898 research outputs found
Sort by
Chelatable Trace Zinc Causes Low, Irreproducible KDAC8 Activity
No full textAcetylation is an important regulatory mechanism in cells, and emphasis is being placed on identifying substrates and small molecule modulators of this post-translational modification. However, the reported in vitro activity of the lysine deacetylase KDAC8 is inconsistent across experimental setups, even with the same substrate, complicating progress in the field. We detected trace levels of zinc, a known inhibitor of KDAC8 when present in excess, even in high-quality buffer reagents, at concentrations that are sufficient to significantly inhibit the enzyme under common reaction conditions. We hypothesized that trace zinc in solution could account for the observed variability in KDAC8 activity. We demonstrate that addition of chelators, including BSA, EDTA, and citrate, and/or the use of a phosphate-based buffer instead of the more common tris-based buffer, eliminates the inhibition from low levels of zinc as well as the dependence of specific activity on enzyme concentration. This results in high KDAC8 activity that is consistent across buffer systems, even using low concentrations of enzyme. We report conditions that are suitable for several assays to increase both enzyme activity and reproducibility. Our results have significant implications for approaches used to identify substrates and small molecule modulators of KDAC8 and interpretation of existing data
Risk Factors for Low Pharmacy Refill Adherence among Older Hypertensive Men and Women by Race.
No full textBackground: Sex-race stratification may lead to identification of risk factors for low antihypertensive medication adherence that are not apparent when assessing risk factors in women and men without race stratification. We examined risk factors associated with low pharmacy refill adherence across sex-race subgroups (white women, black women, white men, black men) within the Cohort Study of Medication Adherence among Older Adults (n = 2,122). Methods: Pharmacy refill adherence was calculated as proportion of days covered using all antihypertensive prescriptions filled in the year prior to a baseline risk factor survey. Sex- and sex-race-stratified multivariable Poisson regression models with robust standard errors were used to estimate adjusted prevalence ratios and 95% confidence intervals for associations between participant characteristics and low adherence. Results: Prevalence of low adherence was 22.9% vs. 40.7% in white vs. black women (P \u3c 0.001) and 26.3% vs. 37.2% in white vs. black men (P = 0.003). In multivariable models, reducing antihypertensive medication due to cost was associated with low adherence within each sex-race subgroup. Additional factors associated with low adherence included shorter hypertension duration and comorbidities in white women; not being married and depressive symptoms in white men; and ≥6 primary care visits/year and complementary and alternative medicine use in black men. Among men, not being married and reporting depressive symptoms were associated with low adherence for whites, but not blacks. Conclusions: Identification of sex-race-specific risk factors for low antihypertensive medication adherence may guide development and implementation of tailored interventions to increase antihypertensive medication adherence and blood pressure control among older patients
Do Long-Acting Injectable Antipsychotics Prevent or Delay Hospital Readmission?
No full textIntroduction: Long-acting injectable (LAI) antipsychotics were developed as a way to decrease pill burden and simplify medication regimens by allowing less frequent administration to assist with medication adherence. Methods: The purpose of this study was to determine whether LAI antipsychotics prevent or delay hospital readmission in patients with a known history of medication non-adherence. The study is a retrospective evaluation of 240 men and women 18-65 years of age diagnosed with bipolar disorder, schizophrenia, or schizoaffective disorder discharged from an inpatient state hospital over a 2 year period of time on a LAI antipsychotic (fluphenazine LAI, haloperidol LAI, risperidone LAI or paliperidone LAI) or oral antipsychotic. Patients on LAIs were matched to patients on an equivalent oral dose, psychiatric diagnosis, number of prior hospital admissions, and length of stay. Results: Those who received a LAI (N = 120) had a significantly longer survival time (mean 278.0 days) without readmission compared to those who did not (N = 120; mean 243.6 days). There was no statistically significant difference in the frequency of one-year readmission between those who did receive a LAI (43.1%) and those who did not (56.9%). Those who received a LAI with administration frequency of a month or longer had a significantly longer survival time without readmission (mean 307.9 days) when compared to those with a shorter administration frequency (mean 245.0 days). Conclusion: This study revealed the use of LAI antipsychotics in those with a history of medication non-adherence, particularly those with longer administration frequency, have potentially promising outcomes
Digital Humanities and Managing Digital Content
No full textAbstract: As part of the Digital Humanities initiative at Xavier University of Louisiana, two faculty members shared their experiences in using digital humanities ideas for student projects. Sr. Stachow who teaches theology, assigned a digital project to present their service learning projects. Dr. Roberts (Mass Communication) and librarians Hannah White and Melinda Williams helped students make multi-media presentations of student projects that were part of My Nola, My story
Reconstructing Ancient Lives Using 3D Technology: A Case Study of Pork and Doughboy Point, Belize
Get PDF3D technology can preserve cultural heritage resources and enhance museum collections and exhibits. Through 3D scanning, an exact digital replica of an artifact is created, which can be printed out or used to create a digital display. For this project, 3D scanning was used to reconstruct ancient Maya lives at Pork and Doughboy Point, Belize. By studying and classifying an inventory of selected artifacts, we were able to determine what activities occurred at the site. goal of this project was to showcase the growing importance of 3D technology in cultural preservation and the variety of ways in which it can be used. Additionally, this project sought to explore the negative and positive aspects of digitization in museum collections, and the feasibility of the implementation of this technology
ZB716, a Steroidal Selective Estrogen Receptor Degrader (SERD), is Orally Efficacious in Blocking Tumor Growth in Mouse Xenograft Models.
Get PDFAdvances in oral SERDs development so far have been confined to nonsteroidal molecules such as those containing a cinnamic acid moiety, which are in earlystage clinical evaluation. ZB716 was previously reported as an orally bioavailable SERD structurally analogous to fulvestrant. In this study, we examined the binding details of ZB716 to the estrogen receptor alpha (ERα) by computer modeling to reveal its interactions with the ligand binding domain as a steroidal molecule. We also found that ZB716 modulates ERα-coregulator interactions in nearly identical manner to fulvestrant. The ability of ZB716 to inhibit cell growth and downregulate ER expression in endocrine resistant, ERα mutant breast cancer cells was demonstrated. Moreover, in both the MCF-7 xenograft and a patient derived xenograft model, orally administered ZB716 showed superior efficacy in blocking tumor growth when compared to fulvestrant. Importantly, such enhanced efficacy of ZB716 was shown to be attributable to its markedly higher bioavailability, as evidenced in the final plasma and tumor tissue concentrations of ZB716 in mice where drug concentrations were found significantly higher than in the fulvestrant treatment group
ePortfolios in the Classroom Saturday Seminar
No full textDuring this half-day workshop, Xavier faculty learned about best practices for using ePortfolios in the classroom, learned how to navigate Brightspace\u27s ePortfolio system, and developed a portfolio assignment that can be integrated into a current or future class
Modafinil for the Improvement of Patient Outcomes Following Traumatic Brain Injury
No full textObjective. The authors sought to assess the literature evidence on the efficacy of modafinil use in patients with fatigue or excessive daytime sleepiness (EDS) secondary to traumatic brain injury (TBI).Method of Research. A literature search of Medline and PubMed was performed using the EBSCOhost database. Primary literature, observational studies, meta-analyses, case reports, and systematic reviews were assessed for content regarding modafinil and psychostimulant use in patients with TBI. Of the 23 articles collected, three randomized, controlled studies, three observational studies, one case report, and two systematic reviews gave a description of modafinil use in TBI patients.Results and Conclusion. Modafinil is a central nervous system stimulant with well-established effectiveness in the treatment of narcolepsy and shift-work sleep disorder. There is conflicting evidence about the benefits of modafinil in the treatment of fatigue and EDS secondary to TBI. One randomized, controlled study states that modafinil does not significantly improve patient wakefulness, while another concludes that modafinil corrects EDS but not fatigue. An observational study provides evidence that modafinil increases alertness in fatigued patients with past medical history of brainstem diencephalic stroke or multiple sclerosis. Modafinil appears to have the potential to improve wakefulness in patients with TBI. A prospective, double-blinded, randomized, crossover trial of modafinil for the management of fatigue in ischemic stroke patients is currently being conducted, and further studies demonstrating consistent results are needed before making a conclusive decision
SPIN1 Promotes Tumorigenesis by Blocking the uL18 (Universal Large Ribosomal Subunit Protein 18)-MDM2-p53 Pathway in Human Cancer.
No full textRibosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here, we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity toward p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 may be attributed to its negative regulation of uL18, leading to p53 inactivation
How can Infra-Red Excitation Both Accelerate and Slow Charge Transfer in the Same Molecule?
No full textA UV-IR-Vis 3-pulse study of infra-red induced changes to electron transfer (ET) rates in a donor-bridge-acceptor species finds that charge-separation rates are slowed, while charge-recombination rates are accelerated as a result of IR excitation during the reaction. We explore the underpinning mechanisms for this behavior, studying IR-induced changes to the donor-acceptor coupling, to the validity of the Condon approximation, and to the reaction coordinate distribution. We find that the dominant IR-induced rate effects in the species studied arise from changes to the density of states in the Marcus curve crossing region. That is, IR perturbation changes the probability of accessing the activated complex for the ET reactions. IR excitation diminishes the population of the activated complex for forward (activationless) ET, thus slowing the rate. However, IR excitation increases the population of the activated complex for (highly activated) charge recombination ET, thus accelerating the charge recombination rate