Photodynamic therapy enhancement of phthalocyanine targeting from modifications on the macrocycle to the use of protein delivery vehicles

Photodynamic therapy is a promising treatment modality that involves the localization of a light-sensitive drug or photosensitizer in the target tissue prior to illumination with visible light. In the presence of molecular oxygen, cytotoxic agents are generated upon illumination and trigger a cascade of biochemical responses that may eradicate both malignant and non-malignant conditions. Phthalocyanine derivatives are second generation photosensitizers with enhanced photophysical, photochemical and photobiological properties as compared to the clinically accepted hematoporphyrin derivative Photofrin ª . The current study aims at improving the targeting of these photosensitizers to cancerous tissues either through modifications on the phthalocyanine macrocycle or through protein carriers. AlPcS[subscript 4] derivatives substituted with long aliphatic chains of varying lengths were photodynamically active in vitro against a lung adenocarcinoma cell line, A549 cells. Activity varied directly with the degree of lipophilicity: AlPcS[subscript 4] (C16) > AlPcS[subscript 4] (C12) > AlPcS[subscript 4] (C8) > AlPcS[subscript 4] (C4)."In vivo" studies using the EMT-6 murine model were promising, requiring 0.2 [mu]mol kg[superscript -1] and 400 J cm[superscript -2] to completely ablate the tumor. LDL receptor expression is often upregulated in cancer cell membranes. Therefore, in order to enhance Pc targeting, LDL was loaded with AlPcS by two different approaches. The AlPcS[subscript 4] (C12) derivative was non-covalently inserted in the phospholipid bilayer of LDL particles. Conversely, AlPcS[subscript 4] substituted with two caproic acid spacer chains were covalently attached to the LDL protein moiety. While the latter had only marginal success, the former proved to be photodynamically active both in vitro and in vivo . To further exploit cell surface receptors as potential targets in PDT, adeno-viral proteins were covalently labeled with AlPcS[subscript 4] . Adenoviruses penetrate the cell via receptor mediated endocytosis. The Ad penton base contains 5 repeats of the peptidic RGD binding sequence. This motif binds with high affinity to several members of the integrin receptor family. Integrin receptors play a major role in tumorigenesis and metastases with altered expression being a factor. The class of integrin receptors with high affinity for the RGD sequence is expressed in high numbers on A549 cells. Cell uptake of the AlPcS[subscript 4]-adenovirus protein conjugates was enhanced over the parental Pc; however, photocytotoxicity results were unfavorable. In vivo studies using the same rodent model as that of the LDL study were encouraging"--Résumé abrégé par UMI

Tests of Remote Association

Do Remote Associates Test (RAT) problems measure the process of remote association? In the present study a new set of RAT problems was generated, and association norms were determined for each test word, providing an index of the remoteness of die association needed to solve each problem. The observed remoteness of each problem correlated with the difficulty of the problems

Impacting Occupational Therapy Assistant Student Knowledge about Occupation and Occupation-Based Practice

It is important for occupational therapy assistant (OTA) programs to teach about occupation and occupation-based practice (OBP). Few have published on this topic in relation to OTA education. This study focuses on determining if an educational module covering occupation and OBP would increase student knowledge of occupation and occupation-based practice. In this mixed-methods parallel convergent study, OTA students were immersed in an author-designed educational module to increase their knowledge of occupation, OBP, and the selection of occupation-based interventions. The students engaged in pretesting activities, prior to the module, consisting of short-answer essay and intervention selection tasks. At the conclusion of the module, the students completed posttest activities. The study results demonstrated significant learning in the areas of occupation, OBP, and the selection of occupation-based interventions. Quantitative analysis indicated a statistically significant increase in student learning, and qualitative analysis revealed increased levels of performance, when classified according to Bloom’s Taxonomy. This study addresses a gap in the OTA education literature by showing evidence that use of the learning module increased OTA student knowledge of occupation, OBP, and the ability to select occupation-based interventions. This module was an efficient and effective method of meeting accreditation standards related to OTA education

Calorie Restriction Enhances Longevity Without Reducing Lifetime Fecundity or Glucose Titers in Female Lubber Grasshoppers

Calorie restriction, under eating while avoiding malnutrition, enhances longevity in many organisms, in part by delaying fecundity or lowering blood glucose. Calorie restriction begun at middle-age can also enhance longevity. We tested four diets on longevity of female lubber grasshoppers: ad libitum (free access to food), calorie restriction (60% or 71% of ad libitum), and delayed calorie restriction (60% after day 50). Constant calorie restriction increased longevity in grasshoppers by at least 66%. These diets lowered body mass, but it did not reduce lifetime fecundity or chronically lower blood glucose levels. Calorie restriction reduced the levels of stored protein after egg laying. Delayed calorie restriction also increased longevity (also by 66%), but because the body mass gain of this group did keep pace with ad libitum grasshoppers when they were fed identically, this result needs retesting. These extensions of lifespan likely are due to slowed aging

Research for Practice: Publishing Academic Research for Managerial Readers

Because Information Systems is an applied field, IS research should contribute to practice. Most academic journals require that authors describe what their research findings imply for managers in the field. But academic journals do not require presentation of the findings or their implications in a manner that readily leads to their dissemination within the practitioner community. In this tutorial we will explore how academic research can actually improve practice— in fact, we will assume that improving practice is the ultimate objective of academic research in our field. This tutorial is intended to help academic researchers recast their work for academic journals such as Sloan Management Review, California Management Review, and MISQ Executive, and others, which target a practitioner audience. Senior editors of MISQ Executive will share with participants their favorite examples of practice-based research. They will list the characteristics that make each article both insightful and “user-friendly.” We will share examples of research articles that led to changes in how managers approached their roles. The objective of the tutorial is to arm participants with examples of world class, practice-based research as well as a process for converting their research into valuable practitioner reading

Translating Hemoglobin A1c Scores across an Ethnically Diverse Population: Is the Language Consistent across All Races?

Hemoglobin A1c testing is an accepted measure of how well the blood glucose level has been controlled in the recent past (six to eight weeks) among individuals with diabetes. The purpose of this study was to evaluate the relationship between hemoglobin A1c (HbA1c) and blood glucose in an ethnically diverse population in a clinical setting. A cross-sectional research design was employed to explore associations between these two diabetes control measures in a sample of African American, White and Hispanic patients receiving diabetes treatment and follow-up in an outpatient clinic in Tallahassee, Florida. Data collection included a questionnaire, medical examinations, and lab results. Although we found a significant association between the glucose level and the HbA1c levels, the A1c value did not predict the mean glucose value as closely as previously found in less diverse groups. These findings suggest there is need for further study of these two variables among minority groups

Dominance, Politics, and Physiology: Voters' Testosterone Changes on the Night of the 2008 United States Presidential Election

BACKGROUND: Political elections are dominance competitions. When men win a dominance competition, their testosterone levels rise or remain stable to resist a circadian decline; and when they lose, their testosterone levels fall. However, it is unknown whether this pattern of testosterone change extends beyond interpersonal competitions to the vicarious experience of winning or losing in the context of political elections. Women's testosterone responses to dominance competition outcomes are understudied, and to date, a clear pattern of testosterone changes in response to winning and losing dominance competitions has not emerged. METHODOLOGY/PRINCIPAL FINDINGS: The present study investigated voters' testosterone responses to the outcome of the 2008 United States Presidential election. 183 participants provided multiple saliva samples before and after the winner was announced on Election Night. The results show that male Barack Obama voters (winners) had stable post-outcome testosterone levels, whereas testosterone levels dropped in male John McCain and Robert Barr voters (losers). There were no significant effects in female voters. CONCLUSIONS/SIGNIFICANCE: The findings indicate that male voters exhibit biological responses to the realignment of a country's dominance hierarchy as if they participated in an interpersonal dominance contest

Sexual function in 16- to 21-year-olds in Britain

Purpose: Concern about young people's sexuality is focused on the need to prevent harmful outcomes such as sexually transmitted infections and unplanned pregnancy. Although the benefit of a broader perspective is recognized, data on other aspects of sexuality, particularly sexual function, are scant. We sought to address this gap by measuring the population prevalence of sexual function problems, help seeking, and avoidance of sex in young people. Methods: A cross-sectional stratified probability sample survey (Natsal-3) of 15,162 women and men in Britain (response rate: 57.7%), using computer-assisted self-interviews. Data come from 1875 (71.9%) sexually active, and 517 sexually inactive (18.7%), participants aged 16–21 years. Measures were single items from a validated measure of sexual function (the Natsal-SF). Results: Among sexually active 16- to 21-year-old participants, 9.1% of men and 13.4% of women reported a distressing sexual problem lasting 3 months or more in the last year. Most common among men was reaching a climax too quickly (4.5%), and among women was difficulty in reaching climax (6.3%). Just over a third (35.5%) of men and 42.3% of women reporting a problem had sought help, but rarely from professional sources. Among those who had not had sex in the last year, just >10% of young men and women said they had avoided sex because of sexual difficulties. Conclusions: Distressing sexual function problems are reported by a sizeable minority of sexually active young people. Education is required, and counseling should be available, to prevent lack of knowledge, anxiety, and shame progressing into lifelong sexual difficulties

The effect of adolescent testosterone on hippocampal BDNF and TrkB mRNA expression: relationship with cell proliferation

Testosterone attenuates postnatal hippocampal neurogenesis in adolescent male rhesus macaques through altering neuronal survival. While brain-derived neurotropic factor (BDNF)/tyrosine kinase receptor B (TrkB) are critical in regulating neuronal survival, it is not known if the molecular mechanism underlying testosterone's action on postnatal neurogenesis involves changes in BDNF/TrkB levels. First, (1) we sought to localize the site of synthesis of the full length and truncated TrkB receptor in the neurogenic regions of the adolescent rhesus macaque hippocampus. Next, (2) we asked if gonadectomy or sex hormone replacement altered hippocampal BDNF and TrkB expression level in mammalian hippocampus (rhesus macaque and Sprague Dawley rat), and (3) if the relationship between BDNF/TrkB expression was altered depending on the sex steroid environment. Results: We find that truncated TrkB mRNA+ cells are highly abundant in the proliferative subgranular zone (SGZ) of the primate hippocampus; in addition, there are scant and scattered full length TrkB mRNA+ cells in this region. Gonadectomy or sex steroid replacement did not alter BDNF or TrkB mRNA levels in young adult male rat or rhesus macaque hippocampus. In the monkey and rat, we find a positive correlation with cell proliferation and TrkB-TK+ mRNA expression, and this positive relationship was found only when sex steroids were present. Conclusions: We suggest that testosterone does not down-regulate neurogenesis at adolescence via overall changes in BDNF or TrkB expression. However, BDNF/TrkB mRNA appears to have a greater link to cell proliferation in the presence of circulating testosterone