Citations

Background— Diastolic dysfunction associated with high blood pressure (BP) leads to cardiac remodeling and fibrosis and progression to congestive heart failure. B-type natriuretic peptide (BNP) has BP-lowering, antifibrotic, and antihypertrophic properties, which makes BNP an attractive agent for attenuating the adverse cardiac remodeling associated with hypertension. In the current study, we tested the effects of sustained cardiac proBNP gene delivery on BP, cardiac function, and remodeling in spontaneously hypertensive rats (SHR). Methods and Results— We used the myocardium-tropic adeno-associated virus serotype 9 (AAV9) vector to achieve continuously enhanced cardiac rat proBNP expression. In SHR, a single systemic administration of AAV9 vector allowed long-term cardiac BNP overexpression, resulting in reductions in systolic and diastolic BP for 9 months after injection. Left ventricular (LV) thickness, LV end-systolic dimensions, and LV mass were reduced, whereas ejection fraction was significantly increased, in BNP-treated compared with untreated SHR. Circumferential systolic strain and strain rate of the early phase of diastole were improved in BNP-treated compared with untreated SHR. Noncardiac overexpression of BNP via AAV2 vector was not associated with changes in BP and plasma BNP in SHR. Furthermore, normal Wistar rats injected with AAV9 proBNP vector showed significantly reduced heart weights 4 weeks after injection without BP reduction. Conclusions— AAV9 vector facilitates sustained cardiac proBNP overexpression and improves LV function in hypertensive heart disease. Long-term proBNP delivery improved both systolic and diastolic function. The effects on cardiac structure and function occurred independently of BP-lowering effects in normal Wistar rats.

The clinical pharmacist in the emergency department is now commonly incorporated as a member of the emergency department trauma team. As such, the emergency pharmacist needs to have detailed knowledge of the pharmacotherapy of resuscitation and be able to apply the skills needed to function as a valuable member of this team. In addition to the traditional skills of the discipline of clinical pharmacy, the emergency pharmacist must be familiar with the intricacies of treating life-threatening injuries in an emergent setting and be able to anticipate the direction of the patient’s care. The ability to provide valuable pharmacological interventions throughout the resuscitation and stabilization process requires familiarity with the process of resuscitation, including rapid sequence induction, analgesia and sedation, seizure prophylaxis, appropriate antibiotic and tetanus prophylaxis, intracranial pressure control, hemodynamic stabilization, and any other specific drug therapy that the clinical situation demands. This article discusses the aforementioned pharmacotherapeutic topics and describes the role of the Emergency Pharmacist on the ED trauma team.

AbstractThis article describes the rationale, implementation and results of a pilot study evaluating the personal and organizational impact of an educational intervention on the stress of health team members. The compelling imperative for the project was to find a positive and effective way to address the documented stress levels of healthcare workers.Pilot study of oncology staff (n = 29) and healthcare leaders (n = 15) exploring the impact of a positive coping approach on Personal and Organizational Quality Assessment‐Revised (POQA‐R) scores at baseline and 7 months using paired t‐tests.Personal and organizational indicators of stress decreased in the expected directions in both groups over the time intervals. The majority of POQA‐R categories were statistically significantly improved in the oncology staff, and many of the categories were statistically significantly improved in the leadership group.The findings from this project demonstrate that stress and its symptoms are problematic issues for hospital and ambulatory clinic staff as evidenced by baseline measures of distress. Further, a workplace intervention was feasible and effective in promoting positive strategies for coping and enhancing well‐being, personally and organizationally. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract Dendritic cells (DCs) are professional APCs that reside in peripheral tissues and survey the body for pathogens. Upon activation by inflammatory signals, DCs undergo a maturation process and migrate to lymphoid organs, where they present pathogen-derived Ags to T cells. DC migration depends on tight regulation of the actin cytoskeleton to permit rapid adaptation to environmental cues. We investigated the role of hematopoietic lineage cell-specific protein 1 (HS1), the hematopoietic homolog of cortactin, in regulating the actin cytoskeleton of murine DCs. HS1 localized to lamellipodial protrusions and podosomes, actin-rich structures associated with adhesion and migration. DCs from HS1−/− mice showed aberrant lamellipodial dynamics. Moreover, although these cells formed recognizable podosomes, their podosome arrays were loosely packed and improperly localized within the cell. HS1 interacts with Wiskott–Aldrich syndrome protein (WASp), another key actin-regulatory protein, through mutual binding to WASp-interacting protein. Comparative analysis of DCs deficient for HS1, WASp or both proteins revealed unique roles for these proteins in regulating podosomes with WASp being essential for podosome formation and with HS1 ensuring efficient array organization. WASp recruitment to podosome cores was independent of HS1, whereas HS1 recruitment required Src homology 3 domain-dependent interactions with the WASp/WASp-interacting protein heterodimer. In migration assays, the phenotypes of HS1- and WASp-deficient DCs were related, but distinct. WASp−/y DCs migrating in a chemokine gradient showed a large decrease in velocity and diminished directional persistence. In contrast, HS1−/− DCs migrated faster than wild-type cells, but directional persistence was significantly reduced. These studies show that HS1 functions in concert with WASp to fine-tune DC cytoarchitecture and direct cell migration.

ObjectiveTo make recommendations concerning cochlear implantation during humanitarian medical trips by exploring the attitudes of US cochlear implant surgeons.Study DesignCross‐sectional survey.SettingAcademic.Subjects and MethodsQuestionnaires were sent to 405 members of the William House Cochlear Implant Study Group. The 198 respondents (49%), all active cochlear implant surgeons, were divided into 3 groups depending on their level of experience working in a developing country.ResultsEighty‐nine percent of respondents supported cochlear implants in these environments, although 42% of these cochlear implant surgeons stated that they would modify their criteria for implantation considering the challenges in developing countries. There was strong support for cochlear implants in postlingual deafened patients and prelingual deafened patients under the age of 3 years, although nearly half of respondents (48%) would not implant prelingual deafened patients after they reached the age of 3 years. Three‐quarters of respondents (74%) believed that developing countries should have the same access to current multichannel devices used in developed countries, as opposed to simpler, possibly lower cost devices. A local audiologist was deemed the most important personnel requirement (83%), and limited audiology and rehabilitative resources were the greatest postoperative concern rather than lack of postoperative care or infection.ConclusionThis survey strongly supports the practice of performing cochlear implants during humanitarian trips to developing countries and makes best‐practice recommendations to make outcomes successful.

Object The object of this study was to determine if the addition of transverse connectors (TCs) to a rod-screw construct leads to increased stabilization of the cervical spine. Methods Eleven human cadaveric cervical spines (C2–T1) were used to examine the effect of adding connectors to a C3–7 rod-screw construct in 3 models of instability: 1) C3–6 wide laminectomy, 2) wide laminectomy and 50% foraminotomy at C4–5 and C5–6, and 3) wide laminectomy with full medial to lateral foraminotomy. Following each destabilization procedure, specimens were tested with no TC, 1 TC between the C-5 screws, and 2 TCs between the C-4 and C-6 screws. Testing of the connectors was conducted in random order. Specimens were subjected to ± 2 Nm of torque in flexion and extension, lateral bending, and axial rotation. Range of motion was determined for each experimental condition. Statistical comparisons were made between the destabilized and intact conditions, and between the addition of TCs and the absence of TCs. Results The progressive destabilization procedures significantly increased motion. The addition of TCs did not significantly change motion in flexion and extension. Lateral bending was significantly decreased with 2 connectors, but not with 1 connector. The greatest effect was on axial rotation. In general, 2 TCs were more restrictive than 1 TC, and decreased motion 10% more than fixation alone. Conclusions Regardless of the degree of cervical destabilization, 1 or 2 TCs decreased motion compared with rods and screws alone. Axial rotation was most affected. Transverse connectors effectively increase the rigidity of rod-screw constructs in the cervical spine. Severe cervical instability can be overcome with the use of 2 TCs, but in cases in which 2 cannot be used, 1 should be adequate and superior to none.

The success in screening for drug candidates is highly dependent on the power of the strategy implemented. In this work, we report and characterize a novel fluorescent benzodiazepine antagonist of the type 1 cholecystokinin receptor (3-(3-(7-fluoro-1-(2-isopropyl(4-methoxyphenyl)amino)-2-oxoethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[ b ][1,4]-diazepin-3-yl)ureido)benzoic acid) that can be used as a receptor ligand in a fluorescence polarization assay, which is ideally suited for the identification of small molecule allosteric modulators of this physiologically important receptor. By binding directly to the small molecule-docking region within the helical bundle of this receptor, this indicator can be displaced by many small molecule candidate drugs, even those that might not affect the binding of an orthosteric cholecystokinin-like peptide ligand. The biological, pharmacological, and fluorescence properties of this reagent are described, and proof-of-concept is provided in a fluorescence polarization assay utilizing this fluorescent benzodiazepine ligand.