Citations

Adhesive interactions between multiple myeloma (MM) cells and marrow stromal cells activate multiple signaling pathways including nuclear factor κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), and Jun N-terminal kinase (JNK) in stromal cells, which promote tumor growth and bone destruction. Sequestosome-1 (p62), an adapter protein that has no intrinsic enzymatic activity, serves as a platform to facilitate formation of signaling complexes for these pathways. Therefore, we determined if targeting only p62 would inhibit multiple signaling pathways activated in the MM microenvironment and thereby decrease MM cell growth and osteoclast formation. Signaling through NF-κB and p38 MAPK was increased in primary stromal cells from MM patients. Increased interleukin-6 (IL-6) production by MM stromal cells was p38 MAPK-dependent while increased vascular cell adhesion molecule-1 (VCAM-1) expression was NF-κB–dependent. Knocking-down p62 in patient-derived stromal cells significantly decreased protein kinase Cζ (PKCζ), VCAM-1, and IL-6 levels as well as decreased stromal cell support of MM cell growth. Similarly, marrow stromal cells from p62−/− mice produced much lower levels of IL-6, tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL) and supported MM cell growth and osteoclast formation to a much lower extent than normal cells. Thus, p62 is an attractive therapeutic target for MM.

Background and Purpose— Adipose tissue is an abundant source of endothelial cells as well as stem and progenitor cells which can develop an endothelial phenotype. It has been demonstrated that these cells have distinct angiogenic properties in vitro and in vivo. However, whether these cells have the capacity to directly improve large vessel form and function after vascular injury remains unknown. To define whether delivery of adipose-derived endothelial cells (ADECs) would improve healing of injured carotid arteries, a rabbit model of acute arterial injury was used. Methods— Autologous rabbit ADECs were generated using defined culture conditions. To test the ability of ADECs to enhance carotid artery repair, cells were delivered intraarterially after acute balloon injury. Additional delivery studies were performed after functional selection of cells before delivery. Results— After rabbit omental fat harvest and digestion, a proliferative, homogenous, and distinctly endothelial population of ADECs was identified. Direct delivery of autologous ADECs resulted in marked reendothelialization 48 hours after acute vascular injury as compared to saline controls (82.2±26.9% versus 4.2±3.0% P <0.001). Delivery of ADECs that were selected for their ability to take up acetylated LDL significantly improved vasoreactivity and decreased intimal formation after vascular injury. Conclusions— Taken together, these data suggest that ADECs represent an autologous source of proliferative endothelial cells, which demonstrate the capacity to rapidly improve reendothelialization, improve vascular reactivity, and decrease intimal formation in a carotid artery injury model.

Abstract Following the death of a youth hockey coach in a fight with a parent in 2000, the Mayo Clinic Sports Medicine Center and Minnesota Hockey collaborated to implement a three-component Hockey Education Program (HEP). HEP was initiated in 2003 to ensure youth players develop sportsmanship, skills, and a Fair Play approach to the game. Another goal was to decrease attrition of players, coaches, and officials. Coaching Excellence, a component of HEP, is based on 25 years of youth sport research. The HEP manuals Coaches Who Never Lose and Sports and Your Child contain the philosophy, objectives, and guidelines to ensure implementation of HEP components across players, coaches, and parents. The Skill Development component emphasizes learning age-appropriate hockey skills though skill progression. Increasing the practice-to-game ratio to 3–4 practices per game greatly increases the maximum time players skate with the puck during developmental years. Pre- and post-season Skills Challenges allow coaches, players, and parents to gauge improvement, and structure practices to address identified skill deficits. The Fair Play (FP) component emphasizes sportsmanship. Teams earn a FP point each game if they incur less than a preset number of penalty minutes. A coach receiving a game misconduct or a parent/spectator asked to leave the game will cause the team to forfeit their FP point. FP points are factored into league standings across the state. This past season, 17 678 records of game data were obtained and 25 % (4420) were randomly selected for analysis. The data analysis permits comparison across seasons and changes are made accordingly. Based on four years of data, most Minnesota youth hockey games are played in a sportsmanlike manner. Checking from behind and head contact penalties have decreased since the penalty minutes for these dangerous infractions were increased.

Abstract Rationale We previously demonstrated that children with obstructive sleep apnea have increased blood pressure associated with changes in left ventricular mass index. Others have shown in adults that blood pressure variability is an important predictor of changes in left ventricular mass. The baroreflex system buffers blood pressure changes by varying heart rate. We have thus hypothesized that (1) baroreflex system gain is increased during sleep, improving blood pressure buffering; (2) children with obstructive sleep apnea lack this baroreflex gain increase; and (3) reduced blood pressure buffering results in exaggerated blood pressure variability that is associated with end-organ damage. Objectives Compare measures of left ventricular mass index and nighttime baroreflex gain of healthy children to those of children with obstructive sleep apnea. Methods A total of 169 children (50 control subjects, 63 with mild obstructive sleep apnea, and 56 with severe obstructive sleep apnea) with a mean age of 9.9 years (±2.2) underwent echocardiography followed by polysomnography with continuous blood pressure measurement. Baroreflex gain was calculated in time and frequency domains. Measurements and Main Results Healthy children demonstrated a nighttime pattern of increasing baroreflex gain. Children with obstructive sleep apnea had decreased nighttime baroreflex gain compared with control subjects. Nighttime blood pressure and blood pressure variability were significantly correlated with left ventricular mass index. Conclusions Obstructive sleep apnea is associated with a decrease in nighttime baroreflex gain and an increase in blood pressure variability. This increase is correlated with changes in left ventricular mass index.

Using elegant mouse models of B-cell lymphoma, Young and colleagues validate targeting syk-mediated B-cell receptor signaling as an effective antitumor strategy for the treatment of non-Hodgkin lymphoma.

Alzheimer's disease and other tauopa‐thies are characterized by the presence of intracellular neurofibrillary tangles composed of hyperphosphorylated, insoluble tau. General anesthesia has been shown to be associated with increased risk of Alzheimer's disease, and we have previously demonstrated that anesthesia induces hypothermia, which leads to overt tau hyperphosphorylation in the brain of mice regardless of the anesthetic used. To investigate whether anesthesia enhances the long‐term risk of developing pathological forms of tau, we exposed a mouse model with tauopathy to anesthesia and monitored the outcome at two time points—during anesthesia, or 1 wk after exposure. We found that exposure to isoflurane at clinically relevant doses led to increased levels of phospho‐tau, increased insoluble, aggregated forms of tau, and detachment of tau from microtubules. Furthermore, levels of phospho‐tau distributed in the neuropil, as well as in cell bodies increased. Interestingly, the level of insoluble tau was increased 1 wk following anesthesia, suggesting that anesthesia precipitates changes in the brain that provoke the later development of tauopathy. Overall, our results suggest that anesthesia‐induced hypothermia could lead to an acceleration of tau pathology in vivo that could have significant clinical implications for patients with early stage, or overt neurofibrillary tangle pathology.— Planel, E.,Bretteville, A., Liu, L., Virag, L., Du, A. L., Yu, W. Y., Dickson, D. W., Whittington, R. A., Duff, K. E. Acceleration and persistence of neurofibrillary pathology in a mouse model of tauopathy following anesthesia. FASEBJ. 23, 2595–2604 (2009)

Due to rising health care costs and resistance to antibiotics, maggot débridement therapy may regain popularity. Nurses must learn about this unusual therapy and be prepared to assist patients who want to try it. J Contin Educ Nurs 2009;40(1):14–15.

Family presence during resuscitation is becoming an increasingly well-known and sometimes controversial issue among health care providers. Institutional support in the form of position statement and guideline development can assist in the implementation of a family presence program; however, more research is needed into all areas of the practice. Nurses can play an integral role in a practice that demonstrates exceptional attention to the needs of the family and, ultimately, the patient. J Contin Educ Nurs 2008;39(12):530–531.

Time and again, hospital code teams are dispatched to a patient in cardiac arrest only to find their resuscitative efforts unsuccessful. Are there earlier interventions that may have saved the patient? Do any warning signs exist before the patient actually goes into a full code or cardiac arrest event? The answer is a repeated yes, and the solution is a rapid response team. J Contin Educ Nurs 2008;39(11):488–489.