Single Nucleotide Polymorphism in BCRP and Effects on Flavopiridol Transport

Flavopiridol is a promising therapeutic agent currently under phase I and phase II clinical investigation for the treatment of Chronic Lymphocytic Leukemia (CLL) and other hematologic and solid tumor malignancies. Flavopiridol is a potent inhibitor of CDks (cyclin-dependent kinases), and its cytotoxic activity is associated with the arrest of cells in G1 or G2 phases of the cell cycle.1 Breast cancer resistance protein (BCRP) is a 70 kDA transmembrane transporter involved in multidrug resistance.2 BCRP exports flavopiridol from cells3 resulting in decreased intracellular drug accumulation and resistance to its cytotoxic effects. A single nucleotide polymorphism in BCRP is known to change amino acid 141 from glutamine to lysine. To determine the effects on flavopiridol transport caused by this mutation, HEK-293 (human embryonic kidney) cells both stably and transiently transfected with wild-type and mutant BCRP were evaluated in flavopiridol cytotoxicity and transport assays. While early differences were observed in cytotoxicity assays with cells stably transfected with empty vector and BCRP, significant differences have not been observed with transiently transfected cells. In addition, no differences between the wild type and Q141K mutant were observed in both cytotoxicity assays comparing IC50 values and transport assays measuring the amount of intracellular flavopiridol. This report summarizes early efforts to develop the methods for evaluating the effects of the Q141K mutant. Further work to clarify the impact of this mutation on BCRP transport of flavopiridol is ongoing.No embarg

The Association between History of Gestational Diabetes Mellitus and Current Type 2 Diabetes Status: An Examination of NHANES Data 2011-2014

Background: Diabetes is a growing chronic disease that affects more than 29 million adults in the United States and 422 million adults globally. Women with a history of gestational diabetes (GDM) are identified to be at higher risk for developing subsequent type 2 diabetes mellitus (T2DM). The prevalence of GDM varies based on the data collection method, response rate, and diagnostic criteria. The aim of this study is to examine the association between history of GDM diagnosis and current T2DM status and how the relationship differs based on the participant’s age, race, and BMI. Methods: Data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Surveys (NHANES) were analyzed to conduct a cross-sectional study of 4,006 U.S. non-pregnant women ages 20 years and older with a history of prior pregnancy. The race/ethnicity of the participants include non-Hispanic Whites, non-Hispanic Blacks, Mexican Americans, non-Hispanic Asians, and Other variables. Univariate and multivariate logistic regression analyses were used to determine the association between history of GDM and current T2DM status stratified by age, race, and BMI. Results: Three hundred and fifteen subjects from a sample size of 4006 were found to have a history of GDM. Of the 315 participants with GDM, 111 (35.2%) were found to develop T2DM. After controlling for age, race, and body mass index (BMI), women with a history of GDM were found to be at greater odds of T2DM (OR=4.71; 95% CI: 3.52-6.28) compared to women without a history of GDM. A multivariate analysis was performed adjusting for other covariates such as age, race, BMI, and cholesterol. When stratified by participant age, women between the ages of 20-44 years with a history of GDM were linked with an increased risk of T2DM (OR= 3.02; 95% CI: 1.88-4.85). Overweight and obese women with a history of GDM have a 2.5-fold risk of developing T2DM (OR=2.51; 95% CI: 1.49-4.23). Discussion: This study provides further understanding and awareness on the role of GDM during the subsequent risk for T2DM. Our study shows women between the ages of 20 and 44 years and with elevated BMIs (25 ≥ kg/m2) are at increased risk of developing subsequent T2DM. Findings suggest the need for health promotion and prevention efforts towards the populations at risk. Early intervention post-pregnancy and education may help prevent women with a history of GDM from developing T2DM

Aloe vera: A Multipurpose Healer and Bacterial Eradicator

The Aloe vera plant is a succulent known for its rich content in vitamins and minerals, thus gaining popularity over the years in healthcare products. With advancements in alternative medicine, it has been recently found useful in dentistry due to properties such as anti-inflammatory, antioxidant and antimicrobial actions that contribute to wound healing. The purpose of this study was to examine and discover how Aloe vera can be used as an alternative therapy in the dental field. The PubMed, Google Scholar and Dentistry & Oral Sciences (DOSS) databases were utilized to find current scientific evidence on the effects of Aloe vera. Relevant articles were summarized to write a review of findings. In this study, 21 articles published from 2015 to present were reviewed. From the studies, there is strong evidence to support that Aloe vera exhibits beneficial effects in prevention of carious lesions, non-surgical scaling and root planing in patients with chronic periodontitis, and oral wounds. Furthermore, it is cost effective and easily accessible. This review’s findings indicate that dental health care providers could recommend Aloe vera as a preventive and an alternative treatment option to improve patients’ oral health status.https://scholarscompass.vcu.edu/denh_student/1005/thumbnail.jp

Public health and the economy could be served by reallocating medical expenditures to social programs.

As much as 30% of US health care spending in the United States does not improve individual or population health. To a large extent this excess spending results from prices that are too high and from administrative waste. In the public sector, and particularly at the state level, where budget constraints are severe and reluctance to raise taxes high, this spending crowds out social, educational, and public-health investments. Over time, as spending on medical care increases, spending on improvements to the social determinants of health are starved. In California the fraction of General Fund expenditures spent on public health and social programs fell from 34.8% in fiscal year 1990 to 21.4% in fiscal year 2014, while health care increased from 14.1% to 21.3%. In spending more on healthcare and less on other efforts to improve health and health determinants, the state is missing important opportunities for health-promoting interventions with a strong financial return. Reallocating ineffective medical expenditures to proven and cost-effective public health and social programs would not be easy, but recognizing its potential for improving the public's health while saving taxpayers billions of dollars might provide political cover to those willing to engage in genuine reform. National estimates of the percent of medical spending that does not improve health suggest that approximately $5 billion of California's public budget for medical spending has no positive effect on health. Up to 10,500 premature deaths could be prevented annually by reallocating this portion of medical spending to public health. Alternatively, the same expenditure could help an additional 418,000 high school students to graduate

Who Gets Needed Mental Health Care? Use of Mental Health Services among Adults with Mental Health Need in California

Background and Purpose. Timely and appropriate treatment could help reduce the burden of mental illness. This study describes mental health services use among Californians with mental health need, highlights underserved populations, and discusses policy opportunities. Methods. Four years of California Health Interview Survey data (2011, 2012, 2013, 2014) were pooled and weighted to the 2013 population to estimate mental health need and unmet need (n=82,706). Adults with mental health need had “unmet need” if they did not use prescription medication and did not have at least four or more mental health visits in the past year. Multivariable logistic regression analysis was performed to predict the probability adults with mental health need did not receive past-year treatment (n=5,315). Results. Seventy-seven percent of Californians with mental health need received no or inadequate mental health treatment in 2013. Men, Latinos, Asians, young people, older adults, people with less education, uninsured adults, and individuals with limited English proficiency were significantly more likely to have unmet need. Cost of treatment and mental health stigma were common reasons for lack of care. Conclusion. Unmet mental health need is predominant in California. Policy recommendations include continued expansion of mental health coverage, early identification, and ensuring that treatment is culturally and linguistically appropriate

The visual performance of the Cooper Vision Frequency 55 aspheric contact lens

Aberration-reducing aspheric soft contact lenses are intended to provide enhanced visual performance, particularly for patients with small amounts of astigmatism. This study was designed to compare visual performance and patient preferences for aspheric soft contact lenses versus spherical soft contact lenses in low astigmats. The aims of the study were: (1) to determine if aspheric soft contact lenses offer better visual performance and patient satisfaction in comparison to standard spherical lenses and, (2) to determine if a difference in the type or magnitude of astigmatism affects the visual performance and patient satisfaction with both types of contact lenses. Satisfaction ratings of overall vision was statistically better with the aspheric design (p=O.Ol). This was especially true for distance tasks including daytime driving and low light, nighttime driving. At the end of the study subjects preferred the Frequency 55 Aspheric lens with regard to vision (p=0.002), and overall. No matter what type of astigmatism, the final preference for the aspheric lens was significant and this was particularly evident for subjects manifesting oblique and against-the-rule cylinder. Objectively, there were no differences demonstrated in visual performance between the two lens designs. Although a correlation was not observed between subjective preference and objective performance, clinically it is most often the patient\u27s perception of the quality of their vision that ultimately determines the final lens choice. This study clearly demonstrates that even though differences in recorded visual acuity may not be observed during an eye examination, low astigmatic patients can perceive better vision with this aberration-reducing aspheric lens design in comparison to standard spherical soft contact lenses

Administrasjonskostnader for ulike formuleringer av rituksimab og trastuzumab i norske helseforetak. En kvalitativ studie

Introduksjon: Kreftklinikken ved Oslo Universitetssykehus (OUS) har estimert administrasjonskostnader for intravenøs infusjon (IV) og subkutan injeksjon (SC) og Sykehusinnkjøp LIS har brukt disse estimatene for å vise at bruk av IV framfor SC av rituksimab og trastuzmab vil være mer kostnadseffektivt. Det er ukjent om disse estimatene er representative for andre helseforetak. Hensikt: Det primære målet er å undersøke om administrasjonskostnader fra OUS er representative for andre helseforetak. De sekundære målene er å undersøke om helseforetakene har kapasitet til å administrere et økt antall IV uten organisatoriske endringer, og om sykehusapotekene har kapasitet til å møte det økte produksjonsvolumet av IV. I tillegg ønsker vi å beskrive sykehusapotekenes kostnadsmodell for å produsere en IV. Metode: Oppgaven er basert på kvalitativ metode og består av tre deler: intervju med representant for OUS for å kartlegge metoden for kostnadsberegning, intervju med representant for hovedkontoret for Sykehusapotekene Helseforetakene (SAHF) for å kartlegge arbeidskostnader ved produksjon av IV, og en spørreundersøkelse sendt til alle helseforetak for å få deres vurderinger av kostnadsestimatene fra OUS. Intervjuene ble tatt opp på lydbånd og transkribert. Transkripsjon fra intervju og besvarelser fra spørreskjema ble analysert ved bruk av systematisk tekstkondensering (STK). Resultater: Ingen andre helseforetak har egen infusjonsenhet for kreftlegemidler tilsvarende den OUS har, men respondentene mente likevel at kostnadsestimatene fra OUS var representative selv om beregningene ikke var transparente. Ifølge alle helseforetakene er det ingenting unikt med administrasjon av IV eller SC trastuzumab som gjør at det skiller seg fra administrasjon av andre kreftlegemidler. Derimot mener et helseforetak at rituksimab krever merarbeid under administrasjon av IV, som gjør det mer kostbart sammenlignet med administrasjon av IV av andre kreftlegemidler. OUS har valgt ulike metoder for å beregne administrasjonskostnader for IV og SC, og beregningene for SC er svært forenklet. Noen helseforetak må utføre organisatoriske tiltak for å administrere et økt antall IV. Sykehusapotekene (SA) i Helse Sør-Øst har små forskjeller i arbeidspris, men økt volum av IV-bestillinger kan føre til at SA må utføre tiltak for å øke kapasitet. Det er usikkert i hvilken grad dette vil påvirke arbeidsprisen. SAHF ønsket ikke at arbeidspriser skulle publiseres i denne oppgaven. Konklusjon: Mangel på transparens og vanskeligheter med å forstå OUS sine beregninger kompromitterer gyldighet av helseforetakenes vurderinger om at OUS sine administrasjonskostnader for IV og SC rituksimab og trastuzumab er representative. Noen helseforetak må utføre organisatoriske tiltak for å kunne administrere et økt antall IV, og det er usikkert om besparelser i legemiddelkostnader vil overveie påløpte kostnader. Det er mulig at sykehusapotek må utføre organisatoriske tiltak for å produsere et økt antall IV, som muligens gir økt arbeidspris. Dette kan føre til større variasjoner i administrasjonskostnader mellom helseforetak på nasjonalt nivå. Videre studier bør utføres med simulering av kostnader supplert med en bottom-up-analyse

The Effects of pressure on wide bandgap GaN semiconductors

Gallium nitride (GaN) is a group-III nitride semiconductor; which may prove useful in developing optical instruments that operate under high ambient pressures. The purpose of this project is to examine the properties of GaN under varying conditions. The methods used in this experiment consist of modeling free energy as a function of lattice constants; calculating bond lengths, bond strengths, and bulk moduli; and comparing the resultant data with values in published literature. We will also compare these results with experimental data drawn from x-ray diffraction scans. By doing so, we hope to determine whether gallium nitride is suitable for use as a semiconductor at high pressures