Recent Research Articles from UNTHSC

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

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 1 hour 39 min ago

Social Determinants of Health and Human Papillomavirus Vaccination Among Young Adults, National Health Interview Survey 2016.

Sat, 02/15/2020 - 05:15
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Social Determinants of Health and Human Papillomavirus Vaccination Among Young Adults, National Health Interview Survey 2016.

J Community Health. 2019 02;44(1):149-158

Authors: Thompson EL, Rosen BL, Maness SB

Abstract
Human papillomavirus (HPV) vaccination has the potential to reduce the burden of anogenital cancers. Vaccine uptake remains suboptimal, especially among young adults. Social determinants of health (SDOH) are societal level conditions that may indirectly influence health behaviors, including HPV vaccination. The purpose of this study was to assess HPV vaccination and SDOH among young adult women and men. The 2016 National Health Interview Survey was restricted to participants ages 18-26 (n = 3593). The Healthy People 2020 SDOH Framework was used to identify variables for economic stability, health and healthcare, education, social and community context, and neighborhood and built environment. Survey-weighted logistic regression models identified SDOH variables significantly associated with HPV vaccination. Reported HPV vaccination occurred for 45.7% of women and 14.5% of men in the sample. Among women, education determinants-highest level of education completed and English language-were significantly associated with HPV vaccination. Men (adjusted OR 0.65, 95% CI 0.54, 0.79) and women (adjusted OR 0.66, 95% CI 0.49, 0.90) who did not use the Internet to look up health information were at lower odds to be vaccinated for HPV. These findings can inform future HPV vaccine uptake efforts by focusing specifically on these SDOH areas-education and health and healthcare. Identifying SDOH leverage points is critical to promoting HPV vaccination and ultimately reducing HPV-associated cancers.

PMID: 30120681 [PubMed - indexed for MEDLINE]

Effects of intermittent pressure imitating rolling manipulation in traditional Chinese medicine on ultrastructure and metabolism in injured human skeletal muscle cells.

Fri, 02/14/2020 - 07:57
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Effects of intermittent pressure imitating rolling manipulation in traditional Chinese medicine on ultrastructure and metabolism in injured human skeletal muscle cells.

Am J Transl Res. 2020;12(1):248-260

Authors: Guan H, Zhao L, Liu H, Xie D, Liu Y, Zhang G, Mason DC, Zhang S, Li Y, Zhang H

Abstract
Skeletal muscle injuries can cause significant change in the ultrastructure and the metabolism of the skeletal muscle cells. Observation of the ultrastructure and measurements of the metabolism biomarkers such as total superoxide dismutase (T-SOD), malondialdehyde (MDA), and creatine kinase (CK) can be used to evaluate the degree of damage in human skeletal muscle injury. Rolling manipulation is the most popular myofascial release technique in Traditional Chinese Medicine. This study aimed to investigate the effects of intermittent pressure imitating rolling manipulation (IPIRM) of Traditional Chinese Medicine on ultrastructure and metabolism in the injured HSKMCs. Methods: In vitro techniques were used to culture HSKMCs, which were injured with high doses of dexamethasone sodium phosphate. Cells were divided into four groups-control normal group (CNG), control injured group (CIG), rolling manipulation group (RMG), and sine pressure group (SPG). RMG and SPG cells were cyclically exposed to 3.0 Kg (6.6 Pounds) of maximum force at a frequency of 2.0 Hz for 10 min in the Flexcell compression system for duration of 3 days continually. The cell ultrastructure, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA) content, and creatine kinase (CK) activity of the groups were assessed. Conclusion: These results suggest that the mechanical effects of rolling manipulation in TCM could not only improve the recovery of injured skeletal muscle cells by ameliorating organelles arrangement, reducing organelle swelling, and maintaining nuclear membrane integrity, but also ameliorate the functions of cellular metabolism by increasing T-SOD activity and decreasing MDA content and CK activity in injured skeletal muscle. Then the Hippo/Yap signal pathway was detected, and the proteins in each group were detected by Western Blot. The protein expression of upstream protein p-LATS1 and downstream protein p-Yap (Ser127) in each group was observed to explore the biomechanical mechanism of the method. The relative protein expression of p-LATS1 and p-Yap in (RMG) group was significantly higher than that in injured (CIG) group (P < 0.05). It was suggested that Hippo/Yap pathway was related to the stimulation of 3D human skeletal muscle cells, and the proliferation pathway of 3D human skeletal muscle cells could be opened by stimulation of three dimensional human skeletal muscle cells. It may be one of the biological mechanisms caused by the mechanical effects of manipulations in TCM.

PMID: 32051750 [PubMed]

Malaria epidemics in India: Role of climatic condition and control measures.

Fri, 02/14/2020 - 07:57
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Malaria epidemics in India: Role of climatic condition and control measures.

Sci Total Environ. 2020 Apr 10;712:136368

Authors: Baghbanzadeh M, Kumar D, Yavasoglu SI, Manning S, Hanafi-Bojd AA, Ghasemzadeh H, Sikder I, Kumar D, Murmu N, Haque U

Abstract
Malaria is a major public health problem in India, which is the second most populous country in the world. This study aimed to investigate the impact of climatic parameters and malaria control efforts implemented by the Indian national malaria control program on malaria epidemics between January of 2009 and December of 2015. A chi-squared test was used to study the correlation of all implemented control methods with occurrence of epidemics within 30, 45, 60 and 90 days and in the same district, 50, 100 and 200 km distance radiuses. The effect of each control method on probability of epidemics was also measured, and the effects of district population, season, and incidence of malaria parasite types were evaluated using logistic regression models. Fever survey was found to be effective for decreasing the odds of epidemics within 45, 60 and 90 days in 100 km. Anti-larval activity was also effective within 30, 45 and 60 days in 200 km. Winter had negative effects on odds ratio while summer and fall were more likely to trigger epidemics. These results contribute to understanding the role of climate variability and control efforts performed in India.

PMID: 32050403 [PubMed - in process]

Survival analysis of extracorporeal membrane oxygenation in neonatal and pediatric patients - A nationwide cohort study.

Fri, 02/14/2020 - 07:57
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Survival analysis of extracorporeal membrane oxygenation in neonatal and pediatric patients - A nationwide cohort study.

J Formos Med Assoc. 2019 Sep;118(9):1339-1346

Authors: Hsu J, Chang CH, Chiang LT, Caffrey JL, Lin JW, Chen YS

Abstract
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides short-term cardiopulmonary support for patients with acute cardiac and respiratory failure. This study reported the survival rate for pediatric patients from Taiwan's national cohort.
METHODS: Patients under the age of 18 who received ECMO from January 1, 2002 to December 31, 2012 were identified from the Taiwan National Health Insurance Research Database. The underlying etiology for ECMO use was categorized into post-operative (n = 410), cardiac (245), pulmonary (146) groups, and others (120). A Cox regression model was used to determine hazard ratios and to compare 30-day and 1-year survival rates using post-operative group as a reference.
RESULTS: The average age of all 921 patients was 4.83 ± 5.84 years, and 59.1% were male. The overall mortality rate was 29.2% at 1 month, and 46.9% at 1 year. The cardiac origin group, consisting mostly of congenital heart disease without surgical intervention, myocarditis, and heart failure had a better outcome with an adjusted hazard ratio of 0.69 (95% CI 0.49-0.96, p = 0.008) at 30 days and 0.50 (95% CI 0.38-0.66, p < 0.001) at 1 year, as compared to the post-operative group.
CONCLUSION: In contrast to the widespread use of ECMO in respiratory distress syndrome in western countries, pediatric ECMO in Taiwan was more often applied to patients with underlying cardiovascular diseases. Mortality rates varied according to age groups and various etiologies. The results of this large pediatric cohort provides a different prospective in critical care outcomes in medical environments where ECMO is more widely available.

PMID: 30612882 [PubMed - indexed for MEDLINE]

Laparoscopic Versus Open Cholecystectomy in Pediatric Patients: A Propensity Score-Matched Analysis.

Wed, 02/12/2020 - 07:40
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Laparoscopic Versus Open Cholecystectomy in Pediatric Patients: A Propensity Score-Matched Analysis.

J Laparoendosc Adv Surg Tech A. 2020 Feb 11;:

Authors: Babb J, Davis J, Tashiro J, Perez EA, Sola JE, Pandya S

Abstract
Background: As minimally invasive pediatric surgery becomes standard approach to many surgical solutions, access has become an important point for improvement. Laparoscopic cholecystectomy (LC) is the gold standard for many conditions affecting the gallbladder; however, open cholecystectomy (OC) is offered as the initial approach in a surprisingly high percentage of cases. Materials and Methods: The Kids' Inpatient Database (1997-2012) was searched for International Classification of Disease, 9th revision, Clinical Modification procedure code (51.2x). LC and OC performed in patients <20 years old were identified. Propensity score-matched analyses using 39 variables were performed to isolate the effects of race, income group, location, gender, payer status, and hospital size on the percentage of LCs and OCs offered. Cases were weighted to provide national estimates. Results: A total of 78,578 cases were identified, comprising LC (88.1%) and OC (11.9%). Girls were 1.6 (CI: 1.4, 1.7) times more likely to undergo LC versus boys. Large facilities were 1.4 (1.3, 1.7) times more likely to perform LCs than small facilities. Children in lower income quartiles were 1.2 (1.1, 1.3) times more likely to undergo LC compared with those in higher income quartiles. Rates of LC were not affected by race, hospital location, or payer status. Conclusions: Risk-adjusted analysis of a large population-based data set demonstrated evidence that confirms, but also refutes, traditional disparities to minimally invasive surgery access. Despite laparoscopic gold standard, OC remains the initial approach in a surprisingly high percentage of pediatric cases independent of demographics or socioeconomic status. Additional research is required to identify factors affecting the distribution of LC and OC within the pediatric population.

PMID: 32045322 [PubMed - as supplied by publisher]

Structural and functional insights into the bona fide catalytic state of Streptococcus pyogenes Cas9 HNH nuclease domain.

Wed, 02/12/2020 - 07:40
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Structural and functional insights into the bona fide catalytic state of Streptococcus pyogenes Cas9 HNH nuclease domain.

Elife. 2019 07 30;8:

Authors: Zuo Z, Zolekar A, Babu K, Lin VJ, Hayatshahi HS, Rajan R, Wang YC, Liu J

Abstract
The CRISPR-associated endonuclease Cas9 from Streptococcus pyogenes (SpyCas9), along with a programmable single-guide RNA (sgRNA), has been exploited as a significant genome-editing tool. Despite the recent advances in determining the SpyCas9 structures and DNA cleavage mechanism, the cleavage-competent conformation of the catalytic HNH nuclease domain of SpyCas9 remains largely elusive and debatable. By integrating computational and experimental approaches, we unveiled and validated the activated Cas9-sgRNA-DNA ternary complex in which the HNH domain is neatly poised for cleaving the target DNA strand. In this catalysis model, the HNH employs the catalytic triad of D839-H840-N863 for cleavage catalysis, rather than previously implicated D839-H840-D861, D837-D839-H840, or D839-H840-D861-N863. Our study contributes critical information to defining the catalytic conformation of the HNH domain and advances the knowledge about the conformational activation underlying Cas9-mediated DNA cleavage.

PMID: 31361218 [PubMed - indexed for MEDLINE]

Examining the association between oral health status and dementia: A nationwide nested case-controlled study.

Tue, 02/11/2020 - 07:22
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Examining the association between oral health status and dementia: A nationwide nested case-controlled study.

Exp Biol Med (Maywood). 2020 Feb 10;:1535370220904924

Authors: Lin JW, Chang CH, Caffrey JL

PMID: 32039633 [PubMed - as supplied by publisher]

Predicting post-experiment fatigue among healthy young adults: Random forest regression analysis.

Tue, 02/11/2020 - 07:22
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Predicting post-experiment fatigue among healthy young adults: Random forest regression analysis.

Psychol Test Assess Model. 2019 Nov 08;61(4):471-493

Authors: Mun EY, Geng F

Abstract
The current study utilized a random forest regression analysis to predict post-experiment fatigue in a sample of 212 healthy participants (mean age = 20.5, SD = 2.21; 52% women) between the ages of 18 and 30 following a mildly stressful experiment. We used a total of 30 features of demographic variables, lifestyle variables, alcohol and other drug use behaviors and problems, state anxiety and depressive symptoms, and physiological indicators that were lab assessed or self-reported. A random forest regression analysis with 10-fold cross-validation resulted in accurate prediction of post-experiment fatigue (R2 equivalent = 0.93) with the average "out-of-bag" (OOB) R2 = 0.52. Not surprisingly, self-reported pre-experiment fatigue was the most important variable (54%) in the prediction of post-experiment fatigue. Feeling anxious (state anxiety) pre- and post-experiment (3%, 7%), feeling less vigorous post experiment (3%), systolic and diastolic blood pressure (3%, 2%) and LF HRV (2%) assessed at baseline, and self-reported alcohol-related problems (3%) and sleep (2%) additionally contributed to the prediction of post-experiment fatigue. Other remaining input variables had relatively minimal importance. Substantively, this study suggests that complex interactions across multiple systems domains that support regulation may be linked to fatigue. A random forest regression analysis can relatively easily be implemented with a built-in cross-validation function and reveal a web of connections undergirding health behavior and risks.

PMID: 32038903 [PubMed]

Enhancing Statin Adherence Using a Motivational Interviewing Intervention and Past Adherence Trajectories in Patients with Suboptimal Adherence.

Tue, 02/11/2020 - 07:22
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Enhancing Statin Adherence Using a Motivational Interviewing Intervention and Past Adherence Trajectories in Patients with Suboptimal Adherence.

J Manag Care Spec Pharm. 2019 Oct;25(10):1053-1062

Authors: Abughosh SM, Vadhariya A, Johnson ML, Essien EJ, Esse TW, Serna O, Gallardo E, Boklage SH, Choi J, Holstad MM, Fleming ML

Abstract
BACKGROUND: Statins have been shown to be effective in reducing the occurrence of cardiovascular (CV) events and are widely prescribed for the risk reduction of CV diseases and recurrent CV events. However, poor adherence prevents some patients from receiving the maximum benefit of the therapy. Motivational interviewing (MoI) is a patient-centered collaborative approach that can be used to improve medication adherence. Group-based trajectory modeling depicts patterns of adherence over time and may help tailor the MoI intervention to further enhance adherence.
OBJECTIVE: To assess the effect of a phone-based MoI intervention tailored by patients' past adherence trajectory in improving adherence to statins among patients in a Medicare Advantage prescription drug plan (MAPD).
METHODS: Patients continuously enrolled in an MAPD from 2013 to 2017 with a statin prescription between January and June 2015 to allow 2 years of pre-index period and 1 year of follow-up were included in the study. Adherence to statins was measured monthly during the 1-year follow-up as proportion of days covered (PDC) and incorporated into a group-based trajectory model to provide 4 distinct patterns of adherence: adherent, rapid decline, gradual decline, and gaps in adherence. Patients in the 3 nonadherent groups were randomized to either control or intervention. The intervention was an initial counseling call and up to 2 monthly follow-up calls by pharmacy students trained in MoI, providing education consistent with a previously identified pattern of use. Refill data at 6 months post-intervention were evaluated to examine the intervention's effect on PDC, as continuous and dichotomized as PDC ≥ 0.8, as well as discontinuation. Multivariable regression adjusted for baseline demographics, clinical characteristics, and past adherence trajectory.
RESULTS: There were 152 patients included in the analysis who received MoI phone calls and 304 randomly selected controls. Mean PDC for the intervention group (0.67 ± 0.3) was significantly higher than the control (0.55 ± 0.4; P < 0.001). The intervention group was also less likely to discontinue (OR = 0.38; 95% CI = 0.19-0.76) and more likely to be adherent in the linear regression model (β = 12.4; P < 0.001) as well as in the logistic regression model (OR = 1.87; 95% CI = 1.18-2.95). Previous adherence trajectories were significantly associated with adherence in the follow-up.
CONCLUSIONS: Patients who received the MoI intervention were more likely to be adherent and less likely to discontinue the statin in the 6 months follow-up compared with controls. Future research can identify other approaches to tailor interventions and expand the intervention to other languages. This intervention may also prove valuable to improve adherence to other medications for chronic and asymptomatic diseases.
DISCLOSURES: This study was funded by Regeneron Pharmaceuticals, which provided critical input during study design, implementation, and manuscript preparation. Abughosh reports grants from Sanofi, BMS/Pfizer, and Valeant Pharmaceuticals, unrelated to this study. Vadhariya reports a past internship at Regeneron Pharmaceuticals, unrelated to this study. Esse, Serna, and Gallardo are employees of CareAllies, a Cigna subsidiary. Boklage is an employee of Regeneron Pharmaceuticals. Choi was an employee of Sanofi during this study. Johnson, Essien, Fleming, and Holstad have nothing to disclose. A poster based on this study was presented at AMCP Nexus 2018; October 22-25, 2018; Orlando, FL.

PMID: 31556824 [PubMed - indexed for MEDLINE]

Awareness and knowledge of HPV and HPV vaccination among adults ages 27-45 years.

Sat, 02/08/2020 - 06:47
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Awareness and knowledge of HPV and HPV vaccination among adults ages 27-45 years.

Vaccine. 2020 Feb 03;:

Authors: Thompson EL, Wheldon CW, Rosen BL, Maness SB, Kasting ML, Massey PM

Abstract
OBJECTIVE: Recent guidelines indicate adults 27-45 years old can receive the human papillomavirus (HPV) vaccine based on a shared-decision with their healthcare provider. With this expansion in recommendations, there is a need to examine the awareness and knowledge of HPV and HPV vaccination among this age group for cancer prevention.
METHODS: HINTS-5 Cycle-2 is a national survey of US adults, and was restricted to a complete case analysis of adults ages 27-45 years (N = 725). Sociodemographic, healthcare, and health information correlates were assessed for the outcomes of HPV awareness, HPV vaccine awareness, knowledge of HPV and cervical cancer, and knowledge of HPV and non-cervical cancers. Survey-weighted logistic regression models were conducted.
RESULTS: Most respondents were aware of HPV (72.9%) and HPV vaccination (67.1%). Respondents were more likely to be aware of HPV and HPV vaccination if they were female, had a higher level of education, and had previous cancer information seeking behaviors. Although there was widespread knowledge of HPV as a cause of cervical cancer (79.6%), knowledge of HPV as a cause of non-cervical cancers was reported by a minority of respondents (36.1%). College education was positively associated with cervical cancer knowledge (aOR = 4.62; 95%CI: 1.81-11.78); however, no significant correlates were identified for non-cervical HPV associated cancer knowledge.
CONCLUSION: While more than half of adults ages 27-45 years are aware of HPV and HPV vaccination, there are opportunities to improve awareness and knowledge, particularly related to non-cervical cancers, as these are critical first steps toward shared decision-making for HPV vaccination in mid-adulthood.

PMID: 32029321 [PubMed - as supplied by publisher]

Epidemic ribotypes of Clostridium (now Clostridioides) difficile are likely to be more virulent than non-epidemic ribotypes in animal models.

Fri, 02/07/2020 - 06:28
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Epidemic ribotypes of Clostridium (now Clostridioides) difficile are likely to be more virulent than non-epidemic ribotypes in animal models.

BMC Microbiol. 2020 Feb 05;20(1):27

Authors: Vitucci JC, Pulse M, Tabor-Simecka L, Simecka J

Abstract
BACKGROUND: Clostridioides difficile infections have become more frequently diagnosed and associated with greater disease severity, which has resulted in an increase burden on the healthcare system. These increases are attributed to the increased prevalence of hypervirulent strains encompassing select ribotypes. These epidemic ribotypes were characterized as hypervirulent due to higher in vitro spore and toxin production, as well as increased incidence, severity and mortality within patients. However, it is unclear whether epidemic ribotypes are truly more virulent than non-epidemic ribotypes in vivo. Furthermore, there is conflicting evidence about the ability of a strain's in vitro phenotype to be predictive of their in vivo virulence. The goals of the current studies were to determine if epidemic ribotypes are more virulent than other ribotypes in animal models, and whether the in vitro virulence phenotype of an isolate or ribotype predict in vivo virulence.
RESULTS: To determine if epidemic strains were truly more virulent than other non-epidemic strains, the in vivo virulence of 13 C. difficile isolates (7 non-epidemic and 6 epidemic ribotype isolates) were determined in murine and hamster models of CDI. The isolates of epidemic ribotype of C. difficile were found to be more virulent in both the murine and hamster models than non-epidemic isolates. In particular, the group of epidemic ribotypes of C. difficile had lower LD50 values in hamsters. The increased severity of disease was associated with higher levels of Toxin A and Toxin B production found in fecal samples, but not numbers of organisms recovered. The isolates were further characterized for their in vitro virulence phenotypes, e.g. toxin production, growth rates, spore formation and adherence of spores to intestinal epithelial cell lines. Although there were higher levels of toxins produced and greater adherence for the group of epidemic ribotypes, the in vitro profiles of individual isolates were not always predictive of their in vivo virulence.
CONCLUSIONS: Overall, the group of epidemic ribotypes of C. difficile were more virulent in vivo despite individual isolates having similar phenotypes to the non-epidemic isolates in vitro.

PMID: 32024477 [PubMed - in process]

Productivity, efficiency, and overall performance comparisons between attendings working solo versus attendings working with residents staffing models in an emergency department: A Large-Scale Retrospective Observational Study.

Thu, 02/06/2020 - 06:07

Productivity, efficiency, and overall performance comparisons between attendings working solo versus attendings working with residents staffing models in an emergency department: A Large-Scale Retrospective Observational Study.

PLoS One. 2020;15(2):e0228719

Authors: Robinson RD, Dib S, Mclarty D, Shaikh S, Cheeti R, Zhou Y, Ghasemi Y, Rahman M, Schrader CD, Wang H

Abstract
BACKGROUND AND OBJECTIVE: Attending physician productivity and efficiency can be affected when working simultaneously with Residents. To gain a better understanding of this effect, we aim to compare productivity, efficiency, and overall performance differences among Attendings working solo versus working with Residents in an Emergency Department (ED).
METHODS: Data were extracted from the electronic medical records of all patients seen by ED Attendings and/or Residents during the period July 1, 2014 through June 30, 2017. Attending productivity was measured based on the number of new patients enrolled per hour per provider. Attending efficiency was measured based on the provider-to-disposition time (PDT). Attending overall performance was measured by Attending Performance Index (API). Furthermore, Attending productivity, efficiency, and overall performance metrics were compared between Attendings working solo and Attendings working with Residents. The comparisons were analyzed after adjusting for confounders via propensity score matching.
RESULTS: A total of 15 Attendings and 266 Residents managing 111,145 patient encounters over the study period were analyzed. The mean (standard deviation) of Attending productivity and efficiency were 2.9 (1.6) new patients per hour and 2.7 (1.8) hours per patient for Attendings working solo, in comparison to 3.3 (1.9) and 3.0 (2.0) for Attendings working with Residents. When paired with Residents, the API decreased for those Attendings who had a higher API when working solo (average API dropped from 0.21 to 0.19), whereas API increased for those who had a lower API when working solo (average API increased from 0.13 to 0.16).
CONCLUSION: In comparison to the Attending working solo staffing model, increased productivity with decreased efficiency occurred among Attendings when working with Residents. The overall performance of Attendings when working with Residents varied inversely against their performance when working solo.

PMID: 32023302 [PubMed - in process]

Identifying and targeting angiogenesis-related microRNAs in ovarian cancer.

Thu, 02/06/2020 - 06:07
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Identifying and targeting angiogenesis-related microRNAs in ovarian cancer.

Oncogene. 2019 08;38(33):6095-6108

Authors: Chen X, Mangala LS, Mooberry L, Bayraktar E, Dasari SK, Ma S, Ivan C, Court KA, Rodriguez-Aguayo C, Bayraktar R, Raut S, Sabnis N, Kong X, Yang X, Lopez-Berestein G, Lacko AG, Sood AK

Abstract
Current anti-angiogenic therapy for cancer is based mainly on inhibition of the vascular endothelial growth factor pathway. However, due to the transient and only modest benefit from such therapy, additional approaches are needed. Deregulation of microRNAs (miRNAs) has been demonstrated to be involved in tumor angiogenesis and offers opportunities for a new therapeutic approach. However, effective miRNA-delivery systems are needed for such approaches to be successful. In this study, miRNA profiling of patient data sets, along with in vitro and in vivo experiments, revealed that miR-204-5p could promote angiogenesis in ovarian tumors through THBS1. By binding with scavenger receptor class B type 1 (SCARB1), reconstituted high-density lipoprotein-nanoparticles (rHDL-NPs) were effective in delivering miR-204-5p inhibitor (miR-204-5p-inh) to tumor sites to suppress tumor growth. These results offer a new understanding of miR-204-5p in regulating tumor angiogenesis.

PMID: 31289363 [PubMed - indexed for MEDLINE]

17β-Estradiol Delivered in Eye Drops: Evidence of Impact on Protein Networks and Associated Biological Processes in the Rat Retina through Quantitative Proteomics.

Wed, 02/05/2020 - 14:51
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17β-Estradiol Delivered in Eye Drops: Evidence of Impact on Protein Networks and Associated Biological Processes in the Rat Retina through Quantitative Proteomics.

Pharmaceutics. 2020 Jan 27;12(2):

Authors: Prokai L, Zaman K, Nguyen V, Prokai-Tatrai K

Abstract
To facilitate the development of broad-spectrum retina neuroprotectants that can be delivered through topical dosage forms, this proteomics study focused on analyzing target engagements through the identification of functional protein networks impacted after delivery of 17β-estradiol in eye drops. Specifically, the retinae of ovariectomized Brown Norway rats treated with daily eye drops of 17β-estradiol for three weeks were compared to those of vehicle-treated ovariectomized control animals. We searched the acquired raw data against a composite protein sequence database by using Mascot, as well as employed label-free quantification to detect changes in protein abundances. Our investigation using rigorous validation criteria revealed 331 estrogen-regulated proteins in the rat retina (158 were up-regulated, while 173 were down-regulated by 17β-estradiol delivered in eye drops). Comprehensive pathway analyses indicate that these proteins are relevant overall to nervous system development and function, tissue development, organ development, as well as visual system development and function. We also present 18 protein networks with associated canonical pathways showing the effects of treatments for the detailed analyses of target engagements regarding potential application of estrogens as topically delivered broad-spectrum retina neuroprotectants. Profound impact on crystallins is discussed as one of the plausible neuroprotective mechanisms.

PMID: 32012756 [PubMed]

Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging.

Wed, 02/05/2020 - 14:51
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Long-term HIV-1 Tat Expression in the Brain Led to Neurobehavioral, Pathological, and Epigenetic Changes Reminiscent of Accelerated Aging.

Aging Dis. 2020 Feb;11(1):93-107

Authors: Zhao X, Fan Y, Vann PH, Wong JM, Sumien N, He JJ

Abstract
HIV infects the central nervous system and causes HIV/neuroAIDS, which is predominantly manifested in the form of mild cognitive and motor disorder in the era of combination antiretroviral therapy. HIV Tat protein is known to be a major pathogenic factor for HIV/neuroAIDS through a myriad of direct and indirect mechanisms. However, most, if not all of studies involve short-time exposure of recombinant Tat protein in vitro or short-term Tat expression in vivo. In this study, we took advantage of the doxycycline-inducible brain-specific HIV-1 Tat transgenic mouse model, fed the animals for 12 months, and assessed behavioral, pathological, and epigenetic changes in these mice. Long-term Tat expression led to poorer short-and long-term memory, lower locomotor activity and impaired coordination and balance ability, increased astrocyte activation and compromised neuronal integrity, and decreased global genomic DNA methylation. There were sex- and brain region-dependent differences in behaviors, pathologies, and epigenetic changes resulting from long-term Tat expression. All these changes are reminiscent of accelerated aging, raising the possibility that HIV Tat contributes, at least in part, to HIV infection-associated accelerated aging in HIV-infected individuals. These findings also suggest another utility of this model for HIV infection-associated accelerated aging studies.

PMID: 32010484 [PubMed]

Activated human astrocyte-derived extracellular vesicles modulate neuronal uptake, differentiation and firing.

Sat, 02/01/2020 - 07:56
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Activated human astrocyte-derived extracellular vesicles modulate neuronal uptake, differentiation and firing.

J Extracell Vesicles. 2020;9(1):1706801

Authors: You Y, Borgmann K, Edara VV, Stacy S, Ghorpade A, Ikezu T

Abstract
Astrocytes in the central nervous system (CNS) provide supportive neural functions and mediate inflammatory responses from microglia. Increasing evidence supports their critical roles in regulating brain homoeostasis in response to pro-inflammatory factors such as cytokines and pathogen/damage-associated molecular pattern molecules in infectious and neurodegenerative diseases. However, the underlying mechanisms of the trans-cellular communication are still unclear. Extracellular vesicles (EVs) can transfer a large diversity of molecules such as lipids, nucleic acids and proteins for cellular communications. The purpose of this study is to characterize the EVs cargo proteins derived from human primary astrocytes (ADEVs) under both physiological and pathophysiological conditions. ADEVs were isolated from human primary astrocytes after vehicle (CTL) or interleukin-1β (IL-1β) pre-treatment. Label-free quantitative proteomic profiling revealed a notable up-regulation of proteins including actin-associated molecules, integrins and major histocompatibility complex in IL-1β-ADEVs compared to CTL-ADEVs, which were involved in cellular metabolism and organization, cellular communication and inflammatory response. When fluorescently labelled ADEVs were added into primary cultured mouse cortical neurons, we found a significantly increased neuronal uptake of IL-1β-ADEVs compared to CTL-ADEVs. We further confirmed it is likely due to the enrichment of surface proteins in IL-1β-ADEVs, as IL-1β-ADEVs uptake by neurons was partially suppressed by a specific integrin inhibitor. Additionally, treatment of neurons with IL-1β-ADEVs also reduced neurite outgrowth, branching and neuronal firing. These findings provide insight for the molecular mechanism of the ADEVs' effects on neural uptake, neural differentiation and maturation, and its alteration in inflammatory conditions.

PMID: 32002171 [PubMed]

Effects of Different Sling Settings on Electromyographic Activities of Selected Trunk Muscles: A Preliminary Research.

Fri, 01/31/2020 - 07:45
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Effects of Different Sling Settings on Electromyographic Activities of Selected Trunk Muscles: A Preliminary Research.

Biomed Res Int. 2020;2020:2945952

Authors: Li X, Liu H, Lin KY, Miao P, Zhang BF, Lu SW, Li L, Wang CH

Abstract
Introduction: The supine and prone sling exercise may facilitate activation of the local trunk muscles. Does the side-lying sling exercise activate trunk muscles more easily than the supine and prone training with sling settings? Clinical work has shown that the side-lying sling exercise could reduce pain in patients with unilateral low back pain (LBP), but the mechanism behind it is unclear. The fundamental purpose of this preliminary study was to examine the electromyography (EMG) characteristics of trunk muscles during different sling lumbar settings on sixteen healthy adults.
Methods: Amplitude and mean power frequency (MPF) of EMG signals were recorded from the transversus abdominis (TA), rectus abdominis (RA), multifidus (MF), erector spinae (ES), gluteus maximus (Gmax), and gluteus medius (Gmed) muscles while the subjects performed the supine lumbar setting (SLS), prone lumbar setting (PLS), left side-lying lumbar setting (LSLS), and right side-lying lumbar setting (RSLS).
Results: During SLS and PLS, TA and MF showed significantly higher activity than RA and ES on the same side, respectively. The EMG activities of ES, TA, MF, Gmax, and Gmed had significant differences between the different sides during LSLS and RSLS, and the dominant-side muscles showed higher activity than the other side. There was no significant difference in core trunk muscles between different sling lumbar settings-only that the SLS of the MF/ES ratio was significantly higher than LSLS and RSLS.
Conclusions: Sling exercises can be an effective measure to enhance MF and TA EMG activity, and the side-lying position can increase dominant-side Gmax and Gmed activity. Side-lying sling training does not activate more core muscles than the supine and prone training. Supine and prone exercise should be preferred over SLT to stabilize the lumbar region because of its high local/global muscle ratio.

PMID: 31998786 [PubMed - in process]

Do Asians Patients Require Only Half of the Clozapine Dose Prescribed for Caucasians? A Critical Review.

Fri, 01/31/2020 - 07:45
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Do Asians Patients Require Only Half of the Clozapine Dose Prescribed for Caucasians? A Critical Review.

Indian J Psychol Med. 2020 Jan-Feb;42(1):1-3

Authors: Jann MW

PMID: 31997859 [PubMed]

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

Thu, 01/30/2020 - 07:38
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Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis.

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

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

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

PMID: 31992335 [PubMed - in process]

Acculturation and the oral health of a nationally representative sample of Hispanic children in the United States: an analysis of 2011-2012 National Survey of Children's Health data.

Thu, 01/30/2020 - 07:38
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Acculturation and the oral health of a nationally representative sample of Hispanic children in the United States: an analysis of 2011-2012 National Survey of Children's Health data.

BMC Public Health. 2020 Jan 28;20(1):111

Authors: Kabani FA, Stockbridge EL, Berly Varghese B, Loethen AD

Abstract
BACKGROUND: Oral disease is a serious public health issue, and Hispanic children in the United States (US) are more likely than children of other racial/ethnic groups to experience dental caries. Although Hispanic children are a growing segment of the US population there is limited research on the association between acculturation and oral health outcomes in this population. This study examined the associations between household acculturation and pediatric oral health in the Hispanic population using a nationally representative sample of children.
METHODS: Data from the 2011-2012 National Survey of Children's Health were analyzed; analyses included Hispanic children ages 1 to 17. Household acculturation was assessed with a combination of language and parental nativity, while oral health was assessed via parents'/guardians' reports of children's dental caries. Logistic regression was used to examine the association between acculturation and oral health, adjusting for other demographic and social determinants of pediatric oral health. We assessed significance at the p < 0.05 level, and all analyses accounted for the survey's complex sample design.
RESULTS: Analyses included 9143 Hispanic children. In total, 24.9% (95% CI: 22.9-27.0%) experienced dental caries, and there were significant associations between household acculturation and oral health. In unadjusted analyses, 32.0% (95% CI: 28.9-35.4%) of children in low acculturation households, 20.3% (95% CI: 16.0-25.4%) of children in moderate acculturation households, and 16.9% (95% CI: 14.2-20.0%) of children in high acculturation households experienced dental caries (p < 0.001). In adjusted analyses, children in high acculturation households were significantly less likely than those in low acculturation households to experience dental caries (p < 0.001; OR = 0.50; 95% CI: 0.35-0.70). The difference between children in moderate and low acculturation households approached but did not reach statistical significance (p = 0.057; OR = 0.69; 95% CI: 0.48-1.01).
CONCLUSIONS: A dose-response relationship was observed between household acculturation and the oral health of Hispanic children in the US. As acculturation increases, the likelihood of a child experiencing dental caries decreases. These findings suggest that public health and community-based interventions intended to reduce oral health disparities in Hispanic children would likely be most impactful if the acculturation levels of the children's households are considered during program development.

PMID: 31992248 [PubMed - in process]

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