Brassinosteroid biosynthesis and signalling in Arabidopsis thaliana and Petunia hybrida

Koes, R.E. [Promotor]Souer, E.J. [Copromotor

Effects of Micronutrients during Pregnancy and Early Infancy on Mental and Psychomotor Development

Spectacular progress has been made in the last decades in the global fight against deficiencies of iodine and vitamin A [1]. As a result, the number of people suffering from iodine deficiency has been reduced from about 1.5 billion in 1990 to about 0.5 billion now, almost entirely due to the introduction in many countries of what has been termed ‘universal salt iodization’. In addition, approximately one million child deaths may have been prevented between 1998 and 2000 by vitamin A supplementation [2]. The political and financial commitment that has allowed these achievements has been generated to a large extent by scientific studies that have shown the extent of human suffering caused by these deficiencies, and that have determined the potential health gains of interventions. Progress in eliminating deficiencies of other micronutrients, notably iron, has been much slower. About two billion people, or about one third of the human population, continue to suffer from iron deficiency. Iron supplementation programs have been advocated for infants and preschool children, largely because of concerns of possible adverse effects of iron deficiency on mental and motor development. Similar concerns were instrumental in establishing salt iodization programs. The questions that will be addressed in this chapter concern the extent to which a shortage of iodine and iron during fetal and infant development impairs mental development, and the extent to which this impairment can be redressed by increasing the intake of these micronutrients. First, the stages of brain development in the fetus and infant will be addressed, followed by an assessment of the timing of vulnerable periods when the brain of the fetus and infant is at high risk of exposure to an inadequate supply of iodine or iron. Where possible, the mechanisms involved will be discussed. Then, observational and intervention studies will be reviewed that have examined the effect of deficiencies of iodine or iron on mental development. Approximately half of the world’s population may be at risk of low zinc intake [3]. Given this high prevalence, inconclusive but mounting evidence that zinc deficiency during pregnancy may possibly impair the infant’s neurobehavioral development and immune function should also raise great concern [4–10]. However, because of space limitations, such effects and those of other micronutrients [11] will not be reviewed in the present report

Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study.

BACKGROUND: Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study's objectives were to assess TNF allele variants (TNF(-1031), TNF(-308)): (1) modulation of malaria rates in young Tanzanian children; (2) modulation of the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes; and (3) the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. METHODS: Data from a placebo-controlled trial in which 612 Tanzanian children aged 6-60 months with height-for-age z-score in the range -3 SD to 1.5 SD was utilised. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. An episode of malaria was predefined as current Plasmodium infection with an inflammatory response (axillary temperature ≥37.5°C or whole blood C-reactive protein concentration ≥8 mg/L) in children reported sick. Linkage disequilibrium (LD) pattern assessment as well as haplotype analysis was conducted using HAPLOVIEW. Cox regression models used in the primary analysis accounted for multiple episodes per child. RESULTS: Genotyping of 94.9% (581/612) children for TNF(-1031) (TNF(-1031)T>C); allele frequency was 0.39. Corresponding values for rs1800629 (TNF(-308)G>A) were 95.4% (584/612) and 0.17. Compared to the wild type genotype (TT), malaria rates were increased in the TNF -1031CC genotype (hazard ratio, HR [95% CI]: 1.41 [1.01‒1.97] and 1.31 [0.97‒1.76] for crude analysis and adjusting for pre-specified baseline factors, respectively) but decreased in those with the TNF(-308)AA genotype (corresponding HR: 0.13 [0.02‒0.63] and 0.16 [0.04‒0.67]). These associations were weaker when analysing first episodes of malaria (P value -0.59 and 0.38, respectively). No evidence that allele variants of TNF(-1031) and TNF(-308) affected haemoglobin concentration at first episode of malaria, or that they modified the association between Plasmodium infection and haemoglobin concentrations at baseline was observed. CONCLUSION: In this cohort of Tanzanian children, the TNF (-1031)CC genotype was associated with increased rates of malarial episodes, whereas the TNF(-308)AA genotype was associated with decreased rates

Emerging importance of multidrug-resistant Acinetobacter species and Stenotrophomonas maltophilia as pathogens in seriously ill patients: Geographic patterns, epidemiological features, and trends in the SENTRY Antimicrobial Surveillance Program (1997-1999)

As part of the SENTRY Antimicrobial Surveillance Program, a total of 1078 Acinetobacter species and 842 Stenotrophomonas maltophilia isolates were collected between January 1997 and December 1999 from 5 geographic regions (Canada, the United States, Latin America, Europe, and the Asia-Pacific). the frequency of infections (by geographic region and body site), including those due to imipenem-resistant Acinetobacter species and trimethoprim-sulfamethoxazole (TMP-SMZ)-resistant S. maltophilia, was evaluated. the possibility of seasonal variations in bloodstream infections caused by Acinetobacter species was studied, as was the activity of several therapeutic antimicrobials against all strains. Acinetobacter species and S. maltophilia were most frequently associated with pulmonary infections, independent of the region evaluated. in contrast, patterns of antimicrobial resistance markedly varied among distinct geographic regions, especially for nosocomial isolates. Although the carbapenems were the most active antimicrobials against Acinetobacter species, nearly 11.0% of the nosocomial isolates were resistant to this drug group in both regions. TMP-SMZ, ticarcillin-clavulanic acid, gatifloxacin, and trovafloxacin were the only agents with consistent therapeutic activity against S. maltophilia isolates. Rates of resistance to TMP-SMZ ranged from 2% in Canada and Latin America to 10% in Europe. the geographic differences in resistance patterns among Acinetobacter species and S. maltophilia isolates observed in this study emphasize the importance of local surveillance in determining the most adequate therapy for acinetobacter and S. maltophilia infections and the possible clonal, epidemic nature of occurrence.Universidade Federal de São Paulo, Div Infect Dis, BR-04025010 São Paulo, BrazilUniv Iowa, Coll Med, Iowa City, IA USAQueen Elizabeth II Hlth Sci Ctr, Halifax, NS, CanadaBellvitge Hosp, Barcelona, SpainUniv Utrecht, Utrecht, NetherlandsUniversidade Federal de São Paulo, Div Infect Dis, BR-04025010 São Paulo, BrazilWeb of Scienc

Giant solitary fibrous tumour of the liver

BACKGROUND: Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm that most frequently affects the pleura, although it has been reported with increasing frequency in various other sites such as in the peritoneum, pericardium and in non-serosal sites such as lung parenchyma, upper respiratory tract, orbit, thyroid, parotid gland, or thymus. Liver parenchyma is rarely affected. Clinically, SFTs cause symptoms after having reached a certain size or when vital structures are involved. In recent years, SFTs are more often identified and distinguished from other tumours with a similar appearance due to the availability of characteristic immunohistochemical markers. CASE PRESENTATION: In this manuscript we report the case of a large tumour of the liver, which was histologically diagnosed as a SFT, and showed involvement of a single hepatic segment. Because of the patient's presentation and clinical course, it may represent a radiation-induced lesion. CONCLUSION: When a SFT has been diagnosed, surgery is the treatment of choice. The small number of patients with a SFT of the liver and its unknown natural behaviour creates the need to a careful registration and follow-up of all identified case

The decision evaluation scales

There are several instruments to assess how patients evaluate their medical treatment choice. These are used to evaluate decision aids. Our objective is to investigate which psychological factors play a role when patients evaluate their medical treatment choices. A pool of 36 items was constructed, covering concepts such as uncertainty about and satisfaction with the decision, informed choice, effective decision making, responsibility for the decision, perceived riskiness of the choice, and social support regarding the decision. This pool was presented to patients at high risk for breast and ovarian cancer, awaiting a genetic test result, and facing the choice between prophylactic surgery or screening. Additional measures were assessed for validation purposes. Factor and Rasch analyses were used for factor and item selection. Construct validity of emerging scales was assessed by relating them with the additional measures. Three factors suminarised the psychological factors concerning decision evaluation: Satisfaction-Uncertainty, Informed Choice, and Decision Control. Reliabilities (Cronbach's alpha) of the three scales were 0.79, 0.85, and 0.75, respectively. Construct validity hypotheses were confirmed. The first two scales were similar to previously developed scales. Of these three scales, the Decision Control scale correlated most strongly with the well-being measures, was associated with partner's agreement and physician's preferences as perceived by patients, and with a negative emotional reaction to the information material. In conclusion, the Decision Control scale is a new scale to evaluate decision aids, and it appears to be rooted in health psychological theories. (c) 2004 Elsevier Ireland Ltd. All rights reserved.</p

The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during Plasmodium falciparum infection

Infection with Plasmodium falciparum enhances extracellular vesicle (EV) production in parasitized red blood cells (pRBCs), an important mechanism for parasite-to-parasite communication during the asexual intraerythrocytic life cycle. The endosomal sorting complex required for transport (ESCRT), and in particular the ESCRT-III sub-complex, participates in the formation of EVs in higher eukaryotes. However, RBCs have lost the majority of their organelles through the maturation process, including an important reduction in their vesicular network. Therefore, the mechanism of EV production in P. falciparum-infected RBCs remains to be elucidated. Here we demonstrate that P. falciparum possesses a functional ESCRT-III machinery activated by an alternative recruitment pathway involving the action of PfBro1 and PfVps32/PfVps60 proteins. Additionally, multivesicular body formation and membrane shedding, both reported mechanisms of EV production, were reconstituted in the membrane model of giant unilamellar vesicles using the purified recombinant proteins. Moreover, the presence of PfVps32, PfVps60 and PfBro1 in EVs purified from a pRBC culture was confirmed by super-resolution microscopy and dot blot assays. Finally, disruption of the PfVps60 gene led to a reduction in the number of the produced EVs in the KO strain and affected the distribution of other ESCRT-III components. Overall, our results increase the knowledge on the underlying molecular mechanisms during malaria pathogenesis and demonstrate that ESCRT-III P. falciparum proteins participate in EV production