p35/Cyclin-dependent kinase 5 is required for protection against β-amyloid-induced cell death but not tau phosphorylation by ceramide

Ceramide is a bioactive sphingolipid that can prevent calpain activation and beta-amyloid (A beta) neurotoxicity in cortical neurons. Recent evidence supports A beta induction of a calpain-dependent cleavage of the cyclin-dependent kinase 5 (cdk5) regulatory protein p35 that contributes to tau hyperphosphorylation and neuronal death. Using cortical neurons isolated from wild-type and p35 knockout mice, we investigated whether ceramide required p35/cdk5 to protect against A beta-induced cell death and tau phosphorylation. Ceramide inhibited A beta-induced calpain activation and cdk5 activity in wild-type neurons and protected against neuronal death and tau hyperphosphorylation. Interestingly, A beta also increased cdk5 activity in p35-/- neurons, suggesting that the alternate cdk5 regulatory protein, p39, might mediate this effect. In p35 null neurons, ceramide blocked A beta-induced calpain activation but did not inhibit cdk5 activity or cell death. However, ceramide blocked tau hyperphosphorylation potentially via inhibition of glycogen synthase kinase-3beta. These data suggest that ceramide can regulate A beta cell toxicity in a p35/cdk5-dependent manner.     

Dynamic patterns in mood among newly diagnosed patients with major depressive episode or panic disorder and normal controls

Objective: The purpose of this pilot study was to compare the dynamic patterns of hourly mood variation among newly diagnosed primary care patients with major depressive disorder or panic disorder with patterns in patients with neither disorder.Method: Five adult patients with major depressive episode, 5 with panic disorder, and 5 with neither disorder were asked to complete hourly self-assessments of anxiety and depression (using 100-mm visual analog scales) for each hour they were awake during a 30-day period. Time series were analyzed using ARIMA (autoregression, integration, moving average) modeling (to assess periodicity), Lyapunov exponents (to assess sensitivity to initial conditions indicative of chaotic patterns), and correlation dimension saturation (to assess whether an attractor is limiting change). The study was conducted from March to June 2003.Results: Controls displayed circadian rhythms with underlying chaotic variability. Depressed patients did not display circadian rhythm, but did show chaotic dynamics. Panic disorder patients showed circadian rhythms, but 2 of the 4 patients completing the self-assessments displayed nonchaotic underlying patterns.Conclusions: Patients with major depressive disorder or panic disorder may differ from controls and from each other in their patterns of mood variability. There is a need for more research on the dynamics of mood among patients with mental disorders.     

Significance of the arthroscopic meniscal flounce sign: a prospective study

BACKGROUND: The meniscal flounce sign is a fold in the free, nonanchored inner edge of the medial meniscus that can be noted during routine arthroscopy of the knee. HYPOTHESIS: The meniscal flounce sign can be a significant indicator of the presence or absence of medial meniscus injury. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 4. METHODS: One hundred sixty-eight patients were prospectively evaluated at the time of the arthroscopy for the presence or absence of the arthroscopic meniscal flounce sign. These results were then correlated with the presence of medial meniscus tears. RESULTS: The presence of the meniscal flounce sign has a positive predictive value of a normal meniscus of 0.97 (63/65). The absence of the meniscal flounce sign has a positive predictive value of an abnormal meniscus of 0.98 (101/103). Specificity is 98%, and sensitivity is 97%. CONCLUSION: The absence of the arthroscopic meniscal flounce sign is a sensitive and specific predictor of the presence of medial meniscus tears that should alert the surgeon to probe carefully for an occult medial meniscus tear.     

Indications for repair of full-thickness rotator cuff tears

Rotator cuff repair surgery for full-thickness tears is common and accepted in orthopaedics today. Given that a significant number of people have asymptomatic rotator cuff tears, the indications for surgery are, however, somewhat unclear. Multiple factors such as duration of symptoms, acuity and size of the tear, patient age, and others require consideration and can influence the decision to perform surgery. This article reviews these variables and the indications for surgery to repair full-thickness rotator cuff tears.     

Elevated N-myristoyltransferase activity and expression in oral squamous cell carcinoma

N-myristoyltransferase (NMT) catalyzes the myristoylation of proteins involved in signal transduction, cellular transformation, differentiation, proliferation and oncogenesis. In this study, we report for the first time on the elevated NMT activity in oral squamous cell carcinoma (OSCC). Increased activity is marked with increased staining for NMT in the OSCC samples compared to the normal adjacent tissues. In addition, we observed increased staining for the N-myristoyltransferase inhibitor protein 71 (NIP71) in the OSCC samples compared to the control tissues. These findings suggest the regulatory relationship between NMT and NIP71 during tumorigenesis. It is possible that the increased activity results in the overexpression of NIP71 in an effort to control NMT activity.     

Considering culture in understanding interpersonal violence

Interpersonal violence is a global phenomenon. Forensic nurses should seek cultural competency to help them better understand the relationship between culture and interpersonal violence.     

Anti-interleukin-2 receptor antibody (daclizumab) treatment of corticosteroid-refractory autoimmune thrombocytopenic purpura

We administered daclizumab, a humanized monoclonal anti-interleukin-2 receptor (IL-2R) antibody, to 11 patients with corticosteroid-refractory autoimmune thrombocytopenic purpura (AITP) every 2 weeks for five treatments. Of nine evaluable patients, one individual experienced a partial response. Lymphocyte phenotyping by flow cytometry indicated post-treatment binding of IL-2Ra by daclizumab in all patients. Mid-study serum soluble IL-2R levels in all patients increased 4-15 -fold over baseline values (p=0.004). Despite these measurable immunologic effects, blockade of the IL-2/IL-2R axis did not effectively abrogate the autoimmune response in this group of patients with corticosteroid-refractory AITP.     

Postretrieval propranolol disrupts a cocaine conditioned place preference

The current study examined whether a postretrieval drug memory could be disrupted by the beta-adrenoceptor antagonist propranolol, administered following reactivation in a cocaine-mediated conditioned place preference paradigm. Following cocaine conditioning, rats were given a test of conditioned place preference, followed immediately by intraperitoneal administration of propranolol or saline. Rats that received propranolol following the preference test showed no preference for the cocaine-paired floor during a subsequent test, while vehicle-treated rats continued to express a preference for the cocaine-paired floor. These deficits in behavior were specific to retrieval of the cocaine-mediated memory, suggesting that postretrieval propranolol induced an impairment of drug-seeking behavior that is consistent with the disruption of a reconsolidation phase following retrieval.