Injury-Dependent and Disability-Specific Lumbar Spinal Gene Regulation following Sciatic Nerve Injury in the Rat

Allodynia, hyperalgesia and spontaneous pain are cardinal sensory signs of neuropathic pain. Clinically, many neuropathic pain patients experience affective-motivational state changes, including reduced familial and social interactions, decreased motivation, anhedonia and depression which are severely debilitating. In earlier studies we have shown that sciatic nerve chronic constriction injury (CCI) disrupts social interactions, sleep-wake-cycle and endocrine function in one third of rats, a subgroup reliably identified six days after injury. CCI consistently produces allodynia and hyperalgesia, the intensity of which was unrelated either to the altered social interactions, sleep-wake-cycle or endocrine changes. This decoupling of the sensory consequences of nerve injury from the affective-motivational changes is reported in both animal experiments and human clinical data. The sensory changes triggered by CCI are mediated primarily by functional changes in the lumbar dorsal horn, however, whether lumbar spinal changes may drive different affective-motivational states has never been considered. In these studies, we used microarrays to identify the unique transcriptomes of rats with altered social behaviours following sciatic CCI to determine whether specific patterns of lumbar spinal adaptations characterised this subgroup. Rats underwent CCI and on the basis of reductions in dominance behaviour in resident-intruder social interactions were categorised as having Pain & Disability, Pain & Transient Disability or Pain alone.We examined the lumbar spinal transcriptomes two and six days after CCI. Fifty-four ‘disability-specific’ genes were identified. Sixty-five percent were unique to Pain & Disability rats, two-thirds of which were associated with neurotransmission, inflammation and/or cellular stress. In contrast, 40% of genes differentially regulated in rats without disabilities were involved with more general homeostatic processes (cellular structure, transcription or translation). We suggest that these patterns of gene expression lead to either the expression of disability, or to resilience and recovery, by modifying local spinal circuitry at the origin of ascending supraspinal pathways

Enhanced expression of PACAP and of its high affinity receptor (PAC1) in the hippocampus and cerebral cortex of dopamine D3 knockout mice

Dopamine (DA) D3 receptor (D3R) is a pre-synaptic autoreceptor whose main role is to modulate DA release through a negative feedback regulatory loop. Immunolocalization studies from our research group have previously described that these receptors, despite being relatively low expressed in the central nervous system (CNS), may still be detected in less discreet brain regions normally associated to memory function, including the hippocampus and the cerebral cortex (1). Consistent with these findings, genetic deletion of the D3R in mice (D3R-/-) has been shown to have profound repercussions on the formation of new memories, especially fear associative memories (2). While it is now well-accepted that such pro-cognitive effects in these mice are presumably due to the increased DA bioavailability caused by the lack of autoreceptor function, it still remains to be established if there are molecular determinants directly or indirectly involved in ameliorating this specific type of associative learning. Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous peptide which is gaining scientific relevance because of its prominent “cognitive enhancer” function and the recent developments suggesting its active participation in the acquisition and consolidation of fear memories (3, 4). Based on these evidences, we thought it could have been of scientific relevance to assess whether PACAP expression, as well as that of its binding receptors, are affected in knockout mice showing this peculiar behavioural phenotype. We found that PACAP immunoreactivity (IR) was present at low levels in CA1 hippocampal subfield while moderate staining was observed in CA2-CA3 fields and in the dentate gyrus (DG) of wild-type (WT) mice. In sharp contrast, PACAP-IR was remarkably increased in all CA subfields, and particularly in CA1, CA3 and the DG regions of D3R-/- mice. Regarding the cerebral cortex (CX), PACAP expression was restricted to the V cortical layer in WT mice, whereas in D3R-/- mice, stained neurons were apparent both in the IV, V and VI cortical layers, with an overall increased staining score. In line with these findings, the expression of the PACAP-preferring PAC1 receptor, which was detectable only at moderate levels in the CA2 subfield of WTs, was enhanced in both CA2 and CA3 of D3R-/- mice. Interestingly, PAC1-IR was already present at moderate levels in the II-III cortical layers of WT mice, but genetic deletion of the D3R caused a remarkable spread of PAC1-stained neurons throughout all cortical layers, with the exception of layer I. We conclude that the absence or blockade of functional D3Rs from the brain enhances both PACAP and PAC1 receptor expression levels in the hippocampus and cerebral cortex. Considering the ameliorative role mediated by PACAP-PAC1 signalling in cognition, we infer that enhanced PACAP peptide and receptor expression may relate to the specific behavioural phenotype of these mice

An International Partnership of 12 Anatomy Departments - Improving Global Health through Internationalization of Medical Education

Background: At a time of global interconnectedness, the internationalization of medical education has become important. Anatomy as an academic discipline, with its close connections to the basic sciences and to medical education, can easily be connected with global health and internationalization of medical education. Here the authors present an international program based on a partnership between twelve anatomy departments in ten countries, on four continents. Details of a proposed plan for the future direction of the program are also discussed. Objective: The aim is to improve global healthcare by preparing future global healthcare leaders via early international networking, international collaboration and exchange, intercultural experience, and connecting two seemingly distant academic disciplines - anatomy and global health - via internationalization of medical education. Methods: Based in the anatomy course, the program involved early international collaboration between preclinical medical and dental students. The program provided a stepwise progression for learning about healthcare and intercultural topics beyond pure anatomy education - starting with virtual small groups of international students, who subsequently presented their work to a larger international audience during group videoconferences. The above progressed to in-person visits for research internships in the basic sciences within industrialized countries. Findings: Students appreciated the international and intercultural interaction, learned about areas outside the scope of anatomy (e.g., differences in healthcare education and delivery systems, Public and Global Health challenges, health ethics, and cultural enrichment), and valued the exchange travel for basic sciences research internships and cultural experience. Conclusions: This unique collaboration of international anatomy departments can represent a new role for the medical anatomy course beyond pure anatomy teaching - involving areas of global health and internationalization of medical education - and could mark a new era of international collaboration among anatomists.Peer reviewe

Alternatives to Student Outbound Mobility-Improving Students' Cultural Competency Skills Online to Improve Global Health Without Travel.

INTRODUCTION: Student outbound mobility is a major element in internationalization of medical education and global health education. However, this approach is often criticized, as it is inherently inequitable. Internationalization at home is a newer concept that aims to provide students with international skills and experiences without exchange travel. We report detailed outcomes of an international online program during the COVID-19 pandemic, which aimed to include acquisition of cultural awareness and competency-similar to what the students would have obtained if they had travelled abroad. METHOD: Sixty-eight students from 12 international universities participated in international small peer group collaborative work, and online networking. Perceived improvement of cultural competency using Likert scale and open-ended questions was used as a measure of success. Furthermore, students' definition of cultural competency in the different countries was obtained. RESULTS: Students improved their cultural competency skills. Data analysis supported statistically significant improvement of the above skills after the program, in comparison to the start of the program. DISCUSSION: Internationalization of medical education can be achieved at home-via structured online peer exchanges-and can provide students with intercultural skills and networking opportunities that are typically achieved via international in-person travel. The above represents a socially just and equitable way to reach all students and can result in improvement of their cultural competency, preparing them for their work in global health, and thereby resulting in improvement of global health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01332-9

Dramatic interannual changes of perennial Arctic sea ice linked to abnormal summer storm activity

Copyright © 2011 American Geophysical UnionThe perennial (September) Arctic sea ice cover exhibits large interannual variability, with changes of over a million square kilometers from one year to the next. Here we explore the role of changes in Arctic cyclone activity, and related factors, in driving these pronounced year-to-year changes in perennial sea ice cover. Strong relationships are revealed between the September sea ice changes and the number of cyclones in the preceding late spring and early summer. In particular, fewer cyclones over the central Arctic Ocean during the months of May, June, and July appear to favor a low sea ice area at the end of the melt season. Years with large losses of sea ice are characterized by abnormal cyclone distributions and tracks: they lack the normal maximum in cyclone activity over the central Arctic Ocean, and cyclones that track from Eurasia into the central Arctic are largely absent. Fewer storms are associated with above-average mean sea level pressure, strengthened anticyclonic winds, an intensification of the transpolar drift stream, and reduced cloud cover, all of which favor ice melt. It is also shown that a strengthening of the central Arctic cyclone maximum helps preserve the ice cover, although the association is weaker than that between low cyclone activity and reduced sea ice. The results suggest that changes in cyclone occurrence during late spring and early summer have preconditioning effects on the sea ice cover and exert a strong influence on the amount of sea ice that survives the melt season

Are greenhouse gas signals of Northern Hemisphere winter extra-tropical cyclone activity dependent on the identification and tracking algorithm?

For Northern Hemisphere extra-tropical cyclone activity, the dependency of a potential anthropogenic climate change signal on the identification method applied is analysed. This study investigates the impact of the used algorithm on the changing signal, not the robustness of the climate change signal itself. Using one single transient AOGCM simulation as standard input for eleven state-of-the-art identification methods, the patterns of model simulated present day climatologies are found to be close to those computed from re-analysis, independent of the method applied. Although differences in the total number of cyclones identified exist, the climate change signals (IPCC SRES A1B) in the model run considered are largely similar between methods for all cyclones. Taking into account all tracks, decreasing numbers are found in the Mediterranean, the Arctic in the Barents and Greenland Seas, the mid-latitude Pacific and North America. Changing patterns are even more similar, if only the most severe systems are considered: the methods reveal a coherent statistically significant increase in frequency over the eastern North Atlantic and North Pacific. We found that the differences between the methods considered are largely due to the different role of weaker systems in the specific methods

IMILAST: a community effort to intercompare extratropical cyclone detection and tracking algorithms

The variability of results from different automated methods of detection and tracking of extratropical cyclones is assessed in order to identify uncertainties related to the choice of method. Fifteen international teams applied their own algorithms to the same dataset—the period 1989–2009 of interim European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERAInterim) data. This experiment is part of the community project Intercomparison of Mid Latitude Storm Diagnostics (IMILAST; see www.proclim.ch/imilast/index.html). The spread of results for cyclone frequency, intensity, life cycle, and track location is presented to illustrate the impact of using different methods. Globally, methods agree well for geographical distribution in large oceanic regions, interannual variability of cyclone numbers, geographical patterns of strong trends, and distribution shape for many life cycle characteristics. In contrast, the largest disparities exist for the total numbers of cyclones, the detection of weak cyclones, and distribution in some densely populated regions. Consistency between methods is better for strong cyclones than for shallow ones. Two case studies of relatively large, intense cyclones reveal that the identification of the most intense part of the life cycle of these events is robust between methods, but considerable differences exist during the development and the dissolution phases

Corporate Governance for Sustainability

The current model of corporate governance needs reform. There is mounting evidence that the practices of shareholder primacy drive company directors and executives to adopt the same short time horizon as financial markets. Pressure to meet the demands of the financial markets drives stock buybacks, excessive dividends and a failure to invest in productive capabilities. The result is a ‘tragedy of the horizon’, with corporations and their shareholders failing to consider environmental, social or even their own, long-term, economic sustainability. With less than a decade left to address the threat of climate change, and with consensus emerging that businesses need to be held accountable for their contribution, it is time to act and reform corporate governance in the EU. The statement puts forward specific recommendations to clarify the obligations of company boards and directors and make corporate governance practice significantly more sustainable and focused on the long term