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Background: Air pollution exposure reduces life expectancy. Air pollution, deprivation and poor-health status combinations can create increased and disproportionate disease burdens. Problems and solutions are rarely considered in a broad public health context, but doing so can add value to air quality management efforts by reducing air pollution risks, impacts and inequalities., Methods: An ecological study assessed small-area associations between air pollution (nitrogen dioxide and particulate matter), deprivation status and health outcomes in Wales, UK., Results: Air pollution concentrations were highest in 'most' deprived areas. When considered separately, deprivation-health associations were stronger than air pollution-health associations. Considered simultaneously, air pollution added to deprivation-health associations; interactions between air pollution and deprivation modified and strengthened associations with all-cause and respiratory disease mortality, especially in 'most' deprived areas where most-vulnerable people lived and where health needs were greatest., Conclusion: There is a need to reduce air pollution-related risks for all. However, it is also the case that greater health gains can result from considering local air pollution problems and solutions in the context of wider health-determinants and acting on a better understanding of relationships. Informed and co-ordinated air pollution mitigation and public health action in high deprivation and pollution areas can reduce risks and inequalities. To achieve this, greater public health integration and collaboration in local air quality management policy and practice is needed., (© The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gastrointestinal stromal tumours often present with insidious upper gastrointestinal symptoms. Initial definitive diagnosis can be difficult and therefore misdiagnosis is not infrequent. Here we report a case of upper GI bleeding caused by a splenic artery aneurysm that was misdiagnosed as a gastric GIST. This rare presentation of splenic artery aneurysm highlights the potential pitfalls of investigation in upper gastrointestinal disease., (© JSCR.)

Background: ICSI is used with increasing frequency, but there is less information about the children born following this method of assisted reproduction than other forms of IVF. Some authors have suggested that it may contribute to more family stress than IVF., Methods: ICSI conceived children were compared with IVF conceived children and naturally conceived (NC) controls. They were selected in five European countries: Belgium, Denmark, Greece, Sweden and the UK, and seen for psychological testing and a paediatric examination when they were 5 years old. In all countries, except Greece, mothers and fathers were asked to complete questionnaires about parental well-being, family relationships, parenting and child behaviour., Results: Very few differences were found between the ICSI and NC group or the ICSI and IVF group. The only significant differences were that mothers in the ICSI conceived group reported fewer hostile or aggressive feelings towards the child and higher levels of commitment to parenting than the mothers of NC children., Conclusions: The study confirms the results of previous work with IVF families. This should be encouraging for families using these techniques in the future.

Cryptococcus neoformans var. gattii has been shown to have a strong association with eucalypts frequently used by koalas and, not surprisingly, it has been shown to colonize the nasal cavities of koalas. The progression from nasal colonization to tissue invasion is critical to understanding the pathogenesis of cryptococcosis in this species and provides a model for pathogenesis of cryptococcosis in other species. Cryptococcal antigenaemia was detected in twenty-eight healthy koalas from three different regions. This was interpreted as representing limited subclinical disease. One koala developed cryptococcal pneumonia 6 months after leaving the study, whereas another developed cryptococcal meningoencephalitis during the course of the study. Opportunistic necropsies on ten antigen-positive koalas resulted in discovery of small cryptococcal lesions in two (paranasal sinus and lung, respectively). Our data suggest that cryptococcal antigenaemia occurs commonly in koalas, especially in areas with a high environmental presence of C n. var. gattii. Subclinical disease appears most likely to manifest as a small focal lesion in the respiratory tract. Possible outcomes include elimination by an effective immune response, quiescence with possibility of later re-activation or direct progression to overt disease. Symptomatic and subclinical cases showed differences in levels of antigenaemia. The data presented have significant implications for koalas in captivity.

Spring wheat (Triticum aestivum cv. Hanno) was grown at ambient (350 micromol mol(-1)) or elevated CO(2) (700 micromol mol(-1)) in charcoal/Purafil-filtered air (CFA <5 nmol mol(-1)) or ozone (CFA +75 nmol mol(-1) 7 h d(-1)) at three levels of N supply (1.5, 4 and 14 mM NO(-3)), to test the hypothesis that the combined impacts of elevated CO(2) and O(3) on plant growth and photosynthetic capacity are affected by nitrogen availability. Shifts in foliar N content reflected the level of N supplied, and the growth stimulation induced by elevated CO(2) was dependent on the level of N supply. At 60 d after transfer (DAT), elevated CO(2) was found to increase total biomass by 44%, 29%, 12% in plants supplied with 14, 4 and 1.5 mM NO(-3), respectively, and there was no evidence of photosynthetic acclimation to elevated CO(2) across N treatments; the maximum in vivo rate of Rubisco carboxylation (V(cmax)) was similar in plants raised at elevated and ambient CO(2). At 60 DAT, ozone exposure was found to suppress plant relative growth rate (RGR) and net photosynthesis (A) in plants supplied with 14 and 4 mM NO(-3). However, O(3) had no effect on the RGR of plants supplied with 1.5 mM NO(-3) and this effect was accompanied by a reduced impact of the pollutant on A. Elevated CO(2) counteracted the detrimental effects of O(3) (i.e. the same ozone concentration that depressed RGR and A at ambient CO(2) resulted in no significant effects when plants were raised at elevated CO(2)) at all levels of N supply and the effect was associated with a decline in O(3) uptake at the leaf level.

The chemical composition of St. John's wort has been well-studied. Documented pharmacological activities, including antidepressant, antiviral, and antibacterial effects, provide supporting evidence for several of the traditional uses stated for St John's wort. Many pharmacological activities appear to be attributable to hypericin and to the flavonoid constituents; hypericin is also reported to be responsible for the photosensitive reactions that have been documented for St. John's wort. With regard to the antidepressant effects of St John's wort, hyperforin, rather than hypericin as originally thought, has emerged as one of the major constituents responsible for antidepressant activity. Further research is required to determine which other constituents contribute to the antidepressant effect. Evidence from randomised controlled trials has confirmed the efficacy of St John's wort extracts over placebo in the treatment of mild-to-moderately severe depression. Other randomised controlled studies have provided some evidence that St John's wort extracts are as effective as some standard antidepressants in mild-to-moderate depression. There is still a need for further trials to assess the efficacy of St John's wort extracts, compared with that of standard antidepressants, particularly newer antidepressant agents, such as the selective serotonin reuptake inhibitors (recent comparative studies with fluoxetine and sertraline have been conducted). Also, there is a need for further studies in well-defined groups of patients, in different types of depression, and conducted over longer periods in order to determine long-term safety. St John's wort does appear to have a more favourable short-term safety profile than do standard antidepressants, a factor that is likely to be important in patients continuing to take medication. Concerns have been raised over interactions between St John's wort and certain prescribed medicines (including warfarin, ciclosporin, theophylline, digoxin, HIV protease inhibitors, anticonvulsants, selective serotonin reuptake inhibitors, triptans, oral contraceptives); advice is that patients taking these medicines should stop taking St John's wort, generally after seeking professional advice as dose adjustment of conventional treatment may be necessary.

Broad bean (Vicia faba L.) plants were exposed, in duplicate controlled environment chambers, to charcoal/Purafil-filtered air (CFA-grown plants) or to 75 nmol mol(-1) ozone (O(3)) for 7 h d(-1) (O(3)-grown plants) for 28 d, and then exposed to 150 nmol mol(-1) O(3 )for 8 h. The concentration of ascorbate (ASC) was determined in leaf extracellular washing fluid (apoplast) and in the residual leaf tissue (symplast) after 0, 4 and 8 h acute fumigation, and after a 16 h "recovery" period in CFA. Changes in stomatal conductance were measured in vivo in order to model pollutant uptake, while the light-saturated rate of CO(2) assimilation (A:(sat)) was recorded as an indicator of O(3)-induced intracellular damage. Measurements of A:(sat) revealed enhanced tolerance to 150 nmol mol(-1) O(3) in plants pre-exposed to the pollutant compared with equivalent plants grown in CFA, consistent with the observed reduction in pollutant uptake due to lower stomatal conductance. The concentration of ASC in the leaf apoplast (ASC(apo)) declined upon O(3)-treatment in both CFA- and O(3)-grown plants, consistent with the oxidation of ASC(apo) under O(3)-stress. Furthermore, the decline in ASC(apo) was reversible in O(3)-grown plants after a 16 h "recovery" period, but not in plants grown in CFA. No significant change in the level and/or redox state of ASC in the symplast (ASC(symp)) was observed in plants exposed to 150 nmol mol(-1) O(3), and there was no difference in the constitutive level of ASC(symp) between CFA- and O(3)-grown plants. Model calculations indicated that the reaction of O(3) with ASC(apo) in the leaves of Vicia faba is potentially sufficient to intercept a substantial proportion (30-40%) of the O(3)entering the plant under environmentally-relevant conditions. The potential role of apoplastic ASC in mediating the tolerance of leaves to O(3) is discussed.

Previously, we showed that the age-dependent deficit in bone formation activity can be attributed in part to a decline in local expression of insulin-like growth factor I (IGF-I) and altered mitogenic response of old osteoprogenitor cells to IGF-I. To establish the cellular basis for using IGF-I as a possible therapeutic agent for osteoporosis, we examined the effect of locally infused (50 ng/day for 14 days) on the expression of osteoblast-related genes in femurs of old rats. Northern and dot blot analyses showed that the expression of procollagen (I), osteopontin, alkaline phosphatase, and osteocalcin was increased 0.4- to 1.5-fold in IGF-I-treated femurs as compared with control femurs. Histomorphometric analyses were carried out in parallel experiments to assess the changes in bone remodeling activity. Trabecular bone volume, trabecular number, and trabecular thickness were increased 56%, 29%, and 23%, respectively, whereas trabecular separation was reduced 26% by IGF-I treatment. IGF-I treatment increased significantly the osteoid volume, osteoid surface, osteoblast number, and osteoblast surface. Mineralizing surface and mineral apposition rate, kinetic indices of bone formation, were also stimulated by IGF-I treatment. The bone formation rate was stimulated 81% in IGF-I-treated femurs as compared with control femurs. In contrast, eroded surface and osteoclast surface, parameters associated with bone resorption, were not affected by IGF-I treatment. These findings suggest that local administration of IGF-I into femurs of old rats can stimulate the expression of matrix proteins and improve trabecular bone status by stimulating bone formation without any appreciable effect on bone resorption.

Mutations that perturb neuronal migration provide important biological clues that can lead to an understanding of the role of specific cells and molecules in the formation of the cortex. The human neuronal migration disorder, Miller-Dieker Lissencephaly, results from a hemideletion of LIS-1, which encodes a subunit of a brain platelet-activating factor acetylhydrolase. The cellular localization of the LIS-1 gene product in human fetal brain and its normal role in neuronal migration have yet to be determined. LIS-1 belongs to a family of genes that have identical coding sequences (LIS-1 [chromosome 17] and LIS-2 [chromosome 2]). In the brain, LIS-1 is the more abundant gene as determined by Northern blot analysis. Using antibodies raised against 2 epitopes of the LIS-1/LIS-2 protein sequence, we have localized the LIS family of gene products in the developing human brain to the Cajal-Retzius cells, some subplate neurons, thalamic neurons, the ventricular neuroepithelium, and at later gestational ages, to the ependyma. Therefore, LIS-1 bears some resemblance to reelin, the gene product involved in the cortical mouse mutant reeler, in that Cajal-Retzius cells demonstrate immunolocalization. However, unlike reelin, LIS proteins are expressed not only in the Cajal Retzius cells, but also in the ventricular neuroepithelium, suggesting a potential role for this structure in neuronal migration.

Previously we reported that uptake of Ca2+ in cells isolated from rat duodenum declined in senescence. In this paper we examined the possible mechanisms for this age-related defect. Duodenal vitamin D-dependent calcium-binding protein decreased steadily from 3-12 months (mo), followed by a minimal decline at 24 mo. On the contrary, Ca2+ uptake was not different in 3-, 6-, and 12-mo-old rats. A significant decline of Ca2+ uptake was observed at 24 mo. ATP contents in duodenal cells from 6- and 24-mo-old rats were not different. This suggests that the metabolic status of the duodenal cells was not the cause of the change in Ca2+ uptake. Ca2+ uptake activity was significantly lower in brush border membrane vesicles isolated from 24-mo-old rats than in those from 6-mo-old rats. The decrease in Ca2+ uptake activity in old rats was not due to a change in the Ca2(+)-binding capacity of the membranes. Kinetic analysis shows that the Vmax, the apparent maximum uptake capacity of membrane vesicles, decreased in senescent rats, whereas the Km, the apparent affinity to Ca2+, was unchanged. Since duodenal Ca2+ influx at the brush border was regulated by 1,25-dihydroxy-vitamin D3 [1,25-(OH)2D3], we tested the effect of 1,25-(OH)2D3 administration on the uptake activity in isolated membrane vesicles. After 1,25-(OH)2D3 treatment, Ca2+ uptake activity in brush border membranes prepared from senescent rats was only slightly lower than that in membranes from adult rats. We conclude that the decline in the influx of Ca2+ at the brush border membrane was the main cause of the decrease in duodenal Ca2+ uptake activity in aging. This defect was probably due to the low serum 1,25-(OH)2D3 concentration and not the result of impaired response to 1,25-(OH)2D3.

Uptake of Ca2+ in cells isolated from rat duodenum declined in the senescent rats. This age-related change was not due to an alteration in the rate of Ca2+ efflux or in the size of the cell. The decrease appeared specific, as alpha-methyl glucoside uptake was not altered. Cell population, as monitored by sucrase activity for villus cells, was not different between duodenal cells isolated from 6- and 24-month-old rats. Kinetic analysis shows the Vmax, the apparent maximum uptake capacity, decreased in the cells from senescent rats whereas the Km, the apparent affinity to Ca2+, was unchanged. Serum levels of 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] were determined as a function of age; the levels of 25OHD were not significantly different in 3-, 6-, 12-, and 24-month-old rats. On the other hand, serum 1,25-(OH)2D decreased throughout the age range studied. Since duodenal Ca2+ uptake is closely regulated by 1,25-(OH)2D3, we tested the hypothesis that low serum 1,25-(OH)2D in the senescent rats may have contributed to the decline in duodenal Ca2+ uptake. In vivo administration of 1,25-(OH)2D3 to senescent rats significantly enhanced Ca2+ uptake activity in the isolated duodenal cells. After 1,25-(OH)2D3 treatment, Ca2+ uptake activity in cells isolated from senescent rats was only slightly less than that in cells from adult rats. We conclude that duodenal Ca2+ uptake declined in the senescent rats, and this age-related change was most likely due to the low serum level of 1,25-(OH)2D and not the result of a decrease in any duodenal response to 1,25-(OH)2D3.