affordability of the MinION device make it an attractive alternative to the labor-intensive, time-consuming, and costly mainstay deep-sequencing platforms. This article describes three approaches to extract, prepare, and sequence mitochondrial DNA on the Oxford Nanopore MinION device. Two of the workflows include enrichment of mitochondrial DNA prior to sequencing, whereas the other relies on direct sequencing of native genomic DNA to allow for simultaneous assessment of the nuclear and mitochondrial genomes. © 2019 by John Wiley & Sons, Inc. Basic Protocol: Enrichment-free mitochondrial DNA sequencing Alternate Protocol 1: Mitochondrial DNA sequencing following enrichment with polymerase chain reaction (PCR) Alternate Protocol 2: Mitochondrial DNA sequencing following enrichment with PCR-free hybridization capture Support Protocol 1: DNA quantification and quality assessment using the Agilent 4200 TapeStation System Support Protocol 2: AMPure XP bead clean-up Support Protocol 3: Suggested data analysis pipeline.

PMID: 31743587 [PubMed - indexed for MEDLINE]

Will There Be an Epidemic of Corollary Illnesses Linked to a COVID-19-Related Recession?

Recent Research Articles from UNTHSC - Fri, 05/15/2020 - 06:58

Will There Be an Epidemic of Corollary Illnesses Linked to a COVID-19-Related Recession?

Am J Public Health. 2020 May 14;:e1-e2

Authors: Brenner MH

Abstract
Currently, US unemployment claims have skyrocketed to 30 million in the past six weeks, continuing in a stark upward trend, and labor economists estimate the unemployment rate at minimally 18.3%. These unemployment figures are a feature of the COVID-19 recession that is characterized by sharp gross domestic product (GDP) growth decline. Despite the greatly damaging impact of the opioid crisis over 2015 to 2017 resulting in a decrease in life expectancy over these three years, the long-term increases in average GDP per capita from 1999 to 2018 managed to save lives on average (i.e., age-adjusted mortality rates declined in the United States). For example, during 1999 to 2018, the average GDP per capita annually increased 1.2%, whereas the related age-adjusted mortality rate has shown an annual decrease of approximately 1% on average (0.99%). However, recessions erase some of this beneficial effect of GDP growth on mortality reduction.1 (Am J Public Health. Published online ahead of print May 14, 2020: e1-e2. doi:10.2105/AJPH.2020.305724).

PMID: 32407135 [PubMed - as supplied by publisher]

Effect of mobile text messages on antiretroviral medication adherence and patient retention in early HIV care: an open-label, randomized, single center study in south Florida.

Recent Research Articles from UNTHSC - Fri, 05/15/2020 - 06:58

Effect of mobile text messages on antiretroviral medication adherence and patient retention in early HIV care: an open-label, randomized, single center study in south Florida.

AIDS Res Ther. 2020 May 13;17(1):16

Authors: Sherman EM, Niu J, Elrod S, Clauson KA, Alkhateeb F, Eckardt P

Abstract
BACKGROUND: People with HIV (PHIV) with limited access to health services often experience suboptimal antiretroviral therapy (ART) adherence. We investigated whether a daily text messaging intervention improves ART adherence and retention in early HIV care in PHIV in a south Florida hospital-based clinic.
METHODS: ART-naïve PHIV receiving care through the clinic's Ryan White HIV/AIDS Program were enrolled and randomly assigned to the intervention or control groups with a 1:1 ratio. The intervention group received a 1-way text message daily and the control group received standard care without receiving text message reminders for 6 months. HIV RNA and CD4 cell count were measured at baseline and post-intervention. Adherence to ART was defined as a visual analog scale of ≥ 90%. Retention in care was defined as continued engagement at study end.
RESULTS: 94 ART-naïve patients were randomized and 83 (85.6%) completed the study, of which 44 were in the intervention group and 39 were in the control group. At the end of the 6-month study period, adherence to ART was 84.4% in the intervention group versus 73.5% in the control group (OR, 1.9; 95% CI 0.7-5.0; p = 0.194). Retention in care significantly improved in the intervention group compared to the control group with the odds of retention increasing by 20% (OR, 1.2; 95% CI 1.1-1.5; p = 0.006). Undetectable HIV RNA (< 50 copies/mL) was 86.7% in the intervention group versus 73.5% in the control group (OR, 2.3; 95% CI 0.8-6.9; p = 0.112). A significant increase in CD4 cell count and a decrease in HIV RNA were found at study end, with no differences between the two groups.
CONCLUSIONS: In this pilot study, a one-way daily text messaging intervention did not improve ART adherence over a 6-month study period, but significantly enhanced patient retention in early HIV care. Implementation of interventions to improve adherence in this population is required.

PMID: 32404130 [PubMed - in process]

Antiretroviral Adherence Level Necessary for HIV Viral Suppression Using Real-World Data.

Recent Research Articles from UNTHSC - Fri, 05/15/2020 - 06:58
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Antiretroviral Adherence Level Necessary for HIV Viral Suppression Using Real-World Data.

J Acquir Immune Defic Syndr. 2019 11 01;82(3):245-251

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

Abstract
BACKGROUND: A benchmark of near-perfect adherence (≥95%) to antiretroviral therapy (ART) is often cited as necessary for HIV viral suppression. However, given newer, more effective ART medications, the threshold for viral suppression may be lower. We estimated the minimum ART adherence level necessary to achieve viral suppression.
SETTINGS: The Patient-centered HIV Care Model demonstration project.
METHODS: Adherence to ART was calculated using the proportion of days covered measure for the 365-day period before each viral load test result, and grouped into 5 categories (<50%, 50% to <80%, 80% to <85%, 85% to <90%, and ≥90%). Binomial regression analyses were conducted to determine factors associated with viral suppression (HIV RNA <200 copies/mL); demographics, proportion of days covered category, and ART regimen type were explanatory variables. Generalized estimating equations with an exchangeable working correlation matrix accounted for correlation within subjects. In addition, probit regression models were used to estimate adherence levels required to achieve viral suppression in 90% of HIV viral load tests.
RESULTS: The adjusted odds of viral suppression did not differ between persons with an adherence level of 80% to <85% or 85% to <90% and those with an adherence level of ≥90%. In addition, the overall estimated adherence level necessary to achieve viral suppression in 90% of viral load tests was 82% and varied by regimen type; integrase inhibitor- and nonnucleoside reverse transcriptase inhibitor-based regimens achieved 90% viral suppression with adherence levels of 75% and 78%, respectively.
CONCLUSIONS: The ART adherence level necessary to reach HIV viral suppression may be lower than previously thought and may be regimen-dependent.

PMID: 31343455 [PubMed - indexed for MEDLINE]

Affordable Care Act and cancer stage at diagnosis in an underserved population.

Recent Research Articles from UNTHSC - Thu, 05/14/2020 - 06:27
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Affordable Care Act and cancer stage at diagnosis in an underserved population.

Prev Med. 2019 09;126:105748

Authors: Lu Y, Jackson BE, Gehr AW, Cross D, Neerukonda L, Tanna B, Ghabach B, Ojha RP

Abstract
The Patient Protection and Affordable Care Act (ACA) has increased insurance coverage among underserved individuals, but the effect of ACA on cancer diagnosis is currently debated, particularly in Medicaid non-expansion states. Therefore, we aimed to assess the effect of ACA implementation on stage at diagnosis among underserved cancer patients in Texas, a Medicaid non-expansion state. We used data from the institutional registry of the JPS Center for Cancer Care, which serves an urban population of underserved cancer patients. Eligible individuals were aged 18 to 64 years and diagnosed with a first primary invasive solid tumor between 2008 and 2015. We used a natural experiment framework and interrupted time-series analysis to assess level (i.e. immediate) and slope (over time) changes in insurance coverage and cancer stage at diagnosis between pre- and post-ACA periods. Our study population comprised 4808 underserved cancer patients, of whom 51% were racial/ethnic minorities. The prevalence of uninsured cancer patients did not immediately change after ACA implementation but modestly decreased over time (PR = 0.94; 95% CL: 0.90, 0.98). The prevalence of early- and advanced-stage diagnosis did not appreciably change overall or when stratified by screen-detectable cancers. Our results suggest that ACA implementation decreased the prevalence of uninsured cancer patients but had little effect on cancer stage at diagnosis in an underserved population. Given that Texas is a Medicaid non-expansion state, Medicaid expansion and alternative approaches may need to be further explored to improve earlier cancer diagnosis among underserved individuals.

PMID: 31195020 [PubMed - indexed for MEDLINE]

Alcohol-specific social comparison as a moderator of the norms-behavior association for young adult alcohol use.

Recent Research Articles from UNTHSC - Thu, 05/14/2020 - 06:27
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Alcohol-specific social comparison as a moderator of the norms-behavior association for young adult alcohol use.

Addict Behav. 2019 03;90:92-98

Authors: Litt DM, Waldron KA, Wallace EC, Lewis MA

Abstract
Research has indicated that individuals high in social comparison orientation (SCO) are more influenced by the behavior and perceived norms of others. However, despite research indicating that behavior is more closely influenced by and modeled on more socially proximal reference groups, most social comparison research to date has utilized global measures of social comparison. As such, research has not examined whether domain-specific (i.e. alcohol-specific social comparisons) and their relation with norms are more predictive of alcohol-related outcomes than global comparisons. As such, the present study aimed to determine whether the previously found relationships between global SCO, descriptive drinking norms and their interaction are still significant when accounting for alcohol-specific SCO and its interaction with descriptive norms in the prediction of drinking willingness and behavior. Results from 355 young adults age 18-20 indicated that the association of alcohol-specific SCO and its interaction with descriptive norms for drinking predicts alcohol-related outcomes (drinking willingness and alcohol consumption), but not alcohol-related negative consequences above and beyond global SCO. Thus, alcohol-specific SCO may be of particular importance when determining for whom normative based preventive interventions may be the most efficacious.

PMID: 30384190 [PubMed - indexed for MEDLINE]

Delayed capsular bag akreos IOL opacification after vitrectomy and gas tamponade.

Recent Research Articles from UNTHSC - Wed, 05/13/2020 - 06:14
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Delayed capsular bag akreos IOL opacification after vitrectomy and gas tamponade.

Am J Ophthalmol Case Rep. 2020 Jun;18:100676

Authors: Shakibai N, Chavala SH

PMID: 32395667 [PubMed]

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and its pathway involved.

Recent Research Articles from UNTHSC - Tue, 05/12/2020 - 05:55

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and its pathway involved.

Am J Physiol Renal Physiol. 2020 May 11;:

Authors: Chaudhari S, Yazdizadeh Shotorbani P, Tao Y, Davis ME, Mallet RT, Ma R

Abstract
Activation of immunologic pathways and disturbances of the extracellular matrix (ECM) dynamics are important contributors to the pathogenesis of chronic kidney diseases. Glomerular mesangial cells (MCs) are critical for homeostasis of glomerular ECM dynamics. Interleukin-6 (IL6) can act as a pro/anti- inflammatory agent relative to cell types and conditions. This study investigated if IL6 influenced ECM protein production by MCs and the regulatory pathways involved. Experiments were carried out in cultured human MCs (HMCs) and in mice. We found that overexpressing IL6 and its receptor decreased the abundance of fibronectin and collagen IV in MCs. Enzyme-linked immunosorbent assay and immunoblot analysis demonstrated that thapsigargin (an activator of store-operated Ca2+ entry, SOCE), but not endoplasmic reticular stress inducer tunicamycin, significantly increased IL6 content. This thapsigargin effect was abolished by GSK-7975A, a selective inhibitor of SOCE, and by silencing Orai1 (the channel protein mediating SOCE). Furthermore, inhibition of NFκB pharmacologically and genetically significantly reduced SOCE-induced IL6 production. Thapsigargin also stimulated the nuclear translocation of p65 subunit of NFκB. Moreover, MCs overexpressing IL6 and its receptor in HMCs increased the content of the receptor for glucagon-like peptide-1 (GLP-1R), and IL6 inhibition of fibronectin was attenuated by the GLP-1R antagonist, exendin 9-39. In agreement with the HMC data, specific knockdown of Orai1 in MCs using the targeted nanoparticle delivery system in mice significantly reduced glomerular GLP-1R level. Taken together, our results suggest a novel SOCE/NFкB/IL6/GLP-1R signaling pathway which inhibits ECM protein production by MCs.

PMID: 32390515 [PubMed - as supplied by publisher]

Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study.

Recent Research Articles from UNTHSC - Tue, 05/12/2020 - 05:55
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Cell-free mitochondrial DNA increases in maternal circulation during healthy pregnancy: a prospective, longitudinal study.

Am J Physiol Regul Integr Comp Physiol. 2020 02 01;318(2):R445-R452

Authors: Cushen SC, Sprouse ML, Blessing A, Sun J, Jarvis SS, Okada Y, Fu Q, Romero SA, Phillips NR, Goulopoulou S

Abstract
Mitochondrial DNA (mtDNA) exposed to the extracellular space due to cell death has immunostimulatory properties. Case-control studies reported a positive association between odds of developing preeclampsia and circulating mtDNA. These findings are based on relative quantification protocols that do not allow determination of absolute concentrations of mtDNA and are highly sensitive to nuclear DNA contamination. Furthermore, circulating mtDNA concentrations in response to normal pregnancy, which is an inflammatory state characterized by continuous placental cell apoptosis, have not been established. The main objective of this study was to determine longitudinal changes in circulating mtDNA from preconception to first trimester, third trimester, and postpartum in healthy pregnant women. Absolute real-time PCR quantification of mtDNA and nuclear DNA (nDNA) was performed on whole genomic extracts from serum using TaqMan probes and chemistry. Serum cell-free mtDNA and nDNA concentrations were greater in late pregnancy as compared with early pregnancy and postpartum. Pregnant women carrying neonates at the upper quartile of birth length distribution had higher concentrations of mtDNA in late pregnancy compared with pregnancies carrying neonates at the lower quartile. The correlation between circulating mtDNA and nDNA concentrations varied by sex (i.e., pregnancies carrying female vs. male fetuses). This study is the first to establish temporal patterns of circulating cell-free mtDNA concentrations in normal human pregnancy using absolute DNA quantification techniques. Concentrations of circulating mtDNA in normal pregnancy may be used as reference values for the development of clinical prognostic or diagnostic tests in pregnant women with, or at risk of developing, gestational complications.

PMID: 31913687 [PubMed - indexed for MEDLINE]

Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats.

Recent Research Articles from UNTHSC - Tue, 05/12/2020 - 05:55
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Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats.

Am J Physiol Heart Circ Physiol. 2020 01 01;318(1):H34-H48

Authors: Marciante AB, Wang LA, Little JT, Cunningham JT

Abstract
Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250-300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension.NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.

PMID: 31675258 [PubMed - indexed for MEDLINE]

Arterial Baroreflex Resetting During Exercise in Humans: Underlying Signaling Mechanisms.

Recent Research Articles from UNTHSC - Tue, 05/12/2020 - 05:55
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Arterial Baroreflex Resetting During Exercise in Humans: Underlying Signaling Mechanisms.

Exerc Sport Sci Rev. 2019 07;47(3):129-141

Authors: Raven PB, Young BE, Fadel PJ

Abstract
The arterial baroreflex (ABR) resets during exercise in an intensity-dependent manner to operate around a higher blood pressure with maintained sensitivity. This review provides a historical perspective of ABR resetting and the involvement of other neural reflexes in mediating exercise resetting. Furthermore, we discuss potential underlying signaling mechanisms that may contribute to exercise ABR resetting in physiological and pathophysiological conditions.

PMID: 30921029 [PubMed - indexed for MEDLINE]

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