B cell reductive therapy with rituximab in the treatment of rheumatoid arthritis.

The approach to treating autoimmune disorders is currently undergoing a significant change in focus. As therapies are developed that are more precise in targeting the pathogenesis for these diseases, patients experience significantly fewer side effects. At the same time, as more precise therapies are discovered, the etiologies of these diseases become further elucidated. It is now widely accepted that B-lymphocytes play a significant role in the pathogenesis of various autoimmune diseases, the extent of which continues to be the focus of ongoing research. Rheumatoid arthritis is one such disease process that has been the focus of various B-lymphocyte-directed therapeutic trials. In this paper we review the current research available on rituximab as treatment for rheumatoid arthritis. This review details results from four main studies, as well as others, which used rituximab in at least one of the arms in treatment of rheumatoid arthritis. The results are promising and will likely lead to longer term studies as well as a potential focus on B cell subsets

Targeting self-renewal pathways in myeloid malignancies

A fundamental property of hematopoietic stem cells (HSCs) is the ability to self-renew. This is a complex process involving multiple signal transduction cascades which control the fine balance between self-renewal and differentiation through transcriptional networks. Key activators/regulators of self-renewal include chemokines, cytokines and morphogens which are expressed in the bone marrow niche, either in a paracrine or autocrine fashion, and modulate stem cell behaviour. Increasing evidence suggests that the downstream signaling pathways induced by these ligands converge at multiple levels providing a degree of redundancy in steady state hematopoiesis. Here we will focus on how these pathways cross-talk to regulate HSC self-renewal highlighting potential therapeutic windows which could be targeted to prevent leukemic stem cell self-renewal in myeloid malignancies

Proteostasis and ageing: insights from long-lived mutant mice

The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age-related disease, and thus improving late-life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis- where proteostasis is defined here as the maintenance of the proteome- appears highly relevant to both ageing and disease. Several studies have shown that multiple proteostatic mechanisms, including the endoplasmic reticulum (ER)-induced unfolded protein response (UPR), the ubiquitin-proteasome system (UPS) and autophagy, all appear indispensable for longevity in many long-lived invertebrate mutants. Similarly, interspecific comparisons suggest that proteostasis may be an important lifespan determinant in vertebrates. Over the last 20 years a number of long-lived mouse mutants have been described, many of which carry single-gene mutations within the growth-hormone, insulin/IGF-1 or mTOR signalling pathways. However, we still do not know how these mutations act mechanistically to increase lifespan and healthspan, and accordingly whether mechanistic commonality occurs between different mutants. Recent evidence supports the premise that the successful maintenance of the proteome during ageing may be linked to the increased lifespan and healthspan of long-lived mouse mutants

Fed cattle market is guardedly optimistic, says K-State\u27s Sands

Returns to cattle feeders should move back into the profit column during most of 1982. but feeding margins will remain narrow, says Mike Sands, extension economist specializing in livestock marketing at K-State. Most of the improvement in profitability compared with last year will result from lower feed and feeder prices, rather than a dramatic rise in fed cattle prices. he points out. With Choice steer prices expected to average in the $64-66 cwt. range during January-June. feeding returns should average on the positive side, in sharp contrast to the average$95-per-head losses suffered during the first half of 1981. Sands believes. Total commercial cattle slaughter reached 34.9 million head in 1981. about 3% larger than a year earlier. Although fed cattle marketings dropped about 1% from 1980 levels, the decline was more than offset by a 14% rise in nonfed steer and heifer and cow slaughter. Certainly, the lack of growth in consumers\u27 inflation-adjusted incomes during the past year has contributed to the dismal economic performance of the cattle industry, Sands comments. But, perhaps more importantly, total red meat and poultry supplies climbed to a record 53.1 billion lbs. in 1981. about 1.5% more than the year-earlier record

Chemical effects in ion mixing of a ternary system (metal-SiO_2)

The mixing of Ti, Cr, and Ni thin films with SiO_2 by low‐temperature (−196–25 °C) irradiation with 290 keV Xe has been investigated. Comparison of the morphology of the intermixed region and the dose dependences of net metal transport into SiO_2 reveals that long range motion and phase formation probably occur as separate and sequential processes. Kinetic limitations suppress chemical effects in these systems during the initial transport process. Chemical interactions influence the subsequent phase formation

Out of Control: The Flawed Regulation of Schedule II Drugs and Its Impact on Pain and Addiction

This paper explores the current state of regulation of controlled substances at the federal and state level and analyzes how such regulations impact the undertreatment of pain and prescription drug abuse. Taking a historical view of the pain treatment movement and using the recent OxyContin crisis as a case study, the future of controlled substance policy as it relates to painkillers is analyzed. It argues that any successful policy will have to do a better job of balancing law enforcement and health care goals

THE IMPACT OF A PEER LEADERSHIP PROGRAM ON HIGH SCHOOL STUDENTS’ SOCIAL CAPITAL, AS MEASURED BY CO-COGNITIVE FACTORS OF THE RENZULLI HOUNDSTOOTH THEORY

This study examined the impact of different volunteer experiences on the development of social capital. The study was grounded in Renzulli’s Operation Houndstooth Intervention Theory, which hypothesizes that six co-cognitive factors are associated with the development of students’ social capital, and that volunteer experiences in which students help others (Direct Involvement I) and take active leadership roles (Direct Involvement II) may be most effective at developing social capital. A sample of convenience, juniors and seniors attending an urban high school in the northeastern U.S., was utilized. Students participated for 16 weeks in one of three programs: (a) a Peer Leadership Program in which they planned a Direct Involvement II project (treatment), (b) a volunteer organization in which they participated in Direct Involvement I activities (comparison), and (c) an Early College Entrance Class that participated in no direct volunteer activities (control). Pretest and posttest data were collected utilizing the Operation Houndstooth Intervention Survey which included subscales to measure each of the co-cognitive factors. Posttest data were analyzed using a multivariate analysis of covariance (MANCOVA) to determine if there was a significant difference in mean scores between students who participated in the three groups. Multiple regression analysis was used to determine the extent to which the factor Romance with a Topic or Discipline predicted the remaining factors. Qualitative methods were used to analyze open-ended items related to students’ perceptions of their Direct Involvement I or II experiences. A significant effect for Program was found (p = .004). Students in the treatment group scored significantly higher on Physical/Mental Energy than students in the control group (p = .015). Students in the comparison group scored significantly higher on Sensitivity to Human Concerns than students in the control group (p = .008) and the treatment group (p = .011). Regression results suggested that pretest mean scores for Romance with a Topic or Discipline did not predict mean posttest scores for the six co-cognitive factors. Qualitative analyses indicated that students in the treatment group viewed their projects in terms of logistical steps to facilitate projects. In contrast, the students in the comparison group viewed their experience in terms of their associations with volunteer recipients

Convex hull method for the determination of vapour-liquid equilibria (VLE) phase diagrams for binary and ternary systems

Amieibibama Joseph wishes to thank Petroleum Technology Development Fund (PTDF) for their financial support which has made this research possible.Peer reviewedPostprin