Recent Research Articles from UNTHSC

Effect of lidocaine iontophoresis combined with exercise intervention on gait and spasticity in children with spastic hemiplegic cerebral palsy: A randomized controlled trial.

Tue, 01/05/2021 - 07:34
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Effect of lidocaine iontophoresis combined with exercise intervention on gait and spasticity in children with spastic hemiplegic cerebral palsy: A randomized controlled trial.

NeuroRehabilitation. 2020;47(2):133-141

Authors: Hegazy FA, Aboelnasr EA, Salem YT

Abstract
BACKGROUND: Gait deviations and spasticity are common impairments seen in children with cerebral palsy (CP) and may interfere with functional performance and effective walking pattern. Lidocaine iontophoresis is effective for reducing muscle spasticity in adults.
PURPOSE: To investigate the effect of lidocaine epinephrine iontophoresis combined with exercises on gait and spasticity in children with spastic hemiplegic cerebral palsy (HCP).
METHODS: Thirty children with spastic HCP aged 4-6 (5.20±0.32) years were randomly assigned to the experimental group (n = 15) and control group (n = 15). Children in both groups received one hour of exercises, three times a week for three months. Children in the experimental group received 2% lidocaine iontophoresis immediately before the exercises. The lidocaine iontophoresis was delivered for 20 minutes (1mA/min). Spatio-temporal gait parameters were assessed within one week before and after the intervention using 3D motion analysis. Surface electromyography was used to assess muscle tone using H/M ratio of the soleus muscle. ANOVA was used to investigate the differences between experimental and control groups. Statistical significance was set at P value less than 0.05.
RESULTS: There was no difference between groups at baseline. Post-intervention, the experimental group showed significant improvements when compared to the control group for gait speed (p = 0.03), stride length (p = 0.04), cadence (p = 0.0001), cycle time (p = 0.0001), and H/M ratio (p = 0.02).
CONCLUSION: Lidocaine iontophoresis combined with exercises was effective in improving gait spatiotemporal parameters and reducing spasticity in children with CP.

PMID: 32716326 [PubMed - indexed for MEDLINE]

Instructional and Assessment Redesign of a Sterile Compounding Course Using Immersive Simulation.

Tue, 01/05/2021 - 07:34
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Instructional and Assessment Redesign of a Sterile Compounding Course Using Immersive Simulation.

Am J Pharm Educ. 2020 02;84(2):7473

Authors: Monestime S, Thomas D, Hooper CD, Day T, Suzuki S, Martin RD

Abstract
Objective. To revise a traditional sterile compounding course to include content, competencies, and immersive simulations relevant to the current practice of sterile compounding pharmacy. Methods. Faculty and staff at the University of North Texas System College of Pharmacy made significant revisions to an existing sterile compounding course. Instruction was provided in didactic and laboratory sessions and delivered in three modules: fundamental skills, integration of skills and knowledge, and exceptions and specialty topics. Integration laboratory sessions consisted primarily of repetitive but increasingly difficult simulations that included both technician and pharmacist activities. Assessment methods included checkpoint assessments, a mock objective structured clinical examination (OSCE), a written examination, and a final comprehensive OSCE. Effectiveness of the course redesign was assessed by comparing student performance on assessments, overall course performance, and student perceptions extracted from the student course evaluation. Results. Of the 364 students enrolled in the sterile compounding course across four terms, 156 were in the pre-implementation cohort (cohort 1) and 208 were in the post-implementation cohort (cohort 2). Two hundred twenty-eight students completed the course evaluation. Course evaluations significantly demonstrated students' improved perceptions related to seven of 11 survey elements, most notably, critical thinking, integration of concepts, and students feeling challenged. Student performance on laboratory summative assessments also improved. However, written examination scores did not change. Conclusion. This novel sterile compounding course provided a practice-oriented blueprint for instruction and assessment of sterile compounding.

PMID: 32226068 [PubMed - indexed for MEDLINE]

Effects of mesencephalic astrocyte-derived neurotrophic factor on cerebral angiogenesis in a rat model of cerebral ischemia.

Tue, 01/05/2021 - 07:34
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Effects of mesencephalic astrocyte-derived neurotrophic factor on cerebral angiogenesis in a rat model of cerebral ischemia.

Neurosci Lett. 2020 01 10;715:134657

Authors: Gao B, Deng J, Zhang X, Sun H, Jia G, Li J, Zhang K, Wan C, Wang L, Yan LJ, Cai Z, Ma J

Abstract
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum stress-related protein that exhibits neuroprotective effects. Recent studies have shown that MANF promotes poststroke functional recovery in rats. However, the underlying mechanisms have not yet been fully understood. Here, we examined the effects of MANF on cerebral angiogenesis in a permanent middle cerebral artery occlusion model in rats. Recombinant human MANF was administered intracerebroventricularly 24 h after stroke. We performed neurobehavioral tests and assessed microvessel density, functional microvessels, and regional cerebral blood flow (rCBF), as well as detected angiogenic factors in the peri-infarct cerebral cortex. Results showed that MANF ameliorated neurobehavioral scores, promoted rCBF, upregulated the expression of CD34, as well as the total vessel surface area and the number of microvessel branch points, and activated the vascular endothelial growth factor (VEGF) pathway. In conclusion, our findings provide insight into the mechanisms of MANF in promoting functional recovery from ischemic stroke. Our results suggest that MANF improves neurobehavioral recovery from cerebral ischemic injury, and that this effect is mediated partly by its proangiogenic effects and augmentation of rCBF, which are possibly associated with VEGF.

PMID: 31785307 [PubMed - indexed for MEDLINE]

A genome-wide association study of tramadol metabolism from post-mortem samples.

Tue, 01/05/2021 - 07:34
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A genome-wide association study of tramadol metabolism from post-mortem samples.

Pharmacogenomics J. 2020 02;20(1):94-103

Authors: Wendt FR, Rahikainen AL, King JL, Sajantila A, Budowle B

Abstract
Phase I tramadol metabolism requires cytochrome p450 family 2, subfamily D, polypeptide 6 (CYP2D6) to form O-desmethyltramadol (M1). CYP2D6 genetic variants may infer metabolizer phenotype; however, drug ADME (absorption, distribution, metabolism, and excretion) and response depend on protein pathway(s), not CYP2D6 alone. There is a paucity of data regarding the contribution of trans-acting proteins to idiosyncratic phenotypes following drug exposure. A genome-wide association study identified five markers (rs79983226/kgp11274252, rs9384825, rs62435418/kgp10370907, rs72732317/kgp3743668, and rs184199168/exm1592932) associated with the conversion of tramadol to M1 (M1:T). These SNPs reside within five genes previously implicated with adverse reactions. Analysis of accompanying toxicological meta-data revealed a significant positive linear relationship between M1:T and degree of sample polypharmacy. Taken together, these data identify candidate loci for potential clinical inferences of phenotype following exposure to tramadol and highlight sample polypharmacy as a possible diagnostic covariate in post-mortem genetic studies.

PMID: 30971809 [PubMed - indexed for MEDLINE]

Exploring college students' sexual and reproductive health literacy.

Tue, 01/05/2021 - 07:34
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Exploring college students' sexual and reproductive health literacy.

J Am Coll Health. 2020 01;68(1):79-88

Authors: Vamos CA, Thompson EL, Logan RG, Griner SB, Perrin KM, Merrell LK, Daley EM

Abstract
Objective: To assess college students' sexual and reproductive health (SRH) literacy experiences, specific to contraception use and STI prevention. Participants: In Spring 2015, participants (n = 43) from a large institution participated in six focus groups (two male and four females groups). Methods: Focus groups were guided by the health literacy domains (access; understand; appraise; apply); data were analyzed in MaxQDA using the constant comparative method. Results: The Internet was the most commonly accessed source for SRH information. Participants discussed facilitators (eg, use of visuals) and barriers (eg, medical jargon) to understanding information; and personal lifestyle, advice from family/friends, symptoms, and sexual partners as appraisal factors. Participants applied information by communicating with friends/providers and seeking healthcare. However, findings were not linear nor mutually exclusive, representing the interaction of health literacy skills. Conclusion: Findings suggest that a patient-centered intervention capitalizing on technology and trusted individuals (providers/peer educators) may facilitate college students' SRH literacy.

PMID: 30388946 [PubMed - indexed for MEDLINE]

Colorectal Cancer: An Emphasis on Factors Influencing Racial/Ethnic Disparities.

Mon, 01/04/2021 - 07:23
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Colorectal Cancer: An Emphasis on Factors Influencing Racial/Ethnic Disparities.

Crit Rev Oncog. 2020;25(2):151-160

Authors: Sharma I, Kim S, Sridhar S, Basha R

Abstract
Current statistics related to cancer incidence and cancer-related death rates clearly show that specific racial/ethnic minorities are more likely to be diagnosed and/or die with cancer. Colorectal cancer (CRC) is one of the leading causes of cancer deaths in the United States and it disproportionately affects the non-Hispanic Black or African American (AA) population. When compared to the non-Hispanic White (nHW) population, incidence and death rates in AAs are 28% and 60% higher, respectively. Hispanics have an overall lower CRC incidence rate than nHWs (Hispanics: 35.5 per 100,000 population; nHWs: 40.2 per 100,000 population), but their incidence continues to rise, unlike nHWs, who are experiencing a decline. This disparity between Hispanics and nHWs is further highlighted in the younger Hispanic population. While the cause of the disparities is associated with CRC-related genetic and environmental factors, the role of specific genes/mutations in each population are still not fully unraveled. However, because CRC is a slowly progressing disease, routine screening and/or early intervention are key to achieving better outcomes in CRC patients and ultimately in closing the disparity gap among different populations. This review discusses the major factors influencing the disparities in CRC and also focuses on factors such as treatment response, family history, and screening that potentially contribute to the racial/ethnic disparities in CRC.

PMID: 33389864 [PubMed - as supplied by publisher]

Cone of economy classification: evolution, concept of stability, severity level, and correlation to patient-reported outcome scores.

Mon, 01/04/2021 - 07:23
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Cone of economy classification: evolution, concept of stability, severity level, and correlation to patient-reported outcome scores.

Eur Spine J. 2021 Jan 03;:

Authors: Haddas R, Sambhariya V, Kosztowski T, Block A, Lieberman I

Abstract
STUDY DESIGN: A prospective cohort study OBJECTIVE: To determine a classification system for cone of economy (CoE) measurements that defines clinically significant changes in altered balance and to assess if the CoE measurements directly impacts patients reported outcome measures (PROMs). Preoperative functional data is a crucial component of determining patient disability and prognosis. The CoE has been theorized to be the foundation of biomechanical changes that leads to increased energy expenditure and disability in spine patients. PROMs have been developed to quantify the level of debilitation in spine patients but have various limitations.
METHODS: A total of 423 symptomatic adult patients with spine pathology completed a series of PROMs preoperatively including VAS, ODI, Tampa Scale for Kinesiophobia (TSK), Fear and Avoidance Beliefs Questionnaire (FABQ), and Demoralization (DS). Functional balance was tested in this group using a full-body reflective marker set to measure head and center of mass (CoM) sway.
RESULTS: PROMs scores were correlated with the magnitude of the CoE measurements. Patients were separated by the following proposed classification: CoM coronal sway > 1.5 cm, CoM sagittal sway > 3.0 cm, CoM total sway > 30.0 cm, head coronal sway > 3.0 cm, head sagittal sway > 6.0 cm, and head total sway > 60.0 cm. Significant differences were noted in the ODI (< 0.001), FABQ physical activity (< 0.001-0.009), DS (< 0.001-0.023), and TSK (< 0.001-0.032) across almost all planes of motion for both CoM and head sway. The ODI was most sensitive to the difference between groups across CoM and head sway planes with a mean ODI of 47.5-49.5 (p < 0.001) in the severe group versus 36.6-39.3 (p < 0.001) in the moderate group.
CONCLUSIONS: By classifying CoE measurements by the cutoffs proposed, clinically significant alterations in balance can be quantified. Furthermore, this study demonstrates that across spinal pathology, higher magnitude CoE and range of sway measurements correlate with worsening PROMs. The Haddas' CoE classification system in this study helps to identify patients that may benefit from surgery and guide their postoperative prognosis.

PMID: 33389136 [PubMed - as supplied by publisher]

The Association Between Depressive Symptoms and Accumulation of Stress Among Black Men in the Health and Retirement Study

Wed, 12/23/2020 - 05:00

Innov Aging. 2020 Sep 29;4(5):igaa047. doi: 10.1093/geroni/igaa047. eCollection 2020.

ABSTRACT

BACKGROUND AND OBJECTIVES: Among the multiple factors posited to drive the health inequities that black men experience, the fundamental role of stress in the production of poor health is a key component. Allostatic load (AL) is considered to be a byproduct of stressors related to cumulative disadvantage. Exposure to chronic stress is associated with poorer mental health including depressive symptoms. Few studies have investigated how AL contributes to depressive symptoms among black men. The purpose of the cross-sectional study was to examine the association between AL and depressive symptoms among middle- to old age black men.

RESEARCH DESIGN AND METHODS: This project used the 2010 and 2012 wave of the Health and Retirement Study enhanced face-to-face interview that included a biomarker assessment and psychosocial questionnaire. Depressive symptoms, assessed by the endorsement of 3 or more symptoms on the Center for Epidemiological Studies-Depression 8-item scale, was the outcome variable. The main independent variable, AL, score was calculated by summing the number values that were in the high range for that particular biomarker value scores ranging from 0 to 7. black men whose AL score was 3 or greater were considered to be in the high AL group. Modified Poisson regression was used to estimate prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs).

RESULTS: There was a larger proportion of black men in the high AL group who reported depressive symptoms (30.0% vs. 20.0%) compared with black men in the low AL group. After adjusting for age, education, income, drinking, and smoking status, the prevalence of reporting 3 or more depressive symptoms was statistically significant among black men in the high AL group (PR = 1.61 [95% CI: 1.20-2.17]) than black men in the low AL group.

DISCUSSION AND IMPLICATIONS: Exposure to chronic stress is related to reporting 3 or more depressive symptoms among black men after controlling for potential confounders. Improving the social and economic conditions for which black men work, play, and pray is key to reducing stress, thereby potentially leading to the reporting of fewer depressive symptoms.

PMID:33354627 | PMC:PMC7737789 | DOI:10.1093/geroni/igaa047

Effect of General Anesthesia on Cardiac Magnetic Resonance-Derived Cardiac Function in Repaired Tetralogy of Fallot.

Tue, 12/22/2020 - 06:49
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Effect of General Anesthesia on Cardiac Magnetic Resonance-Derived Cardiac Function in Repaired Tetralogy of Fallot.

Pediatr Cardiol. 2020 Dec;41(8):1660-1666

Authors: Muyskens S, Roshan T, Honan K, Umejiego J, Raynaud S, Ogunyankin F

Abstract
Cardiac magnetic resonance imaging (CMR)-derived ejection fraction (EF) predicts adverse outcomes in repaired tetralogy of Fallot (rTOF) and drives timing of pulmonary valve replacement. Certain patient populations require sedation for successful CMR image acquisition. General anesthesia (GA) has been shown to depress EF and heart rate (HR) in animal models, however, its effect on congenital heart disease is unknown. A retrospective review was conducted of all CMR patients referred with rTOF between January 2011 and May 2019. The cohort was separated into GA and non-GA groups. Propensity score matching (PSM) adjusted for selection bias. A kernel matching algorithm was used to match subjects and the differences in mean treatment effect on the treated were computed for left ventricular (LV) and right ventricular (RV) EF, HR, and cardiac index (CI). 143 patients met criteria, 37 patients under GA (mean age 15 years, range 2-45, 59% male), and 106 patients without GA (mean age 21 years, range 10-53, 50% male). Unmatched analysis showed significant depression of LV EF (50 vs. 57%, p < 0.001) and RV EF (42 vs. 48%, p < 0.001) in the GA group compared to the non-GA group. There was no significant difference in HR or CI. After matching and PSM adjustment, the GA group had a significant decrease in LV EF (49 vs. 56%, p < 0.001), RV EF (41 vs. 48%, p < 0.001), CI (2728 vs. 3701 ml/min/m2, p < 0.001), and HR (72 vs. 79 bpm, p = 0.04). General anesthesia with sevoflurane results in depressed CMR-derived EF.

PMID: 32740671 [PubMed - indexed for MEDLINE]

Comorbid patterns of anaemia and diarrhoea among children aged under 5 years in Ghana: a multivariate complex sample logistic regression analysis and spatial mapping visualisation.

Sat, 12/19/2020 - 15:21
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Comorbid patterns of anaemia and diarrhoea among children aged under 5 years in Ghana: a multivariate complex sample logistic regression analysis and spatial mapping visualisation.

Int Health. 2020 Dec 18;:

Authors: Duah HO, Amankwa CE, Adomako I, Owusu B, Agbadi P

Abstract
BACKGROUND: Anaemia and diarrhoea are known independent causes of under-five morbidity and mortality. This study sought to investigate predictors of comorbid patterns of anaemia and diarrhoea using the 2014 Ghana Demographic and Health Survey (GDHS).
METHODS: The study employed analysis of secondary data from the 2014 GDHS. We performed a multivariate complex sample logistic regression and spatial analysis.
RESULTS: The weighted prevalence of comorbid anaemia and diarrhoea was 9.28% with the highest burden (16.45%) found in the Upper West region. Independent predictors (risk factors) of comorbid patterns of anaemia and diarrhoea were children aged 6-23 mo (OR=2.17, 95% CI 1.42 to 3.33), male gender (OR=1.50, 95% C1 1.04 to 2.16), history of fever (OR=4.37, 95% CI 2.94 to 6.50) and living in a household with two children aged <5 y (OR=1.80, 95% CI 1.14 to 2.84). Protective factors were having a father with secondary or higher education (OR=0.57, 95% CI 0.33 to 0.97), living in a household with ≥6 members (OR=0.46, 95% CI 0.28 to 0.75) and living in a richer household (OR=0.38, 95% CI 0.16 to 0.89). Surface maps revealed inter-regional and subregional variations.
CONCLUSION: The study shows that the independent predictors of comorbid patterns of anaemia and diarrhoea among children aged <5 y in Ghana are age, gender, history of fever, the number of children aged <5 y in the household, parental education, household size and household wealth. The study identified zones to be targeted for cost-effective policy interventions.

PMID: 33339041 [PubMed - as supplied by publisher]

Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome.

Sat, 12/19/2020 - 15:21
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Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome.

J Alzheimers Dis. 2020 Dec 16;:

Authors: Petersen ME, Rafii MS, Zhang F, Hall J, Julovich D, Ances BM, Schupf N, Krinsky-McHale SJ, Mapstone M, Silverman W, Lott I, Klunk W, Head E, Christian B, Foroud T, Lai F, Diana Rosas H, Zaman S, Wang MC, Tycko B, Lee J, Handen B, Hartley S, Fortea J, O'Bryant S, Alzheimer’s Biomarker Consortium –Down Syndrome (ABC-DS)

Abstract
BACKGROUND: The need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population.
OBJECTIVE: This study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults.
METHODS: Plasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome.
RESULTS: In distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS.
CONCLUSION: Advanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.

PMID: 33337378 [PubMed - as supplied by publisher]

Potential for Kappa-Opioid Receptor Agonists to Engineer Nonaddictive Analgesics: A Narrative Review.

Fri, 12/18/2020 - 10:03
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Potential for Kappa-Opioid Receptor Agonists to Engineer Nonaddictive Analgesics: A Narrative Review.

Anesth Analg. 2020 Dec 16;:

Authors: Kaski SW, White AN, Gross JD, Siderovski DP

Abstract
A serious adverse effect of prescription opioid analgesics is addiction, both to these analgesics and to illicit drugs like heroin that also activate the µ-opioid receptor (MOR). Opioid use disorder (OUD) and opioid overdose deaths represent a current American health crisis, and the prescription of opioid analgesics has contributed significantly to this crisis. While prescription opioids are highly effective analgesics, there currently exists no facile way to use them for extended periods without the risk of addiction. If addiction caused by MOR-targeting analgesics could be blocked by blending in a new "antiaddiction" ingredient that does not diminish analgesia and does not introduce its own therapeutically limiting side effects, then continued clinical use of prescription opioids for treating pain could be maintained (or even enhanced) instead of curtailed. In this narrative review, we contextualize this hypothesis, first with a brief overview of the current American opioid addiction crisis. The neurobiology of 2 key receptors in OUD development, MOR and the κ-opioid receptor (KOR), is then discussed to highlight the neuroanatomical features and circuitry in which signal transduction from these receptors lie in opposition-creating opportunities for pharmacological intervention in curtailing the addictive potential of MOR agonism. Prior findings with mixed MOR/KOR agonists are considered before exploring new potential avenues such as biased KOR agonists. New preclinical data are highlighted, demonstrating that the G protein-biased KOR agonist nalfurafine reduces the rewarding properties of MOR-targeting analgesics and enhances MOR-targeting analgesic-induced antinociception. Finally, we discuss the recent discovery that a regulator of G protein signaling (namely, RGS12) is a key component of signaling bias at KOR, presenting another drug discovery target toward identifying a single agent or adjuvant to be added to traditional opioid analgesics that could reduce or eliminate the addictive potential of the latter drug.

PMID: 33332902 [PubMed - as supplied by publisher]

Editorial: Cancer Informatics Toward Precision Medicine.

Fri, 12/18/2020 - 10:03
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Editorial: Cancer Informatics Toward Precision Medicine.

Front Med (Lausanne). 2020;7:576611

Authors: Zhang F, Wu X, Chen W, Deng Y

PMID: 33330533 [PubMed]

Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia.

Fri, 12/18/2020 - 10:03
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Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia.

Front Neurol. 2020;11:577927

Authors: Wang K, Sun Z, Ru J, Wang S, Huang L, Ruan L, Lin X, Jin K, Zhuge Q, Yang S

Abstract
Ischemia/reperfusion (I/R) injury is a significant cause of mortality and long-term disability worldwide. Recent evidence has proved that pyroptosis, a novel cell death form, contributes to inflammation-induced neuron death and neurological function impairment following ischemic stroke. Gasdermin D (GSDMD) is a newly discovered key molecule of cell pyroptosis, but its biological function and precise role in ischemic stroke are still unclear. The present study investigates the cleavage activity of GSDMD, localization of pyroptotic cells, and global neuroinflammation in gsdmd -/- mice after I/R. The level of cell pyroptosis around the infarcted area was significantly increased in the acute phase of cerebral I/R injury. The ablation of GSDMD reduced the infraction volume and improved neurological function against cerebral I/R injury. Furthermore, we confirmed I/R injury induced cell pyroptosis mainly in microglia. Knockdown of GSDMD effectively inhibited the secretion of mature IL-1β and IL-18 from microglia cells but did not affect the expression of caspase-1/11 in vitro and in vivo. In summary, blocking GSDMD expression might serve as a potential therapeutic strategy for ischemic stroke.

PMID: 33329317 [PubMed]

Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer's Disease.

Fri, 12/18/2020 - 10:03
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Characterization of the Meal-Stimulated Incretin Response and Relationship With Structural Brain Outcomes in Aging and Alzheimer's Disease.

Front Neurosci. 2020;14:608862

Authors: Morris JK, John CS, Green ZD, Wilkins HM, Wang X, Kamat A, Swerdlow RS, Vidoni ED, Petersen ME, O'Bryant SE, Honea RA, Burns JM

Abstract
Background: Individuals with Alzheimer's Disease (AD) are often characterized by systemic markers of insulin resistance; however, the broader effects of AD on other relevant metabolic hormones, such as incretins that affect insulin secretion and food intake, remains less clear.
Methods: Here, we leveraged a physiologically relevant meal tolerance test to assess diagnostic differences in these metabolic responses in cognitively healthy older adults (CH; n = 32) and AD (n = 23) participants. All individuals also underwent a comprehensive clinical examination, cognitive evaluation, and structural magnetic resonance imaging.
Results: The meal-stimulated response of glucose, insulin, and peptide tyrosine tyrosine (PYY) was significantly greater in individuals with AD as compared to CH. Voxel-based morphometry revealed negative relationships between brain volume and the meal-stimulated response of insulin, C-Peptide, and glucose-dependent insulinotropic polypeptide (GIP) in primarily parietal brain regions.
Conclusion: Our findings are consistent with prior work that shows differences in metabolic regulation in AD and relationships with cognition and brain structure.

PMID: 33328877 [PubMed]

Prospects of Directly Reprogrammed Adult Human Neurons for Neurodegenerative Disease Modeling and Drug Discovery: iN vs. iPSCs Models.

Fri, 12/18/2020 - 10:03
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Prospects of Directly Reprogrammed Adult Human Neurons for Neurodegenerative Disease Modeling and Drug Discovery: iN vs. iPSCs Models.

Front Neurosci. 2020;14:546484

Authors: Zhang Y, Xie X, Hu J, Afreen KS, Zhang CL, Zhuge Q, Yang J

Abstract
A reliable disease model is critical to the study of specific disease mechanisms as well as for the discovery and development of new drugs. Despite providing crucial insights into the mechanisms of neurodegenerative diseases, translation of this information to develop therapeutics in clinical trials have been unsuccessful. Reprogramming technology to convert adult somatic cells to induced Pluripotent Stem Cells (iPSCs) or directly reprogramming adult somatic cells to induced Neurons (iN), has allowed for the creation of better models to understand the molecular mechanisms and design of new drugs. In recent times, iPSC technology has been commonly used for modeling neurodegenerative diseases and drug discovery. However, several technological challenges have limited the application of iN. As evidence suggests, iN for the modeling of neurodegenerative disorders is advantageous compared to those derived from iPSCs. In this review, we will compare iPSCs and iN models for neurodegenerative diseases and their potential applications in the future.

PMID: 33328842 [PubMed]

School-entry requirements for HPV vaccination: part of the patchwork for HPV-related cancer prevention.

Fri, 12/18/2020 - 10:03
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School-entry requirements for HPV vaccination: part of the patchwork for HPV-related cancer prevention.

Hum Vaccin Immunother. 2020 Dec 17;:1-5

Authors: Thompson EL, Daley EM, Washburn T, Salisbury-Keith K, Saslow D, Fontenot HB, Zimet GD

Abstract
Human papillomavirus (HPV) vaccination can prevent six types of HPV-related cancers, and approximately, 54.2% of adolescents are up-to-date with the HPV vaccine in the United States. While moderate success has been achieved with provider- and parent-focused interventions, HPV vaccination in the U.S. lags well behind desired goals. In order to maximize HPV vaccination and prevention of HPV-related cancers, it may be prudent to consider state policy approaches, such as school-entry requirements as part of the patchwork of provider, parent, and structural interventions. In this paper, we reviewed the history of efforts to implement school-entry requirements for HPV vaccine, the challenges and benefits associated with implementing these requirements, and the evidence for the effectiveness of school-entry requirements. In addition, we presented new data from Rhode Island's Immunization Information System (IIS) showing how their school-entry requirement, implemented in 2015, has impacted HPV vaccination rates. These registry data indicate that HPV vaccination rates improved significantly after the 2014-2015 school year and policy implementation, and add to the ongoing evidence supporting the value of school-entry requirements for HPV vaccination. School-entry requirements should be considered alongside other initiatives and policies for promoting HPV vaccine uptake. Taking a comprehensive systems approach to HPV vaccination is needed.

PMID: 33327839 [PubMed - as supplied by publisher]

Ancestry inference and admixture component estimations of Chinese Kazak group based on 165 AIM-SNPs via NGS platform.

Fri, 12/18/2020 - 10:03
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Ancestry inference and admixture component estimations of Chinese Kazak group based on 165 AIM-SNPs via NGS platform.

J Hum Genet. 2020 May;65(5):461-468

Authors: Xie T, Shen C, Liu C, Fang Y, Guo Y, Lan Q, Wang L, Ge J, Zhou Y, Wen S, Yang Q, Zhu B

Abstract
Predicting the biogeographical ancestries of populations and unknown individuals based on ancestry-informative markers (AIMs) has been widely applied in providing DNA clues to criminal investigations, correcting the factor of population stratification in genome-wide association studies (GWAS), and working as the basis of predicting the externally visible characteristics (EVCs) of individuals. The present study chose Chinese Xinjiang Kazak (XJK) group as research object using a 165 AIM-SNPs panel via next generation sequencing (NGS) technology to reveal its ancestral information and genetic background by referencing the populations' data from 1000 Genomes Phase 3. After the Bonferroni correction, there were no significant deviations at the 165 AIM-SNP loci except two loci with homozygote in the studied XJK group. Ancestry information inference and populations genetic analyses were conducted basing on multiplex statistical methods such as forensic statistical parameter analyses, estimation of the success ratios with cross-validation, population tree, principal component analysis (PCA), and genetic structure analysis. The present results revealed that XJK group had the admixed ancestral components of East Asian and European populations with the ratio of about 62:37.

PMID: 32081902 [PubMed - indexed for MEDLINE]

Methamphetamine Activates Trace Amine Associated Receptor 1 to Regulate Astrocyte Excitatory Amino Acid Transporter-2 via Differential CREB Phosphorylation During HIV-Associated Neurocognitive Disorders.

Thu, 12/17/2020 - 10:22
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Methamphetamine Activates Trace Amine Associated Receptor 1 to Regulate Astrocyte Excitatory Amino Acid Transporter-2 via Differential CREB Phosphorylation During HIV-Associated Neurocognitive Disorders.

Front Neurol. 2020;11:593146

Authors: Cisneros IE, Ghorpade A, Borgmann K

Abstract
Methamphetamine (METH) use, referred to as methamphetamine use disorder (MUD), results in neurocognitive decline, a characteristic shared with HIV-associated neurocognitive disorders (HAND). MUD exacerbates HAND partly through glutamate dysregulation. Astrocyte excitatory amino acid transporter (EAAT)-2 is responsible for >90% of glutamate uptake from the synaptic environment and is significantly decreased with METH and HIV-1. Our previous work demonstrated astrocyte trace amine associated receptor (TAAR) 1 to be involved in EAAT-2 regulation. Astrocyte EAAT-2 is regulated at the transcriptional level by cAMP responsive element binding (CREB) protein and NF-κB, transcription factors activated by cAMP, calcium and IL-1β. Second messengers, cAMP and calcium, are triggered by TAAR1 activation, which is upregulated by IL-1β METH-mediated increases in these second messengers and signal transduction pathways have not been shown to directly decrease astrocyte EAAT-2. We propose CREB activation serves as a master regulator of EAAT-2 transcription, downstream of METH-induced TAAR1 activation. To investigate the temporal order of events culminating in CREB activation, genetically encoded calcium indicators, GCaMP6s, were used to visualize METH-induced calcium signaling in primary human astrocytes. RNA interference and pharmacological inhibitors targeting or blocking cAMP-dependent protein kinase A and calcium/calmodulin kinase II confirmed METH-induced regulation of EAAT-2 and resultant glutamate clearance. Furthermore, we investigated METH-mediated CREB phosphorylation at both serine 133 and 142, the co-activator and co-repressor forms, respectively. Overall, this work revealed METH-induced differential CREB phosphorylation is a critical regulator for EAAT-2 function and may thus serve as a mechanistic target for the attenuation of METH-induced excitotoxicity in the context of HAND.

PMID: 33324330 [PubMed]

Breastfeeding practices among childhood cancer survivors.

Wed, 12/16/2020 - 07:47
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Breastfeeding practices among childhood cancer survivors.

J Cancer Surviv. 2020 08;14(4):586-599

Authors: Ogg S, Klosky JL, Chemaitilly W, Srivastava DK, Wang M, Carney G, Ojha R, Robison LL, Cox CL, Hudson MM

Abstract
PURPOSE: This cross-sectional study compared breastfeeding outcomes among childhood cancer survivors to those of women in the general population and evaluated whether breastfeeding is adversely affected by cancer treatment or endocrine-related late effects.
METHODS: A self-reported survey ascertained breastfeeding practices and incorporated items from the questionnaires used in the Infant Feeding Practices Study II (IFPS II) to allow comparison with the general population. Among 710 eligible survivors, 472 (66%) responded. The participants were predominantly non-Hispanic White (84%), married (73%), and had some college or less (60%). The mean maternal age at the time of birth of the first child after cancer treatment was 24 years (SD 24.3 ± 4.8).
RESULTS: Fewer survivors planned to breastfeed than did IFPS II controls (67% vs. 82%, P < .0001), and fewer survivors initiated breastfeeding (66% vs. 85%, P < .0001). The median breastfeeding duration was shorter among survivors, with early undesired weaning occurring sooner in the survivor group (1.4 months, interquartile range (IQR) 0.5-3.5 months) than in the IFPS II group (2.7 months, IQR 0.9-5.4 months). A higher proportion of survivors reported an unfavorable breastfeeding experience (19% vs. 7.5%, P < .0001) and early, undesired weaning (57.5%, 95% CI 51-64) than did IFPS II participants (45.2%, 95% CI 44-47, P = .0164). Among survivors who expressed intention and chose to breastfeed, 46% endorsed disrupted lactation related to physiologic problems with high risk in those overweight/obese.
CONCLUSIONS: Survivors are at risk of negative breastfeeding experiences; however, lactation outcomes were not significantly associated with cancer diagnosis, treatments, or endocrine complications.
IMPLICATIONS FOR CANCER SURVIVORS: Prior research has not examined the association of cancer treatments and clinically validated late effects with lactation outcomes in a clinically diverse childhood cancer survivor cohort. Findings from this study suggest that childhood cancer survivors, especially those who are overweight/obese, are at risk of having negative breastfeeding experiences. Early undesired weaning, physiologic problems related to lactation and misconceptions about breastfeeding, especially fears of passing on cancer through breastmilk, highlight the need for counseling and specialized support to optimize lactation outcomes in this vulnerable population.

PMID: 32291564 [PubMed - indexed for MEDLINE]

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