Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA

One of the most frequent genetic aberrations in acute myeloid leukemia (AML) is chromosomal translocation between AML1/RUNX1 on chromosome 21 and ETO gene on chromosome 8 resulting in the expression of chimeric oncogene AML1-ETO. Although patients with t(8;21) translocation have good prognosis, 5-year survival is observed only in 50% of the cases. AML1-ETO translocation is usually accompanied by overexpression of mutant C-Kit, a tyrosine kinase, which contributes to uncontrolled proliferation of premature blood cells leading to relapse and poor prognosis. We illustrate the potential use of esculetin on leukemic cell line, Kasumi-1, bearing t(8;21) translocation and mutated C-Kit gene. Esculetin decreases the expression of AML1-ETO at both protein and transcript level within 24 hours of treatment. Half-life of AML1-ETO mRNA was reduced from 7 hours to 1.5 hours. Similarly half-life of C-Kit mRNA was reduced to 2 hours from 5 hours in esculetin treated cells. Esculetin also perturbed the expression of ectopically expressed AML1-ETO in U937 cells. The decreased expression of AML1-ETO chimeric gene was associated with increased expression of LAT1 and RUNX3 genes, targets of AML1. We envisage that discovery of a drug candidate which could target both these mutated genes would be a considerable breakthrough for future application

Miocene Leptomerycidae (Artiodactyla, Ruminantia) and their relationships. American Museum novitates ; no. 2596

22 p. : ill. ; 26 cm.Includes bibliographical references (p. 21-22)."Leptomerycidae, previously thought to have survived only from the Arikareean, are here recognized from the medial Miocene (late Hemingfordian into Valentinian) deposits of New Mexico, Texas, and Nebraska. These late-surviving Leptomerycidae belong to the species Pseudoparablastomeryx scotti and P. francesita, previously assigned to the Blastomerycinae. Likewise, Pronodens silberlingi from Arikareean deposits in Montana and possibly South Dakota is transferred to the Leptomerycidae from incertae sedis in the Cervidae. The relationships between these late Leptomerycidae and contemporaneous Blastomerycinae are shown to be remote despite several parallel features in common. Separation of the family Leptomerycidae from the family Hypertragulidae is advocated"--P. [1]

Hornless ruminants

p. 121-157 : ill. ; 26 cm.Includes bibliographical references (p. 154-157)."We analyze the interrelationships of the several groups of hornless ruminants and show which of them lie nearest the higher ruminants. The phylogenetic progression within Ruminantia proceeds from Hypertragulidae through Tragulidae to Leptomerycidae to Gelocidae to Moschidae and thence to the horned ruminants. Archaeomeryx of the late Eocene is recognized as a primitive member of the Leptomerycidae; the living Tragulidae actually represent a more primitive ruminant stock. We introduce the name Moschina for the Gelocidae and the Moschidae and the term Eupecora for the higher ruminant groups bearing horns, antlers, and ossicones. We also propose Neoselenodontia, above the subordinal level, to include both the Ruminantia and their sister group, the Tylopoda. The stratigraphic records of the five lower ruminant families appear relatively complete with the exception of the Tragulidae, which are poorly known prior to the Miocene. The exclusively North American distribution of the family Hypertragulidae and many of the Tylopoda suggests that the Ruminantia may have originated in North America. The Tragulidae, exclusively Old World and predominantly subtropical, presumably originated by colonization and isolation in the Old World. Thereafter ruminant evolution centered in the Old World, but representatives of every major group reached North America"--P. 121

Poly(glutamic acid) poly(ethylene glycol) hydrogels prepared by photoinduced polymerization: Synthesis, characterization, and preliminary release studies of protein drugs

A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly(glutamic acid), swelling behavior was found to be pH-responsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 14–21, 2002Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34426/1/10219_ftp.pd

A Cluster-Randomised Trial Evaluating an Intervention for Patients with Stress-Related Mental Disorders and Sick Leave in Primary Care

Objective: Mental health problems often affect functioning to such an extent that they result in sick leave. The worldwide reported prevalence of mental health problems in the working population is 10%–18%. In developed countries, mental health problems are one of the main grounds for receiving disability benefits. In up to 90% of cases the cause is stress-related, and health-care utilisation is mainly restricted to primary care. The aim of this study was to assess the effectiveness of our Minimal Intervention for Stress-related mental disorders with Sick leave (MISS) in primary care, which is intended to reduce sick leave and prevent chronicity of symptoms. Design: Cluster-randomised controlled educational trial. Setting: Primary health-care practices in the Amsterdam area, The Netherlands. Participants: A total of 433 patients (MISS n ¼ 227, usual care [UC] n ¼ 206) with sick leave and self-reported elevated level of distress. Interventions: Forty-six primary care physicians were randomised to either receive training in the MISS or to provide UC. Eligible patients were screened by mail. Outcome Measures: The primary outcome measure was duration of sick leave until lasting full return to work. The secondary outcomes were levels of self-reported distress, depression, anxiety, and somatisation. Results: No superior effect of the MISS was found on duration of sick leave (hazard ratio 1.06, 95% confidence interval 0.87–1.29) nor on severity of self-reported symptoms. Conclusions: We found no evidence that the MISS is more effective than UC in our study sample of distressed patients. Continuing research should focus on the potential beneficial effects of the MISS; we need to investigate which elements of the intervention might be useful and which elements should be adjusted to make the MISS effective

Returning to work after stroke: perspectives of employer stakeholders, a qualitative study.

Purpose: More than 40 % of working age adults with stroke fail to return to work. The work context is a key factor in return to work, but little is known about the experiences of employers in supporting employees with stroke. The aim of this study was to explore return to work after stroke from the employer perspective, to identify key features associated with success and to seek participants’ views regarding the role of healthcare in return to work. Methods: Data was gathered through 18 semi-structured interviews with employer stakeholders and included small business owners, line managers, human resources and occupational health staff. Data was analysed thematically. Results: The main themes identified were: the impact of stroke on the employer, characteristics of the employee, communication, knowledge and information, experience of other stakeholders, integrating healthcare in return to work. Conclusion: Employers face complex emotional and practical issues when helping an employee return to work after stroke, for which many lack knowledge and experience. The range and quality of support networks that they access is variable and advice and support from clinicians is welcomed. Further research is necessary to investigate how such support could be funded and integrated within existing service provision

Young People’s Experiences of Attending a Theater-in-Education Program on Child Sexual Exploitation

Child sexual exploitation and abuse (CSEA) has grave implications for the mental health and wellbeing of children and young people. It has been linked to a wide range of difficulties which may extend into adulthood. School-based prevention programs that aim to raise awareness (and thereby have the potential to prevent CSEA) are popular, however, have historically lacked robust and consistent evaluation. The purpose of the present study was therefore to explore young people’s experiences of attending a school-based theater-in-education program, and the impact this had on their awareness and understanding of CSEA. Four focus groups of between four to six participants each were conducted with young people from two co-educational State schools in the United Kingdom. The approach of Template Analysis was used to analyze the data, and revealed a number of themes related to the superordinate themes of “Information and Detail Delivered” and “Format and Timing.” The results suggest that participants gained new awareness and understanding of aspects related to CSEA, including other forms of (criminal) exploitation, as well as how to avoid harm and what to do “if bad things happen.” Participants further reported that the theater performance/live element of the program was particularly impactful, feeling that this was delivered to them at the right time, but suggesting that younger people would also benefit from the important messages. In addition, areas for improvement were identified in terms of the delivery of the program, and the issue of victim blaming. Findings are discussed with a view to practical implications and directions for future research

The Importance of the Relationship Between Growth Rates & Discount Rates in Assessing the Value of Economic Damages

Examining the implied net discount rates in the reports of several economists, we illustrate how easily these economists end up increasing, when they should be, decreasing to present value. To avoid this trap, when experts use data from different sources and time periods, they should insure, the relationship between their growth and discount rates is theoretically and empirically sound, and their valuation model is independent of the decision to invest the amount of an award