Propofol selectively alters GluA1 AMPA receptor phosphorylation in the hippocampus but not prefrontal cortex in young and aged mice.

Propofol is a commonly used general anesthetic agent which has been previously shown to enhance the inhibitory GABAergic transmission in the central nervous system. In addition to the GABAergic element, the excitatory transmission may be another central molecular site impacted by propofol. Increasing evidence implies that the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor represents an excitatory amino acid receptor subtype subjected to the regulation by propofol. Indeed, in this study, we found that a single injection of propofol at an anesthetic dose increased AMPA receptor GluA1 subunit phosphorylation in young (2-3 months old) and aged (20-21 months old) mice in vivo. Propofol caused an increase in GluA1 phosphorylation in the hippocampus but not in the prefrontal cortex. The propofol effect was also site-selective as the drug elevated GluA1 phosphorylation at serine 831 (S831) but not serine 845. Interestingly, while propofol induced a moderate and transient increase in S831 phosphorylation in young mice, the drug caused a substantial and sustained S831 phosphorylation in aged animals. Total GluA1 abundance remained stable in the hippocampus and prefrontal cortex in both young and aged mice in response to propofol. These results provide evidence supporting the sensitivity of GluA1 AMPA receptors to propofol. A single dose of propofol was able to upregulate GluA1 phosphorylation in the confined hippocampus in an age-dependent manner.

Meaning-making appraisals relevant to adjustment for veterans with spinal cord injury.

The purpose of the present study was to conduct a mixed-methods investigation of meaning-making appraisals generated from spinal cord injury survivors' narratives of their injury experience. The sample consisted of 79 participants from an urban midwestern Veterans Affairs facility. The study design was cross-sectional and incorporated semistructured, face-to-face interviews, taking approximately 1 hr to complete. Measures of posttraumatic stress disorder, depression, psychological well-being, and purpose in life were completed as part of the interview. A data analytic approach based on grounded theory that allowed qualitative themes to be transformed to quantitative data was employed. Seven salient meaning-making themes were identified. Significant relationships were identified between certain meaning-making themes (e.g., identity integration positively related to positive growth), and certain themes were also significantly related to postinjury psychological health and distress separately (e.g., perceived burden on others was significantly related to greater depression scores). Findings are discussed within the context of clinical interventions that foster positive posttrauma outcomes.

Synergistic activity of ceftobiprole and vancomycin in a rat model of infective endocarditis caused by methicillin-resistant and glycopeptide-intermediate Staphylococcus aureus.

The therapeutic activity of ceftobiprole medocaril, the prodrug of ceftobiprole, was compared to that of vancomycin, daptomycin, and the combination of a subtherapeutic dose of ceftobiprole and vancomycin in a rat model of infective endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300) or glycopeptide-intermediate Staphylococcus aureus (GISA) (NRS4 and HIP 5836) strains. The minimum bactericidal concentrations of ceftobiprole, vancomycin, and daptomycin at bacterial cell densities similar to those encountered in the cardiac vegetation in the rat endocarditis model were 2, >64, and 8 µg/ml, respectively, for MRSA ATCC 43300 and 4, >64, and 8 µg/ml, respectively, for the GISA strain. Ceftobiprole medocaril administered in doses of 100 mg/kg of body weight given intravenously (i.v.) twice a day (BID) every 8 h (q8h) (equivalent to a human therapeutic dose of ceftobiprole [500 mg given three times a day [TID]) was the most effective monotherapy, eradicating nearly 5 log(10) CFU/g MRSA or 6 log(10) CFU/g GISA organisms from the cardiac vegetation and had the highest incidence of sterile vegetation compared to the other monotherapies in the endocarditis model. In in vitro time-kill studies, synergistic effects were observed with ceftobiprole and vancomycin on MRSA and GISA strains, and in vivo synergy was noted with combinations of subtherapeutic doses of these agents for the same strains. Additionally, sterile vegetations were achieved in 33 and 60%, respectively, of the animals infected with MRSA ATCC 43300 or GISA NRS4 receiving ceftobiprole-vancomycin combination therapy. In summary, ceftobiprole was efficacious both as monotherapy and in combination with vancomycin in treating MRSA and GISA infections in a rat infective endocarditis model and warrants further evaluation.

Redeeming behaviours: a push, not a shove.

By now, it's no secret that Canadians are struggling to maintain a healthy body weight, eat right and get enough physical activity to promote their health and prevent the early onset of or to manage, chronic disease. Considered with our tendency to have poor adherence rates to prescribed medications and difficulties overcoming addictive substances, this struggle threatens to shorten our life spans and overburden our healthcare system. To turn the tide, layered and coordinated initiatives at the population level are needed that educate, motivate and support individuals to embrace healthy living. In this commentary, the authors respond to Oliver's recent paper on the utility of user financial incentives and architectural choice interventions as mechanisms for facilitating voluntary behaviour change. They concur with many of his ideas and argue that a more comprehensive approach, particularly adhering to the principles and strategies of social marketing, is needed to stimulate and sustain behaviour change.

Prevalence of testosterone deficiency after spinal cord injury.

OBJECTIVE: To define the prevalence of testosterone deficiency in persons with chronic spinal cord injury (SCI) and to identify factors associated with this deficiency. DESIGN: Cross-sectional study. SETTING: A U.S. Department of Veterans Affairs SCI unit. PARTICIPANTS: Participants (n = 60) included male veterans completing annual evaluations from July 2006 to April 2007. METHODS: In addition to routine annual evaluation laboratory examination, which included measurements of serum albumin levels, participants underwent measurements of serum total testosterone, luteinizing hormone, follicle stimulating hormone, and prolactin levels. Outcome measures included the prevalence of testosterone deficiency (defined as total serum testosterone <325 ng/dL) and the relationship of testosterone level with participant's age, serum albumin level, narcotic medication use, time since injury, American Spinal Injury Association Impairment Scale (AIS) grade, and neurologic level of injury. RESULTS: A low serum testosterone level (<325 ng/dL) was detected in 43.3% of participants. The testosterone level was significantly associated with severity of injury as defined by AIS grade (t = -2.59, P = .012). The prevalence of testosterone deficiency was significantly greater in participants with motor complete (AIS A and B) injuries compared with those with motor incomplete (AIS C, D, and E) injuries. Testosterone levels were significantly lower in participants who were taking narcotic medications for pain management (t = -0.25, P < .05). There was no relationship between the use of narcotic medications and severity of injury. Given the small number of participants, the SCI levels, age, duration of injuries, serum albumin levels, and serum levels of luteinizing hormone, follicle stimulating hormone, and prolactin did not reach statistical significance in predicting testosterone level. CONCLUSIONS: These findings confirm both a substantial population of men with SCI and with testosterone deficiency, and a significant association between testosterone level and severity of SCI. Measuring serum total testosterone levels should be included in standard screenings for patients with SCI, particularly those with motor complete injuries.

Prevalence of prostate cancer in patients with chronic spinal cord injury.

OBJECTIVE: To determine the prevalence of prostate cancer in patients with chronic spinal cord injury (SCI), with regard to the duration, level, and severity of injury. DESIGN: Retrospective chart review study. SETTING: Inpatient and outpatient Veterans Affairs spinal cord unit. PARTICIPANTS: The electronic medical records of 350 veterans with chronic SCI and 344 veterans without SCI as a control group were reviewed. MAIN OUTCOME MEASURE: Prevalence of prostate cancer in patients with chronic SCI with regard to the duration, level, and severity of injury. RESULTS: Of 350 veterans with chronic SCI, 7 individuals (2%) had prostate cancer. In comparison, of 344 age-matched veterans without SCI, 18 (5.2%) had prostate cancer. In SCI group with prostate cancer, 2 patients had motor complete injury (American Spinal Cord Injury Association Impairment Scale [AIS] A and B), and 5 patients had motor incomplete injury (AIS C, D, and E). Patients with SCI and with prostate cancer were slightly older (mean [SD] age, 72.14 ± 8.25 years) than the control group (mean [SD] age, 69.83 ± 8.79 years) with cancer. CONCLUSION: Findings from this study indicate a lower prevalence of prostate cancer among veterans with chronic SCI in comparison with age-matched veterans without SCI. Given the small number of patients with SCI and with prostate cancer in this study, we did not find any statistically significant correlation between the prevalence of prostate cancer and the level, duration, and severity of injury.

Psychological well-being after spinal cord injury: perception of loss and meaning making.

OBJECTIVE: This study examined the influence of medical injury severity, perceived loss of physical functioning (conceptualized as physical resource loss), and global meaning making on psychological well-being among 79 veterans living with a spinal cord injury. MEASURES: Structured interviews were completed to assess perceived loss of physical abilities using the Conservation of Resources-Evaluation and SF-36 Health Survey, global meaning making (Purpose in Life scale), and psychological well-being (Sense of Well-Being Inventory). Medical injury severity was calculated from medical records. RESULTS: Medical injury severity was not related to psychological well-being, whereas perceived loss of physical functioning was inversely associated. Global meaning making was significantly related to and accounted for a large portion of the variance in psychological well-being. Results suggest that global meaning making partially mediates perceived loss of physical resources and psychological well-being. CONCLUSION: The perceived loss of physical abilities and the generation of meaning and purpose in life are important variables that relate to positive adaptation following spinal cord injury. Treatment implications related to factors that increase quality of life following spinal cord injury are discussed.