The Psychosocial Effects of the Li-Fraumeni Education and Early Detection (LEAD) Program on Indivdiuals with Li-Fraumeni Syndrome

Li-Fraumeni syndrome (LFS) is a hereditary cancer syndrome that leads to an increased risk of multiple cancers. In the past five years new screening protocols have been developed that provide improved screening options for individuals with LFS. However, very little has been published on the psychosocial impact of these screening protocols. The goals of this study were to determine how participation in screening impacts individuals psychosocially, to examine the benefits and drawbacks of screening, and to evaluate possible barriers to continued screening. This qualitative study consisted of phone interviews with 20 individuals that took part in an LFS screening program at M.D. Anderson Cancer Center. Data analysis showed that benefits of screening include early detection, peace of mind, centralized screening, knowledge providing power, and screening making LFS seem more livable. Perceived drawbacks included logistical issues, difficulty navigating the system, screening being draining, and significant negative emotional reactions such as anxiety, fear, and skepticism. Regardless of the emotions that were present, 100% of participants plan on continuing screening in the program. Our data indicates that the perceived benefits of screening outweigh the drawbacks of screening. Individuals in this screening program appear to have improved psychosocial well-being because of their access to the screening program

Web 2.0 Projects at Warwick University Library

About 2 years ago at Warwick our senior managers encouraged Academic Support staff to really explore web 2.0 technologies and find out if anything particularly lent itself to supporting library work or marketing. We were given free reign to find out what worked and what suited the library, and what didn’t. The following brief overviews cover only four of the projects that have been running since then. We have also investigated much more, including Twitter, Google Documents, wiki reading lists, You-Tube and more, but we couldn’t possibly fit it all in here. The brief articles below are just to give a taste of the kind of projects we have worked on. There are many more members of staff involved and many more web 2.0 adventures underway..

ER stress in temozolomide-treated glioblastomas interferes with DNA repair and induces apoptosis

Glioblastoma multiforme (GBM) is a deadly grade IV brain tumor. Radiation in combination with temozolomide (TMZ), the current chemotherapeutic for GBMs, only provides 12-14 months survival post diagnosis. Because GBMs are dependent on both activation of the DNA damage pathway and the endoplasmic reticulum (ER) stress response, we asked if a novel ER stress inducing agent, JLK1486, increases the efficacy of TMZ. We found that the combination of TMZ+JLK1486 resulted in decreased proliferation in a panel of adherent GBM cells lines and reduced secondary sphere formation in non-adherent and primary lines. Decreased proliferation correlated with increased cell death due to apoptosis. We found prolonged ER stress in TMZ+JLK1486 treated cells that resulted in sustained activation of the unfolded protein response (UPR) through increased levels of BiP, ATF4, and CHOP. In addition, TMZ+JLK1486 treatment caused decreased RAD51 levels, impairing DNA damage repair. Furthermore, we found delayed time to tumor doubling in TMZ+JLK1486 treated mice. Our data shows that the addition of JLK1486 to TMZ increases the efficaciousness of the treatment by decreasing proliferation and inducing cell death. We propose increased cell death is due to two factors. One, prolonged ER stress driving the expression of the pro-apoptotic transcription factor CHOP, and, second, unresolved DNA double strand breaks, due to decreased RAD51 levels. The combination of TMZ+JLK1486 is a potential novel therapeutic combination and suggests an inverse relationship between unresolved ER stress and the DNA damage response pathway

Climate Change and International Deforestation: Legislative Analysis

Deforestation accounts for nearly 20% of anthropogenic greenhouse gas emissions in the world. Deforestation results in carbon emissions when trees and underlying vegetation are burning or decomposing. Deforested areas that are later cultivated also release carbon to the atmosphere when soil carbon is oxidized. Further, deforested areas converted to other land uses (e.g., pastures) might sequester less carbon than forests, enabling greater levels of CO2 in the atmosphere. Providing incentives to prevent deforestation in foreign countries has been proposed in climate change legislation. An objective of this legislation is to provide funding from carbon markets to assist foreign countries in reducing deforestation and increasing forest restoration and afforestation. Challenges to this approach include implementing deforestation reduction activities in developing countries that may lack the capacity to monitor and enforce measures, avoiding harm to indigenous communities who rely on forest resources, and matching policies with the various drivers of deforestation in different regions around the world. Legislative policies on deforestation and climate change are analyzed in this report, and challenges for restoring forests in the tropics are discussed

BAF180 promotes cohesion and prevents genome instability and aneuploidy

BAF180, a subunit of the PBAF chromatin remodeling complex, is frequently mutated in cancer. Although PBAF regulates transcription, it remains unclear whether this is what drives tumorigenesis in cells lacking BAF180. Based on data from yeast, we hypothesized that BAF180 may prevent tumorigenesis by promoting cohesion. Here, we show BAF180 is required for centromeric cohesion in mouse and human cells. Mutations identified in tumor samples are unable to support this activity, and also compromise cohesion-dependent functions in yeast. We provide evidence of genome instability in line with loss of cohesion, and importantly, we find dynamic chromosome instability following DNA damage in cells lacking BAF180. These data demonstrate a function for BAF180 in promoting genome stability that is distinct from its well-characterized role in transcriptional regulation, uncovering a potent mechanism for its tumor-suppressor activity

Athlete perceptions of flavored, menthol-enhanced energy gels ingested prior to endurance exercise in the heat

Background L-menthol evokes a cooling sensation by activating cold sensing cation channels. Menthol-enhanced fluids can be ergogenic during exercise in the heat by improving thermal perception; hence, the addition of menthol to energy gels may benefit athletes. Previously, unflavored menthol gels were deemed acceptable at 0.1% concentration, but no research has been undertaken on menthol gels with additional flavoring. Therefore, we determined athlete perceptions of flavored energy gels with different menthol concentrations. Methods With a randomized, crossover, double-blind, placebo-controlled design, 27 athletes (34.8 ± 6.7 y, 9 females) ingested an energy gel with either 0.1%, 0.3%, 0.5%, or 0.7% menthol concentration, or a non-menthol, flavor-matched placebo (CON), on separate occasions before outdoor exercise. Gels were rated for cooling sensation, irritation, flavor, and overall experience on 100-point sensory and hedonic labeled magnitude scales. The duration of any cooling sensation was also reported. Results All menthol gels delivered a greater cooling sensation compared to CON (7.4 ± 8.1 AU) with a significantly greater response for 0.7% (59.9 ± 20.5 AU) and 0.5% (57.7 ± 21.8 AU), compared to all others. Irritation was higher for all menthol gels compared to CON (3.4 ± 7.2 AU) and for 0.7% compared to 0.1% (31.1 ± 31.0 vs. 16.3 ± 21.0 AU, p = 0.041), with none rated above a ‘mild-moderate’ intensity. The menthol gels delivered a significantly longer cooling sensation duration (12.3-19.6 min) versus CON (2.2 ± 4.8 min) with no difference between menthol gels. Conclusion A flavored menthol energy gel at 0.1–0.7% concentration provides a cooling sensation for athletes when ingested before exercise. The 0.5% concentration is recommended to maximize the cooling sensation whilst minimizing irritation

Multiple Versus Single Antipsychotic Agents for Hospitalized Psychiatric Patients: Case-Control Study of Risks Versus Benefits

OBJECTIVE: Since use of multiple drugs to treat psychiatric patients is increasing, and research on this practice is rare, the authors carried out a retrospective case-control study of multiple versus single antipsychotic treatment in psychiatric inpatients. METHOD: Inpatient treatment groups receiving either antipsychotic monotherapy or polytherapy were matched in terms of age, sex, diagnostic category, and admission clinical ratings (Global Assessment of Functioning [GAF] and Clinical Global Impression [CGI]), which yielded 70 subject pairs. They were compared in terms of total chlorpromazine-equivalent daily dose, changes in total daily dose, length of hospitalization, incidence of adverse effects, and changes in clinical ratings (CGI, GAF, Positive and Negative Syndrome Scale score) between admission and discharge. RESULTS: Initial doses were closely similar at admission for both treatment groups, but the median total final antipsychotic dose was 78% higher for those receiving antipsychotic polytherapy versus monotherapy. Also, median length of stay in the hospital was 55% (8.5 days) longer, and risk of adverse effects was 56% higher with polytherapy, whereas clinical improvement scores were similar (within 11%) for both treatments. CONCLUSIONS: Short-term treatment with multiple antipsychotics was associated with major increases in drug exposure, adverse events, and time in the hospital but with no apparent gain in clinical benefit. These findings require further testing in controlled prospective studies

Diet, Digestion and Energy Intake in Captive Common Marmosets (Callithrix jacchus): Research and Management Implications

Common marmosets (Callithrix jacchus) are susceptible to intestinal inflammation which leads to chronic diarrhea, weight loss, and vitamin D deficiency. We examined food intake and digestion in three mixed-sex groups of adult marmosets maintained on three commercial base diets. Animals underwent two consecutive 4-day digestion trials. Body mass stayed constant. Feces and diet were assayed for Mn, fat, and gross energy (GE). Apparent digestibility of dry matter (ADDM) was calculated by the total collection method and from dietary and fecal Mn; the methods produced correlated results (r = 0.658, p \u3c 0.001). Apparent digestibility of energy (ADE) was calculated from ADDM and the GE of feces and diet; apparent digestibility of fat (ADfat) was calculated from ADDM and fecal fat. ADDM and ADE varied by diet (p \u3c 0.001). We found poor digesters on all three diets. The concentration of fecal fat was inversely related to ADE (r = −0.729, p \u3c 0.001). High fecal fat (\u3e10%) was associated with ADfat of zero, consistent with lipid malabsorption. Mean digestible energy intake (DEI) was equal to 1.5 the estimated metabolic rate, but varied widely between individuals. The diet with the fewest animals with high fecal fat had the highest mean DEI and most animals above 450 g, suggesting it may be obesogenic

Inpatient Antipsychotic Drug Use in 1998, 1993, and 1989

OBJECTIVE: Patterns of clinical use of antipsychotic agents have changed greatly in the past decade. The authors’ goal was to examine these patterns. METHOD: They evaluated medication use in all McLean Hospital inpatients treated with antipsychotic drugs during 3 months in 1998 (N=349) and compared the results with McLean Hospital inpatients treated with antipsychotics in 1993 (N=299) and Boston area inpatients in 1989 (N=50). RESULTS: The most commonly prescribed antipsychotics in 1998 were atypical agents; olanzapine was prescribed more often than risperidone or quetiapine, which were prescribed more often than other antipsychotics. Two or more antipsychotics were prescribed at some time during their hospitalization for 150 (43%) of the patients in 1998. The total discharge dose in chlorpromazine equivalents for the 349 patients for whom antipsychotics were prescribed at discharge was 371 mg/day, 29% higher than the total discharge dose for patients in 1993 and 46% greater than the dose in 1989. The dose of antipsychotics was greater for patients with psychotic illnesses than for those with affective illnesses. Higher doses were associated with greater clinical improvement, polypharmacotherapy, and younger patient age. CONCLUSIONS: Emerging trends toward higher total antipsychotic doses and polypharmacotherapy require critical assessments of cost-benefit relationships