Antiinflammatory Effects of Glucocorticoids in Brain Cells, Independent of NF-kB

Glucocorticoids are potent antiinflammatory drugs. They inhibit the expression of proinflammatory cytokines and adhesion molecules. It has recently been proposed that the underlying basis to such inhibition is the induction of the protein IkB, which inhibits the transcription factor NF-kB. The latter is a key activator of the genes encoding cytokines and adhesion molecules. The present study shows that the synthetic glucocorticoid, dexamethasone, inhibits the induction of the proinflammatory cytokine IL-8 and the adhesion molecules VCAM-1 and ICAM-1 in human 1321N1 astrocytoma and SK.N.SH neuroblastoma cells. However, dexamethasone failed to induce IkB or inhibit activation of NF-kB by IL-1 in the two cell types. EMSA confirmed the identity of the activated NF-kB by demonstrating that an oligonucleotide, containing the wild-type NF-kB-binding motif, inhibited formation of the NF-kB-DNA complexes whereas a mutated form of the NF-kB-binding motif was ineffective. In addition, supershift analysis showed that the protein subunits p50 and p65 were prevalent components in the activated NF-kB complexes. The lack of effect of dexamethasone on the capacity of IL-1 to activate NF-kB correlated with its inability to induce IkB and the ability of IL-1 to cause degradation of IkB, even in the presence of dexamethasone. The results presented in this paper strongly suggest that glucocorticoids may exert antiinflammatory effects in cells of neural origin by a mechanism(s) independent of NF-kB

EVALUATION OF THE NATIONAL YOUTHREACH PROGRAMME. ESRI RESEARCH SERIES NUMBER 82 MAY 2019

This report provides a comprehensive evaluation of the National Youthreach Programme. Commissioned by SOLAS, the study is part of an agreed schedule of independent evaluations of key Further Education and Training (FET) provision under the Department of Education and Skills-led FET Strategy 2014-2019 Implementation Plan. Established in 1989, the Youthreach programme continues to be the government’s primary response to early school leaving by providing second-chance education for young people who leave mainstream second-level school before Leaving Certificate level. Youthreach is provided in 112 Youthreach centres and 35 Community Training Centres (CTCs) nationally, with 11,104 learners taking part in the programme in 2017 and with a total cost of €98.7 million (SOLAS, 2018). Reflecting the multiple challenges (including socio-economic disadvantage and special educational needs) faced by many Youthreach learners and the necessity to capture a broader range of outcomes in assessing programme effectiveness, this study adopts a mixed methods approach combining survey data on centres as well as in-depth interviews with staff and learners. This report therefore draws on a range of data sources, including a survey of senior managers at Education and Training Board (ETB) level, a survey of Youthreach co-ordinators and CTC managers, in-depth qualitative data collected as part of case studies in ten centres and two consultative workshops with key national stakeholders in the areas of education and social inclusion. The case studies are a significant feature of the report in that they utilise the multiple perspectives of learners, staff and coordinators/ managers. The report emphasises the voice of young people who have disengaged from school by capturing their views about the Youthreach programme. Using this broad range of data, this report examines all aspects of Youthreach provision including: the profile of learners; referral to the programme; governance and reporting structures; programme funding; curriculum and approaches to teaching and learning; and the learner experience and outcomes

Susceptibility of Larvae of Galleria mellonella to Infection by Asperillus fumigatus is Dependent upon Stage of Conidial Germination

The ability of conidia of the human pathogenic fungus Aspergillus fumigatus to kill larvae of the insect Galleria mellonella was investigated. Conidia at different stages of the germination process displayed variations in their virulence as measured using the Galleria infection model. Non-germinating (ârestingâ) conidia were avirulent except when an inoculation density of 1 à 107 conidia per insect was used. Conidia that had been induced to commence the germination process by pre-culturing in growth medium for 3 h were capable of killing larvae at densities of 1 à 106 and 1 à 107 per insect. An inoculation density of 1 à 105 conidia per insect remained avirulent. Conidia in the outgrowth phase of germination (characterised as the formation of a germ tube) were the most virulent and were capable of killing 100% of larvae after 5 or 24 h when 1 à 107 or 1 à 106 conidia, that had been allowed to germinate for 24 h, were used. Examination of the response of insect haemocytes to conidia at different stages of the germination process established that haemocytes could engulf non-germinating conidia and those in the early stages of the germination process but that conidia, which had reached the outgrowth stages of germination were not phagocytosed. The results presented here indicate that haemocytes of G. mellonella are capable of phagocytosing A. fumigatus conidia less than 3.0 μm in diameter but that conidia greater than this are too large to be engulfed. The virulence of A. fumigatus in G. mellonella larvae can be ascertained within 60â90 h if infection densities of 1 à 106 or 1 à 107 activated conidia (pre-incubated for 2â3 h) per insect are employed

Susceptibility of Larvae of Galleria mellonella to Infection by Asperillus fumigatus is Dependent upon Stage of Conidial Germination

The ability of conidia of the human pathogenic fungus Aspergillus fumigatus to kill larvae of the insect Galleria mellonella was investigated. Conidia at different stages of the germination process displayed variations in their virulence as measured using the Galleria infection model. Non-germinating (ârestingâ) conidia were avirulent except when an inoculation density of 1 à 107 conidia per insect was used. Conidia that had been induced to commence the germination process by pre-culturing in growth medium for 3 h were capable of killing larvae at densities of 1 à 106 and 1 à 107 per insect. An inoculation density of 1 à 105 conidia per insect remained avirulent. Conidia in the outgrowth phase of germination (characterised as the formation of a germ tube) were the most virulent and were capable of killing 100% of larvae after 5 or 24 h when 1 à 107 or 1 à 106 conidia, that had been allowed to germinate for 24 h, were used. Examination of the response of insect haemocytes to conidia at different stages of the germination process established that haemocytes could engulf non-germinating conidia and those in the early stages of the germination process but that conidia, which had reached the outgrowth stages of germination were not phagocytosed. The results presented here indicate that haemocytes of G. mellonella are capable of phagocytosing A. fumigatus conidia less than 3.0 μm in diameter but that conidia greater than this are too large to be engulfed. The virulence of A. fumigatus in G. mellonella larvae can be ascertained within 60â90 h if infection densities of 1 à 106 or 1 à 107 activated conidia (pre-incubated for 2â3 h) per insect are employed

Amphotericin B enhances the synthesis and release of the immunosuppressive agent gliotoxin from the pulmonary pathogen Aspergillus fumigatus

Exposure of the pulmonary pathogen Aspergillus fumigatus to amphotericin B alters membrane permeability as indicated by the escape of amino acids and protein from the mycelium. Amphotericin B exposure for periods of 2-4 h also leads to increased release of the immunosuppressive agent gliotoxin into the surrounding culture medium. Examination of the intracellular gliotoxin concentration following exposure to amphotericin B indicated elevated levels within the hyphae as well as in the culture medium - an effect which was also evident upon exposure of A. fumigatus to DMSO. These results indicate that in parallel with the ability of amphotericinBto act as a fungistatic agent it can also induce the synthesis of gliotoxin and facilitate its release by increasing the permeability of the fungal cell membrane. Increased synthesis of gliotoxin may result from the commencement of secondary metabolism in the presence of amphotericin B. The ability of amphotericin B to enhance the synthesis and release of gliotoxin may exacerbate the effects of the toxin and facilitate fungal invasion of pulmonary tissue

Delayed Diagnosis of Atypical Presentation of Myasthenia Gravis

Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction, resulting in muscle fatiguability and weakness. The pathological characteristics of the disorder include ocular weakness resulting in diplopia and/or ptosis. More generally, the disease can result in fluctuant weakness of skeletal muscle, predominantly affecting ocular, bulbar and respiratory muscles. Autoimmunity in this instance is mediated by IgG anti-acetylcholine receptor antibodies that results in an impaired structure of postsynaptic neurotransmission. Approximately 15% of patients with myasthenia gravis present with bulbar symptoms, of which isolated bulbar symptoms are seen only on occasion. As with our patient, this presentation is most commonly seen in men with late-onset myasthenia gravis. We present a case of an 83-year-old male who presented with a 1 year history of dysphagia for solids and fatigable dysarthria. Following a diagnosis of myasthenia gravis, he was initiated on corticosteroid treatment. He later descended into myasthenic crisis, requiring invasive ventilation measures due to a failure of both non-invasive ventilation and intravenous immunoglobulin G (IVIG) to achieve therapeutic goals

Effects of Diet during the First Winter on Replacement Heifer Weight Gain and Body Condition Score during the Subsequent Grazing Season

In seasonal calving dairy production systems it is important that heifers attain puberty in an appropriate timeframe especially when they are bred to calve at 2 years of age and in systems that impose restricted breeding periods (Ferrell, 1982). Achieving target weights at key time points is critical because, for example, the onset of puberty usually occurs in dairy heifers at 30-40% of their expected mature BW (Heinrichs 1993) which corresponds to approximately 240-320 kg in Holstein heifers. Furthermore, heifers should be managed to achieve 55% to 60% of mature bodyweight (BW) at mating start date (MSD; Patterson et al. 1992). Archbold et al. (2012) has shown that both heifer BW and body condition score (BCS) at MSD are positively associated with calving date and potential milk fat plus milk protein yield when they enter the lactating herd. Heifer rearing is the second largest expense in the dairy system, accounting for approximately 20% of total costs (Gabler et al. 2000). Therefore, it is necessary to focus on reducing costs of production, particularly feed costs, as they account for approximately 80% of total variable costs (Shalloo et al., 2004). One of the methods of reducing feed costs in particular, is by sourcing lower cost feeds. Finneran et al. (2010) reported that kale grazed in-situ ranked as the cheapest alternative to grazed grass and was considerably cheaper than grass silage. Kale has higher crude protein (CP) content than grass silage (Keogh et al. 2009) and may be suitable for inclusion in the diet of replacement dairy heifers. However, kale also tends to have a low neutral-detergent fibre (NDF) concentration (Keogh et al. 2009) suggesting that feeds with a higher NDF concentration (\u3e 500 g/kg DM), such as silage may need to be offered in order to avoid acidosis. The objectives of this study were to i) investigate five contrasting winter feeding regimes on heifer bodyweight (BW) gain and body condition score (BCS), ii) establish if similar BW gain is achieved from a kale only diet compared to a kale + grass silage diet and iii) determine if compensatory growth during the following grazing season exists in replacement heifer rearing systems

Cultivar Influences Milk Production of Grazing Dairy Cows

Perennial ryegrass is considered one of the most important forage grass species used in temperate ruminant animal production systems. Maximizing milk production from grazed grass is a major objective of pastoral-based dairy systems. While DM yield is an important trait, it fails to define the ultimate value of a grass cultivar, which is its potential to improve animal performance from a pasture sward (Reed 1994). The majority of cultivar evaluation trials are conducted under cutting, so therefore inferior cultivars from an animal production perspective may not be identified until commercialisation when animals graze a pasture sward. Reed (1978) reported that ryegrass pastures of similar digestibility can have different animal production responses depending on the season. Without exposure to animal production trials, practical differences between cultivars under field conditions may not be detected. The objective of the current study was to evaluate the effect of four perennial ryegrass cultivars with different sward characteristics on milk yield, milk composition and dry matter intake (DMI) of lactating dairy cows during the spring and mid-season period

Review of the Droichead Teacher Induction Pilot Programme. ESRI WP514. November 2015

The Droichead pilot programme is designed to provide whole-school support for teacher induction. The programme is innovative in being led at school level, by a Professional Support Team (PST) consisting of the principal, mentor(s) and other member(s). This working paper presents preliminary findings from a large-scale study of the programme, placing them in the context of previous international and national research on teacher induction

A Tutoring Framework to Support Computer Science Programmes in Higher Education

Computing Support is the provision of academic supports such as individual tutoring and support classes to students studying computing at third level. Students can struggle with computing as it requires practice involving trial and error. This work proposes a research informed tutoring framework to support computer science students at third level. The tutoring framework combines three pillars; staff and training, pedagogies and activities. Support is put in place to help students develop technical and programming skills. Essential tutoring is provided for those who might otherwise drop out of college. The framework was applied to first and second-year undergraduate programmes and to the first semester in Higher Diploma conversion programmes. Results demonstrate that students\u27 attendance has increased by 14%. In addition, student feedback shows that the framework supports students in computer science. This framework is a useful resource for academic managers that wish to implement computing support at third level