The Open Source GAITOR Suite for Rodent Gait Analysis

Locomotive changes are often associated with disease or injury, and these changes can be quantified through gait analysis. Gait analysis has been applied to preclinical studies, providing quantitative behavioural assessment with a reasonable clinical analogue. However, available gait analysis technology for small animals is somewhat limited. Furthermore, technological and analytical challenges can limit the effectiveness of preclinical gait analysis. The Gait Analysis Instrumentation and Technology Optimized for Rodents (GAITOR) Suite is designed to increase the accessibility of preclinical gait analysis to researchers, facilitating hardware and software customization for broad applications. Here, the GAITOR Suite’s utility is demonstrated in 4 models: a monoiodoacetate (MIA) injection model of joint pain, a sciatic nerve injury model, an elbow joint contracture model, and a spinal cord injury model. The GAITOR Suite identified unique compensatory gait patterns in each model, demonstrating the software’s utility for detecting gait changes in rodent models of highly disparate injuries and diseases. Robust gait analysis may improve preclinical model selection, disease sequelae assessment, and evaluation of potential therapeutics

Cooperative learning in the first year of undergraduate medical education

<p>Abstract</p> <p>Background</p> <p>Despite extensive research data indicating that cooperative learning promotes higher achievement, the creation of positive relationships, and greater psychological health for students at all levels in their education, cooperative learning as a teaching strategy is still underutilized in undergraduate medical education.</p> <p>Methods</p> <p>A cooperative learning task was introduced as part of the mandatory first Year undergraduate Pathology course. The task was to create an 8.5" × 11" poster summary of pre-assigned content in self-chosen groups of four or five students. On the designated "Poster Day," the posters were displayed and evaluated by the students using a group product evaluation. Students also completed an individual group process reflection survey. An objective evaluation of their understanding was gauged at the midterm examination by specific content-related questions.</p> <p>Results</p> <p>Majority (91–96%) of students judged the group products to be relevant, effective, easy-to-understand, and clearly communicated. The majority of the students (90–100%) agreed that their group process skills of time management, task collaboration, decision-making and task execution were effective in completing this exercise. This activity created a dynamic learning environment as was reflected in the students' positive, professional discussion, and evaluation of their posters. The content-related questions on the midterm examination were answered correctly by 70–92% of the students. This was a mutually enriching experience for the instructor and students.</p> <p>Conclusion</p> <p>These findings demonstrate that cooperative learning as a teaching strategy can be effectively incorporated to address both content <it>and </it>interpersonal skill development in the early years of undergraduate medical education.</p

Persönlichkeitsentwicklung und Leistungsbereitschaft junger Arbeiter in Jugendbrigaden

Es werden zusammenfassende Auswertungen von empirischen Untersuchungen zu den Jugendbrigaden in der DDR gegeben. Behandelt werden Leistungsmotivation, Einstellung zum wissenschaftlich-technischen Fortschritt, Beteiligung und Einstellung zur MMM ("Messe der Meister von morgen"), FDJ-Aktivitäten, Freizeit sowie Probleme der Förderung und Bildung von Jugendbrigaden. Hintergrund der Untersuchungen war die Situation, daß es mit den geburtenschwachen Jahrgängen immer schwieriger wurde, Jugendbrigaden in dem gewünschten Ausmaß zu erhalten. Es wird kritisiert, daß Jugendbrigaden vielerorts "formalistischer Selbstzweck" geworden seien und sie daher ungeeignet seien, die Leistungsbereitschaft zu stimulieren oder politisches Verantwortungsgefühl zu fördern. (psz

The Pine River Statement: Human Health Consequences of DDT Use

Objectives: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction: We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDThttp://dx.doi.org/10.1289/ehp.1174

Multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI) in the evaluation of the mandibular invasion by squamous cell carcinomas (SCC) of the oral cavity. Correlation with pathological data

<p>Abstract</p> <p>Background</p> <p>To retrospectively compare the diagnostic accuracy of magnetic resonance imaging (MRI) and multidetector-row computed tomography (MDCT) in the assessment of the mandibular invasion by squamous cell carcinoma (SCC) having histopathological exams as standard of reference.</p> <p>Materials and methods</p> <p>Institutional review board approval with a waiver of informed patient consent was obtained. Of the 147 patients selected from our database who underwent surgical excision of a tumour arising into the oral cavity, thirty-six patients (26 men, 10 women; mean age, 56 years; range, 30-75 years) with hystologically proven SCC who performed both a preoperative MRI and MDCT, composed our final study population.</p> <p>Images were qualitatively analyzed in consensus by two expert radiologist in head and neck imaging. Sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were assessed for both MRI and MDCT.</p> <p>Differences in sensitivity, specificity, positive and negative predictive values were calculated at a statistical significance of p < .05.</p> <p>Results</p> <p>The sensitivity, the specificity and the accuracy of MRI and MDCT in the detection of the mandibular involvement were respectively 93%, 82%, 86% and 79%, 82%, 81%, while the positive predictive value (PPV) and negative predictive value (NPV) were respectively 76%, 95% and 73%, 86%. There wasn't any statistically significant difference in overall diagnostic accuracy between MRI and MDCT in the evaluation of mandibular tumour invasion (p > .05).</p> <p>Conclusion</p> <p>MRI showed to have a higher sensitivity compare to MDCT in the assessment of mandibular involvement from SCC arising in the oral cavity although none statistically significant differences were noted.</p

Accounting for Diffusion in Agent Based Models of Reaction-Diffusion Systems with Application to Cytoskeletal Diffusion

Diffusion plays a key role in many biochemical reaction systems seen in nature. Scenarios where diffusion behavior is critical can be seen in the cell and subcellular compartments where molecular crowding limits the interaction between particles. We investigate the application of a computational method for modeling the diffusion of molecules and macromolecules in three-dimensional solutions using agent based modeling. This method allows for realistic modeling of a system of particles with different properties such as size, diffusion coefficients, and affinity as well as the environment properties such as viscosity and geometry. Simulations using these movement probabilities yield behavior that mimics natural diffusion. Using this modeling framework, we simulate the effects of molecular crowding on effective diffusion and have validated the results of our model using Langevin dynamics simulations and note that they are in good agreement with previous experimental data. Furthermore, we investigate an extension of this framework where single discrete cells can contain multiple particles of varying size in an effort to highlight errors that can arise from discretization that lead to the unnatural behavior of particles undergoing diffusion. Subsequently, we explore various algorithms that differ in how they handle the movement of multiple particles per cell and suggest an algorithm that properly accommodates multiple particles of various sizes per cell that can replicate the natural behavior of these particles diffusing. Finally, we use the present modeling framework to investigate the effect of structural geometry on the directionality of diffusion in the cell cytoskeleton with the observation that parallel orientation in the structural geometry of actin filaments of filopodia and the branched structure of lamellipodia can give directionality to diffusion at the filopodia-lamellipodia interface

Are sedatives and hypnotics associated with increased suicide risk of suicide in the elderly?

<p>Abstract</p> <p>Background</p> <p>While antidepressant-induced suicidality is a concern in younger age groups, there is mounting evidence that these drugs may reduce suicidality in the elderly. Regarding a possible association between other types of psychoactive drugs and suicide, results are inconclusive. Sedatives and hypnotics are widely prescribed to elderly persons with symptoms of depression, anxiety, and sleep disturbance. The aim of this case-control study was to determine whether specific types of psychoactive drugs were associated with suicide risk in late life, after controlling for appropriate indications.</p> <p>Methods</p> <p>The study area included the city of Gothenburg and two adjacent counties (total 65+ population 210 703 at the start of the study). A case controlled study of elderly (65+) suicides was performed and close informants for 85 suicide cases (46 men, 39 women mean age 75 years) were interviewed by a psychiatrist. A population based comparison group (n = 153) was created and interviewed face-to-face. Primary care and psychiatric records were reviewed for both suicide cases and comparison subjects. All available information was used to determine past-month mental disorders in accordance with DSM-IV.</p> <p>Results</p> <p>Antidepressants, antipsychotics, sedatives and hypnotics were associated with increased suicide risk in the crude analysis. After adjustment for affective and anxiety disorders neither antidepressants in general nor SSRIs showed an association with suicide. Antipsychotics had no association with suicide after adjustment for psychotic disorders. Sedative treatment was associated with an almost fourteen-fold increase of suicide risk in the crude analyses and remained an independent risk factor for suicide even after adjustment for any DSM-IV disorder. Having a current prescription for a hypnotic was associated with a four-fold increase in suicide risk in the adjusted model.</p> <p>Conclusion</p> <p>Sedatives and hypnotics were both associated with increased risk for suicide after adjustment for appropriate indications. Given the extremely high prescription rates, a careful evaluation of the suicide risk should always precede prescribing a sedative or hypnotic to an elderly individual.</p

Diversity of Protein and mRNA Forms of Mammalian Methionine Sulfoxide Reductase B1 Due to Intronization and Protein Processing

Background: Methionine sulfoxide reductases (Msrs) are repair enzymes that protect proteins from oxidative stress by catalyzing stereospecific reduction of oxidized methionine residues. MsrB1 is a selenocysteine-containing cytosolic/nuclear Msr with high expression in liver and kidney. Principal Findings: Here, we identified differences in MsrB1 gene structure among mammals. Human MsrB1 gene consists of four, whereas the corresponding mouse gene of five exons, due to occurrence of an additional intron that flanks the stop signal and covers a large part of the 3′-UTR. This intron evolved in a subset of rodents through intronization of exonic sequences, whereas the human gene structure represents the ancestral form. In mice, both splice forms were detected in liver, kidney, brain and heart with the five-exon form being the major form. We found that both mRNA forms were translated and supported efficient selenocysteine insertion into MsrB1. In addition, MsrB1 occurs in two protein forms that migrate as 14 and 5 kDa proteins. We found that each mRNA splice form generated both protein forms. The abundance of the 5 kDa form was not influenced by protease inhibitors, replacement of selenocysteine in the active site or mutation of amino acids in the cleavage site. However, mutation of cysteines that coordinate a structural zinc decreased the levels of 5 and 14 kDa forms, suggesting importance of protein structure for biosynthesis and/stability of these forms. Conclusions: This study characterized unexpected diversity of protein and mRNA forms of mammalian selenoprotein MsrB1