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Faculty development: the essence of curriculum development.

For years, nurse educators' approach to curriculum building has been one entrenched in the behaviourist school of thinking. The outcome for nursing was a graduate who could function well in a predictable environment. However, as nursing practice is becoming increasingly complex, nurse educators feel more and more disenchanted with this approach and are turning to orientations which support a professional model of education. Shifting orientation to a paradigm for professional education requires that educators change their views and practices to reflect the assumptions underlying the new paradigm. This paper examines the process involved in shifting orientations to curriculum development and proposes strategies to mobilise educators in their own resocialisation to their new roles as educators and learners.

Curriculum↗

Chain elongation-desaturation of linoleic acid during the development of the pig. Implications for the supply of polyenoic fatty acids to the developing brain.

Rates of chain elongation-desaturation of C18:2 omega 6 were compared for liver and brain microsomes in fetal, neonatal and postnatal piglets. Rates of chain elongation-desaturation of C18:2 omega 6 were greatest in liver and increased during perinatal development on a per organ basis. These results suggest that fetal liver and brain has the capability to chain elongate and desaturate essential fatty acids to longer chain homologues. For brain rates of synthesis of chain elongation-desaturation products was greatest during the newborn period whereas this metabolic function was greatest in liver in the postnatal stages of life examined.

Animals↗

Development of corticospinal tract fibers and their plasticity I: quantitative analysis of the developing corticospinal tract in mice.

This study was undertaken to elucidate ultrastructurally and quantitatively the development of the corticospinal tract (CST) axons of mouse at the intumescence level of the cervical cord. An anterograde HRP study showed that the CST was located at the ventral one-third of the dorsal funiculus, and a few HRP-positive fibers were noted at the medialmost part of the ipsilateral anterior funiculus. Ultrastructurally, the CST was composed of unmyelinated axons, growth cones and a few degenerating axons until postnatal day 10 (P10), then the axons in CST gradually increased in size. The number of axons constituting the right CST was calculated at different days of age. The total numbers of axons at P0, P4, P14, P21 and P56 were 2.3 x 10(4), 6.2 x 10(4), 10.4 x 10(4), 7.1 x 10(4) and 3.5 x 10(4), respectively. These results indicate that the number of CST axons at the cervical intumescence of mouse becomes maximum at P14, and then decreases rapidly to reach the adult level of 3.5 x 10(4) (at P56), about 68% of them thus being lost.

Animals↗

Development of corticospinal tract fibers and their plasticity. II. Neonatal unilateral cortical damage and subsequent development of the corticospinal tract in mice.

In this study, the right cerebral cortices of mice on postnatal day 0 (P0) were cryocoagulated with dry ice. Subsequent development of the corticospinal tract (CST) was studied morphologically and quantitatively, and was compared with that in age-matched controls. When the pyramidal tract was traced anterogradely by injecting HRP into the sensorimotor area of the left cerebral cortex of adult operated mice, the right CST originating from the healthy left hemisphere showed remarkable hypertrophy. The number of axons in the CST at the C4-C6 level became maximum on P14 in the control mice and rapidly decreased thereafter. In the operated mice, the axonal number in the right CST also was maximal on P14 and then rapidly decreased. However, the decrease in axonal number after P21 was less in the operated mice than in the controls. Moreover, the number of axons showed a slight increase after P56. These results indicate that the physiological elimination of the parent axons and their collaterals is much lower in the operated mice than in the controls, and that the increase in axon collaterals from parent axons in the hypertrophic right CST persists a long time in the operated mice.

Animals↗

Final report of the Bawnmore Personal Development Programme: staff attitudes and sexuality programme development in an Irish service organisation for people with mental handicap.

In this paper, issues on sexuality and mental handicap are reviewed, and recognition of the growing importance of sex education to integration is noted. The development of a sex education programme and staff training provided within a service organisation, with some involvement from other services within an Irish setting, are described, and their evaluation is reported. Attitudes towards involvement prove of particular interest, and factors influencing continuation or discontinuation are identified. The need for attitude change among staff and administration towards the priority given to sex education is highlighted, and a need for structural change in staffing arrangements to facilitate such education is indicated. Failure to recognise sexuality as a research issue in evaluating the success of integration efforts is noted, and such research is recommended as a top priority for the future.

Adult↗

Cortical development and topographic maps: patterns of cell dispersion in developing cerebral cortex.

Cortical neurons are organized into highly patterned ensembles of cells, each with a distinct physiological function. The precursors of these cells arise in the ventricular zone, itself a highly patterned mosaic of cells. To determine whether the ventricular pattern presages the adult, investigators examine the process of cell migration. Recent evidence suggests that both radial (pattern-preserving) and tangential (pattern-blurring) cell movements occur during development.

Animals↗

BARHL1 homeogene, the human ortholog of the mouse Barhl1 involved in cerebellum development, shows regional and cellular specificities in restricted domains of developing human central nervous system.

The mouse homeobox gene Barhl1 plays a central role in cerebellum development and its expression is activated by the transcription factor Math1 which is involved in bone morphogenetic protein response pathways. We studied the human ortholog BARHL1 and we found that human, mouse, monkey, rat, and zebrafish orthologs were highly conserved and are members of the BarH homeogene family, containing Drosophila BarH1 and BarH2. The N-terminus of BARHL1 protein presents two FIL domains and an acidic domain rich in serine/threonine and proline, while the C-terminus contains a canonical proline-rich domain. Secondary structure analysis showed that outside the three helixes of the homeodomain, BARHL1 protein has essentially random coil structure. We isolated BARHL1 and defined its expression pattern in human embryonic and fetal central nervous system (CNS) and compared it to the mouse Barhl1 transcription. BARHL1 mRNA was found exclusively in the CNS restricted to p1-p4 prosomeres of the diencephalon, to the dorsal cells of the mesencephalon, to the dorsal dl1 sensory neurons of the spinal cord, and to the rhombic lips yielding the cerebellar anlage. Detailed analysis of BARHL1 expression in fetal cerebellar cell layers using our new optic microscopy technology showed BARHL1 expression in external and internal granular cells and also in mouse adult granular cells, in agreement to Barhl1 null mouse phenotype affecting the differentiation and migration of granular cells. These findings indicate that the regional and cellular specificities of BARHL1 transcriptional control well correspond to the mouse Barhl1 transcription and suggest a potential role of this gene in the differentiation of BARHL1-expressing neuronal progenitors involved in the pattern formation of human cerebral and cerebellar structures.

Amino Acid Sequence↗

Development of a harmonised method for the profiling of amphetamines: III. Development of the gas chromatographic method.

This study focused on gas chromatographic analysis of target compounds found in illicit amphetamine synthesised by the Leuckart reaction, reductive amination of benzyl methyl ketone, and the nitrostyrene route. The analytical method was investigated and optimised with respect to introduction of amphetamine samples into the gas chromatograph and separation and detection of the target substances. Sample introduction using split and splitless injection was tested at different injector temperatures, and their ability to transfer the target compounds to the GC column was evaluated using cold on column injection as a reference. Taking the results from both techniques into consideration a temperature of 250 degrees C was considered to be the best compromise. The most efficient separation was achieved with a DB-35MS capillary column (35% diphenyl 65% dimethyl silicone; 30 m x 0.25 mm, d(f) 0.25 microm) and an oven temperature program that started at 90 degrees C (1 min) and was increased by 8 degrees C/min to 300 degrees C (10 min). Reproducibility, repeatability, linearity, and limits of determination for the flame ionisation detector (FID), nitrogen phosphorous detector (NPD), and mass spectrometry (MS) in scan mode and selected ion monitoring (SIM) mode were evaluated. In addition, selectivity was studied applying FID and MS in both scan and SIM mode. It was found that reproducibility, repeatability, and limits of determination were similar for FID, NPD, and MS in scan mode. Moreover, the linearity was better when applying FID or NPD whereas the selectivity was better when utilising the MS. Finally, the introduction of target compounds to the GC column when applying injection volumes of 0.2 microl, 1 microl, 2 microl, and 4 microl with splitless injection respectively 1 microl with split injection (split ratio, 1:40) were compared. It was demonstrated that splitless injections of 1 microl, 2 microl, and 4 microl could be employed in the developed method, while split injection and splitless injections of 0.2 microl should be avoided.

Journal Article↗

The effectiveness of hylan G-F 20 in patients with knee osteoarthritis: an application of two sets of response criteria developed by the OARSI and one set developed by OMERACT-OARSI.

OBJECTIVE: Secondary analyses of a previously conducted 1-year randomized controlled trial were performed to assess the application of responder criteria in patients with knee osteoarthritis (OA) using different sets of responder criteria developed by the Osteoarthritis Research Society International (OARSI) (Propositions A and B) for intra-articular drugs and Outcome Measures in Arthritis Clinical Trials (OMERACT)-OARSI (Proposition D). METHODS: Two hundred fifty-five patients with knee OA were randomized to "appropriate care with hylan G-F 20" (AC+H) or "appropriate care without hylan G-F 20" (AC). A patient was defined as a responder at month 12 based on change in Western Ontario and McMaster Universities Osteoarthritis Index pain and function (0-100 normalized scale) and patient global assessment of OA in the study knee (at least one-category improvement in very poor, poor, fair, good and very good). All propositions incorporate both minimum relative and absolute changes. RESULTS: Results demonstrated that statistically significant differences in responders between treatment groups, in favor of hylan G-F 20, were detected for Proposition A (AC+H=53.5%, AC=25.2%), Proposition B (AC+H=56.7%, AC=32.3%) and Proposition D (AC+H=66.9%, AC=42.5%). The highest effectiveness in both treatment groups was observed with Proposition D, whereas Proposition A resulted in the lowest effectiveness in both treatment groups. The treatment group differences always exceeded the required 20% minimum clinically important difference between groups established a priori, and were 28.3%, 24.4% and 24.4% for Propositions A, B and D, respectively. CONCLUSION: This analysis provides evidence for the capacity of OARSI and OMERACT-OARSI responder criteria to detect clinically important statistically detectable differences between treatment groups.

Analgesics↗

Delayed somatic growth and pubertal development in human immunodeficiency virus-infected hemophiliac boys: Hemophilia Growth and Development Study.

As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin.

Adolescent↗

Hepatic glucose-6-phosphatase development in preterm and full-term guinea-pigs: comparison with rat and human development.

In term infants, hepatic glucose-6-phosphatase activity rises several-fold in the first few days after birth. In contrast, in many preterm infants, the postnatal rise in activity does not occur and the abnormally low levels can persist. In an attempt to determine if prematurity causes long-term changes in levels of glucose-6-phosphatase in liver of all mammals, we have studied the ontogeny of glucose-6-phosphatase in term guinea-pigs, and also in guinea-pigs delivered prematurely by Caesarean section. The activity of hepatic glucose-6-phosphatase in preterm guinea-pigs is about 5-fold lower than in term guinea-pigs at birth but the activity rises rapidly to very similar values to those found in term guinea-pigs. This indicates that prematurity alone does not result in abnormal development of hepatic glucose-6-phosphatase activity in guinea pigs. The changes in liver glucose-6-phosphatase activity in the postnatal period in term guinea-pigs were much smaller than those occurring in term postnatal rats or term infants.

Age Factors↗

Efficient in utero gene transfer system to the developing mouse brain using electroporation: visualization of neuronal migration in the developing cortex.

We report a novel gene transfer system using electroporation. We used this technique to introduce a marker gene plasmid containing enhanced green fluorescent protein into mouse brains at embryonic day 12-17 without removing the embryos from the uterus. The embryos were allowed to continue to develop in utero, and more than 80% were born normally expressing the exogenous gene. Enhanced green fluorescent protein driven by the cytomegalovirus promoter was strongly expressed in the ventricular zone, radial fibers and migrating neuroblasts, but not in mature neurons, suggesting that the cytomegalovirus promoter is silenced after the cells differentiate into mature neurons. Since there is still no convenient way of visualizing the migrating neuroblasts, especially of distinguishing them from the surrounding mature neurons in the cortical plate, this system should provide a good tool for analysing neuronal migration. In the postnatal lateral cortex, neuroblasts migrated almost "tangentially" along the obliquely running "radial" fibers beneath the cortical plate, and after entering the cortical plate, turned towards the marginal zone and migrated radially. Neurons with primitive dendrites were observed only along the border between the marginal zone and the cortical plate, and never at other sites, such as in the middle of the cortical plate. These results imply that the neuroblasts do terminate migration and start differentiation to mature neurons when they encounter the marginal zone, as has long been suggested. By contrast, when elongation factor 1alpha promoter was used, prominent fluorescence allowed visualization of the entire mature neurons as well. The labeled neurons were observed to send axons to the contralateral cortex where they arborized extensively.Thus, this system is much easier and more efficient than virus-mediated gene transfer, and is useful for gain-of-function analysis of neural cell fate determination, migration, positioning and axon path-finding in mouse embryos.

Animals↗

Development of inner ear afferent connections: forming primary neurons and connecting them to the developing sensory epithelia.

The molecular and cellular origin of the primary neurons of the inner ear, the vestibular and spiral neurons, is reviewed including how they connect to the specific sensory epithelia and what the molecular nature of their survival is. Primary neurons of the ear depend on a single basic Helix-Loop-Helix (bHLH) protein for their formation, neurogenin 1 (ngn1). An immediate downstream gene is the bHLH gene neuronal differentiation (NeuroD). Targeted null mutations of ngn1 results in absence of primary neuron formation; targeted null mutation of NeuroD results in loss of almost all spiral and many vestibular neurons. NeuroD and a later expressed gene, Brn3a, play a role in pathfinding to and within sensory epithelia. The molecular nature of this pathfinding property is unknown. Reduction of hair cells in ngn1 null mutations suggests a clonal relationship with primary neurons. This relationship may play some role in specifying the identity of hair cells and the primary neurons that connect with them. Primary neuron neurites growth to sensory epithelia is initially independent of trophic factors released from developing sensory epithelia, but becomes rapidly dependent on those factors. Null mutations of specific neurotrophic factors lose distinct primary neuron populations which undergo rapid embryonic cell death.

Animals↗

Development of an equilibrium immunoassay using electrochemiluminescent detection for a novel recombinant protein product and its application to pre-clinical product development.

In order for a biotechnology derived protein product to be considered 'well characterized', a thorough understanding of the pharmacokinetic and metabolic fate of the product is essential. Specifications for such products need to be based on historical data obtained in the pre-clinical, clinical and manufacturing experience through the use of specific, accurate, precise and validated assays. Typically, assays such as ELISA or RIA that have the disadvantages of limited dynamic range, matrix interactions and hazardous waste generation are used to gather this data. We present data in this abstract that demonstrates the utility of an equilibrium immunoassay that uses electrochemiluminescent detection in the assessment of the pharmacokinetic and metabolic fate of a biotechnology derived product based on either the human (AMG1h) or murine (AMG1m) protein sequence. The assay uses biotinylated antibody in a sandwich format with antibody labeled with the N-hydroxysuccinimide ester of a ruthenium (II) tris-bipyridine chelate for detection in the Origen System. Streptavidin-coated paramagnetic beads are used to capture the antibody-antigen-antibody sandwich complex and facilitate electrochemiluminescent detection. The assay standard curve for AMG1h ranges from a lower limit of quantitation (LOQ) of 2.5 ng ml(-1) to an upper limit of quantitation (ULQ) of 2000 ng ml(-1) with accuracy and precision of not greater then 15% CV and deviation from nominal over the range. The corresponding LOQ (0.5 ng ml(-1)) and ULQ (200 ng ml(-1)) values determined for AMG1m displayed similar accuracy and precision. In addition, we demonstrate that the assay as performed is insensitive to matrix effect up to addition of 7%, of the total reaction volume. General guidelines for developing similar electrochemiluminescent based assays and their applications, advantages and limitations will be discussed.

2,2'-Dipyridyl↗

GABAergic system in the developing mammalian retina: dual sources of GABA at early stages of postnatal development.

In the present work, we have characterized the maturation of the GABAergic system in mammalian retina. Immunoreactivity for GABA, GAD (glutamic acid decarboxylase, EC 4.1.1.15) -65 and -67 in the adult rat retina was localized in cells in the inner nuclear and ganglion cell layers. This pattern was established around postnatal day 8 and included transient GABA and GAD-67 expression in horizontal cells. GAD activity was very low at P1 and P4, increasing after P8, reaching maximal activity by P21 and decreasing to attain adult values by P30. GABA content was approximately constant from P1 to P13, increasing thereafter to reach adult levels. GAD protein content increased progressively with postnatal development and the two isoforms could be distinguished at P8. The disparity between retinal GABA content vs. presence and activity of the synthesizing enzyme, led us to investigate the alternative pathway for GABA synthesis that utilizes putrescine as a substrate. Highest levels of ornithine decarboxylase activity (the limiting step for putrescine synthesis) were found between P1 and P4, decreasing to very low levels after P13. The same pattern was observed for putrescine content in the retina. Highest amounts were found at P1, that decreased and remained constant after P13. Additionally, approximately 40% of tritiated putrescine incorporated by P1, P4 and adult retinas was converted into GABA. Our results suggest the existence of two different sources of GABA in mammalian retina, one that uses glutamate as a precursor and predominates in the mature nervous system and another that utilizes putrescine and is present transiently at early developmental stages.

Animals↗

The development of an instrumented tamp-filling capsule machine II. Investigations of plug development and tamping pressure at different filling stations.

A previously described [Eur. J. Pharm. Sci. 10 (2000) 267] pneumatic tamping head with attached instrumentation, capable of recording tamping forces generated on a Bosch GKF tamp-filling machine with high precision was employed to investigate the development and density of plugs during capsule tamp-filling of two soft, ductile powders. The study aimed to make a contribution to control capsule fill weight by monitoring the tamping force. The results indicated that the tamping station utilised to measure the tamping force and that involved in the regulation of the pressure of the pneumatic chamber of the tamping head should preferably not be the same. A possible solution would be to install the instrumented pneumatic tamping head on tamping station 4, after which in all cases plugs had formed to their maximum length and density. A second pneumatic tamping head, without instrumentation, could be installed on tamping station 3, which would receive signals from the instrumentation, and as a result the inner chamber pressure of this second pneumatic tamping head could be changed to adjust fill weight. The cumulative tamping distance should be large enough to produce a force reading well above the limit set by the inner chamber pressure, but small enough to avoid overfilling of the capsules. The latter can be detected monitoring the variability of the tamping forces recorded. A larger standard deviation of the tamping forces obtained from tamping station 4 was found to be a strong indicator of overfilling.

Capsules↗

Development. The decade of the developing brain.

Our understanding of neural development has advanced dramatically over the past decade. Significant insights have now been obtained into seven fundamental developmental processes: first, induction of the neural plate; second, regionalization of the neural tube along the dorsoventral and anteroposterior axes; third, generation of neurons and glia from multipotential precursors; fourth, apoptotic cell death; fifth, migration of neurons; sixth, guidance of axons to their targets; and seventh, formation of synapses.

Animals↗