Periodicity of high-order functions in the CNS Final progress report, year ending 30 Jun. 1971

Analysis of cerebral slow potentials underlying human attentive processes in central nervous syste

Periodicity of high-order neural functions

The results of recent studies on higher order, integrative processes in the central nervous system are reported. Attempts were made to determine whether these processes exhibit any ongoing rhythmicity which might manifest itself in alterations of attention and alertness. Experiments were also designed to determine if a periodicity approximating that of the REM could be detected in various parameters of brain electrical activity

Development of ibuprofen-loaded electrospun materials suitable for surgical implantation in peripheral nerve injury

The development of nerve wraps for use in the repair of peripheral nerves has shown promise over recent years. A pharmacological effect to improve regeneration may be achieved by loading such materials with therapeutic agents, for example ibuprofen, a non-steroidal anti-inflammatory drug with neuroregenerative properties. In this study, four commercially available polymers (polylactic acid (PLA), polycaprolactone (PCL) and two co-polymers containing different ratios of PLA to PCL) were used to fabricate ibuprofen-loaded nerve wraps using blend electrospinning. In vitro surgical handling experiments identified a formulation containing a PLA/PCL 70/30 molar ratio co-polymer as the most suitable for in vivo implantation. In a rat model, ibuprofen released from electrospun materials significantly improved the rate of axonal growth and sensory recovery over a 21-day recovery period following a sciatic nerve crush. Furthermore, RT-qPCR analysis of nerve segments revealed that the anti-inflammatory and neurotrophic effects of ibuprofen may still be observed 21 days after implantation. This suggests that the formulation developed in this work could have potential to improve nerve regeneration in vivo

From sleep spindles of natural sleep to spike and wave discharges of typical absence seizures: is the hypothesis still valid?

The temporal coincidence of sleep spindles and spike-and-wave discharges (SWDs) in patients with idiopathic generalized epilepsies, together with the transformation of spindles into SWDs following intramuscular injection of the weak GABAA receptor (GABAAR) antagonist, penicillin, in an experimental model, brought about the view that SWDs may represent ‘perverted’ sleep spindles. Over the last 20 years, this hypothesis has received considerable support, in particular by in vitro studies of thalamic oscillations following pharmacological/genetic manipulations of GABAARs. However, from a critical appraisal of the evidence in absence epilepsy patients and well-established models of absence epilepsy it emerges that SWDs can occur as frequently during wakefulness as during sleep, with their preferential occurrence in either one of these behavioural states often being patient dependent. Moreover, whereas the EEG expression of both SWDs and sleep spindles requires the integrity of the entire cortico-thalamo-cortical network, SWDs initiates in cortex while sleep spindles in thalamus. Furthermore, the hypothesis of a reduction in GABAAR function across the entire cortico-thalamo-cortical network as the basis for the transformation of sleep spindles into SWDs is no longer tenable. In fact, while a decreased GABAAR function may be present in some cortical layers and in the reticular thalamic nucleus, both phasic and tonic GABAAR inhibitions of thalamo-cortical neurons are either unchanged or increased in this epileptic phenotype. In summary, these differences between SWDs and sleep spindles question the view that the EEG hallmark of absence seizures results from a transformation of this EEG oscillation of natural sleep

Management Ideologies and Organizational Spirituality: a Typology

The topic of spirituality is gaining an increasing visibility in organization studies. It is our contention that every theory of organization is a theory of organizational spirituality. Based on Barley and Kunda’s 1992 Administrative Science Quarterly article, we discuss the evolution of management theories as spirituality theories. From such analysis, we suggest that there may be both a meaningful/liberating and an instrumental/exploitative side in the relationship between organizations and spirituality. Such a possibility is illustrated with a typology that advances four possible types of organizations regarding spirituality: the soulful organization, the holistic organization, the ascetic organization, and the professional organization. The expression of spirituality in each of these forms is discussed with the aim of contributing to a theoretically-based analysis of organizational spirituality.N/

Powers of Romance: The Liminal Challenges of Managing Organizational Intimacy

© The Author(s) 2014 Problematic organizational relationships have recently been at the core of highly visible media coverage. Most analyses of sexual relations in organizations have been, however, simplistic and unidimensional, and have placed insufficient systematic emphasis on the role of governmentality in the social construction of organizational romance. In this article, we proceed in two theoretical steps. First, we elaborate a typology of organizational romance that covers different manifestations of this nuanced process. We think of these as organizational strategies of governmentality. Second, we elaborate and identify liminal cases that fall into the interstices of the four predominant ways of managing sexual relationships in organizations. We think of these as vases of liquid love and life that evade the border controls of regulation by governmentality. Finally, we relate these issues to debates about the nature of the civilizational process and suggest hypotheses for future research

TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis

BACKGROUND: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. METHODS: We generated neuron-specific TNF-deficient (NsTNF / ) mice and compared outcomes of disease against TNF f/f control and global TNF / mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracerebral M. tuberculosis infection of TNF / mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF / mice were resistant to infection and presented with a phenotype similar to that in TNF f/f control mice. Impaired immunity in TNF / mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. CONCLUSION: Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population