Effect of Chemotherapeutic Treatment Schedule on a Tissue Transport Model

Current chemotherapeutic treatment schedule prediction methods rely heavily on PK/PD-based models and overlook the important contribution of tissue-level transport and binding. Tissue-level transport and binding phenomena are essential to understanding drug delivery and efficacy in tumors. Drugs with desirable PK/PD properties often fail in vivo due to poor tissue-level transport. We developed an in silico method to predict the effect of treatment schedule on efficacy that couples PK/PD with tissue-level transport. Treatment schedules were implemented on theoretical drugs with different PK/PD and transport properties. For each drug with a given clearance rate, diffusivity, and binding, treatment schedules consisting of one to 20 doses were simulated. Results show that at binding constants around one, high diffusivities, and high clearance rates, implementation of a treatment schedule becomes more significant. At low clearance rates, regardless of tissue-level transport and binding, one dose was predicted to be most efficacious. Tissue Drug Exposure (TDE) was shown to be to a crucial factor for treatment schedule efficacy. Efficacy was improved by increasing TDE. Implementation of a treatment schedule with more doses than one curbed the effect of poor retention with drugs. This model investigates the effect of treatment schedule on a tissue transport model and shows implementation of a proper dosing regimen is crucial to maximize TDE and chemotherapeutic efficacy

The Relationship Between Afrocentric Worldview and Marital Satisfaction in African-American Couples

Problem. It has been argued that many of the theories attempting to explain African-American culture derive from a Eurocentric framework, and thus paint a negative and pathological picture of the African-American family and community. What is needed is research examining African-American family life which holds Afrocentric culture and beliefs as its foundation. Consequently, this study is an attempt to investigate the relationship between Afrocentric cultural consciousness (Afrocentric worldview) and marital satisfaction of spouses of African descent. Method. This study used a correlational and ex post facto research design involving surveys to assess the relationship between the dependent variable (marital satisfaction) and the independent variable (Afrocentric cultural consciousness, or components thereof) in married couples of African descent. The research involved subjects answering 57 questions on two self-report questionnaires (15 on marital satisfaction and 42 onAfrocentric cultural consciousness) as well as some demographic information. The two instruments used were:the Marital Adjustment Test (MAT) and the African Self-Consciousness Scale (ASC). Results. No significant correlation was found between the two main variables; however, socioeconomic status, educational attainment, denominational affiliation, and the number of children a couple has all have an influence on marital satisfaction and/or Afrocentric cultural consciousness and or the relationship between these.Afrocentric cultural consciousness was more affected by these variables than marital satisfaction. Conclusions. Although no main effect was found in this study the results do suggest what may really be important to marital satisfaction is not the particular worldview that one holds as much as whether or not that particular worldview matches one\u27s spouse\u27s belief system

Reproductive Differences among Delmarva Grass Shrimp (Palaemonetes pugio and P. vulgaris) Populations

Populations of female grass shrimps (Palaemonetes pugio and P. vulgaris) were sampled from five coastal embayments in Delaware, Maryland, and Virginia (Delmarva) and compared with respect to reproductive and life history attributes. We observed interspecific differences in timing of reproduction, carapace length, ratio of carapace length to total body length, body weight, clutch weight, clutch size, and egg volume. Onset of reproduction in P. vulgaris lagged behind P. pugio. Although there was no difference in the relationship between clutch size and carapace length for the two species, carapace length/total body length in P. pugio was greater than that in P. vulgaris. A multivariate analysis of variance indicated significant differences in carapace length, clutch weight, body weight, clutch size, and egg volume attributable to effects of species, population, and interactions between them. At all sites, P. pugio produced larger eggs than P. vulgaris. Although the two species did not differ in reproductive effort, both species exhibited increases in reproductive effort with latitude. Clutch size also tended to increase with latitude for both species. In populations where both species were abundant, adult females of P. pugio were longer and heavier and produced heavier egg masses comprised of fewer, larger eggs

Childhood maltreatment, psychological resources, and depressive symptoms in women with breast cancer.

Childhood maltreatment is associated with elevated risk for depression across the human lifespan. Identifying the pathways through which childhood maltreatment relates to depressive symptoms may elucidate intervention targets that have the potential to reduce the lifelong negative health sequelae of maltreatment exposure. In this cross-sectional study, 271 women with early-stage breast cancer were assessed after their diagnosis but before the start of adjuvant treatment (chemotherapy, radiation, endocrine therapy). Participants completed measures of childhood maltreatment exposure, psychological resources (optimism, mastery, self-esteem, mindfulness), and depressive symptoms. Using multiple mediation analyses, we examined which psychological resources uniquely mediated the relationship between childhood maltreatment and depressive symptoms. Exposure to maltreatment during childhood was robustly associated with lower psychological resources and elevated depressive symptoms. Further, lower optimism and mindfulness mediated the association between childhood maltreatment and elevated depressive symptoms. These results support existing theory that childhood maltreatment is associated with lower psychological resources, which partially explains elevated depressive symptoms in a sample of women facing breast cancer diagnosis and treatment. These findings warrant replication in populations facing other major life events and highlight the need for additional studies examining childhood maltreatment as a moderator of treatment outcomes

New Results from NA49

We present recent results of the SPS experiment NA49 on production of strange particles and event-by-event fluctuations of mean $p_t$ and of charged particle ratios in central Pb+Pb collisions at various beam energies (40, 80, 158 AGeV) as well as in different collisions at 158 AGeV, going from p+p over light-ion collisions to peripheral and central Pb+Pb.Comment: 5 pages, 6 figures (in eps) talk given at XXXI International Symposium on Multiparticle Dynamics, Sep. 1-7, 2001, Datong China URL http://ismd31.ccnu.edu.cn

Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Bacteria isolated from Bengal cat (Felis catus × Prionailurus bengalensis) anal sac secretions produce volatile compounds potentially associated with animal signaling.

In social animals, scent secretions and marking behaviors play critical roles in communication, including intraspecific signals, such as identifying individuals and group membership, as well as interspecific signaling. Anal sacs are an important odor producing organ found across the carnivorans (species in the mammalian Order Carnivora). Secretions from the anal sac may be used as chemical signals by animals for behaviors ranging from defense to species recognition to signaling reproductive status. In addition, a recent study suggests that domestic cats utilize short-chain free fatty acids in anal sac secretions for individual recognition. The fermentation hypothesis is the idea that symbiotic microorganisms living in association with animals contribute to odor profiles used in chemical communication and that variation in these chemical signals reflects variation in the microbial community. Here we examine the fermentation hypothesis by characterizing volatile organic compounds (VOC) and bacteria isolated from anal sac secretions collected from a male Bengal cat (Felis catus × Prionailurus bengalensis), a cross between the domestic cat and the leopard cat. Both left and right anal sacs of a male Bengal cat were manually expressed (emptied) and collected. Half of the material was used to culture bacteria or to extract bacterial DNA and the other half was used for VOC analysis. DNA was extracted from the anal sac secretions and used for a 16S rRNA gene PCR amplification and sequencing based characterization of the microbial community. Additionally, some of the material was plated out in order to isolate bacterial colonies. Three taxa (Bacteroides fragilis, Tessaracoccus, and Finegoldia magna) were relatively abundant in the 16S rRNA gene sequence data and also isolated by culturing. Using Solid Phase Microextraction (SPME) gas chromatography-mass spectrometry (GC-MS), we tentatively identified 52 compounds from the Bengal cat anal sac secretions and 67 compounds from cultures of the three bacterial isolates chosen for further analysis. Among 67 compounds tentatively identified from bacterial isolates, 51 were also found in the anal sac secretion. We show that the bacterial community in the anal sac consists primarily of only a few abundant taxa and that isolates of these taxa produce numerous volatiles that are found in the combined anal sac volatile profile. Several of these volatiles are found in anal sac secretions from other carnivorans, and are also associated with known bacterial biosynthesis pathways. This is consistent with the fermentation hypothesis and the possibility that the anal sac is maintained at least in part to house bacteria that produce volatiles for the host

DNA methylation age is elevated in breast tissue of healthy women

BACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. METHODS: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. RESULTS: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10-11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = -0.53, p = 4.4 × 10-4). CONCLUSIONS: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure