Fungal co-culture as a new source of antifungal metabolites

Background: Over the last two decades, mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD) declined by about 30% in the European Union (EU). Design: We analyzed trends in CHD (X ICD codes: I20-I25) and CVD (X ICD codes: I60-I69) mortality in young adults (age 35-44 years) in the EU as a whole and in 12 selected European countries, over the period 1980-2007. Methods: Data were derived from the World Health Organization mortality database. With joinpoint regression analysis, we identified significant changes in trends and estimated average annual percent changes (AAPC). Results: CHD mortality rates at ages 35-44 years have decreased in both sexes since the 1980s for most countries, except for Russia (130/100,000 men and 24/100,000 women, in 2005-7). The lowest rates (around 9/100,000 men, 2/100,000 women) were in France, Italy and Sweden. In men, the steepest declines in mortality were in the Czech Republic (AAPC = -6.1%), the Netherlands (-5.2%), Poland (-4.5%), and England and Wales (-4.5%). Patterns were similar in women, though with appreciably lower rates. The AAPC in the EU was -3.3% for men (rate = 16.6/100,000 in 2005-7) and -2.1% for women (rate = 3.5/100,000). For CVD, Russian rates in 2005-7 were 40/100,000 men and 16/100,000 women, 5 to 10-fold higher than in most western European countries. The steepest declines were in the Czech Republic and Italy for men, in Sweden and the Czech Republic for women. The AAPC in the EU was -2.5% in both sexes, with steeper declines after the mid-late 1990s (rates = 6.4/100,000 men and 4.3/100,000 women in 2005-7). Conclusions: CHD and CVD mortality steadily declined in Europe, except in Russia, whose rates were 10 to 15-fold higher than those of France, Italy or Sweden. Hungary and Poland, and also Scotland, where CHD trends were less favourable than in other western European countries, also emerge as priorities for preventive interventions.

Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization.

Inhibitory receptors mediate CD8 T-cell hyporesponsiveness against cancer and infectious diseases. PD-1 and CTLA-4 have been extensively studied, and blocking antibodies have already shown clinical benefit for cancer patients. Only little is known on extended co-expression of inhibitory receptors and their ligands. Here we analyzed the expression of eight inhibitory receptors by tumor-antigen specific CD8 T-cells. We found that the majority of effector T-cells simultaneously expressed four or more of the inhibitory receptors BTLA, TIM-3, LAG-3, KRLG-1, 2B4, CD160, PD-1 and CTLA-4. There were major differences depending on antigen-specificity, differentiation and anatomical localization of T-cells. On the other hand, naive T-cells were only single or double positive for BTLA and TIM-3. Extended co-expression is likely relevant for effector T-cells, as we found expression of multiple ligands in metastatic lesions of melanoma patients. Together, our data suggest that naive T-cells are primarily regulated by BTLA and TIM-3, whereas effector cells interact via larger numbers of inhibitory receptors. Blocking multiple inhibitory receptors simultaneously or sequentially may improve T-cell based therapies, but further studies are necessary to clarify the role of each receptor-ligand pair.

High-frequency linkage of co-expressing T-DNA in transgenic Arabidopsis thaliana transformed by vacuum-infiltration of Agrobacterium tumefaciens

The efficiency of co-expression and linkage of distinct T-DNAs present in separate Agrobacterium tumefaciens was analysed in Arabidopsis thaliana transformed by the vacuum infiltration method. Co-expression was monitored by the synthesis of three bacterial proteins involved in the production of polyhydroxybutyrate (PHB) in the plastids. Out of 80 kanamycin-resistant transgenic plants analysed, 13 plants were co-transformed with the two distinct T-DNAs and produced PHB. Of those, 7 lines had a kanamycin-resistance segregation ratio consistent with the presence of a single functional insert. Genetic linkage between the distinct T-DNAs was demonstrated for all 13 PHB-producing lines, while physical linkage between the distinct T-DNAs was shown for 12 out of 13 lines. T-DNAs were frequently linked in an inverted orientation about the left borders. Transformation of A. thaliana by the co-infiltration of two A. tumefaciens containing distinct T-DNAs is, thus, an efficient approach for the integration and expression of several transgenes at a single locus. This approach will facilitate the creation and study of novel metabolic pathways requiring the expression of numerous transgenes.

Different arbuscular mycorrhizal fungi alter coexistence and resource distribution between co-occurring plants

It is often thought that the coexistence of plants and plant diversity is determined by resource heterogeneity of the abiotic environment. However, the presence and heterogeneity of biotic plant resources, such as arbuscular mycorrhizal fungi (AMF), could also affect plant species coexistence. In this study, Brachypodium pinnatum and Prunella vulgaris were grown together in pots and biotic resource heterogeneity was simulated by inoculating these pots with one of three different AMF taxa, with a mixture of these three taxa, or pots remained uninoculated. The AMF acted as biotic plant resources since the biomass of plants in pots inoculated with AMF was on average 11.8 times higher than uninoculated pots. The way in which the two plant species coexisted, and the distribution of phosphorus and nitrogen between the plant species, varied strongly depending on which AMF were present. The results showed that the composition of AMF communities determines how plant species coexist and to which plant species nutrients are allocated. Biotic plant resources such as AMF should therefore be considered as one of the factors that determine how plant species coexist and how soil resources are distributed among co-occurring plant species.

Haut potentiel intellectuel et TDA/H: ressemblances, différences, co-existence ?

Si les particularités du haut potentiel intellectuel (HPI) et du trouble déficit d'attention avec/sans hyperactivité (TDA/H) sont largement décrites dans la littérature, les liens entre ces deux profils sont moins connus. Il est pourtant établi que HPI et TDA/H partagent des manifestations communes comme l'agitation, les difficultés scolaires ou les troubles du comportement. Cette similitude sémiologique est responsable de confusions, d'errance diagnostique, voire de choix thérapeutiques discutables. Et la mission du médecin devient même particulièrement délicate lorsqu'il s'agit d'envisager une éventuelle « co-morbidité ». La clinique nous apprend en effet que le HPI et le TDA/H peuvent cohabiter chez le même enfant. Ainsi, les identifier et les prendre en charge devient un exercice complexe mais indispensable, car l'approche et le soutien de ces enfants aux besoins particuliers est très différente selon les cas de figure.

Composition and cost of drugs stored at home by elderly patients.

BACKGROUND: Elderly people often have multiple chronic diseases, are frequently treated by several physicians, and also use over-the-counter medications. Excessive prescribing, imperfect therapeutic adherence, treatment modifications after hospitalization, and oversized drug packages result in home storage of leftover drugs, resulting in a waste of healthcare resources. PATIENTS AND METHODS: All patients aged >/=75 years hospitalized for >24 hours during a 6-month period in an urban teaching hospital in Switzerland were eligible for inclusion in a study collecting sociodemographics, medical, functional, and psychosocial characteristics. Six months later, a research nurse visited the patients at home and recorded the names, number of tablets, and expiration dates of all open or intact drug packages, and the doses actually taken. Acquisition costs of these drugs were computed. RESULTS: One hundred ninety-five patients were included (127 women; mean age 82.2 +/- 4.8 y, range 75-96). They had a total of 2059 drugs (mean per patient 10.3 +/- 6.7, range per patient 1-42), corresponding to a total cost of (US) $62 826 (mean per patient 322 +/- 275, range per patient 10-1571). Self-reported drug intake was regular for 36% of the drugs (46.5% of total costs) and occasional for 11% (6.1%), whereas 35.7% (30.1%) had been stopped during the last month. Cardiovascular drugs amounted to 36.6% of the drugs and 55.5% of the costs. None of the patients' characteristics was significantly associated with a greater number of drugs and higher costs. CONCLUSIONS: Drugs stored at home by elderly patients were worth about $320 per patient. Only about one-third of these drugs were regularly taken. In the context of resources shortage, innovative solutions should be found to reduce the waste linked with drugs stopped in previous months.

Effectiveness of a pediatric palliative home care team as experienced by parents and health care professionals.

OBJECTIVES: Little data are available on palliative home care for children. The objective of this study was to evaluate the effectiveness of a specialized pediatric palliative home care team (PPHCT) as experienced by parents and health care professionals (HCPs). METHODS: Parents and HCPs involved in the care of terminally ill children who died and whom the PPHCT was in charge of were surveyed with questionnaires focusing on satisfaction with the PPHCT, satisfaction with the course of the dying phase, and the development of anxiety, depression, and prolonged grief disorder. RESULTS: Forty-three parent dyads participated (return rate, 88%). Satisfaction with the PPHCT scored a median of 10 (numeric rating scale, 0-10). The child's death was predominantly experienced as very peaceful (median, 9); 71% died at home. According to parents, involvement of the PPHCT led to highly significant (p<0.001) improvements in the children's symptoms and quality of life, as well as in aspects of communication and administrative barrier reduction. Anxiety was detected in 25% of parents, depression in 19%, and prolonged grief disorder in 13%. HCPs (return rate, 83%) evaluated all investigated care domains (particularly cooperation/communication/family support) as being significantly improved (p<0.001). Thirty-five percent of HCPs felt uncertain concerning pediatric palliative care; 79% would welcome specific training opportunities. CONCLUSIONS: Involvement of a PPHCT is experienced as a substantial improvement of care by parents and HCPs. Coordination of palliative care during the last phase of life appears to be an important quality factor for the home care of dying children and their families.

Geological setting of the Guelb Moghrein Fe oxide-Cu-Au-Co mineralization, Akjoujt area, Mauritania

The Guelb Moghrein Fe oxide-Cu-Au-Co deposit is located at the western boundary of the West African craton in NW Mauritania. The wall rocks to the mineralization represent a meta-volcanosedimentary succession typical of Archaean greenstone belts. Two types of meta-volcanic rocks are distinguished: (1) volcanoclastic rocks of rhyodacite-dacite composition (Sainte Barbe volcanic unit), which form the stratigraphic base; (2) tholeiitic andesites-basalts (Akjoujt meta-basalt unit). The trace element signature of both types is characteristic of a volcanic arc setting. A small meta-pelitic division belongs to the Sainte Barbe volcanic unit. A meta-carbonate body, which contains the mineralization, forms a tectonic lens in the Akjoujt meta-basalt unit. It can be defined by the high X(mg) (=36) of Fe-Mg carbonate, the REE pattern and the delta(13)C values of -18 to -17 parts per thousand as a marine precipitate similar to Archaean banded iron formation (BIF). Additionally, small slices of Fe-Mg clinoamphibole-chlorite schist in the meta-carbonate show characteristics of marine shale. This assemblage, therefore, does not represent an alteration product, but represents an iron formation unit deposited on a continental shelf, which probably belongs to the Lembeitih Formation. The hydrothermal mineralization at 2492 Ma was contemporaneous with regional D(2) thrusting of the Sainte Barbe volcanic unit and imbrications of the meta-carbonate in the upper greenschist facies. This resulted in the formation of an ore breccia in the meta-carbonate, which is enriched in Fe, Ni, Co, Cu, Bi, Mo, As and Au. Massive sulphide ore breccia contains up to 20 wt% Cu. The ore fluid was aqueous-carbonic in nature and either changed its composition from a Mg-rich oxidizing to an Fe-rich reducing fluid or the two fluid types mixed at the trap site. All lithologies at Guelb Moghrein were deformed by D(3) thrusting to the east in the lower greenschist facies. The mobility of REE in the retrogressed rocks explains the formation of a second generation of hydrothermal monazite, which was dated at c. 1742 Ma. Archaean rocks of the West African craton extend to the west to Guelb Moghrein. The active continental margin was deformed and mineralized in the Late Archaean-Early Proterozoic and again reactivated in the Mid-Proterozoic and Westphalian, showing that the western boundary of the craton was reactivated several times.