Inhalation of the Rho-kinase inhibitor Y-27632 reverses allergen-induced airway hyperresponsiveness after the early and late asthmatic reaction

BACKGROUND: In guinea pigs, we have previously demonstrated that the contribution of Rho-kinase to airway responsiveness in vivo and ex vivo is enhanced after active sensitization with ovalbumin (OA). Using conscious, unrestrained OA-sensitized guina pigs, we now investigated the role of Rho-kinase in the development of airway hyperresponsiveness (AHR) after the allergen-induced early (EAR) and late asthmatic reaction (LAR) in vivo. METHODS: Histamine and PGF(2α )PC(100)-values (provocation concentrations causing 100% increase in pleural pressure) were assessed before OA-challenge (basal airway responsiveness) and after the OA-induced EAR (5 h after challenge) and LAR (23 h after challenge). Thirty minutes later, saline or the specific Rho-kinase inhibitor Y-27632 (5 mM, nebulizer concentration) were nebulized, after which PC(100)-values were reassessed. RESULTS: In contrast to saline, Y-27632 inhalation significantly decreased the basal responsiveness toward histamine and PGF(2α )before OA-challenge, as indicated by increased PC(100 )-values. Both after the allergen-induced EAR and LAR, AHR to histamine and PGF(2α )was present, which was reversed by Y-27632 inhalation. Moreover, there was an increased effectiveness of Y-27632 to reduce airway responsiveness to histamine and PGF(2α )after the EAR and LAR as compared to pre-challenge conditions. Saline inhalations did not affect histamine or PGF(2α )PC(100)-values at all. Interestingly, under all conditions Y-27632 was significantly more effective in reducing airway responsiveness to PGF(2α )as compared to histamine. Also, there was a clear tendency (P = 0.08) to a more pronounced degree of AHR after the EAR for PGF(2α )than for histamine. CONCLUSION: The results indicate that inhalation of the Rho-kinase inhibitor Y-27632 causes a considerable bronchoprotection to both histamine and PGF(2α). Moreover, the results are indicative of a differential involvement of Rho-kinase in the agonist-induced airway obstruction in vivo. Increased Rho-kinase activity contributes to the allergen-induced AHR to histamine and PGF(2α )after both the EAR and the LAR, which is effectively reversed by inhalation of Y-27632. Therefore, Rho-kinase can be considered as a potential pharmacotherapeutical target in allergic asthma

Poorer without It? The Neglected Role of the Natural Environment in Poverty and Wellbeing

The relationship between sustainable development’s prime goal, human wellbeing, and the natural environment has been narrowly conceived. This paper focuses on the possibility and the implications of treating the natural environment as a ‘constituent’, or internal element, of the concepts of wellbeing and poverty, as opposed to a ‘determinant’, or instrumental, external factor. Our review of philosophical accounts and conceptual frameworks of wellbeing and poverty suggests that treating the environment as a constituent element is philosophically sound, conceptually robust and empirically grounded. We argue that failing to consider these missing environmental aspects can result in an incomplete capturing of the multiple dimensions of wellbeing and poverty, and their underlying drivers. This broader framing of the environment– wellbeing relationship has the potential to inform a new generation of individual level wellbeing and poverty indicators, creating measures of multidimensional poverty that reflect the broadened scope ambitiously articulated in the Sustainable Development Goals

Accounting students' expectations and transition experiences of supervised work experience

Political and economic discourses position employability as a responsibility of higher education, which utilise mechanisms such as supervised work experience (SWE) to embed employability into the undergraduate curriculum. However, sparse investigation of students' contextualised experiences of SWE results in little being known about the mechanisms through which students derive employability benefits from SWE. The aim of this study is to examine the impact of students' expectation and conception of workplace learning on their transition into SWE. Analysis of accounting students' experiences reveal two broad conceptions of workplace learning, the differing impacts of which on transition experience are explored using existing learning transfer perspectives. Students displaying the more common 'technical' conception construct SWE as an opportunity to develop technical, knowledge-based expertise and abilities that prioritize product-based or cognitive learning transfer. Students with an 'experiential' conception were found to construct SWE primarily as an experience through which the development of personal skills and abilities beyond technical expertise are prioritized using process-based or socio-cultural learning transfer. Further data analysis suggests that these two learning transfer approaches have differing impacts on students' employability development which may indicate a need for universities to consider how to develop appropriate student expectations of and approaches to SWE and meaningful support for students' SWE transition

Integrated modelling for economic valuation of the role of forests and woodlands in drinking water provision to two African cities

Rapidly growing economies often have high population growth, resulting in agricultural expansion in rural areas and increased water demand in urban areas. Conversion of forests and woodlands to agriculture may threaten safe and reliable water supply in cities. This study assesses the regulating functions and economic values of forests and woodlands in meeting the water needs of two major cities in Tanzania and proposes an integrated modelling approach with a scenario-based analysis to estimate costs of water supply avoided by forest conservation. We use the process-based hydrological Soil and Water Assessment Tool (SWAT) to simulate the role of woody habitats in the regulation of hydrological flow and sediment control. We find that the forests and woodlands play a significant role in regulating sediment load in rivers and reducing peak flows, with implications for the water supply from the Ruvu River to Dar es Salaam and Morogoro. A cost-based value assessment under water treatment works conditions up to 2016 suggests that water supply failure due to deforestation would cost Dar es Salaam USD 4.6-17.6 million per year and Morogoro USD 308 thousand per year. Stronger enforcement of forest and woodland protection in Tanzania must balance water policy objectives and food security

Influence of daily 10-85 mu g vitamin D supplements during pregnancy and lactation on maternal vitamin D status and mature milk antirachitic activity

Pregnant and lactating women and breastfed infants are at risk of vitamin D deficiency. The supplemental vitamin D dose that optimises maternal vitamin D status and breast milk antirachitic activity (ARA) is unclear. Healthy pregnant women were randomised to 10 (n 10), 35 (n 11), 60 (n 11) and 85 (n 11) mu g vitamin D-3/d from 20 gestational weeks (GW) to 4 weeks postpartum (PP). The participants also received increasing dosages of fish oil supplements and a multivitamin. Treatment allocation was not blinded. Parent vitamin D and 25-hydroxyvitamin D (25(OH)D) were measured in maternal plasma at 20 GW, 36 GW and 4 weeks PP, and in milk at 4 weeks PP. Median 25(OH)D and parent vitamin D at 20 GW were 85 (range 25-131) nmol/l and 'not detectable (nd)' (range nd-40) nmol/l. Both increased, seemingly dose dependent, from 20 to 36 GW and decreased from 36 GW to 4 weeks PP. In all, 35 mu g vitamin D/d was needed to increase 25(OH)D to adequacy (80-249 nmol/l) in >97 center dot 5 % of participants at 36 GW, while >85 mu g/d was needed to reach this criterion at 4 weeks PP. The 25(OH)D increments from 20 to 36 GW and from 20 GW to 4 weeks PP diminished with supplemental dose and related inversely to 25(OH)D at 20 GW. Milk ARA related to vitamin D-3 dose, but the infant adequate intake of 513 IU/l was not reached. Vitamin D-3 dosages of 35 and >85 mu g/d were needed to reach adequate maternal vitamin D status at 36 GW and 4 weeks PP, respectively

Effect of an EBM course in combination with case method learning sessions: an RCT on professional performance, job satisfaction, and self-efficacy of occupational physicians

Objective An intervention existing of an evidence-based medicine (EBM) course in combination with case method learning sessions (CMLSs) was designed to enhance the professional performance, self-efficacy and job satisfaction of occupational physicians. Methods A cluster randomized controlled trial was set up and data were collected through questionnaires at baseline (T0), directly after the intervention (T1) and 7 months after baseline (T2). The data of the intervention group [T0 (n = 49), T1 (n = 31), T2 (n = 29)] and control group [T0 (n = 49), T1 (n = 28), T2 (n = 28)] were analysed in mixed model analyses. Mean scores of the perceived value of the CMLS were calculated in the intervention group. Results The overall effect of the intervention over time comparing the intervention with the control group was statistically significant for professional performance (p <0.001). Job satisfaction and self-efficacy changes were small and not statistically significant between the groups. The perceived value of the CMLS to gain new insights and to improve the quality of their performance increased with the number of sessions followed. Conclusion An EBM course in combination with case method learning sessions is perceived as valuable and offers evidence to enhance the professional performance of occupational physicians. However, it does not seem to influence their self-efficacy and job satisfactio

Case study of temporal changes in maternal dietary intake and the association with breast milk mineral contents

Minerals play important roles in infant growth and development, even though they only make up to 0.2 g% of the mature breast milk contents. Limited studies examined the association between maternal dietary intake and breast milk mineral contents in a temporal manner. Twenty Malaysian Malay postpartum mothers were recruited by either convenience or snow balling sampling from the urban lower middle income residential areas. Dietary intake of the subjects was obtained by 24-hour recall during each breast milk collection. Adequacy of maternal mineral intake was compared with the latest Recommended Nutrient Intake for Malaysia. Each of the subject provided breast milk samples for three times (T1, T2, and T3) at consecutive 2-week intervals. Breast milk concentrations of selected macro- and micro-minerals, including Ca, P, K, Na, Mg, Fe, Zn, Cu, Mn, Se, I, Cr and Mo were determined by inductively coupled plasma mass spectrometry (ICP-MS). Subjects were aged 31.4 +/- 6.1 years with a majority (60 %) having post-secondary school/college education. While maternal intake of macro-minerals, Ca, P, K and Mg, did not display a significant temporal changes from T1 to T3, the intake of micro-minerals, Cu, Mn and I decreased significantly over time from T1 to T3. Breast milk K, Fe, Zn and Cu concentrations showed a significant decreased with the progression of lactation from transitional (2-3 weeks) to established stage (>8-12 weeks). Significant correlations were established between maternal intake of K, Na, Fe and Se and their respective concentrations in breast milk in the present study. This case study revealed an inadequate maternal intake of several key micro-minerals (Cu, Mn, I) among the postpartum Malay mothers and a decreasing concentrations of certain essential minerals (K, Fe, Zn and Cu) in breast milk with lactation stage

Temporal Changes in Breast Milk Fatty Acids Contents:A Case Study of Malay Breastfeeding Women

The composition of human breast milk changes in the first two months of life, adapting itself to the evolving needs of the growing new-born. Lipids in milk are a source of energy, essential fatty acids (FA), fat-soluble vitamins, and vital bioactive components. Information on breast milk FA of Malaysian lactating women is scarce. Based on convenience sampling, a total of 20 Malay breastfeeding women who fulfilled the inclusion criteria were recruited. Breast milk was collected three times from each subject at consecutive intervals of 2-3 weeks apart. A total of 60 breast milk samples were collected and classified into "transitional milk" (n = 8), "early milk" (n = 26) and "mature milk" (n = 26). All milk samples were air freighted to University of Groningen, Netherlands for analysis. The dominant breast milk FA were oleic acid, constituting 33% of total fatty acids, followed by palmitic acid (26%). Both these FA and the essential FA, linoleic acid (10%) and alpha-linolenic acid (0.4%), showed no significant changes from transitional to mature milk. Breast milk ratio of n-6:n-3 polyunsaturated fatty acids (PUFA) was comparatively high, exceeding 10 throughout the lactation period, suggesting a healthier balance of PUFA intake is needed in pregnancy and at postpartum