Occupational injuries and stressors among Canadian air medical health care professionals in rotor-wing programs

INTRODUCTION: Air medical health care providers work in a unique environment that may affect occupational injury rates and patterns. Despite this knowledge, little high-quality evidence exists regarding occupational injuries specifically incurred by air medical health care professionals. We sought to characterize the epidemiology of occupational injuries experienced by Canadian rotor-wing health care providers. METHODS: A survey was sent to the 4 rotor-wing programs in Canada. All crewmembers participating directly in patient care were asked to complete the survey detailing any acute occupational injuries sustained within the previous year. A series of both open- and closed-ended questions was used to collect participant demographics and information regarding any injuries sustained. RESULTS: One hundred and six (40.6%) participants completed the survey. Three hundred and thirty acute injuries were reported. Hand lacerations and leg contusions were most prevalent (31 and 24 individuals incurred these injuries, respectively). Acute back injuries were also prevalent with 25 (23.6%) participants reporting at least one back injury. Overall, an injury rate of 3.2 injuries per person per year was reported. Lifting was cited as a common factor in injury (30 cases). Most injuries required little treatment, with only 17 needing physician intervention, and only 6 required more than 1 week off work. CONCLUSION: Injuries among Canadian air medical crews are common, but fortunately, the majority are minor. Specific injury prevention strategies may focus on stretcher design, cabin ergonomics, and extremity protective equipment.     

Examining Type A behavior pattern to explain the relationship between job stressors and psychosocial outcomes

Despite cautions against using a global measure of Type A behavior pattern (TABP), few studies have examined the TABP components of Achievement Striving (AS) and Impatience/Irritability (II). The authors examined these 2 components to assess whether they moderated the relationships between job stressors and psychosocial outcomes. Results based on 106 employees from a large Canadian organization supported the independence of the 2 TABP components. After controlling for the job stressors (i.e., overload, ambiguity, intrarole conflict, and lack of job control), II and AS accounted for additional variance in job satisfaction, perceived stress, and life satisfaction, although these components were uniquely related to different outcomes. Finally, AS and II moderated several of the stressor-psychosocial outcome relationships.     

HIV-1 integrase inhibitors: 2005-2006 update

HIV-1 integrase (IN) catalyzes the integration of proviral DNA into the host genome, an essential step for viral replication. Inhibition of IN catalytic activity provides an attractive strategy for antiretroviral drug design. Currently two IN inhibitors, MK-0518 and GS-9137, are in advanced stages of human clinical trials. The IN inhibitors in clinical evaluation demonstrate excellent antiretroviral efficacy alone or in combination regimens as compared to previously used clinical antiretroviral agents in naive and treatment-experienced HIV-1 infected patients. However, the emergence of viral strains resistant to clinically studied IN inhibitors and the dynamic nature of the HIV-1 genome demand a continued effort toward the discovery of novel inhibitors to keep a therapeutic advantage over the virus. Continued efforts in the field have resulted in the discovery of compounds from diverse chemical classes. In this review, we provide a comprehensive report of all IN inhibitors discovered in the years 2005 and 2006.     

The Effectiveness of Naltrexone in Treating Task Attending, Aggression, Self-Injury, and Stereotypic Mannerisms of Six Young Males with Autism or Pervasive Developmental Disorders

An 8-week trial of 2 mg/kg/day of naltrexone (Trexan, now called ReVia) was conducted with four males with autism and two males with pervasive developmental disorders. Two dependent measures were employed: (a) direct behavioral measurement conducted by blind observers using videotape recordings of periodic learning task sessions, and (b) performance measures of the learning activity. Direct behavior measures revealed one participant's attending-to-task improved while receiving naltrexone. However, two of the participants' rates of self-injury increased, as did one of those participant's rate of aggression. Significant improvement was observed on performance measures of the learning task; however, the improved performance continued during the non-drug return to baseline for the three participants who experienced this additional condition. Discussion is provided relating these findings to previously published results.     

QSAR analysis of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole derivatives as selective COX-2 inhibitors

Quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations were based on Hansch's extra thermodynamic multi-parameter approach and receptor surface analysis (RSA). QSAR investigations reveal that steric and electrostatic interactions are primarily responsible for COX-2 enzyme-ligand interaction. QSAR model derived from Hansch analysis demonstrated that COX-2 inhibitory activity is correlated with sum of atomic polarizability (Apol), number of hydrogen-bond donor groups (HBD), energy of the highest occupied molecular orbital (HOMO), desolvation free energy for water (F(H(2)O)) and fraction of areas of molecular shadow in the XY and ZX planes over area of enclosing rectangle (Sxyf and Sxzf) with r ranges 0.870-0.904. The best model was obtained from RSA model having r = 0.940 with good predictive ability (predicted compounds in training set and test set within +/- 1.0 unit of pIC(50)) and can be used in designing better selective COX-2 inhibitors among the congeners in future.     

Synthesis of 1,7-bis(4-hydroxypenyl)-4-hydroxy-1,3-heptadiene-5-one, an antiplatelet diarylheptanoid from Alpinia blepharocalyx K. schum

A general and straight forward total synthesis of 1,7-bis(4-hydroxyphenyl)-3-hydroxy-1,3-heptadiene-5-one (5) starting from 4-methoxycinnamic acid (6) via ethyl 5-(4-methoxyphenyl)-3-hydroxy-2,4-pentadienoate (14) was accomplished in 19% overall yield.     

Significance of ER–Src axis in hormonal therapy resistance

The estrogen receptor (ER) is implicated in the progression of breast cancer. Despite positive effects of hormonal therapy, initial or acquired resistance to endocrine therapies frequently occurs. Recent studies suggested ERα-coregulator PELP1 and growth factor receptor ErbB2/HER2 play an essential role in hormonal therapy responsiveness. Src axis couples ERα with HER2 and PELP1, thus representing a new pathway for targeted therapy resistance. To establish the significance of ER–Src axis in PELP1 and HER2 mediated therapy resistance, we have generated model cells that stably express Src-shRNA under conditions of PELP1, HER2 deregulation. Depletion of Src using shRNA substantially reduced E2 mediated activation of Src and MAPK activation in resistant model cells. Pharmacological inhibition of Src using dasatinib, an orally available inhibitor substantially inhibited the growth of therapy resistant MCF7–PELP1, MCF7–HER2, and MCF7–Tam model cells in proliferation assays. In post-menopausal xenograft based studies, treatment with dasatinib significantly inhibited the growth of therapy resistant cells. IHC analysis revealed that the tumors were ERα positive, and dasatinib treated tumors exhibited alterations in Src and MAPK signaling pathways. Combinatorial therapy of tamoxifen with dasatinib showed better therapeutic effect compared to single agent therapy on the growth of therapy resistant PELP1 driven tumors. The results from our study showed that ER–Src axis play an important role in promoting hormonal resistance by proto-oncogenes such as HER2, PELP1, and blocking this axis prevents the development of hormonal independence in vivo. Since PELP1, HER2, and Src kinase are commonly deregulated in breast cancers, combination therapies using both endocrine agents and dasatinib may have better therapeutic effect by delaying the development of hormonal resistance.