Numerous treatment strategies for spinal cord injury seek to maximize recovery of function and two strategies that show substantial promise are olfactory bulb-derived olfactory ensheathing glia (OEG) transplantation and treadmill step training. In this study we re-examined the issue of the effectiveness of OEG implantation but used objective, quantitative measures of motor performance to test if there is a complementary effect of long-term step training and olfactory bulb-derived OEG implantation. We studied complete mid-thoracic spinal cord transected adult female rats and compared four experimental groups: media-untrained, media-trained, OEG-untrained and OEG-trained. To assess the extent of hindlimb locomotor recovery at 4 and 7 months post-transection we used three quantitative measures of stepping ability: plantar stepping performance until failure, joint movement shape and movement frequency compared to sham controls. OEG transplantation alone significantly increased the number of plantar steps performed at 7 months post-transection, while training alone had no effect at either time point. Only OEG-injected rats plantar placed their hindpaws for more than two steps by the 7-month endpoint of the study. OEG transplantation combined with training resulted in the highest percentage of spinal rats per group that plantar stepped, and was the only group to significantly improve its stepping abilities between the 4- and 7-month evaluations. Additionally, OEG transplantation promoted tissue sparing at the transection site, regeneration of noradrenergic axons and serotonergic axons spanning the injury site. Interestingly, the caudal stump of media- and OEG-injected rats contained a similar density of serotonergic axons and occasional serotonin-labelled interneurons. These data demonstrate that olfactory bulb-derived OEG transplantation improves hindlimb stepping in paraplegic rats and further suggest that task-specific training may enhance this OEG effect.

Reports based primarily on anatomical evidence suggest that olfactory ensheathing glia (OEG) transplantation promotes axon regeneration across a complete spinal cord transection in adult rats. Based on functional, electrophysiological, and anatomical assessments, we found that OEG promoted axon regeneration across a complete spinal cord transection and that this regeneration altered motor responses over time. At 7 months after transection, 70% of OEG-treated rats showed motor-evoked potentials in hindlimb muscles after transcranial electric stimulation. Furthermore, a complete spinal cord retransection performed 8 months after injury demonstrated that this axon regeneration suppressed locomotor performance and decreased the hypersensitive hindlimb withdrawal response to mechanical stimulation. OEG transplantation alone promoted reorganization of lumbosacral locomotor networks and, when combined with long-term training, enhanced some stepping measures. These novel findings demonstrate that OEG promote regeneration of mature axons across a complete transection and reorganization of spinal circuitry, both of which contribute to sensorimotor function.

Aims: This study was designed to assess the impact of diabetes on the risk and severity of herpes zoster (HZ), and the impact of HZ on diabetes. It focused primarily on immunocompetent patients aged ≥ 50 years who would be eligible for preventive vaccination.Methods: Using population and healthcare databases of Valencia Region (Spain), a retrospective cohort of all subjects ≥ 50 years was followed up between 2009 and 2014. HZ and diabetes were defined using ICD-9 codes. We compared the incidence of HZ between non-diabetes and diabetes groups and healthcare resource consumption due to HZ in the 6 months following HZ diagnosis using different statistical generalized linear models (GLM). We also compared resources consumption due to diabetes treatment and haemoglobinA1c(HbA1c) levels before and after HZ.Results: The cohort consisted of 2,289,485 individuals ≥ 50 years old, 397,940 of whom had diabetes. HZ incidence rate was 9.3 cases/1000 persons with diabetes-year (95% CI: 9.1–9.4). Incidence increased with age in all groups. The risk of HZ increased in the diabetes group compared to the non-diabetes group (RR 1.2, 95% credibility interval [CrI] 1.17–1.22). Patients with diabetes utilized more health care resources due to their HZ episodes than patients without diabetes. In 24% of well controlled patients with diabetes (HbA1C levels ≤ 6.5%), HbA1C increased after HZ.Conclusions: Diabetes increased by 20% the risk of HZ. HZ contributed to the deterioration of glycaemic control and higher healthcare resource consumption in people with diabetes, becoming a priority population for HZ immunization.

Olfactory bulb ensheathing glia (OB-OEG) from adult rodents promote functional and morphological repair after grafting into injured spinal cords. To provide insight into the feasibility of using OB-OEG in human therapy, we studied OB-OEG in primates to determine their suitability for spinal cord transplantation. Here, we show that OEG can be obtained from olfactory bulbs of adult macaca mulatta and nemestrina monkeys and compare their characteristics to those obtained from rats. In contrast to rodent OB-OEG, primate OB-OEG are nonsenescent, exhibit a longer lifespan, are less sensitive to high oxygen culture environment, and maintain a phenotype suitable for grafting for up to 2.5 months in vitro. Three-week cultures (short term) derived from a single macaca olfactory bulb provide enough OEG for autologous transplantation at the acute stage of injury, and after long-term cultures (2.5 months) may yield an additional 20 billion. OEG can be frozen for later use. Therefore, primate adult olfactory bulbs constitute a reliable source of OEG for cell therapy, and successful culture of these cells make autologous transplantation feasible.

Most (87%) bronchiolitis cases are managed in primary care offices. Approximately 2 out of every 10 children <2 are diagnosed of bronchiolitis, 3 out of every 100 are hospitalized and 1.6 out of every 100 are hospitalized with RSV bronchiolitis in our cohort. Infants between 2 and 10 weeks constitute a risk group for severe bronchiolitis.

Repair of spinal cord injuries (SCIs) is still a major clinical challenge. Several attempts have been made to find a cure for this condition in experimental animals that could be extrapolated to humans. A key for success seems the availability of optimum animal models for testing different therapies. Complete spinal cord lesion in mammals is considered the most accurate injury model. In addition, long-term survival of animals seems more appropriate, as this increases the efficacy of the repair strategies. However, paraplegic animals require special care and treatment for proper longterm maintenance, and to date, there are no published protocols. This lack of available information has discouraged scientists from working with this injury model. Over the past 7 years, we have tested the repair efficacy of olfactory ensheathing glia in paraplegic rats for survival periods of more than 8 months. To keep these animals healthy for this long time, we adapted and administered treatments used in people with paraplegia. These same protocols (developed for rodents in our group) are being applied to paraplegic monkeys. In this review, we provide an overview of the proper handling and care of paraplegic adult laboratory mammals for long periods. This information might help other groups to optimize the outcome obtained and to better evaluate the prospect of a given experimental repair strategy. In addition, the use of human treatments in paraplegic animals provides a more realistic model for a later transfer to the clinical arena.

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Olfactory bulb ensheathing glia (OB-OEG) promote repair of spinal cord injury (SCI) in rats after transplantation at acute or subacute (up to 45 days) stages. The most relevant clinical scenario in humans, however, is chronic SCI, in which no more major cellular or molecular changes occur at the injury site; this occurs after the third month in rodents. Whether adult OB-OEG grafts promote repair of severe chronic SCI has not been previously addressed. Rats with complete SCI that were transplanted with OB-OEG 4 months after injury exhibited progressive improvement in motor function and axonal regeneration from different brainstem nuclei across and beyond the SCI site. A positive correlation between motor outcome and axonal regeneration suggested a role for brainstem neurons in the recovery. Functional and histological outcomes did not differ at subacute or chronic stages. Thus, autologous transplantation is a feasible approach as there is time for patient stabilization and OEG preparation in human chronic SCI; the healing effects of OB-OEG on established injuries may offer new therapeutic opportunities for chronic SCI patients.