A New Minimal-Stress Freely-Moving Rat Model for Preclinical Studies on Intranasal Administration of CNS Drugs

Purpose. To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. Methods. Male Wistar rats received one intranasal cannula, an intra-cerebral microdialysis probe, and two blood cannulas for drug administration and serial blood sampling respectively. To evaluate this novel model, the following experiments were conducted. 1) Evans Blue was administered to verify the selectivity of intranasal exposure. 2) During a 1 min infusion 10, 20, or 40 μl saline was administered intranasally or 250 µl intravenously. Corticosterone plasma concentrations over time were compared as biomarkers for stress. 3) 200 µg of the model drug acetaminophen was given in identical setup and plasma, and brain pharmacokinetics were determined. Results. In 96 % of the rats, only the targeted nasal cavity was deeply colored. Corticosterone plasma concentrations were not influenced, neither by route nor volume of administration. Pharmacokinetics of acetaminophen were identical after intravenous and intranasal administration, although the Cmax in microdialysates was reached a little earlier following intravenous administration. Conclusion. A new minimal-stress model for intranasal administration in freely moving rats has been successfully developed and allows direct comparison with intravenous administration. KEY WORDS: acetaminophen; brain; intranasal infusion; microdialysis; pharmacokinetics

Life satisfaction and resilience in medical school – a six-year longitudinal, nationwide and comparative study

BACKGROUND: This study examined the relationship between life satisfaction among medical students and a basic model of personality, stress and coping. Previous studies have shown relatively high levels of distress, such as symptoms of depression and suicidal thoughts in medical undergraduates. However despite the increased focus on positive psychological health and well-being during the past decades, only a few studies have focused on life satisfaction and coping in medical students. This is the first longitudinal study which has identified predictors of sustained high levels of life satisfaction among medical students. METHODS: This longitudinal, nationwide questionnaire study examined the course of life satisfaction during medical school, compared the level of satisfaction of medical students with that of other university students, and identified resilience factors. T-tests were used to compare means of life satisfaction between and within the population groups. K-means cluster analyses were applied to identify subgroups among the medical students. Analysis of Variance (ANOVA) and logistic regression analyses were used to compare the subgroups. RESULTS: Life satisfaction decreased during medical school. Medical students were as satisfied as other students in the first year of study, but reported less satisfaction in their graduation year. Medical students who sustained high levels of life satisfaction perceived medical school as interfering less with their social and personal life, and were less likely to use emotion focused coping, such as wishful thinking, than their peers. CONCLUSION: Medical schools should encourage students to spend adequate time on their social and personal lives and emphasise the importance of health-promoting coping strategies

Beneficial effects of reading aloud and solving simple arithmetic calculations (learning therapy) on a wide range of cognitive functions in the healthy elderly: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Almost all cognitive functions decline with age. Results of previous studies have shown that cognitive training related to everyday life (reading aloud and solving simple arithmetic calculations), namely learning therapy, can improve two cognitive function (executive functions and processing speed) in elderly people. However, it remains unclear whether learning therapy engenders improvement of various cognitive functions or not. We investigate the impact of learning therapy on various cognitive functions (executive functions, episodic memory, short-term memory, working memory, attention, reading ability, and processing speed) in healthy older adults.</p> <p>Methods</p> <p>We use a single-blinded intervention with two parallel groups (a learning therapy group and a waiting list control group). Testers are blind to the study hypothesis and the group membership of participants. Through an advertisement in local newspaper, 64 healthy older adults are recruited. They will be assigned randomly to a learning therapy group or a waiting list control group. In the learning therapy group, participants are required to perform two cognitive tasks for 6 months: reading Japanese aloud and solving simple calculations. The waiting list group does not participate in the intervention. The primary outcome measure is the Stroop test score: a measure of executive function. Secondary outcome measures are assessments including the following: verbal fluency task, logical memory, first and second names, digit span forward, digit span backward, Japanese reading test, digit cancellation task, digit symbol coding, and symbol search. We assess these outcome measures before and after the intervention.</p> <p>Discussion</p> <p>This report is the first study which investigates the beneficial effects of learning therapy on a wide range of cognitive functions of elderly people. Our study provides sufficient evidence of learning therapy effectiveness. Most cognitive functions, which are correlated strongly with daily life activities, decrease with age. These study results can elucidate effects of cognitive training on elderly people.</p> <p>Trial registration</p> <p>This trial was registered in The University Hospital Medical Information Network Clinical Trials Registry (No. <a href="http://www.clinicaltrials.gov/ct2/show/UMIN000006998">UMIN000006998</a>).</p

The scale, governance, and sustainability of central places in pre-Hispanic Mesoamerica

Examinations of the variation and relative successes or failures of past large-scale societies have long involved attempts to reconcile efforts at generalization and the identification of specific factors with explanatory value for regional trajectories. Although historical particulars are critical to understanding individual cases, there are both scholarly and policy rationales for drawing broader implications regarding the growing corpus of cross-cultural data germane to understanding variability in the constitution of human societies, past and present. Archaeologists have recently highlighted how successes and failures in communal-resource management can be studied over the long term through the material record to both engage and enhance transdisciplinary research on cooperation and collective action. In this article we consider frameworks that have been traditionally employed in studies of the rise, diversity, and fall of preindustrial urban aggregations. We suggest that a comparative theoretical perspective that foregrounds collective-action problems, unaligned individual and group interests, and the social mechanisms that promote or hamper cooperation advances our understanding of variability in these early cooperative arrangements. We apply such a perspective to an examination of pre-Hispanic Mesoamerican urban centers to demonstrate tendencies for more collective systems to be larger and longer lasting than less collective ones, likely reflecting greater sustainability in the face of the ecological and cultural perturbations specific to the region and era.Accepted manuscrip

The interstitium in cardiac repair: role of the immune-stromal cell interplay

Cardiac regeneration, that is, restoration of the original structure and function in a damaged heart, differs from tissue repair, in which collagen deposition and scar formation often lead to functional impairment. In both scenarios, the early-onset inflammatory response is essential to clear damaged cardiac cells and initiate organ repair, but the quality and extent of the immune response vary. Immune cells embedded in the damaged heart tissue sense and modulate inflammation through a dynamic interplay with stromal cells in the cardiac interstitium, which either leads to recapitulation of cardiac morphology by rebuilding functional scaffolds to support muscle regrowth in regenerative organisms or fails to resolve the inflammatory response and produces fibrotic scar tissue in adult mammals. Current investigation into the mechanistic basis of homeostasis and restoration of cardiac function has increasingly shifted focus away from stem cell-mediated cardiac repair towards a dynamic interplay of cells composing the less-studied interstitial compartment of the heart, offering unexpected insights into the immunoregulatory functions of cardiac interstitial components and the complex network of cell interactions that must be considered for clinical intervention in heart diseases