Quantification of Silver Nanoparticle Interactions with Yeast Saccharomyces Cerevisiae Studied using Single-Cell ICP-MS

Silver nanoparticles (AgNPs) have been used in many fields due to their anticancer, antimicrobial, and antiviral potential. Single-cell ICP-MS (SC-ICP-MS) is an emerging technology that allows for the rapid characterization and quantification of a metal analyte across a cell population in a single analysis. In this study, a new rapid and sensitive SC-ICP-MS method was developed to quantitatively study the interactions of AgNPs with yeast Saccharomyces cerevisiae. The method can quantify the cell concentration, silver concentration per cell, and profile the nanoparticle distribution in a yeast cell population. AgNP dosing time, concentration, and AgNP size were quantitatively evaluated for their effects on AgNP-yeast cell interactions. The results showed that the initial uptake of AgNPs was rapid and primarily driven by the mass of Ag per cell. The optimal dosing particle concentrations for highest uptake were approximately 1820, 1000, and 300 AgNPs/cell for 10, 20, and 40 nm AgNPs, respectively. Furthermore, this study also validated a washing method for the application to a microorganism for the first time and was used to quantitatively determine the amount of cell surface–adsorbed AgNPs and intracellular AgNPs. These results indicated that the mass (Ag in ag/cell) ratios of intracelluar vs cell surface-adsorbed AgNPs were similar for different AgNP sizes. This high throughput and ultrasensitive SC-ICP-MS method is expected to have many potential applications, such as optimization of methods for green synthesis of AgNPs, nanotoxicity studies, and drug delivery. This is the first quantification study on the interactions of AgNPs and S. cerevisiae using SC-ICP-MS. Graphical abstract: [Figure not available: see fulltext.]

COMMUNITY HEALTH EDUCATION IN RILEY COUNTY

Master of Public HealthPublic Health Interdepartmental ProgramRichard R. RosenkranzChronic diseases are on the rise in the American population and as such, the top killers have shifted from nonpreventable diseases to those that are preventable. Many of these diseases could be prevented through better diets and food choices (Slawson, Fitzgerald, & Morgan, 2013). Local health departments, health educators, and extension offices play a major role in this prevention through providing education, resources, and support for building healthier habits in families. These resources can be a leading force in making changes toward healthier families, which can help reduce the number of youths, and consequently adults, who develop obesity, Type 2 diabetes, and other chronic diseases (Ogagata & Hayes, 214). Chronic disease prevention, primarily through better nutrition and better diets, was the public health issue that was the main focus of my time at Lafene Health Center and the Riley County Extension Office. While at Lafene I worked with the Health Promotion office, whose purpose is to provide leadership in health maintenance promotion, and disease and illness prevention for Kansas State University students, staff, faculty and surrounding community members. The primary focus of my projects were to provide healthy eating tips, tricks, and education that is feasible with college students’ busy schedule, limited resources, and tight budget. This information was handed out at various health promotion events on campus. While at the Riley County Extension Office I planned and executed a healthy eating course for families, as well as a freezer meals class for community members. The healthy families course consisted of four one-hour classes that provided families with tools and resources to facilitate dialog, planning, and activities that would assist in developing healthier eating habits for the entire family. Due to unforeseeable circumstances, half of the courses had to be canceled but an increase in vegetable consumption was still reported among participants. At both locations, addressing the different socio-ecological barriers faced by the intended audiences increased the likelihood that participants would make healthier changes to their diets

Establishing Pteridine Metabolism in a Progressive Isogenic Breast Cancer Cell Model – Part II

Introduction: Determining the biological significance of pteridines in cancer development and progression remains an important step in understanding the altered levels of urinary pteridines seen in certain cancers. Our companion study revealed that several folate-derived pteridines and lumazines correlated with tumorigenicity in an isogenic, progressive breast cancer cell model, providing direct evidence for the tumorigenic origin of pteridines. Objectives: This study sought to elucidate the pteridine biosynthetic pathway in a progressive breast cancer model via direct pteridine dosing to determine how pteridine metabolism changes with tumorigenicity. Methods: First, MCF10AT breast cancer cells were dosed individually with 15 pteridines to determine which pteridines were being metabolized and what metabolic products were being produced. Second, pteridines that were significantly metabolized were dosed individually across the progressive breast cancer cell model (MCF10A, MCF10AT, and MCF10ACA1a) to determine the relationship between each metabolic reaction and breast cancer tumorigenicity. Results: Several pteridines were found to have altered metabolism in breast cancer cell lines, including pterin, isoxanthopterin, xanthopterin, sepiapterin, 6-biopterin, lumazine, and 7-hydroxylumazine (p \u3c 0.05). In particular, isoxanthopterin and 6-biopterin concentrations were differentially expressed (p \u3c 0.05) with respect to tumorigenicity following dosing with pterin and sepiapterin, respectively. Finally, the pteridine biosynthetic pathway in breast cancer cells was proposed based on these findings. Conclusions: This study, along with its companion study, demonstrates that pteridine metabolism becomes disrupted in breast cancer tumor cells. This work highlights several key metabolic reactions within the pteridine biosynthetic pathway that may be targeted for further investigation and clinical applications

Detection of Post-translational Modifications on Native Intact Nucleosomes by ELISA

The genome of eukaryotes exists as chromatin which contains both DNA and proteins. The fundamental unit of chromatin is the nucleosome, which contains 146 base pairs of DNA associated with two each of histones H2A, H2B, H3, and H41. The N-terminal tails of histones are rich in lysine and arginine and are modified post-transcriptionally by acetylation, methylation, and other post-translational modifications (PTMs). The PTM configuration of nucleosomes can affect the transcriptional activity of associated DNA, thus providing a mode of gene regulation that is epigenetic in nature 2,3. We developed a method called nucleosome ELISA (NU-ELISA) to quantitatively determine global PTM signatures of nucleosomes extracted from cells. NU-ELISA is more sensitive and quantitative than western blotting, and is useful to interrogate the epiproteomic state of specific cell types. This video journal article shows detailed procedures to perform NU-ELISA analysis

Albuterol Use in Children Hospitalized with Human Metapneumovirus Respiratory Infection

Introduction. Human metapneumovirus (HMPV) is a paramyxovirus from the same subfamily as respiratory syncytial virus (RSV) and causes similar acute lower respiratory tract infection. Albuterol in the setting of acute RSV infection is controversial and has not yet been studied in HMPV. We sought to determine the frequency of albuterol use in HMPV infection and the association between albuterol administration and patient outcomes. Methods. We conducted a retrospective cohort study identifying all patients hospitalized in a tertiary care children's hospital with laboratory-confirmed HMPV infection between January 2010 and December 2010. Results. There were 207 patients included in the study; 57% had a chronic medical condition. The median hospital length of stay was 3 days. Only 31% of patients in the study had a documented wheezing history, while 69% of patients received at least one albuterol treatment. There was no difference in length of stay between patients who received albuterol and those who did not. Conclusion. There is a high frequency of albuterol use in children hospitalized with HMPV infection. As with RSV, evidence may not support routine use of bronchodilators in patients with acute HMPV respiratory infection. Research involving additional patient outcomes and illness severity indicators would be useful in future studies

Correlates of comorbid anxiety and externalizing disorders in childhood obsessive compulsive disorder

The present study examines the influence of diagnostic comorbidity on the demographic, psychiatric, and functional status of youth with a primary diagnosis of obsessive compulsive disorder (OCD). Two hundred and fifteen children (ages 5–17) referred to a university-based OCD specialty clinic were compared based on DSM-IV diagnostic profile: OCD without comorbid anxiety or externalizing disorder, OCD plus anxiety disorder, and OCD plus externalizing disorder. No age or gender differences were found across groups. Higher OCD severity was found for the OCD + ANX group, while the OCD + EXT group reported greater functional impairment than the other two groups. Lower family cohesion was reported by the OCD + EXT group compared to the OCD group and the OCD + ANX group reported higher family conflict compared to the OCD + EXT group. The OCD + ANX group had significantly lower rates of tic disorders while rates of depressive disorders did not differ among the three groups. The presence of comorbid anxiety and externalizing psychopathology are associated with greater symptom severity and functional and family impairment and underscores the importance of a better understanding of the relationship of OCD characteristics and associated disorders. Results and clinical implications are further discussed

Hospital-level associations with 30-day patient mortality after cardiac surgery: a tutorial on the application and interpretation of marginal and multilevel logistic regression

Background: Marginal and multilevel logistic regression methods can estimate associations between hospital-level factors and patient-level 30-day mortality outcomes after cardiac surgery. However, it is not widely understood how the interpretation of hospital-level effects differs between these methods. Methods. The Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) registry provided data on 32,354 patients undergoing cardiac surgery in 18 hospitals from 2001 to 2009. The logistic regression methods related 30-day mortality after surgery to hospital characteristics with concurrent adjustment for patient characteristics. Results: Hospital-level mortality rates varied from 1.0% to 4.1% of patients. Ordinary, marginal and multilevel regression methods differed with regard to point estimates and conclusions on statistical significance for hospital-level risk factors; ordinary logistic regression giving inappropriately narrow confidence intervals. The median odds ratio, MOR, from the multilevel model was 1.2 whereas ORs for most patient-level characteristics were of greater magnitude suggesting that unexplained between-hospital variation was not as relevant as patient-level characteristics for understanding mortality rates. For hospital-level characteristics in the multilevel model, 80% interval ORs, IOR-80%, supplemented the usual ORs from the logistic regression. The IOR-80% was (0.8 to 1.8) for academic affiliation and (0.6 to 1.3) for the median annual number of cardiac surgery procedures. The width of these intervals reflected the unexplained variation between hospitals in mortality rates; the inclusion of one in each interval suggested an inability to add meaningfully to explaining variation in mortality rates. Conclusions: Marginal and multilevel models take different approaches to account for correlation between patients within hospitals and they lead to different interpretations for hospital-level odds ratios. © 2012 Sanagou et al; licensee BioMed Central Ltd

Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells

Sjögren’s disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren’s cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.Research reported in this publication was supported by the National Institutes of Health (NIH): R01AR073855 (C.J.L.), R01AR065953 (C.J.L.), R01AR074310 (A.D.F.), P50AR060804 (K.L.S.), R01AR050782 (K.L.S), R01DE018209 (K.L.S.), R33AR076803 (I.A.), R21AR079089 (I.A.); NIDCR Sjögren’s Syndrome Clinic and Salivary Disorders Unit were supported by NIDCR Division of Intramural Research at the National Institutes of Health funds - Z01-DE000704 (B.W.); Birmingham NIHR Biomedical Research Centre (S.J.B.); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2155 – Projektnummer 390874280 (T.W.); Research Council of Norway (Oslo, Norway) – Grant 240421 (TR.R.), 316120 (M.W-H.); Western Norway Regional Health Authority (Helse Vest) – 911807, 912043 (R.O.); Swedish Research Council for Medicine and Health (L.R., G.N., M.W-H.); Swedish Rheumatism Association (L.R., G.N., M.W-H.); King Gustav V’s 80-year Foundation (G.N.); Swedish Society of Medicine (L.R., G.N., M.W-H.); Swedish Cancer Society (E.B.); Sjögren’s Syndrome Foundation (K.L.S.); Phileona Foundation (K.L.S.). The Stockholm County Council (M.W-H.); The Swedish Twin Registry is managed through the Swedish Research Council - Grant 2017-000641. The French ASSESS (Atteinte Systémique et Evolution des patients atteints de Syndrome de Sjögren primitive) was sponsored by Assistance Publique-Hôpitaux de Paris (Ministry of Health, PHRC 2006 P060228) and the French society of Rheumatology (X.M.).publishedVersio