Recent Research Articles from UNTHSC

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

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Comparison of diabetic nephropathy between male and female eNOS-/- db/db mice.

Thu, 01/30/2020 - 07:38
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Comparison of diabetic nephropathy between male and female eNOS-/- db/db mice.

Am J Physiol Renal Physiol. 2019 05 01;316(5):F889-F897

Authors: Ma Y, Li W, Yazdizadeh Shotorbani P, Dubansky BH, Huang L, Chaudhari S, Wu P, Wang LA, Ryou MG, Zhou Z, Ma R

Abstract
Sex is an important biological variable that impacts diverse physiological and pathological processes, including the progression of diabetic nephropathy. Diabetic nephropathy is one of the most common complications of diabetes mellitus and is the leading cause of end-stage renal disease. The endothelial nitric oxide synthase-deficient (eNOS-/-) db/db mouse is an appropriate and valuable model to study mechanisms in the development of diabetic nephropathy because of the similarities of the features of diabetic kidney disease in this model to those in humans. The aim of the present study was to determine whether there was a sex difference in renal injury in eNOS-/- db/db mice. Both male and female eNOS-/- db/db mice showed hyperglycemia, obesity, and renal hypertrophy. However, there was no significant difference in those variables between male and female mice. Furthermore, both male and female diabetic mice showed progressive albuminuria and significantly greater levels of serum creatinine and blood urea nitrogen compared with the same sex of wild-type mice (nondiabetic controls). Although all three variables in female eNOS-/- db/db mice had a tendency to be greater than those in male eNOS-/- db/db mice, those sex differences were not statistically significant. Moreover, both male and female eNOS-/- db/db mice showed significant mesangial expansion, higher glomerular injury scores, profound renal fibrosis, and substantial accumulation of fibronectin and collagen type IV proteins. However, sex differences in those structural changes were not observed. Similarly, survival rates of male and female eNOS-/- db/db mice were comparable. Taken together, the results from the present study suggest no sex difference in renal structural and functional damage in eNOS-/- db/db mice.

PMID: 30810354 [PubMed - indexed for MEDLINE]

Validity and diagnostic accuracy of foot posture Index-6 using radiographic findings as the gold standard to determine paediatric flexible flatfoot between ages of 6-18 years: A cross-sectional study.

Wed, 01/29/2020 - 07:22
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Validity and diagnostic accuracy of foot posture Index-6 using radiographic findings as the gold standard to determine paediatric flexible flatfoot between ages of 6-18 years: A cross-sectional study.

Musculoskelet Sci Pract. 2020 Jan 13;46:102107

Authors: Hegazy FA, Aboelnasr EA, Salem Y, Zaghloul AA

Abstract
BACKGROUND: Diagnosis of flexible flatfoot is usually based upon radiographic or clinical measures. Radiographic measures pose a potential risk of radiation exposure especially in Paediatric population. Clinicians need a valid, accurate, easily used, noninvasive and cost effective measure to evaluate static foot posture clinically. Although, foot posture index-6 (FPI-6) are commonly used in clinical practice, its validity and diagnostic accuracy in evaluation of paediatric flexible flatfoot have not been fully proven yet.
OBJECTIVES: To investigate validity and diagnostic accuracy of FPI-6 to determine Paediatric flexible flatfoot between ages of 6-18 years using radiographic findings as the gold standard measure.
STUDY DESIGN: Cross-sectional study.
METHODS: A cross-sectional study conducted on 612 participants (1224 feet) with flexible flatfoot aged 6-18 years (mean age ± standard deviation of 12.36 ± 3.39 years). The results of FPI-6 were compared to the gold standard radiographic measures and displayed on the receiver operating characteristic curve. Intra-rater reliability, sensitivity, specificity, predictive values and likelihood ratios were calculated. Posttest probability was calculated from Fagan nomogram.
RESULTS: FPI-6 demonstrate high intra-rater reliability (ICC = 0.96) with p value < 0.001. FPI-6 showed a sensitivity of 83.7%, a specificity of 80.4, a positive predictive value of 64.7, a negative predictive value of 92, a positive likelihood ratio of 4.62 and a negative likelihood ratio of 0.20. FPI-6 shows moderate diagnostic accuracy [AUC = 0.82; 95%CI (0.78-0.85)].
CONCLUSION: FPI-6 is valid with moderate diagnostic accuracy to determine paediatric flexible flatfoot between ages of 6-18 years.

PMID: 31989966 [PubMed - as supplied by publisher]

Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging.

Wed, 01/29/2020 - 07:22
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Contributions of Age-Related Thymic Involution to Immunosenescence and Inflammaging.

Immun Ageing. 2020;17:2

Authors: Thomas R, Wang W, Su DM

Abstract
Immune system aging is characterized by the paradox of immunosenescence (insufficiency) and inflammaging (over-reaction), which incorporate two sides of the same coin, resulting in immune disorder. Immunosenescence refers to disruption in the structural architecture of immune organs and dysfunction in immune responses, resulting from both aged innate and adaptive immunity. Inflammaging, described as a chronic, sterile, systemic inflammatory condition associated with advanced age, is mainly attributed to somatic cellular senescence-associated secretory phenotype (SASP) and age-related autoimmune predisposition. However, the inability to reduce senescent somatic cells (SSCs), because of immunosenescence, exacerbates inflammaging. Age-related adaptive immune system deviations, particularly altered T cell function, are derived from age-related thymic atrophy or involution, a hallmark of thymic aging. Recently, there have been major developments in understanding how age-related thymic involution contributes to inflammaging and immunosenescence at the cellular and molecular levels, including genetic and epigenetic regulation, as well as developments of many potential rejuvenation strategies. Herein, we discuss the research progress uncovering how age-related thymic involution contributes to immunosenescence and inflammaging, as well as their intersection. We also describe how T cell adaptive immunity mediates inflammaging and plays a crucial role in the progression of age-related neurological and cardiovascular diseases, as well as cancer. We then briefly outline the underlying cellular and molecular mechanisms of age-related thymic involution, and finally summarize potential rejuvenation strategies to restore aged thymic function.

PMID: 31988649 [PubMed]

Discrimination in the United States: Experiences of Native Americans.

Wed, 01/29/2020 - 07:22
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Discrimination in the United States: Experiences of Native Americans.

Health Serv Res. 2019 12;54 Suppl 2:1431-1441

Authors: Findling MG, Casey LS, Fryberg SA, Hafner S, Blendon RJ, Benson JM, Sayde JM, Miller C

Abstract
OBJECTIVE: To examine reported racial discrimination and harassment against Native Americans, which broadly contribute to poor health outcomes.
DATA SOURCE AND STUDY DESIGN: Data come from a nationally representative, probability-based telephone survey including 342 Native American and 902 white US adults, conducted January-April 2017.
METHODS: We calculated the percent of Native Americans reporting discrimination in several domains, including health care. We used logistic regression to compare the Native American-white difference in odds of discrimination and conducted exploratory analyses among Native Americans only to examine variation by socioeconomic and geographic/neighborhood characteristics.
PRINCIPAL FINDINGS: More than one in five Native Americans (23 percent) reported experiencing discrimination in clinical encounters, while 15 percent avoided seeking health care for themselves or family members due to anticipated discrimination. A notable share of Native Americans also reported they or family members have experienced violence (38 percent) or have been threatened or harassed (34 percent). In adjusted models, Native Americans had higher odds than whites of reporting discrimination across several domains, including health care and interactions with the police/courts. In exploratory analyses, the association between geographic/neighborhood characteristics and discrimination among Native Americans was mixed.
CONCLUSIONS: Discrimination and harassment are widely reported by Native Americans across multiple domains of their lives, regardless of geographic or neighborhood context. Native Americans report major disparities compared to whites in fair treatment by institutions, particularly with health care and police/courts. Results suggest modern forms of discrimination and harassment against Native Americans are systemic and untreated problems.

PMID: 31657013 [PubMed - indexed for MEDLINE]

Does Current General Mental Health Status Relate to Current Smoking Status in Pregnant Women?

Wed, 01/29/2020 - 07:22
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Does Current General Mental Health Status Relate to Current Smoking Status in Pregnant Women?

J Pregnancy. 2019;2019:7801465

Authors: Liu D, Younger E, Baker S, Touch S, Willmoth T, Hartos JL

Abstract
Purpose: Research shows that smoking during pregnancy is related to mental health diagnoses. The purpose of this study was to assess whether current general mental health status is related to current smoking status in pregnant women after controlling for other factors related to both mental health and tobacco use during pregnancy.
Methods: This cross-sectional analysis used 2017 Behavioral Risk Factor Surveillance Survey (BRFSS) data for 621 pregnant women aged 18-38 from Florida (N=136), Kansas (N=116), Minnesota (N=105), Nebraska (N=90), New York (N=78), and Utah (N=96). Multiple logistic regression analysis was used to assess the relationship between current mental health status and current tobacco use, while controlling for state, depression diagnosis, routine checkup, healthcare plan, age, marital status, ethnicity/race, education level, income level, and employment status.
Results: Overall, very few participants reported current smoking (6%) and about one-third reported low or moderate mental health status in the past 30 days. Adjusted results indicated that those who reported high mental health status were about 3 times less likely (OR=0.29, 95% CI=0.09, 0.88) to report current smoking status compared to those who reported low mental health status.
Conclusions: Overall, current mental health status was highly related to current smoking status in pregnant women. Clinicians in obstetrics may expect a very low proportion of pregnant women to report smoking and up to one-third to report low or moderate current general mental health status. Given that current mental health issues and current tobacco use may harm both mother and child, be highly related in pregnant women, and change throughout the pregnancy, pregnant women should be screened automatically for both at each visit.

PMID: 31186961 [PubMed - indexed for MEDLINE]

Inhibitor of MyoD family a (I-mfa), a new positive regulator of fibronectin production by glomerular mesangial cells.

Tue, 01/28/2020 - 07:04
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Inhibitor of MyoD family a (I-mfa), a new positive regulator of fibronectin production by glomerular mesangial cells.

Am J Physiol Renal Physiol. 2020 Jan 27;:

Authors: Yazdizadeh Shotorbani P, Chaudhari S, Tao Y, Tsiokas L, Ma R

Abstract
Overproduction of extracellular matrix proteins, including fibronectin by MCs contributes to diabetic nephropathy. Inhibitor of myogenic differentiation family isoform a (I-mfa) is a multifunctional cytosolic protein, functioning as a transcriptional modulator or plasma channel protein regulator. However, its renal effects are unknown. The present study was conducted to determine if I-mfa regulated fibronectin production by glomerular mesangial cells (MCs). In human MCs, overexpression of I-mfa significantly increased fibronectin abundance. Silencing I-mfa significantly reduced the level of fibronectin mRNA and blunted TGF-β1-stimulated production of fibronectin. We further found that high glucose increased I-mfa protein content at a time course (≥ 48 h) and concentration (≥ 25 mM) dependent manner. Although high glucose exposure increased I-mfa at protein level, it did not significantly alter the transcripts of I-mfa in MCs. Furthermore, abundance of I-mfa protein was significantly increased in the renal cortex of rats with diabetic nephropathy. I-mfa protein level was also elevated in the glomerulus of mice with diabetic kidney disease. However, there was no significant difference in glomerular I-mfa mRNA levels between the mice with and without diabetic nephropathy. Moreover, hydrogen peroxide significantly increased I-mfa protein abundance at a dose dependent manner in cultured human MCs. Antioxidants polyethylene glycol-catalase, ammonium pyrrolidithiocarbamate and N-acetyl cysteine significantly blocked high glucose-induced increase of I-mfa protein. Taken together, our results suggest that I-mfa, increased by high glucose/diabetes through production of reactive oxygen species stimulates fibronectin production by MCs.

PMID: 31984795 [PubMed - as supplied by publisher]

Getting to the heart of low sensitivity to alcohol: Context moderates low cardiovascular response to alcohol in persons with a family history of alcohol use disorder.

Tue, 01/28/2020 - 07:04
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Getting to the heart of low sensitivity to alcohol: Context moderates low cardiovascular response to alcohol in persons with a family history of alcohol use disorder.

Alcohol Clin Exp Res. 2020 Jan 27;:

Authors: Bates ME, Mun EY, Buckman JF, Vaschillo E, Vaschillo B, Lehrer P, Udo T, Lesnewich LM

Abstract
BACKGROUND: Low sensitivity to alcohol in persons with a family history of alcoholism (FH+), compared to those without (FH-), contributes to risk for alcohol use disorder (AUD). However, sensitivity of FH+ cardiovascular response to alcohol is not well understood. This gap is significant because cardiovascular processes contribute to emotional regulation and stress response problems theorized to be central to the development and persistence of AUD. This study compared changes in heart rate (HR) and HR variability (HRV) between FH groups after consuming alcohol and control beverages and examined how these changes were moderated by emotional and alcohol-related contexts.
METHODS: Young adults (N=165) with FH+ (n=110) or FH- (n=55) each completed two sessions, separated by one week. They received one of three different beverages (alcohol, placebo, told-no-alcohol) in each session. Electrocardiogram data were recorded during pre- and post-beverage consumption baselines, and then during four picture cue tasks (neutral, positive, negative, alcohol-related). Generalized Estimating Equations were used to examine differences in cardiovascular reactivity (changes in HR and HRV power at ~0.1 Hz) across FH groups, beverage conditions, and picture cue tasks.
RESULTS: A significant beverage condition x cue task x FH interaction effect on HRV was observed. The FH+ compared to the FH- group, showed (a) significantly less HRV suppression in specific cue contexts following alcohol, (b) a mixed pattern of more and less HRV suppression across cue contexts following placebo, and (c) a similar HRV reactivity pattern in the told-no-alcohol condition across cue tasks. For HR, there were no significant effects involving FH.
CONCLUSIONS: Diminished cardiovascular sensitivity to oral alcohol in FH+ persons varied within a given drinking episode depending on emotional and alcohol-related features of the context, suggesting that environmental characteristics play a role in the expression of low sensitivity to alcohol among FH+ individuals.

PMID: 31984514 [PubMed - as supplied by publisher]

The Impact of Grantsmanship Self-Efficacy on Early Stage Investigators of The National Research Mentoring Network Steps Toward Academic Research (NRMN STAR).

Fri, 01/24/2020 - 06:10
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The Impact of Grantsmanship Self-Efficacy on Early Stage Investigators of The National Research Mentoring Network Steps Toward Academic Research (NRMN STAR).

Ethn Dis. 2020;30(1):75-82

Authors: Thorpe RJ, Vishwanatha JK, Harwood EM, Krug EL, Unold T, Boman KE, Jones HP

Abstract
The NRMN STAR program was created to address the persistent underrepresentation in grant submissions and receipt of National Institutes of Health (NIH) awards by racial/ethnic minority groups. In our current study, we assessed program impact on trainees' self-efficacy related to grant writing. The program was conducted with two cohorts: one in June 2014 and one in June 2015. We used a 19-item grant writing self-efficacy scale drawn from the 88-item Clinical Research Assessment Inventory of three domains (conceptualizing, designing, and funding a study) to predict whether self-efficacy influences researchers' grant submissions. Trainees were assessed prior to and following program completion with subsequent assessments at 6 and 12 months beyond participation. The majority of trainees were Black (62%), female (62%), and had obtained a PhD (90%). More than half (52%) were assistant professors and 57% had none or <1 year of research experience beyond postdoctoral training. However, 24% of trainees reported no postdoctoral research training. NRMN STAR trainees' self-efficacy significantly improved on all three domains exhibiting a 2.0-point mean change score on two domains (conceptualizing and design) and 3.7 point mean change score on the domain, funding a study. Findings suggest that NRMN's STAR provides impactful, confidence-building training for diverse, early stage investigators with little-to-no skills, experiences, or low self-efficacy in writing research grants.

PMID: 31969786 [PubMed - in process]

Knee osteoarthritis, potential mediators, and risk of all-cause mortality: data from the Osteoarthritis Initiative.

Wed, 01/22/2020 - 05:32

Knee osteoarthritis, potential mediators, and risk of all-cause mortality: data from the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken). 2020 Jan 21;:

Authors: Wang Y, Nguyen UDT, Lane NE, Lu N, Wei J, Lei G, Zeng C, Zhang Y

Abstract
OBJECTIVE: To assess the relation of symptomatic knee osteoarthritis (OA), knee pain, and radiographic knee OA to all-cause mortality and identify mediators in the causal pathway.
METHODS: Participants from the Osteoarthritis Initiative were divided into four groups: (1) symptomatic knee OA (i.e., both radiographic knee OA [Kellgren and Lawrence grade ≥2] and knee pain); (2) knee pain only; (3) radiographic knee OA only; and (4) neither radiographic knee OA nor knee pain. We examined the relation of knee OA status to all-cause mortality using a multivariable Cox-proportional model and assessed the extent to which the association was mediated by disability, physical (PCS) and mental component summary scores (MCS) of quality of life (QoL), and oral pain-relief medications (i.e. nonsteroidal anti-inflammatory drugs and opioids) use.
RESULTS: Among 4,796 participants, 282 died over the 96-month follow-up period. Compared with those with neither radiographic knee OA nor knee pain, multivariable-adjusted hazard ratios (HRs) of mortality were 2.2 (95% confidence interval [CI]: 1.6-3.1) for symptomatic knee OA, 0.9 (95%CI: 0.6-1.4) for knee pain only, and 2.0 (95%CI: 1.4-2.9) for radiographic knee OA only, respectively. Indirect effects (HRs) of symptomatic knee OA on mortality via disability and PCS of QoL were 1.1 (95%CI: 1.0-1.4) and 1.2 (95%CI: 1.0-1.4), respectively. No apparent mediation effect was observed through either MCS of QoL or oral pain-relief medications use.
CONCLUSION: Participants with either symptomatic or radiographic knee OA were at an increased risk of all-cause mortality. Increased risk of mortality from symptomatic knee OA was partially mediated through its effect on disability and PCS of QoL.

PMID: 31961495 [PubMed - as supplied by publisher]

Identification of Binding Sites for Efflux Pump Inhibitors of the AcrAB-TolC Component AcrA.

Wed, 01/22/2020 - 05:32
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Identification of Binding Sites for Efflux Pump Inhibitors of the AcrAB-TolC Component AcrA.

Biophys J. 2019 02 19;116(4):648-658

Authors: Darzynkiewicz ZM, Green AT, Abdali N, Hazel A, Fulton RL, Kimball J, Gryczynski Z, Gumbart JC, Parks JM, Smith JC, Zgurskaya HI

Abstract
The overexpression of multidrug efflux pumps is an important mechanism of clinical resistance in Gram-negative bacteria. Recently, four small molecules were discovered that inhibit efflux in Escherichia coli and interact with the AcrAB-TolC efflux pump component AcrA. However, the binding site(s) for these molecules was not determined. Here, we combine ensemble docking and molecular dynamics simulations with tryptophan fluorescence spectroscopy, site-directed mutagenesis, and antibiotic susceptibility assays to probe binding sites and effects of binding of these molecules. We conclude that clorobiocin and SLU-258 likely bind at a site located between the lipoyl and β-barrel domains of AcrA.

PMID: 30691677 [PubMed - indexed for MEDLINE]

Copper-tolfenamic acid: evaluation of stability and anti-cancer activity.

Wed, 01/22/2020 - 05:32
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Copper-tolfenamic acid: evaluation of stability and anti-cancer activity.

Invest New Drugs. 2019 02;37(1):27-34

Authors: Hurtado M, Sankpal UT, Chhabra J, Brown DT, Maram R, Patel R, Gurung RK, Simecka J, Holder AA, Basha R

Abstract
The non-steroidal anti-inflammatory drug, Tolfenamic acid (TA) acts as an anti-cancer agent in several adult and pediatric cancer models. Copper (Cu) is an important element with multiple biological functions and has gained interest in medical applications. Recently, [Cu(TA)2(bpy)] (Cu-TA) has been synthesized in order to enhance therapeutic activity. In this study, we synthesized Cu-TA using an established method, characterized it by UV visible spectroscopy and Fourier-transform infrared spectroscopy (FTIR), and tested its anti-cancer activity using twelve cell lines representing various cancers, such as Ewing sarcoma, glioblastoma, medulloblastoma, neuroblastoma, pancreatic and prostate. The anti-proliferative activity of Cu-TA was determined at 48 h post-treatment and compared with the parental compound, TA. The IC50 values were calculated using GraphPad Prism software. The biological stability of Cu-TA was evaluated using twelve-month-old powder and six-month-old stock solution. Cardiomyocytes (H9C2) were used to test the cytotoxicity in non-malignant cells. Cu-TA showed higher anti-proliferative activity, and the IC50 values were 30 to 80% lower when compared with TA. H9C2 cells were non-responsive to Cu-TA, suggesting that it is selective towards malignant cells. Comparison of the twelve-month-old powder and six-month-old stock solution using the Panc1 cell line showed similar IC50 values (<5% variation), confirming the stability of Cu-TA either in powder or solution form. These findings demonstrate the potential of Cu-TA as an effective anti-cancer agent. Further studies to delineate the detailed mechanism of action of Cu-TA for specific cancer model are underway.

PMID: 29761244 [PubMed - indexed for MEDLINE]

Muscular architecture of the popliteus muscle and the basic science implications.

Mon, 01/20/2020 - 07:33
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Muscular architecture of the popliteus muscle and the basic science implications.

Knee. 2020 Jan 15;:

Authors: Wood A, Boren M, Dodgen T, Wagner R, Patterson RM

Abstract
BACKGROUND: The function of the popliteus muscle is largely treated as a static stabilizer and has a lack of basic muscular architectural data to enable study of its dynamic function. A large volume of literature supports its static function and the essential need for reconstruction in the posterolateral knee when injured to restore knee stability.
HYPOTHESIS/PURPOSE: We hypothesize that the popliteus muscle is more significant as a dynamic presence in the knee.
METHODS: A collection of popliteus architectural data was collected from 28 cadaver specimens (mean (SD) 76 years (11)). Physiological cross-sectional area of the popliteus and semimembranosus muscles were calculated from muscle volume and fiber length to power future muscle force prediction models. Posterior knee muscle trajectories were measured with respect to the longitudinal axis of the tibia. A 2-tailed T test was performed.
RESULTS: Significant differences between males and females were found for both the popliteus (p = 1.1E-05) and semimembranosus (p = 2.0E-05) muscle volumes. Significant differences between males and females were also found in PCSA for the popliteus (p = 0.005) and semimembranosus (p = 4.1E-05) muscles. There were no significant differences in fiber length, overall muscle length (with tendon removed), age, and orientation.
CONCLUSION: Further consideration should be given to include the popliteus muscle as a dynamic entity in the knee given its mechanical properties, trajectory, and prior biomechanical evidence showing when and how it is activated. The present study provides data that may shape future directions of research and treatment with regard to posterolateral corner injuries and ligamentous balancing of the knee.

PMID: 31954610 [PubMed - as supplied by publisher]

Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain.

Sat, 01/18/2020 - 06:17
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Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain.

Int J Mol Sci. 2020 Jan 05;21(1):

Authors: Manukhina EB, Tseilikman VE, Karpenko MN, Pestereva NS, Tseilikman OB, Komelkova MV, Kondashevskaya MV, Goryacheva AV, Lapshin MS, Platkovskii PO, Sarapultsev AP, Alliluev AV, Downey HF

Abstract
Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC's ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day exposure to cat urine scent (PTSD rats). Some rats were then adapted to 14-day IHC (PTSD+IHC rats), while PTSD and untreated control rats were cage rested. PTSD rats had a higher anxiety index (AI, X-maze test), than control or PTSD+IHC rats. This higher AI was associated with reduced glycogen content and histological signs of metabolic and hypoxic damage and of impaired contractility. The livers of PTSD rats had reduced glycogen content. Liver and blood alanine and aspartate aminotransferase activities of PTSD rats were significantly increased. PTSD rats had increased norepinephrine concentration and decreased monoamine oxidase A activity in cerebral cortex. The PTSD-induced elevation of carbonylated proteins and lipid peroxidation products in these organs reflects oxidative stress, a known cause of organ pathology. IHC alleviated PTSD-induced metabolic and structural injury and reduced oxidative stress. Therefore, IHC is a promising preventive treatment for PTSD-related morphological and functional damage to organs, due, in part, to IHC's reduction of oxidative stress.

PMID: 31948051 [PubMed - in process]

Glycyrrhizin Protects γ-Irradiated Mice from Gut Bacteria-Associated Infectious Complications by Improving miR-222-Associated Gas5 RNA Reduction in Macrophages of the Bacterial Translocation Site.

Fri, 01/17/2020 - 06:02
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Glycyrrhizin Protects γ-Irradiated Mice from Gut Bacteria-Associated Infectious Complications by Improving miR-222-Associated Gas5 RNA Reduction in Macrophages of the Bacterial Translocation Site.

J Immunol. 2020 Jan 15;:

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, gut bacteria-associated sepsis caused high mortality rates in mice exposed to 6-9 Gy of γ-rays. IL-12+CD38+ iNOS+ Mϕ (M1Mϕ) located in the bacterial translocation site (mesenteric lymph nodes [MLNs]) of unirradiated mice were characterized as host defense antibacterial effector cells. However, cells isolated from the MLNs of GIARS mice were mostly CCL1+IL-10+LIGHT+miR-27a+ Mϕ (M2bMϕ, inhibitor cells for the M1Mϕ polarization). Reduced long noncoding RNA Gas5 and increased miR-222 expression in MLN-Mϕ influenced by the irradiation were shown to be associated with M2bMϕ polarization. In this study, the mortality of mice exposed to 7 Gy of γ-rays (7 Gy GIARS mice) was completely controlled after the administration of glycyrrhizin (GL), a major active ingredient in licorice root (Glycyrrhiza glabra). Bacterial translocation and subsequent sepsis were minimal in 7 Gy GIARS mice treated with GL. Increased Gas5 RNA level and decreased miR-222 expression were shown in MLN-Mϕ isolated from 7 Gy GIARS mice treated with GL, and these macrophages did not display any properties of M2bMϕ. These results indicate that gut bacteria-associated sepsis in 7 Gy GIARS mice was controlled by the GL through the inhibition of M2bMϕ polarization at the bacteria translocation site. Expression of Ccl1, a gene required for M2bMϕ survival, is silenced in the MLNs of 7 Gy GIARS mice because of Gas5 RNA, which is increased in these cells after the suppression of miR-222 (a Gas5 RNA expression inhibitor) by the GL.

PMID: 31941655 [PubMed - as supplied by publisher]

Kinematic Analysis of Combined Suture-Button and Suture Anchor Augment Constructs for Ankle Syndesmosis Injuries.

Fri, 01/17/2020 - 06:02
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Kinematic Analysis of Combined Suture-Button and Suture Anchor Augment Constructs for Ankle Syndesmosis Injuries.

Foot Ankle Int. 2020 Jan 15;:1071100719898181

Authors: Wood AR, Arshad SA, Kim H, Stewart D

Abstract
BACKGROUND: Syndesmosis injuries are common, with up to 25% of all ankle injuries being reported to involve an associated syndesmosis injury. These injuries are typically treated with cortical screw fixation or suture-button implants when indicated, but the addition of a suture anchor augment implant has yet to be evaluated. The purpose of this study was to evaluate the ability of a suture anchor augment to add sagittal plane translational and transverse plane rotational constraint to suture-button constructs with syndesmosis injuries. We hypothesized that the suture anchor augment oriented in parallel with the fibers of an injured anterior-inferior tibiofibular ligament (AITFL) in addition to a suture-button construct would achieve physiological motion and stability at the syndesmosis through increased rotational and translational constraint of the fibula.
METHODS: Eleven fresh-frozen cadaver ankles were stressed in external rotation using a custom-made ankle rig. Each ankle had simultaneous recording of ultrasound video, 6 degrees-of-freedom kinematics of the fibula and tibia, and torque as the ankle was stressed by an examiner. The ankles were tested in 6 different states: native uninjured; injured with interosseous ligament and AITFL sectioned; 1× suture button; 2× suture buttons, divergent; 1× suture anchor augment with 2× suture buttons, divergent; and 1× suture anchor augment with 1× suture buttons.
RESULTS: Only the suture anchor augment + 2× suture buttons and suture anchor augment + 1× suture-button constructs were found to be significantly different from the injured state (P = .0003, P = .002) with mean external rotation of the fibula.
CONCLUSION: Overall, the most important finding of this study was that the addition of a suture anchor augment to suture-button constructs provided a mechanism to increase external rotational constraint of the fibula.
CLINICAL RELEVANCE: This study provides a mechanistic understanding of how the combined suture-button and suture anchor augment construct provides an anatomically similar reconstruction of constraints found in the native ankle. However, none of the constructs examined in this study were able to fully restore physiologic motion.

PMID: 31941352 [PubMed - as supplied by publisher]

Electronic Nicotine Delivery Systems Marketing and Initiation Among Youth and Young Adults.

Fri, 01/17/2020 - 06:02
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Electronic Nicotine Delivery Systems Marketing and Initiation Among Youth and Young Adults.

Pediatrics. 2019 09;144(3):

Authors: Loukas A, Paddock EM, Li X, Harrell MB, Pasch KE, Perry CL

Abstract
BACKGROUND AND OBJECTIVES: Electronic nicotine delivery systems (ENDS) have become the most popular tobacco products among young people, yet ENDS marketing remains unregulated, and its effects on ENDS use behavior across age groups is poorly understood. In this study, using a longitudinal design, we examined how recall of ENDS marketing through 5 different channels predicted subsequent ENDS initiation up to 2.5 years later among youth (ages 12-17 years) and young adults (ages 18-29 years).
METHODS: Data were drawn from 2 large cohort studies in Texas. The analysis included school-going youth (n = 2288) and college-going young adults (n = 2423) who reported never having used ENDS at baseline in 2014. Logistic regression was used to assess the influence of recalled ENDS marketing exposure via television (TV), radio or Internet radio, billboards, retail stores, and the Internet on subsequent ENDS initiation, with adjustment for these channels, baseline sociodemographics, other past-30-day tobacco use, sensation seeking, and peer ENDS use.
RESULTS: Recall of retail store-based ENDS marketing at baseline was associated with significantly higher odds of subsequent ENDS initiation among youth (adjusted odds ratio [aOR] = 1.99; 95% confidence interval [CI]: 1.25-3.17) and young adults (aOR = 1.30; 95% CI: 1.05-1.61) up to 2.5 years later. Young adult initiation was also associated with recalled ENDS marketing on TV at baseline (aOR = 1.29; 95% CI: 1.03-1.63).
CONCLUSIONS: Marketing of ENDS at retail stores predicts youth and young adult ENDS initiation, and marketing on TV predicts young adult initiation. Future research and regulation should be used to address the most influential marketing channels.

PMID: 31451608 [PubMed - in process]

Development of zebrafish demyelination model for evaluation of remyelination compounds and RORγt inhibitors.

Fri, 01/17/2020 - 06:02
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Development of zebrafish demyelination model for evaluation of remyelination compounds and RORγt inhibitors.

J Pharmacol Toxicol Methods. 2019 Jul - Aug;98:106585

Authors: Zhu XY, Guo SY, Xia B, Li CQ, Wang L, Wang YH

Abstract
RAR-related orphan receptor-γt (RORγt) directs differentiation of proinflammatory T helper 17 cells and is a potential therapeutic target for chronic autoimmune and inflammatory diseases including multiple sclerosis. In this study, zebrafish at days post fertilization treated with ethidium bromide (EB) at a concentration of 75 μM for 72 h were determined as the optimum conditions for the demyelination model development. Zebrafish motility was recorded automatically using a video-track motion detector and quantitative myelin assay was measured by FluoroMyelin staining. A well-known remyelination agent thyroxine (T4) was tested to confirm whether EB-induced motility and myelin damage could be rescued. Two RORγt lead inhibitors GSK805 and SR1001 were assessed for their therapeutic effects on remyelination, axon regeneration, motor neuron promotion and anti-inflammation. T4 significantly improved EB-induced motility dysfunction and myelin damage and promoted myelin basic protein (MBP) regeneration in the demyelinated zebrafish. GSK805 and SR1001 enhanced remyelination in a dose-dependent manner and promoted MBP regeneration. Both GSK805 and SR1001 markedly recovered EB-induced axon and motor neuron damage, and exhibited significantly inhibitory effects of neutrophil infiltration and macrophage recruitment. These results indicate that EB treatment can induce zebrafish demyelination; and the zebrafish demyelination model in combination with quantitative motility and myelin assays is a predictive, reproducible and relatively high throughput screening for rapidly in vivo identification of remyelination compounds and RORγt inhibitors.

PMID: 31112751 [PubMed - in process]

Optimizing Patient Outcomes with PD-1/PD-L1 Immune Checkpoint Inhibitors for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer.

Tue, 01/14/2020 - 05:15
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Optimizing Patient Outcomes with PD-1/PD-L1 Immune Checkpoint Inhibitors for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer.

Pharmacotherapy. 2020 Jan 12;:

Authors: La-Beck NM, Nguyen DT, Le AD, Alzghari SK, Trinh ST

Abstract
The rapidly expanding repertoire of immune checkpoint inhibitors (ICIs) now includes two agents, pembrolizumab and atezolizumab, approved for first-line treatment of advanced non-small cell lung cancer (aNSCLC) as monotherapy or as part of combination chemo-immunotherapy. This review summarizes the clinical evidence supporting these indications, with a focus on strategies to optimize patient outcomes. These strategies include patient and tumor factors, adverse-effect profiles, pharmacokinetic and pharmacodynamic drug interactions, and quality of life and cost-effectiveness considerations. We performed a systematic literature search of the PubMed, Scopus, and Google Scholar databases, as well as a search of the conference proceedings of the American Society of Clinical Oncology, European Society for Medical Oncology, and American Association for Cancer Research (through August 31, 2019). The addition of ICIs to conventional chemotherapy as first-line treatment against aNSCLC is now part of the standard of care options. However, even though ICIs may be cost-effective in patients with aNSCLC, high drug and other associated costs can still be a barrier to treatment for patients. Moreover, the adverse-effect profiles of ICIs differ significantly from conventional chemotherapy, and some immune-related adverse effects may have a lasting impact on quality of life. Therefore, in adhering to a patient-centered model of care, clinicians should be mindful of patient- and treatment-specific factors when considering therapeutic options for patients with aNSCLC. Although the role of the immune system in cancer progression and regression has not been fully elucidated, it is likely that the full clinical potential of immunotherapeutics in the treatment of cancer remains to be unleashed.

PMID: 31930528 [PubMed - as supplied by publisher]

Children with Psychogenic Nonepileptic Seizures.

Tue, 01/14/2020 - 05:15
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Children with Psychogenic Nonepileptic Seizures.

Pediatr Neurol Briefs. 2019 Dec 31;33:4

Authors: Gillan A, Shareef S

Abstract
A large multicenter retrospective cohort study was conducted by researchers from the Pediatric Health Information System hospital network to determine differences in demographics, clinical characteristics, testing, treatment, and healthcare use between children aged 8-20 years with epilepsy (n = 13,241) and those with psychogenic nonepileptic seizures (PNES) secondary to conversion disorder (n = 399).

PMID: 31929715 [PubMed]

Racial discrimination and telomere shortening among African Americans: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Tue, 01/14/2020 - 05:15
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Racial discrimination and telomere shortening among African Americans: The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Health Psychol. 2020 Jan 13;:

Authors: Chae DH, Wang Y, Martz CD, Slopen N, Yip T, Adler NE, Fuller-Rowell TE, Lin J, Matthews KA, Brody GH, Spears EC, Puterman E, Epel ES

Abstract
OBJECTIVE: Telomeres are protective sequences of DNA capping the ends of chromosomes that shorten over time. Leukocyte telomere length (LTL) is posited to reflect the replicative history of cells and general systemic aging of the organism. Chronic stress exposure leads to accelerated LTL shortening, which has been linked to increased susceptibility to and faster progression of aging-related diseases. This study examined longitudinal associations between LTL and experiences of racial discrimination, a qualitatively unique source of minority psychosocial stress, among African Americans.
METHOD: Data are from 391 African Americans in the Coronary Artery Risk Development in Young Adults (CARDIA) Telomere Ancillary Study. We examined the number of domains in which racial discrimination was experienced in relation to LTL collected in Years 15 and 25 (Y15: 2000/2001; Y25: 2010/2011). Multivariable linear regression examined if racial discrimination was associated with LTL. Latent change score analysis (LCS) examined changes in racial discrimination and LTL in relation to one another.
RESULTS: Controlling for racial discrimination at Y15, multivariable linear regression analyses indicated that racial discrimination at Y25 was significantly associated with LTL at Y25. This relationship remained robust after adjusting for LTL at Y15 (b = -.019, p = .015). Consistent with this finding, LCS revealed that increases in experiences of racial discrimination were associated with faster 10-year LTL shortening (b = -.019, p = .015).
CONCLUSIONS: This study adds to evidence that racial discrimination contributes to accelerated physiologic weathering and health declines among African Americans through its impact on biological systems, including via its effects on telomere attrition. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

PMID: 31928029 [PubMed - as supplied by publisher]

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