Nurses' and nurse educators' experiences of a Pediatric Nursing Continuing Professional Development program in Rwanda.

OBJECTIVES: In 2016, a Pediatric Nursing Continuing Professional Development (PNCPD) program was created and implemented in Kigali, Rwanda, through the Training, Support, and Access Model (TSAM) for Maternal, Newborn, and Child Health (MNCH). This partnership project between Canada and Rwanda provided pediatric nursing education to forty-one Rwandan nurses and nurse educators in 2018 and 2019. The objective of this research study was to explore the experiences of nurses and nurse educators applying pediatric knowledge and skills to academic and clinical settings after participating in the PNCPD program. METHODS: This study was situated within an interpretive descriptive perspective to explore the ways in which knowledge gained during the PNCPD program in Rwanda was applied by nurses and nurse educators in their nursing practice, both academically and clinically. Data was collected through individual interviews. Inductive content analysis was used for data analysis. RESULTS: The analysis of the interviews resulted in the emergence of five themes: Transformations in Pediatric Nursing Practice, Knowledge Sharing, Relationship-Based Nursing, Barriers and Facilitators to Knowledge Implementation, and Scaling-up PNCPD within the Health System. CONCLUSIONS: The results of this study have the potential to inform positive changes to child health care in Rwanda, including scaling up pediatric nursing education to other areas of the healthcare system.

Microglial Inflammation and Cognitive Dysfunction in Comorbid Rat Models of Striatal Ischemic Stroke and Alzheimer's Disease: Effects of Antioxidant Catalase-SKL on Behavioral and Cellular Pathology.

Ischemic stroke often co-occurs with Alzheimer's disease (AD) leading to a worsened clinical outcome. Neuroinflammation is a critical process implicated in AD and ischemic pathology, associated with cognitive decline. We sought to investigate the combined effects of ischemic stroke induced by endothelin-1 injection in two AD rat models, using motor function, memory and microglial inflammation in the basal forebrain and striatum as readouts. In addition, we sought to determine the effectiveness of the antioxidant biologic CAT-SKL in one of the models. The early AD model employed the bilateral intracerebroventricular injections of the toxic ß-amyloid peptide Aß25-35, the prodromal AD model used the transgenic Fischer 344 rat overexpressing a pathological mutant human amyloid precursor protein. Motor function was assessed using a cylinder, modified sticky tape and beam-walk tasks; learning and memory were tested in the Morris water maze. Microglial activation was examined using immunohistochemistry. Aß25-35 toxicity and stroke combination greatly increased microglial inflammation in the basal forebrain. Prodromal AD-pathology coupled with ischemia in the transgenic rat resulted in a greater microgliosis in the striatum. Combined transgenic rats showed balance alterations, comorbid Aß25-35 rats showed a transient sensorimotor deficit, and both demonstrated spatial reference memory deficit. CAT-SKL treatment ameliorated memory impairment and basal forebrain microgliosis in Aß25-35 rats with stroke. Our results suggest that neuroinflammation could be one of the early processes underlying the interaction of AD with stroke and contributing to the cognitive impairment, and that therapies such as antioxidant CAT-SKL could be a potential therapeutic strategy.

Developing and implementing a model of equitable distribution of mentorship in districts with spatial inequities and maldistribution of human resources for maternal and newborn care in Rwanda.

BACKGROUND: The shortage of health care providers (HCPs) and inequity in their distribution along with the lack of sufficient and equal professional development opportunities in low-income countries contribute to the high mortality and morbidity of women and newborns. Strengthening skills and building the capacity of all HCPs involved in Maternal and Newborn Health (MNH) is essential to ensuring that mothers and newborns receive the required care in the period around birth. The Training, Support, and Access Model (TSAM) project identified onsite mentorship at primary care Health Centers (HCs) as an approach that could help reduce mortality and morbidity through capacity building of HCPs in Rwanda. This paper presents the results and lessons learnt through the design and implementation of a mentorship model and highlights some implications for future research. METHODS: The design phase started with an assessment of the status of training in HCs to inform the selection of Hospital-Based Mentors (HBMs). These HBMs took different courses to become mentors. A clear process was established for engaging all stakeholders and to ensure ownership of the model. Then the HBMs conducted monthly visits to all 68 TSAM assigned HCs for 18 months and were extended later in 43 HCs of South. Upon completion of 6 visits, mentees were requested to assist their peers who are not participating in the mentoring programme through a process of peer mentoring to ensure sustainability after the project ends. RESULTS: The onsite mentorship in HCs by the HBMs led to equal training of HCPs across all HCs regardless of the location of the HC. Research on this mentorship showed that the training improved the knowledge and self-efficacy of HCPs in managing postpartum haemorrhage (PPH) and newborn resuscitation. The lessons learned include that well trained midwives can conduct successful mentorships at lower levels in the healthcare system. The key challenge was the inconsistency of mentees due to a shortage of HCPs at the HC level. CONCLUSIONS: The initiation of onsite mentorship in HCs by HBMs with the support of the district health leaders resulted in consistent and equal mentoring at all HCs including those located in remote areas.

"I cannot say no when a pregnant woman needs my support to get to the health centre": involvement of community health workers in Rwanda's maternal health.

BACKGROUND: In Rwanda, maternal community health workers (M-CHWs) are involved in the country's overall health system. In maternal health, their role includes the provision of preventive and promotional health services at the community level. They provide services such as health education on maternal health wellbeing, advice and information on access and timely utilization of health facilities for prenatal, delivery and postpartum care. The contribution of M-CHWs in the health sector combined with other government initiatives led the country to achieving the fifth Millennium Development Goal (MDG) - target 5A- that aimed to improve maternal health through the reduction of maternal mortality ratio by 75% between 1990 and 2015). The objective of this study was to explore M-CHWs' perceptions and experiences on access and provision of maternal health services. METHODS: We used a case study methodology, a qualitative research approach to explore M-CHWs' experiences and perceptions on access and provision of maternal health services at the community level in Rwanda. For the period of June-August 2014, in-depth interviews were conducted with sixteen M-CHWs who had been providing maternal health services in the Eastern Province of Rwanda. Participants shared their experiences and perceptions on access and provision of maternal health service in their communities. RESULTS: The results of this research highlight the role of M-CHWs in promoting the use of health facilities for prenatal care and delivery and the ways they use to reach out to women. Several challenges prohibit M-CHWs to deliver adequate maternal health services and these are related to the poor resources settings in which they operate. CONCLUSION: The results of this study highlight the experiences and perceptions of M-CHWs on the provision and access to maternal health services in their communities. The fact that M-CHWs are volunteers operating in limited resources settings with no formal training in maternal health and with considerable workloads translates into challenges regarding the quality and quantity of services they provide in their communities. Such challenges create an impact on M-CHWs service provision, satisfaction and retention. The voices of M-CHWs and the communities they serve are needed to explore areas that are specific to each community context that would contribute to making the M-CHW program sustainable to achieve equitable access to maternal health services.

Pathological Changes in Microvascular Morphology, Density, Size and Responses Following Comorbid Cerebral Injury.

Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aß deposition observed in Alzheimer's disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic substrate to disturbed microperfusion as well as an overlapping etiologic mechanism between AD and ischemia has not been thoroughly explored. In this study, we employ temporal histopathology of cerebral vasculature in a rat model of ß-amyloid (Aß) toxicity and endothelin-1 induced-ischemia (ET1) to investigate the panorama of cerebral pathology and the protein expression on d1, d7, and d28 post-injury. The combination of Aß and ET1 pathological states leads to an alteration in microvascular anatomy, texture, diameter, density, and protein expression, in addition to disturbed vessel-matrix-connections, inter-compartmental water exchange and basement membrane profile within the lesion epicenter localized in the striatum of Aß+ET1 brains compared to Aß and ET1 rats. We conclude that the neural microvascular network, in addition to the neural tissue, is not only sensitive to structural deterioration but also serves as an underlying vascular etiology between ischemia and AD pathologies. Such investigation can provide prospects to appreciate the interrelationships between structure and responses of cerebral microvasculature and to provide a venue for vascular remodeling as a new treatment strategy.

Spatio-temporal disparities in maternal health service utilization in Rwanda: What next for SDGs?

The Sustainable Development Goals (SDGs) in part aim to further improve maternal health outcomes by reducing spatial disparities in utilization of critical services such as antenatal and assisted delivery, with emphasis on decentralization and integration of strategies. Yet, our understanding of within country spatial disparities in maternal health services (MHS) utilization over time has been scant. By fitting multiple regression models to a pooled dataset of the 2010/11 and 2014/15 Rwanda Demographic and Health Surveys (n = 12,273), and employing post-estimation margins analysis, we examined spatial differentiation of MHS trends prior to the SDGs in Rwanda. Our study found that women in 2014/15 were more likely to utilize antenatal services and assisted delivery (OR = 1.757, p ≤ 0.001) compared with 2010/11, but with nuanced spatial variations. Compared with Nyarugenge, women in nineteen out of the twenty-nine remaining districts were more likely to report utilization of antenatal services and skilled birth delivery, while the probability of accessing four or more antenatal services in seven districts declined between 2010/11 and 2014/15. Physical, financial and socio-cultural factors were associated with maternal health service utilization over the period. Based on our findings, we present policy suggestions for improving utilization of MHS in Rwanda and in similar contexts in the SDGs period.

Fluctuation of primary motor cortex excitability during cataplexy in narcolepsy.

Objective: Cataplexy is a complicated and dynamic process in narcolepsy type 1 (NT1) patients. This study aimed to clarify the distinct stages during a cataplectic attack and identify the changes of the primary motor cortex (PMC) excitability during these stages. Methods: Thirty-five patients with NT1 and 29 healthy controls were recruited to this study. Cataplectic stages were distinguished from a cataplectic attack by video-polysomnogram monitoring. Transcranial magnetic stimulation motor-evoked potential (TMS-MEP) was performed to measure the excitability of PMC during quiet wakefulness, laughter without cataplexy, and each cataplectic stage. Results: Based on the video and electromyogram observations, a typical cataplectic attack (CA) process is divided into four stages: triggering (CA1), resisting (CA2), atonic (CA3), and recovering stages (CA4). Compared with healthy controls, NT1 patients showed significantly decreased intracortical facilitation during quiet wakefulness. During the laughter stage, both patients and controls showed increased MEP amplitude compared with quiet wakefulness. The MEP amplitude significantly increased even higher in CA1 and 2, and then dramatically decreased in CA3 accompanied with prolonged MEP latency compared with the laughter stage and quiet wakefulness. The MEP amplitude and latency gradually recovered during CA4. Interpretation: This study identifies four stages during cataplectic attack and reveals the existence of a resisting stage that might change the process of cataplexy. The fluctuation of MEP amplitude and MEP latency shows a potential participation of PMC and motor control pathway during cataplexy, and the increased MEP amplitude during CA1 and 2 strongly implies a compensatory mechanism in motor control that may resist or avoid cataplectic attack.

Chloroquine Restores Ganglioside Homeostasis and Improves Pathological and Behavioral Outcomes Post-stroke in the Rat.

Perturbations of ganglioside homeostasis have been observed following stroke whereby toxic simple gangliosides GM2 and GM3 accumulate, while protective complex species GM1 and GD1 are reduced. Thus, there is a need for therapeutic interventions which can prevent ganglioside dysregulation after stroke. A pharmacological intervention using chloroquine was selected for its transient lysosomotropic properties which disrupt the activity of catabolic ganglioside enzymes. Chloroquine was administered both in vitro (0.1 µM), to primary cortical neurons exposed to GM3 toxicity, and in vivo (45 mg/kg i.p.), to 3-month-old male Wistar rats that underwent a severe stroke injury. Chloroquine was administered for seven consecutive days beginning 3 days prior to the stroke injury. Gangliosides were examined using MALDI imaging mass spectrometry at 3 and 21 days after the injury, and motor deficits were examined using the ladder task. Chloroquine treatment prevented ganglioside dysregulation 3 days post-stroke and partially prevented complex ganglioside depletion 21 days post-stroke. Exogenous GM3 was found to be toxic to primary cortical neurons which was protected by chloroquine treatment. Motor deficits were prevented in the forelimbs of stroke-injured rats with chloroquine treatment and was associated with decreased inflammation, neurodegeneration, and an increase in cell survival at the site of injury. Chloroquine administration prevents ganglioside dysregulation acutely, protects against GM3 toxicity in neurons, and is associated with long-term functional and pathological improvements after stroke in the rat. Therefore, targeting lipid dysregulation using lysosomotropic agents such as chloroquine may represent a novel therapeutic avenue for stroke injuries.

The Dynamics of Impaired Blood-Brain Barrier Restoration in a Rat Model of Co-morbid Injury.

Defect in brain microperfusion is increasingly recognized as an antecedent event to Alzheimer's disease (AD) and ischemia. Nevertheless, studies on the role of impaired microperfusion as a pathological trigger to neuroinflammation, Aß deposition as well as blood-brain barrier (BBB) disruption, and the etiological link between AD and ischemia are lacking. In this study, we employ in vivo sequential magnetic resonance imaging (MRI) and computed tomography (CT) imaging in a co-morbid rat model of ß-amyloid toxicity (Aß) and ischemia (ET1) with subsequent histopathology of striatal lesion core and penumbra at 1, 7, and 28 days post injury. Within 24 h, cerebral injury resulted in increased BBB permeability due to the dissolution of ß-dystroglycan (ß-DG) and basement membrane laminin by active matrix metalloproteinase9 (MMP9). As a result, net flow of circulating IgG down a hydrostatic gradient into the parenchyma led to vasogenic edema and impaired perfusion, thus increasing the apparent hyperintensity in true fast imaging with steady-state free precession (true FISP) imaging and acute hypoperfusion in CT. This was followed by a slow recruitment of reactive astroglia to the affected brain and depolarization of aquaporin4 (AQP4) expression resulting in cytotoxic edema-in an attempt to resolve vasogenic edema. On d28, functional BBB was restored in ET1 rats as observed by astrocytic MMP9 release, ß-DG stabilization, and new vessel formation. This was confirmed by reduced hyperintensity on true FISP imaging and normalized cerebral blood flow in CT. While, Aß toxicity alone was not detrimental enough, Aß+ET1 rats showed delayed differential expression of MMP9, late recruitment of astroglial cells, protracted loss of AQP4 depolarization, and thus delayed BBB restoration and cerebral perfusion.

Membrane-lipid homeostasis in a prodromal rat model of Alzheimer's disease: Characteristic profiles in ganglioside distributions during aging detected using MALDI imaging mass spectrometry.

BACKGROUND: Accumulation of simple gangliosides GM2 and GM3, and gangliosides with longer long-chain bases (d20:1) have been linked to toxicity and the pathogenesis of Alzheimer's disease (AD). Conversely, complex gangliosides, such as GM1, have been shown to be neuroprotective. Recent evidence using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) has demonstrated that a-series gangliosides are differentially altered during normal aging, yet it remains unclear how simple species are shifting relative to complex gangliosides in the prodromal stages of AD. METHODS: Ganglioside profiles in wild-type (Wt) and transgenic APP21 Fischer rats were detected and quantified using MALDI-IMS at P0 (birth), 3, 12, and 20 months of age and each species quantified to allow for individual species comparisons. RESULTS: Tg APP21 rats were found to have a decreased level of complex gangliosides in a number of brain regions as compared to Wt rats and showed higher levels of simple gangliosides. A unique pattern of expression was observed in the white matter as compared to gray matter regions, with an age-dependent decrease in GD1 d18:1 species observed and significantly elevated levels of GM3 in Tg APP21 rats. CONCLUSIONS: These results are indicative of a pathological shift in ganglioside homeostasis during aging that is exacerbated in Tg APP21 rats. GENERAL SIGNIFICANCE: Ganglioside dysregulation may occur in the prodromal stages of neurodegenerative diseases like AD.

Altered Insulin/Insulin-Like Growth Factor Signaling in a Comorbid Rat model of Ischemia and ß-Amyloid Toxicity.

Ischemic stroke and diabetes are vascular risk factors for the development of impaired memory such as dementia and/or Alzheimer's disease. Clinical studies have demonstrated that minor striatal ischemic lesions in combination with ß-amyloid (Aß) load are critical in generating cognitive deficits. These cognitive deficits are likely to be associated with impaired insulin signaling. In this study, we examined the histological presence of insulin-like growth factor-I (IGF-1) and insulin receptor substrate (IRS-1) in anatomically distinct brain circuits compared with morphological brain damage in a co-morbid rat model of striatal ischemia (ET1) and Aß toxicity. The results demonstrated a rapid increase in the presence of IGF-1 and IRS-1 immunoreactive cells in Aß + ET1 rats, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion. These regions included subcortical white matter, motor cortex, thalamus, dentate gyrus, septohippocampal nucleus, periventricular region and horizontal diagonal band of Broca in the basal forebrain. The alteration in IGF-1 and IRS-1 presence induced by ET1 or Aß rats alone was not severe enough to affect the entire brain circuit. Understanding the causal or etiologic interaction between insulin and IGF signaling and co-morbidity after ischemia and Aß toxicity will help design more effective therapeutics.

Dipyridamole plus Triflusal versus Triflusal Alone in Infarct Reduction after Middle Cerebral Artery Occlusion.

BACKGROUND AND PURPOSE: The objective of this work is to study the dose-dependent effect of combination therapy with dipyridamole and triflusal over that of triflusal alone on infarct size after middle cerebral artery occlusion (MCAO) ischemia. MATERIALS AND METHODS: Male Wistar rats were subjected to a permanent MCAO in the right hemisphere. Rats received triflusal alone and with dipyridamole via oral route. Three days after surgery, infarct volumes were measured. RESULTS: The lower dose regime of triflusal (10 mg/kg) and dipyridamole (200 mg/kg) caused the greatest decrease in infarct size compared with higher dose regime of triflusal (30 mg/kg) and dipyridamole (200 mg/kg) (P <.01), triflusal (30 mg/kg) alone (P <.07), and vehicle-treated controls. CONCLUSIONS: The lower dose combination of dipyridamole and triflusal appears to be more effective than triflusal alone after MCAO-induced cerebral ischemia. Therefore, there is a strong rationale to continue to examine the protective effects of triflusal and dipyridamole after cerebral ischemia.

Sublimation of DAN Matrix for the Detection and Visualization of Gangliosides in Rat Brain Tissue for MALDI Imaging Mass Spectrometry.

Sample preparation is key for optimal detection and visualization of analytes in Matrix-assisted Laser Desorption/Ionization (MALDI) Imaging Mass Spectrometry (IMS) experiments. Determining the appropriate protocol to follow throughout the sample preparation process can be difficult as each step must be optimized to comply with the unique characteristics of the analytes of interest. This process involves not only finding a compatible matrix that can desorb and ionize the molecules of interest efficiently, but also selecting the appropriate matrix deposition technique. For example, a wet matrix deposition technique, which entails dissolving a matrix in solvent, is superior for desorption of most proteins and peptides, whereas dry matrix deposition techniques are particularly effective for ionization of lipids. Sublimation has been reported as a highly efficient method of dry matrix deposition for the detection of lipids in tissue by MALDI IMS due to the homogeneity of matrix crystal deposition and minimal analyte delocalization as compared to many wet deposition methods 1,2. Broadly, it involves placing a sample and powdered matrix in a vacuum-sealed chamber with the samples pressed against a cold surface. The apparatus is then lowered into a heated bath (sand or oil), resulting in sublimation of the powdered matrix onto the cooled tissue sample surface. Here we describe a sublimation protocol using 1,5-diaminonaphthalene (DAN) matrix for the detection and visualization of gangliosides in the rat brain using MALDI IMS.

Pediatric emergency care capacity in a low-resource setting: An assessment of district hospitals in Rwanda.

BACKGROUND: Health system strengthening is crucial to improving infant and child health outcomes in low-resource countries. While the knowledge related to improving newborn and child survival has advanced remarkably over the past few decades, many healthcare systems in such settings remain unable to effectively deliver pediatric advance life support management. With the introduction of the Emergency Triage, Assessment and Treatment plus Admission care (ETAT+)-a locally adapted pediatric advanced life support management program-in Rwandan district hospitals, we undertook this study to assess the extent to which these hospitals are prepared to provide this pediatric advanced life support management. The results of the study will shed light on the resources and support that are currently available to implement ETAT+, which aims to improve care for severely ill infants and children. METHODS: A cross-sectional survey was undertaken in eight district hospitals across Rwanda focusing on the availability of physical and human resources, as well as hospital services organizations to provide emergency triage, assessment and treatment plus admission care for severely ill infants and children. RESULTS: Many of essential resources deemed necessary for the provision of emergency care for severely ill infants and children were readily available (e.g. drugs and laboratory services). However, only 4/8 hospitals had BVM for newborns; while nebulizer and MDI were not available in 2/8 hospitals. Only 3/8 hospitals had F-75 and ReSoMal. Moreover, there was no adequate triage system across any of the hospitals evaluated. Further, guidelines for neonatal resuscitation and management of malaria were available in 5/8 and in 7/8 hospitals, respectively; while those for child resuscitation and management of sepsis, pneumonia, dehydration and severe malnutrition were available in less than half of the hospitals evaluated. CONCLUSIONS: Our assessment provides evidence to inform new strategies to enhance the capacity of Rwandan district hospitals to provide pediatric advanced life support management. Identifying key gaps in the health care system is required in order to facilitate the implementation and scale up of ETAT+ in Rwanda. These findings also highlight a need to establish an outreach/mentoring program, embedded within the ongoing ETAT+ program, to promote cross-hospital learning exchanges.

Targeted Antioxidant, Catalase-SKL, Reduces Beta-Amyloid Toxicity in the Rat Brain.

Accumulation of beta-amyloid (Aß) in the brain has been implicated as a major contributor to the cellular pathology and cognitive impairment observed in Alzheimer's disease. Beta-amyloid may exert its toxic effects by increasing reactive oxygen species and neuroinflammation in the brain. This study set out to investigate whether a genetically engineered derivative of the peroxisomal antioxidant enzyme catalase (CAT-SKL), is able to reduce the toxicity induced by intracerebroventricular injection of Aß25-35 in the mature rat brain. Histopathological and immunohistochemical analyses were used to evaluate neuroinflammation, and neuronal loss. Spatial learning and reference memory was assessed using the Morris water maze. CAT-SKL treatment was able to reduce the pathology induced by Aß25-35 toxicity by significantly decreasing microglia activation in the basal forebrain and thalamus, and reducing cholinergic loss in the basal forebrain. Aß25-35 animals showed deficits in long-term reference memory in the Morris water maze, while Aß25-35 animals treated with CAT-SKL did not demonstrate long-term memory impairments. This preclinical data provides support for the use of CAT-SKL in reducing neuroinflammation and long-term reference memory deficits induced by Aß25-35.

Assessing the Effects of Acute Amyloid ß Oligomer Exposure in the Rat.

Alzheimer's disease (AD) is the most common form of dementia, yet there are no therapeutic treatments that can either cure or delay its onset. Currently, the pathogenesis of AD is still uncertain, especially with respect to how the disease develops from a normal healthy brain. Amyloid ß oligomers (AßO) are highly neurotoxic proteins and are considered potential initiators to the pathogenesis of AD. Rat brains were exposed to AßO via bilateral intracerebroventricular injections. Rats were then euthanized at either 1, 3, 7 or 21-days post surgery. Rat behavioural testing was performed using the Morris water maze and open field tests. Post-mortem brain tissue was immunolabelled for Aß, microglia, and cholinergic neurons. Rats exposed to AßO showed deficits in spatial learning and anxiety-like behaviour. Acute positive staining for Aß was only observed in the corpus callosum surrounding the lateral ventricles. AßO exposed rat brains also showed a delayed increase in activated microglia within the corpus callosum and a decreased number of cholinergic neurons within the basal forebrain. Acute exposure to AßO resulted in mild learning and memory impairments with co-concomitant white matter pathology within the corpus callosum and cholinergic cell loss within the basal forebrain. Results suggest that acute exposure to AßO in the rat may be a useful tool in assessing the early phases for the pathogenesis of AD.

Correlates of Performance of Healthcare Workers in Emergency, Triage, Assessment and Treatment plus Admission Care (ETAT+) Course in Rwanda: Context Matters.

BACKGROUND: The Emergency, Triage, Assessment and Treatment plus Admission care (ETAT+) course, a comprehensive advanced pediatric life support course, was introduced in Rwanda in 2010 to facilitate the achievement of the fourth Millennium Development Goal. The impact of the course on improving healthcare workers (HCWs) knowledge and practical skills related to providing emergency care to severely ill newborns and children in Rwanda has not been studied. OBJECTIVE: To evaluate the impact of the ETAT+ course on HCWs knowledge and practical skills, and to identify factors associated with greater improvement in knowledge and skills. METHODS: We used a one group, pre-post test study using data collected during ETAT+ course implementation from 2010 to 2013. The paired t-test was used to assess the effect of ETAT+ course on knowledge improvement in participating HCWs. Mixed effects linear and logistic regression models were fitted to explore factors associated with HCWs performance in ETAT+ course knowledge and practical skills assessments, while accounting for clustering of HCWs in hospitals. RESULTS: 374 HCWs were included in the analysis. On average, knowledge scores improved by 22.8/100 (95% confidence interval (CI) 20.5, 25.1). In adjusted models, bilingual (French & English) participants had a greater improvement in knowledge 7.3 (95% CI 4.3, 10.2) and higher odds of passing the practical skills assessment (adjusted odds ratio (aOR) = 2.60; 95% CI 1.25, 5.40) than those who were solely proficient in French. Participants who attended a course outside of their health facility had higher odds of passing the skills assessment (aOR = 2.11; 95% CI 1.01, 4.44) than those who attended one within their health facility. CONCLUSIONS: The current study shows a positive impact of ETAT+ course on improving participants' knowledge and skills related to managing emergency pediatric and neonatal care conditions. The findings regarding key factors influencing ETAT+ course outcomes demonstrate the importance of considering key contextual factors (e.g., language barriers) that might affect HCWs performance in this type of continuous medical education.

Motor and Hippocampal Dependent Spatial Learning and Reference Memory Assessment in a Transgenic Rat Model of Alzheimer's Disease with Stroke.

Alzheimer's disease (AD) is a debilitating neurodegenerative disease that results in neurodegeneration and memory loss. While age is a major risk factor for AD, stroke has also been implicated as a risk factor and an exacerbating factor. The co-morbidity of stroke and AD results in worsened stroke-related motor control and AD-related cognitive deficits when compared to each condition alone. To model the combined condition of stroke and AD, a novel transgenic rat model of AD, with a mutated form of amyloid precursor protein (a key protein involved in the development of AD) incorporated into its DNA, is given a small unilateral striatal stroke. For a model with the combination of both stroke and AD, behavioral tests that assess stroke-related motor control, locomotion and AD-related cognitive function must be implemented. The cylinder task involves a cost-efficient, multipurpose apparatus that assesses spontaneous forelimb motor use. In this task, a rat is placed in a cylindrical apparatus, where the rat will spontaneously rear and contact the wall of the cylinder with its forelimbs. These contacts are considered forelimb motor use and quantified during video analysis after testing. Another cost-efficient motor task implemented is the beam-walk task, which assesses forelimb control, hindlimb control and locomotion. This task involves a rat walking across a wooden beam allowing for the assessment of limb motor control through analysis of forelimb slips, hindlimb slips and falls. Assessment of learning and memory is completed with Morris water maze for this behavioral paradigm. The protocol starts with spatial learning, whereby the rat locates a stationary hidden platform. After spatial learning, the platform is removed and both short-term and long-term spatial reference memory is assessed. All three of these tasks are sensitive to behavioral differences and completed within 28 days for this model, making this paradigm time-efficient and cost-efficient.

Increased Expression of Simple Ganglioside Species GM2 and GM3 Detected by MALDI Imaging Mass Spectrometry in a Combined Rat Model of Aß Toxicity and Stroke.

The aging brain is often characterized by the presence of multiple comorbidities resulting in synergistic damaging effects in the brain as demonstrated through the interaction of Alzheimer's disease (AD) and stroke. Gangliosides, a family of membrane lipids enriched in the central nervous system, may have a mechanistic role in mediating the brain's response to injury as their expression is altered in a number of disease and injury states. Matrix-Assisted Laser Desorption Ionization (MALDI) Imaging Mass Spectrometry (IMS) was used to study the expression of A-series ganglioside species GD1a, GM1, GM2, and GM3 to determine alteration of their expression profiles in the presence of beta-amyloid (Aß) toxicity in addition to ischemic injury. To model a stroke, rats received a unilateral striatal injection of endothelin-1 (ET-1) (stroke alone group). To model Aß toxicity, rats received intracerebralventricular (i.c.v.) injections of the toxic 25-35 fragment of the Aß peptide (Aß alone group). To model the combination of Aß toxicity with stroke, rats received both the unilateral ET-1 injection and the bilateral icv injections of Aß25-35 (combined Aß/ET-1 group). By 3 d, a significant increase in the simple ganglioside species GM2 was observed in the ischemic brain region of rats who received a stroke (ET-1), with or without Aß. By 21 d, GM2 levels only remained elevated in the combined Aß/ET-1 group. GM3 levels however demonstrated a different pattern of expression. By 3 d GM3 was elevated in the ischemic brain region only in the combined Aß/ET-1 group. By 21 d, GM3 was elevated in the ischemic brain region in both stroke alone and Aß/ET-1 groups. Overall, results indicate that the accumulation of simple ganglioside species GM2 and GM3 may be indicative of a mechanism of interaction between AD and stroke.

Comorbid rat model of ischemia and ß-amyloid toxicity: striatal and cortical degeneration.

Levels of cerebral amyloid, presumably ß-amyloid (Abeta), toxicity and the incidence of cortical and subcortical ischemia increases with age. However, little is known about the severe pathological condition and dementia that occur as a result of the comorbid occurrence of this vascular risk factor and Abeta toxicity. Clinical studies have indicated that small ischemic lesions in the striatum are particularly important in generating dementia in combination with minor amyloid lesions. These cognitive deficits are highly likely to be caused by changes in the cortex. In this study, we examined the viability and morphological changes in microglial and neuronal cells, gap junction proteins (connexin43) and neuritic/axonal retraction (Fer Kinase) in the striatum and cerebral cortex using a comorbid rat model of striatal injections of endothelin-1 (ET1) and Abeta toxicity. The results demonstrated ventricular enlargement, striatal atrophy, substantial increases in ß-amyloid, ramified microglia and increases in neuritic retraction in the combined models of stroke and Abeta toxicity. Changes in connexin43 occurred equally in both groups of Abeta-treated rats, with and without focal ischemia. Although previous behavioral tests demonstrated impairment in memory and learning, the visual discrimination radial maze task did not show significant difference, suggesting the cognitive impairment in these models is not related to damage to the dorsolateral striatum. These results suggest an insight into the relationship between cortical/striatal atrophy, pathology and functional impairment.