ATF3 upregulation in glia during Wallerian degeneration: differential expression in peripheral nerves and CNS white matter

Background: Many changes in gene expression occur in distal stumps of injured nerves but the transcriptional control of these events is poorly understood. We have examined the expression of the transcription factors ATF3 and c-Jun by non-neuronal cells during Wallerian degeneration following injury to sciatic nerves, dorsal roots and optic nerves of rats and mice, using immunohistochemistry and in situ hybridization.Results: Following sciatic nerve injury-transection or transection and reanastomosis-ATF3 was strongly upregulated by endoneurial, but not perineurial cells, of the distal stumps of the nerves by 1 day post operation (dpo) and remained strongly expressed in the endoneurium at 30 dpo when axonal regeneration was prevented. Most ATF3+ cells were immunoreactive for the Schwann cell marker, S100. When the nerve was transected and reanastomosed, allowing regeneration of axons, most ATF3 expression had been downregulated by 30 dpo. ATF3 expression was weaker in the proximal stumps of the injured nerves than in the distal stumps and present in fewer cells at all times after injury. ATF3 was upregulated by endoneurial cells in the distal stumps of injured neonatal rat sciatic nerves, but more weakly than in adult animals. ATF3 expression in transected sciatic nerves of mice was similar to that in rats. Following dorsal root injury in adult rats, ATF3 was upregulated in the part of the root between the lesion and the spinal cord (containing Schwann cells), beginning at 1 dpo, but not in the dorsal root entry zone or in the degenerating dorsal column of the spinal cord. Following optic nerve crush in adult rats, ATF3 was found in some cells at the injury site and small numbers of cells within the optic nerve displayed weak immunoreactivity. The pattern of expression of c-Jun in all types of nerve injury was similar to that of ATF3.Conclusion: These findings raise the possibility that ATF3/c-Jun heterodimers may play a role in regulating changes in gene expression necessary for preparing the distal segments of injured peripheral nerves for axonal regeneration. The absence of the ATF3 and c-Jun from CNS glia during Wallerian degeneration may limit their ability to support regeneration

Visual representation of National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network criteria for anaphylaxis

We present a user-friendly visual representation of The National Institute of Allergy and Infectious Disease and the Food Allergy and Anaphylaxis Network criteria so as to enhance recognition of anaphylaxis and active teaching and learning

The Atmospheric Coupling and Dynamics Across the Mesopause (ACaDAMe) mission

The Atmospheric Coupling and Dynamics Across the Mesopause (ACaDAMe) is a mission designed to uniquely address critical questions involving multi-scale wave dynamics at key space weather (SWx) “gateway altitudes” of the mesosphere and lower thermosphere (MLT) at ∼70–150 km. ACaDAMe observes with a nadir-pointing resonant lidar that utilizes the fluorescence of atomic Na present in the MLT. By tuning a laser to the Na absorption wavelength (589 nm), ACaDAMe would perform very high resolution measurements of temperature and Na densities across the mesopause during both day and night. In this manner, Na is used as tracer for observing and characterizing MLT waves generated by tropospheric weather that represent the dominant terrestrial source of energy and momentum affecting space weather and transport of mesospheric species

Distinguishing Family from Friends

Kinship and friendship are key human relationships. Increasingly, data suggest that people are not less altruistic toward friends than close kin. Some accounts suggest that psychologically we do not distinguish between them; countering this is evidence that kinship provides a unique explanatory factor. Using the Implicit Association Test, we examined how people implicitly think about close friends versus close kin in three contexts. In Experiment 1, we examined generic attitudinal dispositions toward friends and family. In Experiment 2, attitude similarity as a marker of family and friends was examined, and in Experiments 3 and 4, strength of in-group membership for family and friends was examined. Findings show that differences exist in implicit cognitive associations toward family and friends. There is some evidence that people hold more positive general dispositions toward friends, associate attitude similarity more with friends, consider family as more representative of the in-group than friends, but see friends as more in-group than distant kin

REST4Mobile: A framework for enhanced usability of REST services on smartphones

Considering end-user research and proliferation of smartphones and REpresentational State Transfer (REST) interfaces, we envisage that smartphone owners can innovate to compose applications on the small screen. This paper presents the design and evaluation of a REST service development framework (viz, REST4Mobile) with the aim to enhance the usability when consuming on smartphones. Our design process uses the usability factors identified in our previous work as primary constraints for modeling the framework and a corresponding composition tool. Thus, sample REST services are developed with and then without the framework, and usability of composing the services on smartphones is evaluated. Evaluation was conducted by deploying the component REST services, the composition tool, and the resulting composite apps on a local machine. As the task of service composition is conducted directly on the smartphone's screen, the evaluation process is designed to be repeatable on remote servers and on the cloud. Results showed that constraints can be added into the REST architectural style on the basis of the influences of domain specific terms and human cognitive capabilities on the naming and size of the Uniform Resource Identifiers (URIs). In addition, the principles embodying the framework are found to be influential factors in enhancing the usability of REST services on smartphones

Pharmacotherapy of Schizophrenic Patients: Preponderance of Off-Label Drug Use

Multiple drug class combinations are often prescribed for the treatment of schizophrenia, although antipsychotic monotherapy reflects FDA labeling and scientific justification for combinations is highly variable. This study was performed to gain current data regarding drug treatment of schizophrenia as practiced in the community and to assess the frequencies of off-label drug class combinations. 200 DSM IV-diagnosed schizophrenic patients recruited from community treatment sources participated in this cross-sectional study of community based schizophrenic patients. Drug class categories include First and Second Generation Antipsychotic drugs (FGA and SGA, respectively), mood stabilizers, antidepressants and anti-anxiety drugs. 25.5% of patients received antipsychotic monotherapy; 70% of patients received an antipsychotic and another drug class. A total of 42.5% of patients received more than one antipsychotic drug. The most common drug class combination was antipsychotic and a mood stabilizer. Stepwise linear discriminant function analysis identified the diagnosis of schizoaffective schizophrenia, history of having physically hurt someone and high scores on the General Portion of the PANSS rating scale predicted the combined use of an antipsychotic drug and a mood stabilizer. “Real world” pharmacotherapy of schizophrenia has developed its own established practice that is predominantly off-label and may have outstripped current data support. The economic implications for public sector payers are substantial as well as for the revenue of the pharmaceutical industry, whose promotion of off-label drug use is an increasingly problematic. These data are consistent with the recognition of the therapeutic limitations of both first and second generation antipsychotic drugs

Are Canadian General Internal Medicine training program graduates well prepared for their future careers?

BACKGROUND: At a time of increased need and demand for general internists in Canada, the attractiveness of generalist careers (including general internal medicine, GIM) has been falling as evidenced by the low number of residents choosing this specialty. One hypothesis for the lack of interest in a generalist career is lack of comfort with the skills needed to practice after training, and the mismatch between the tertiary care, inpatient training environment and "real life". This project was designed to determine perceived effectiveness of training for 10 years of graduates of Canadian GIM programs to assist in the development of curriculum and objectives for general internists that will meet the needs of graduates and ultimately society. METHODS: Mailed survey designed to explore perceived importance of training for and preparation for various aspects of Canadian GIM practice. After extensive piloting of the survey, including a pilot survey of two universities to improve the questionnaire, all graduates of the 16 universities over the previous ten years were surveyed. RESULTS: Gaps (difference between importance and preparation) were demonstrated in many of the CanMEDS 2000/2005(® )competencies. Medical problems of pregnancy, perioperative care, pain management, chronic care, ambulatory care and community GIM rotations were the medical expert areas with the largest gaps. Exposure to procedural skills was perceived to be lacking. Some procedural skills valued as important for current GIM trainees and performed frequently (example ambulatory ECG interpretation) had low preparation ratings by trainees. Other areas of perceived discrepancy between training and practice included: manager role (set up of an office), health advocate (counseling for prevention, for example smoking cessation), and professional (end of life issues, ethics). CONCLUSION: Graduates of Canadian GIM training programs over the last ten years have identified perceived gaps between training and important areas for practice. They have identified competencies that should be emphasized in Canadian GIM programs. Ongoing review of graduate's perceptions of training programs as it applies to their current practice is important to ensure ongoing appropriateness of training programs. This information will be used to strengthen GIM training programs in Canada

Comparative Analysis of DNA Replication Timing Reveals Conserved Large-Scale Chromosomal Architecture

Recent evidence suggests that the timing of DNA replication is coordinated across megabase-scale domains in metazoan genomes, yet the importance of this aspect of genome organization is unclear. Here we show that replication timing is remarkably conserved between human and mouse, uncovering large regions that may have been governed by similar replication dynamics since these species have diverged. This conservation is both tissue-specific and independent of the genomic G+C content conservation. Moreover, we show that time of replication is globally conserved despite numerous large-scale genome rearrangements. We systematically identify rearrangement fusion points and demonstrate that replication time can be locally diverged at these loci. Conversely, rearrangements are shown to be correlated with early replication and physical chromosomal proximity. These results suggest that large chromosomal domains of coordinated replication are shuffled by evolution while conserving the large-scale nuclear architecture of the genome

Physical activity and risk of colon adenoma: A meta-analysis

BACKGROUND: Little evidence is available on the relation of physical activity with colon adenomas, a colon cancer precursor. METHODS: We conducted a systematic literature review and meta-analysis of published studies (in English) through April 2010, examining physical activity or exercise and risk or prevalence of colon adenoma or polyp. Random effects models were used to estimate relative risks (RRs) and corresponding confidence intervals (CIs). A total of 20 studies were identified that examined the association and provided RRs and corresponding 95% CIs. RESULTS: A significant inverse association between physical activity and colon adenomas was found with an overall RR of 0.84 (CI: 0.77–0.92). The association was similar in men (RR=0.81, CI: 0.67–0.98) and women (RR=0.87, CI: 0.74–1.02). The association appeared slightly stronger in large/advanced polyps (RR=0.70, CI: 0.56–0.88). CONCLUSION: This study confirms previous reports of a significant inverse association of physical activity and colon adenoma, and suggests that physical activity can have an important role in colon cancer prevention

Clinical and economic ramifications of switching antipsychotics in the treatment of schizophrenia

<p>Abstract</p> <p>Background</p> <p>Switching between antipsychotic medications is common in the treatment of schizophrenia. However, data on clinical and economic outcomes from antipsychotic switching, in particular acute care service use, is fairly limited. The goal of this research was to assess the clinical and economic ramifications of switching antipsychotics during outpatient management of schizophrenia.</p> <p>Methods</p> <p>Data from a 1-year randomized, open-label cost-effectiveness study involving typical and atypical antipsychotics were assessed. The study protocol permitted switching of antipsychotics when clinically warranted. The risk of crisis-related events, use of acute-care services, and the time to the initial use of such services were determined in outpatients who switched antipsychotics compared with those who continued with their initial medications. Health care resource utilization data were abstracted from medical records and other sources (e.g., patient self-report), and direct costs were estimated using previously published benchmarks.</p> <p>Results</p> <p>Almost one-third of patients (29.3%) underwent a switch from their initial antipsychotic agent, with an average duration of 100 days before such treatment alterations. Compared with their counterparts who remained on their initial therapies, individuals who switched antipsychotics experienced a significantly higher risk of acute-care services, including hospitalization (p = .013) and crisis services (p = .011). Patients undergoing medication switches also used acute-care services significantly sooner (p = .004) and accrued an additional $3,000 (a 25% increase) in annual total health care costs per patient, most of which was due to acute-care expenditures.</p> <p>Conclusion</p> <p>Switching antipsychotic medications was found to be associated with considerably poorer clinical and economic outcomes, as reflected by, more frequent and more rapid use of acute-care services compared with persons remaining on their initial treatments.</p> <p>Trial Registration</p> <p>Trial ID 2325 in LillyTrials.com (also accessible via ClinicalStudyResults.org).</p