National neonatal resuscitation training program in Nigeria (2008-2012): a preliminary report.

BACKGROUND: Routine institutional training of doctors and nurses on newborn resuscitation have commenced, to improve the quality of resuscitation available to high-risk babies, in Nigeria, as a means of reducing newborn deaths in the country. Perinatal asphyxia contributes to 26% of newborn deaths in Nigeria. Perinatal asphyxia results when babies have difficulty establishing spontaneous respiration after birth. MATERIALS AND METHODS: Between 2008 and 2012, doctors and nurses drawn from all the geo-political zones were trained using the Neonatal Resuscitation Training (NRT) manual of the American Heart Association and the American Academy of Pediatrics. Questionnaire-based, cross-sectional surveys of doctor and nurse trainees from the six geo-political zones in Nigeria were conducted eight months after the primary training, to evaluate the post-training neonatal resuscitation activities. RESULTS: Over the period of study, 357 doctors and 370 nurse/midwives were primarily trained in NRT. The overall ratio of step down training was 1:22 with 1:18 for doctors and 1:26 for nurses. In 2008, the delivery attendance rates were 11 per doctor and 9 per nurse/midwife. These rates increased to 30 per doctor and 47 per nurse in 2012. Between 88 and 94% of the doctors and between 72 and 93% of the nurses successfully used bag and mask to help babies breathe in the post-training period. The nurses used bag and mask for infant resuscitation more frequently, compared to doctors, with the rate fluctuating between two-to-one and four-to-one. Over the years, 87 to 94% of the doctors and 92 to 97% of the nurses/midwives trained other birth attendants. CONCLUSION: The NRT in Nigeria is well-subscribed and the frequency of secondary training is good.

Phagocytosis of bacteria by olfactory ensheathing cells and Schwann cells.

Opportunistic bacterial infections of the nasal cavity could potentially lead to infection of the brain if the olfactory or trigeminal nerves are colonised. The olfactory nerve may be a more susceptible route because primary olfactory neurons are in direct contact with the external environment. Peripheral glia are known to be able to phagocytose some species of bacteria and may therefore provide a defence mechanism against bacterial infection. As the nasal cavity is frequently exposed to bacterial infections, we hypothesised that the olfactory and trigeminal nerves within the nasal cavity could be subjected to bacterial colonisation and that the olfactory ensheathing cells and Schwann cells may be involved in responding to the bacterial invasion. We have examined the ability of mouse OECs and Schwann cells from the trigeminal nerve and dorsal root ganglia to phagocytose Escherichia coli and Burkholderia thailandensis in vitro. We found that all three sources of glia were equally able to phagocytose E. coli with 75-85% of glia having phagocytosed bacteria within 24h. We also show that human OECs phagocytosed E. coli. In contrast, the mouse OECs and Schwann cells had little capacity to phagocytose B. thailandensis. Thus subtypes of peripheral glia have similar capacities for phagocytosis of bacteria but show selective capacity for the two different species of bacteria that were examined. These results have implications for the understanding of the mechanisms of bacterial infections as well as for the use of glia for neural repair therapies.

Neurotrophin expression in the adult olfactory epithelium.

Published reports of neurotrophin expression in the olfactory system are incomplete because of missing data and conflicting results. Previous studies used a variety of fixation procedures and antibodies on different species and different ages. The aim of the present study was to examine expression of neurotrophins and their receptors using optimized methodologies: five methods of fixation, multiple antibodies, a variety of immunochemical protocols, and RT-PCR. We show here that (i) transcripts for all neurotrophins and their receptors are found in the adult olfactory epithelium; (ii) all neurotrophins are expressed in the supporting cells and the neuronal layers of the undisturbed adult olfactory epithelium while NT4 is found additionally in the horizontal basal cells; (iii) neurotrophin immunoreactivity required a fixative that included parabenzoquinone (not used in previous studies of olfactory tissue); (iv) TrkB and TrkC are restricted to the globose basal cell and neuron layers while TrkA is found in the horizontal basal cells and in the supporting cells where it co-localizes with the low affinity receptor for NGF (p75NTR). These findings confirm that neurotrophins are produced within the olfactory epithelium, suggesting autocrine and paracrine regulation of olfactory neurogenesis.

Filaria/Wolbachia activation of dendritic cells and development of Th1-associated responses is dependent on Toll-like receptor 2 in a mouse model of ocular onchocerciasis (river blindness).

Toll-like receptors (TLRs) regulate dendritic cell function and activate signals that mediate the nature of the adaptive immune response. The current study examined the role of TLRs in dendritic cell activation and in regulating T cell and antibody responses to antigens from the filarial parasites Onchocerca volvulus and Brugia malayi, which cause river blindness and lymphatic filariasis, respectively. Bone-marrow-derived CD11c(+) cells from C57BL/6 and TLR4(-/-) mice produced high levels of IL-6 and RANTES, and showed elevated surface CD40 expression, whereas CD11c(+) cells from myeloid differentiation factor 88(-/-) (MyD88(-/-)), TLR2(-/-) and TLR2/4(-/-) mice were not activated. Similarly, IFN-gamma production by splenocytes from immunized TLR2(-/-) mice was significantly impaired compared with splenocytes from C57BL/6 and TLR4(-/-) mice. In contrast, there was no difference among these strains in Th2-associated responses including IL-5 production by splenocytes from immunized animals, serum IgE and IgG(1), or eosinophil infiltration into the corneal stroma. Neutrophil recruitment to the cornea and CXC chemokine production was inhibited in immunized TLR2(-/-) mice compared with C57BL/6 and TLR4(-/-) mice. Taken together, these findings demonstrate an essential role for TLR2 in filaria-induced dendritic cell activation, IFN-gamma production and neutrophil migration to the cornea, but does not affect filaria-induced Th2-associated responses.

The role of endosymbiotic Wolbachia bacteria in filarial disease.

In this review, we describe the pathogenic role of Wolbachia endosymbiotic bacteria in filarial diseases, focusing on the host innate immune responses to filarial and Wolbachia products. A description of the host pathogen recognition and early inflammatory responses including TLR4-mediated signalling, chemokine and cytokine responses and inflammatory cell recruitment is provided from human studies and from animal models of filarial disease. Finally, the impact of the discovery and characterization of Wolbachia on filarial research and treatment programmes is discussed.

Changes in gravitational force induce alterations in gene expression that can be monitored in the live, developing zebrafish heart.

Little is known about the effect of microgravity on gene expression, particularly in vivo during embryonic development. Using transgenic zebrafish that express the gfp gene under the influence of a beta-actin promoter, we examined the affect of simulated-microgravity on GFP expression in the heart. Zebrafish embryos, at the 18-20 somite-stage, were exposed to simulated-microgravity for 24 hours. The intensity of GFP fluorescence associated with the heart was then determined using fluorescence microscopy. Our measurements indicated that simulated-microgravity induced a 23.9% increase in GFP-associated fluorescence in the heart. In contrast, the caudal notochord showed a 17.5% increase and the embryo as a whole showed only an 8.5% increase in GFP-associated fluorescence. This suggests that there are specific effects on the heart causing the more dramatic increase. These studies indicate that microgravity can influence gene expression and demonstrate the usefulness of this in vivo model of 'reporter-gene' expression for studying the effects of microgravity.

Irreversible damage to the spinal cord following spinal anesthesia.

The authors report five patients with damage to the distal spinal cord following spinal anesthesia. The patients developed leg weakness and sensory disturbance. MRI of the lumbosacral spine showed an abnormal area of high signal within the conus medullaris in all patients. Symptoms and signs persisted at 1- to 2.5-year follow-ups. Incorrect needle placement and type of needle used are possible factors leading to spinal cord injury.

Polymyositis as a cause of total gut failure.

BACKGROUND: Gastrointestinal manifestations are seen in systemic sclerosis and mixed connective tissue disorders but are rare in pure polymyositis. CASE REPORT: A 44 year old woman with polymyositis who developed total gut failure requiring treatment with total parenteral nutrition is described. RESULTS: The patient's polymyositis is now fully controlled biochemically, but her gastrointestinal symptoms persist.

Comparison of wheat germ agglutinin-horseradish peroxidase and biotinylated dextran for anterograde tracing of corticospinal tract following spinal cord injury.

Established methods for monitoring regeneration of the corticospinal tract involve anterograde labelling of the cortical motor neuron. While wheat germ agglutinin-horseradish peroxidase conjugate has been used to anterogradely label these neurons, we demonstrate that this technique may not completely label the whole axon and fine terminal processes when this tracer is administered in dried form. An alternative method is described for anterograde labelling of cortical motor neurons using biotinylated dextran. This tracer may be applied by either microinjection of 10% biotinylated dextran or implanting small globules of the dried tracer into the motor cortex. While more laborious, microinjection results in better anterograde labelling than implantation of dried biotinylated dextran. A procedure is also described for preparing serial coronal sections through the entire spinal cord and thaw-mounted on a minimum number of slides. The labelled nerve processes in these tissue sections can be visualised in the spinal cord under a fluorescent microscope following incubation with cy3-streptavidin complex. Permanent labelling of the biotinylated nerve processes is achieved by incubation of tissue sections with streptavidin-horseradish peroxidase conjugate followed by stringent washes and staining with tetramethylbenzidine. Use of tetramethylbenzidine allows resolution of a greater number of finer labelled processes than diaminobenzindine and allows clear visualisation of individual regenerating corticospinal tract processes. Using these procedures, we demonstrate that the corticospinal tract is completely lesioned by a standardised contusion spinal cord injury produced by the New York University weight-drop device.

Stimulation of corticospinal tract regeneration in the chronically injured spinal cord.

Acute spinal cord injury models have proved popular in studies aimed at identifying factors capable of influencing axonal regeneration within the central nervous system. In these models, the test factors (e.g. graft tissues or cells, antibodies, growth factors, etc.) are typically administered at the time of spinal cord injury. In this study, we use a rat chronic spinal cord injury model to identify possible factors which can stimulate regeneration of the chronically lesioned corticospinal tract axons. We demonstrate that surgical grafting of segments of autologous, preligated sural nerve, into the syrinx, stimulates sprouting and regeneration of the corticospinal tract as evidenced by the presence of anterograde labelled corticospinal tract processes within the cavity walls two or more weeks after treatment. Regrowing corticospinal processes were not observed within control animals. The anterogradely labelled corticospinal tract axons were found exclusively within the central grey tissue comprising the cavity walls with no regrowing corticospinal process observed within the white matter. A similar pattern of regeneration was observed following injection into the cavity of a suspension of minced autologous preligated sural nerve. Evidence of corticospinal tract regeneration was seen when either wheat germ agglutinin--horseradish peroxidase or biotinylated--dextran was used as an anterograde tracer. These data demonstrate that the chronically injured cortical motor neurons retain the capacity to regenerate for extended periods and that regeneration can be stimulated using grafts of minced, preligated autologous peripheral nerve tissue.

The electric Moho.

Since Mohorovicic discovered a dramatic increase in compressional seismic velocity at a depth of 54 km beneath the Kulpa Valley in Croatia, the 'Moho' has become arguably the most important seismological horizon in Earth owing to its role in defining the crust-mantle boundary. It is now known to be a ubiquitous feature of the Earth, being found beneath both the continents and the oceans, and is commonly assumed to separate lower-crustal mafic rocks from upper-mantle ultramafic rocks. Electromagnetic experiments conducted to date, however, have failed to detect a corresponding change in electrical conductivity at the base of the crust, although one might be expected on the basis of laboratory measurements. Here we report electromagnetic data from the Slave craton, northern Canada, which show a step-change in conductivity at Moho depths. Such resolution is possible because the Slave craton is highly anomalous, exhibiting a total crustal conductance of less than 1 Siemens--more than an order of magnitude smaller than other Archaean cratons. We also found that the conductivity of the uppermost continental mantle directly beneath the Moho is two orders of magnitude more conducting than laboratory studies on olivine would suggest, inferring that there must be a connected conducting phase.

Estimating genetic correlations from measurements of field-caught waterstriders.

Lynch (1999) proposed a method for estimation of genetic correlations from phenotypic measurements of individuals for which no pedigree information is available. This method assumes that shared environmental effects do not contribute to the similarity of relatives, and it is expected to perform best when sample sizes are large, many individuals in the sample are paired with close relatives, and heritability of the traits is high. We tested the practicality of this method for field biologists by using it to estimate genetic correlations from measurements of field-caught waterstriders (Aquarius remigis). Results for sample sizes of less than 100 pairs were often unstable or undefined, and even with more than 500 pairs only half of those correlations that had been found to be significant in standard laboratory experiments were statistically significant in this study. Statistically removing the influence of environmental effects (shared between relatives) weakened the estimates, possibly by removing some of the genetic similarity between relatives. However, the method did generate statistically significant estimates for some genetic correlations. Lynch (1999) anticipated the problems found, and proposed another method that uses estimates of relatedness between members of pairs (from molecular marker data) to improve the estimates of genetic correlations, but that approach has yet to be tested in the field.

Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models.

Evidence for interactive locomotor and oculomotor deficits in cerebellar patients during visually guided stepping.

Eight patients suffering from primary cerebellar degenerative diseases undertook a walkway task, demanding precise foot placement at each step, and a visual fixation task, requiring only eye movements. Step cycle and horizontal eye movements were recorded throughout the tasks and compared to those of healthy adults (including age- and sex-matched controls). Cerebellar patients displayed both locomotor and oculomotor deficits. Increases in duration of the stance, swing and double support phases of the step cycle were all shown to contribute to ataxic gait. Dysmetric saccades to fixate the footfall targets were seen more frequently in patients than in controls. These hypometric saccades were followed by one or more corrective saccades (patients: >45% accompanied by one or more corrective saccades; controls: <10% accompanied by a single corrective saccade). Similarities between the oculomotor deficits displayed by patients during the visual fixation task and when walking indicate that the latter are not merely a consequence of ataxic gait. The existence of several links between these locomotor and oculomotor deficits provides evidence for considerable interaction between the two control systems in the production of patterned eye and stepping movements. These results also suggest that the cerebellum plays an active role in the co-ordination of visually guided eye and limb movements during visually guided stepping.

Psychotropic drug utilization in long-term-care facilities for the elderly in Ontario, Canada.

OBJECTIVE: Despite considerable data from a number of countries regarding psychotropic utilization in long-term-care facilities for the elderly, there has been a lack of similar data from Canada. The purpose of this study was to gather prescription data from a series of institutions in Ontario and to compare the results to those of other international studies. METHOD: Single-day surveys were carried out in six homes for the aged, four nursing, homes, two retirement homes, and a veterans' center. The results were compared to those of recent studies from other countries. RESULTS: The data revealed considerable differences in rates of prescription between different classes of institutions and between similarly classified institutions. The prescription rate of neuroleptics ranged from 11.8% (of patients) in retirement homes to 29.8% in nursing homes. Antidepressant use ranged from 12.2% in nursing homes to 24.6% in homes for the aged, and benzodiazepine use ranged from 22.5% in nursing homes to 36.4% in retirement homes. CONCLUSIONS: The overall rate of prescription for psychotropic medications was somewhat lower than in most international studies. The rate of prescription of neuroleptics in nursing homes fell in the midrange of studies, somewhat higher than in recent studies from the United States and an earlier Italian study, but lower than in recent reports from Sweden, Austria, and Australia. The rate of neuroleptic use in homes for the aged was comparable to the rate in the U.S. studies. The overall rate of prescription of antidepressants and benzodiazepines appears to be comparable to that in recent studies from other countries.

Serotonergic neurons in the brainstem of the wallaby, Macropus eugenii.

The organisation and cytoarchitecture of the serotonergic neurons in a diprotodont marsupial were examined by using serial sections of the brainstem processed for serotonin immunohistochemistry and routine histology. The topographic distribution of serotonergic neurons in the brainstem of the adult wallaby (Macropus eugenii) was similar to that of eutherian mammals. Serotonergic neurons were divided into rostral and caudal groups, separated by an oblique boundary through the pontomedullary junction. Approximately 52% of the serotonergic neurons in the wallaby brainstem were located in the rostral midline nuclei (caudal linear nucleus, dorsal, median, and pontine raphe nuclei and the interpeduncular nucleus), whereas 21% were found in the caudal midline region (nuclei raphe magnus, obscurus, and pallidus). The remaining serotonergic neurons (27%) were located in more lateral regions such as the pedunculopontine tegmental nuclei, the supralemniscal nuclei (B9 group), and the ventrolateral medulla. The largest serotonergic group, the dorsal raphe, contained one-third of the brainstem serotonergic neurons and showed five subdivisions, similar to that described in other species. In contrast, the median raphe did not show clear subdivisions. The internal complexity of the raphe nuclei and the degree of lateralisation of serotonergic neurons suggest that the wallaby serotonergic system is similar in organisation to that described for the cat and rabbit. This study supports the suggestion that the serotonergic system is evolutionally well conserved and provides baseline data for a quantitative study of serotonergic innervation of the developing cortex in the wallaby.

Major changes in chromatin condensation suggest the presence of an apoptotic pathway in plant cells.

A large decrease in fluorescence intensity of propidium iodide (PI)-stained nuclei is observed during senescence of plant cells. The phenomenon reflects a decrease in accessibility of DNA to this fluorochrome and is a consequence of chromatin condensation. This decrease is substantially greater than usually found in animal nuclei whose chromatin undergoes condensation, e.g., during differentiation or quiescence. Chromatin condensation was confirmed by analyses of (i) DNA accessibility to DNase I, (ii) histone disassociation induced by HCl, (iii) saturation of binding sites by the PI fluorochrome (iv), and (v) visual inspection by fluorescence and confocal microscopy. The extent of changes revealed by these assays was used to map progressive changes in chromatin condensation which allowed us to identify different stages in an apoptosis-like pathway in plants. The initial step of chromatin condensation which occurred prior to endonucleolytic DNA degradation was detected by fluorescence and confocal microscopy and confirmed by a variety of assays employing flow cytometry. The initial chromatin condensation appears to be a reversible step in the early stage of apoptosis. The loss of reversibility of chromatin condensation observed subsequently may be a critical point in the cascade of apoptotic events, leading to further irreversible changes during apoptosis in plants.