Treatment of the Mayer-Rokitansky-Küster-Hauser syndrome with autologous in vitro cultured vaginal tissue: descriptive study of long-term results and patient outcomes.

OBJECTIVE: Evaluating sexual function and quality of life (QoL) in patients treated with a modified Abbé-McIndoe technique using in vitro cultured autologous vaginal mucosa. DESIGN: Descriptive study. SETTING: Policlinico Umberto I, Sapienza University of Rome. POPULATION: From 2006 to 2016, 39 women affected by Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) underwent vaginoplasty at our centre using a modified Abbé-McIndoe technique with in vitro cultured autologous vaginal tissue. METHODS: For each patient, vaginal tissue was obtained by full-thickness biopsy of the vaginal vestibule. Following enzymatic dissociation, cells were cultured for 2-3 weeks before the transplant. MAIN OUTCOME MEASURES: Each patient completed two validated questionnaires to quantify sexual function and QoL: the Female Sexual Function Index (FSFI), administered at 12, 36, and 60 months, and the Psychological General Well Being Index (PGWBI) administered at 0, 6, and 36 months after surgery. RESULTS: Twelve months after surgery, 29 patients were engaging in regular sexual activity. The FSFI test results showed a satisfactory sexual function compared to the general population, with median values of 25.85 (range 4.6-30.5) at 12 months, 27.2 (range 4.4-33.6) at 36 months, and 29.6 (range 23.9-33.6) at 60 months. The PGWBI questionnaire showed a median score of 420.5 (range 108-540) before surgery, and 459 (range 252-533) at the 60-month follow-up. CONCLUSIONS: Vaginoplasty performed with the use of autologous vaginal tissue, besides ensuring a long-term satisfying sex life, helps in achieving an improvement in QoL that is maintained over time. TWEETABLE ABSTRACT: Vaginoplasty using in vitro vaginal tissue ensures a satisfactory sexual function and improves quality of life.

Assessment of genetic diversity and yield performance in Jordanian barley (Hordeum vulgare L.) landraces grown under Rainfed conditions.

BACKGROUND: Barley (Hordeum vulgare L.) is a major cereal crop, which is cultivated under variable environmental conditions and abiotic stresses in marginal areas around the globe. In this study, we evaluated 150 Jordanian landraces obtained from ICARDA Gene Bank and four local checks for yield and yield components related-traits in two locations across Jordan for three growing seasons under rainfed conditions. The study aims to identify superior Jordanian barley genotypes under dry conditions, to understand the genotype × environment (G × E) interactions, to analyze stability parameters and to identify markers associated with yield and yield components under rainfed conditions. RESULTS: The barley accessions exhibited significant variation for all traits studied. Three accessions with high yield, cultivar superiority and stability under specific environments were identified with accession G69 is the highest yielding and superior for Madaba and overall environments and G144 is the highest yielding at Ramtha. Accession G123 was high yielding in all environments and was stable across different environments. At the genetic level, the Jordanian landraces were found to be diverse with a clustering that was based on row-type. The GWAS analysis identified 77 significant markers-traits associations for multiple traits including grain yield (GY) with three significant QTLs located at 1H, 2H and 7H, which seem important for dry environments. CONCLUSION: Utilizing Jordanian barley landraces can effectively improve and adapt the current barley cultivars for cultivation under environmental stresses in dry regions. Utilization of markers associated with important agronomical traits and their incorporation in breeding using marker assisted selection can improve barley tolerance to drought stress.

Urinary (1)H-NMR-based metabolic profiling of children with NAFLD undergoing VSL#3 treatment.

BACKGROUND: Nowadays, non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children. Our recent clinical trial demonstrated that dietary and VSL#3-based interventions may improve fatty liver by ultrasound and body mass index (BMI) after 4 months. OBJECTIVES: As in this short-term trial, as in others, it is impracticable to monitor response to therapy or treatment by liver biopsy, we aimed to identify a panel of potential non-invasive metabolic biomarkers by a urinary metabolic profiling. METHODS: Urine samples from a group of 31 pediatric NAFLD patients, enrolled in a VSL#3 clinical trial, were analyzed by high-resolution proton nuclear magnetic resonance spectroscopy in combination with analysis of variance-Simultaneous Component Analysis model and multivariate data analyses. Urinary metabolic profiles were interpreted in terms of clinical patient feature, treatment and chronology pattern correlations. RESULTS: VSL#3 treatment induced changes in NAFLD urinary metabolic phenotype mainly at level of host amino-acid metabolism (that is, valine, tyrosine, 3-amino-isobutyrate or ß-aminoisobutyric acid (BAIBA)), nucleic acid degradation (pseudouridine), creatinine metabolism (methylguanidine) and secondarily at the level of gut microbial amino-acid metabolism (that is, 2-hydroxyisobutyrate from valine degradation). Furthermore, some of these metabolites correlated with clinical primary and secondary trial end points after VSL#3 treatment: tyrosine and the organic acid U4 positively with alanine aminotransferase (R=0.399, P=0.026) and BMI (R=0.36, P=0.045); BAIBA and tyrosine negatively with active glucagon-like-peptide 1 (R=-0.51, P=0.003; R=-0.41, P=0.021, respectively). CONCLUSIONS: VSL#3 treatment-dependent urinary metabotypes of NAFLD children may be considered as non-invasive effective biomarkers to evaluate the response to treatment.

Variation at the vernalisation genes Vrn-H1 and Vrn-H2 determines growth and yield stability in barley (Hordeum vulgare) grown under dryland conditions in Syria.

KEY MESSAGE: Spring growth in barley controlled by natural variation at Vrn-H1 and Vrn-H2 improved yield stability in marginal Syrian environments. The objective of the present study was to identify QTL influencing agronomic performance in rain-fed Mediterranean environments in a recombinant inbred line (RIL) population, ARKE derived from the Syrian barley landrace, Arta and the Australian feed cultivar, Keel. The population was field tested for agronomic performance at two locations in Syria for 4 years with two sowing dates, in autumn and winter. Genotypic variability in yield of the RIL population was mainly affected by year-to-year variation presumably caused by inter-annual differences in rainfall distribution. The spring growth habit and early flowering inherited from the Australian cultivar Keel increased plant height and biomass and improved yield stability in Syrian environments. QTL for yield and biomass coincided with the map location of flowering time genes, in particular the vernalisation genes Vrn-H1 and Vrn-H2. In marginal environments with terminal drought, the Vrn-H1 allele inherited from Keel improved final biomass and yield. Under changing climate conditions, such as shorter winters, reduced rainfall, and early summer drought, spring barley might thus outperform the traditional vernalisation-sensitive Syrian landraces. We present the ARKE population as a valuable genetic resource to further elucidate the genetics of drought adaptation of barley in the field.

Inhibiting DNA methylation as a strategy to enhance adipose-derived stem cells differentiation: Focus on the role of Akt/mTOR and Wnt/ß-catenin pathways on adipogenesis.

Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, due to their ability to repair damaged tissues and to mitigate the inflammatory/immune response. A better understanding of the underlying mechanisms regulating ASC biology might represent the chance to modulate their in vitro characteristics and differentiation potential for regenerative medicine purposes. Herein, we investigated the effects of the demethylating agent 5-azacytidine (5-aza) on proliferation, clonogenicity, migration, adipogenic differentiation and senescence of ASCs, to identify the molecular pathways involved. Through functional assays, we observed a detrimental effect of 5-aza on ASC self-renewal capacity and migration, accompanied by actin cytoskeleton reorganization, with decreased stress fibers. Conversely, 5-aza treatment enhanced ASC adipogenic differentiation, as assessed by lipid accumulation and expression of lineage-specific markers. We analyzed the involvement of the Akt/mTOR, MAPK and Wnt/ß-catenin pathways in these processes. Our results indicated impairment of Akt and ERK phosphorylation, potentially explaining the reduced cell proliferation and migration. We observed a 5-aza-mediated inhibition of the Wnt signaling pathway, this potentially explaining the pro-adipogenic effect of the drug. Finally, 5-aza treatment significantly induced ASC senescence, through upregulation of the p53/p21 axis. Our data may have important translational implications, by helping in clarifying the potential risks and advantages of using epigenetic treatment to improve ASC characteristics for cell-based clinical approaches.

Mixed model association scans of multi-environmental trial data reveal major loci controlling yield and yield related traits in Hordeum vulgare in Mediterranean environments.

An association panel consisting of 185 accessions representative of the barley germplasm cultivated in the Mediterranean basin was used to localise quantitative trait loci (QTL) controlling grain yield and yield related traits. The germplasm set was genotyped with 1,536 SNP markers and tested for associations with phenotypic data gathered over 2 years for a total of 24 year × location combinations under a broad range of environmental conditions. Analysis of multi-environmental trial (MET) data by fitting a mixed model with kinship estimates detected from two to seven QTL for the major components of yield including 1000 kernel weight, grains per spike and spikes per m(2), as well as heading date, harvest index and plant height. Several of the associations involved SNPs tightly linked to known major genes determining spike morphology in barley (vrs1 and int-c). Similarly, the largest QTL for heading date co-locates with SNPs linked with eam6, a major locus for heading date in barley for autumn sown conditions. Co-localization of several QTL related to yield components traits suggest that major developmental loci may be linked to most of the associations. This study highlights the potential of association genetics to identify genetic variants controlling complex traits.

Hyper-IgM, neutropenia, mild infections and low response to polyclonal stimulation: hyper-IgM syndrome or common variable immunodeficiency?

A young woman presenting respiratory infections, polyarthritis, severe neutropenia, and increased serum IgM was treated with intravenous immunoglobulin (IVIG) with good clinical and laboratory outcome followed by a loss of efficacy. The increased serum IgM associated to recurrent infections and autoimmune manifestations suggested the diagnosis of a hyper-IgM syndrome (HIGMs). The frequency of peripheral T cells, the expression of CD40 on the patients' B cells and CD40L on T cells and the activation-induced cytidine deaminase (AID) and uracil-DNA glycosylase (UNG) at mRNA level was comparable to controls. In contrast, the frequency of B cells was one half of the healthy control and all cells showed an atypical phenotype. Although AID and UNG were normal, class-switch recombination was not very efficient because circulating switched memory were reduced and, once stimulated with CpG, generated less antibody-secreting cells than controls. An increase in serum B Lymphocytes stimulator (BLyS) was also found. The patient presented a peculiar clinical and immunological phenotype fitting for many aspects of both HIGM4 and Common Variable Immunodeficiency (CVID). These findings underline the need to better explore the complex link between these two diseases.

Complex multipathways alterations and oxidative stress are associated with Hailey-Hailey disease.

BACKGROUND: Hailey-Hailey disease (HHD) is an autosomal dominant disorder characterized by suprabasal cutaneous cell separation (acantholysis) leading to the development of erosive and oozing skin lesions. While a strong relationship exists between mutations in the gene that encodes the Ca(2+)/Mn(2+)-adenosine triphosphatase ATP2C1 and HHD, we still have little understanding of how these mutations affect manifestations of the disease. OBJECTIVES: This study was designed to determine early signalling events that affect epithelial cell growth and differentiation during HHD development. METHODS: Expression of key regulatory signals important for maintaining skin homeostasis were evaluated by Western blot analysis and by reverse transcriptase-polymerase chain reaction in primary keratinocytes obtained from skin biopsies of patients with HHD. Reactive oxygen species accumulation in primary keratinocytes derived from lesional skin of patients with HHD was assessed by dihydrorhodamine 123 (DHR) assay. RESULTS: HHD-derived keratinocytes showed downregulation of both Notch1 and differential regulation of different p63 isoforms. Itch and p63 are co-expressed in the epidermis and in primary keratinocytes where Itch controls the p63 protein steady-state level. We found that the Itch protein was significantly decreased in HHD-derived keratinocytes whereas the expression of its target, c-Jun, remained unaffected. We also found that HHD-derived keratinocytes undergo oxidative stress, which may explain both Notch1 and Itch downregulation. CONCLUSIONS: Our attempt to explore the molecular mechanism underlying HHD indicates a complex puzzle in which multi-hit combinations of altered signal pathways may explain the wide spectrum of defects in HHD.

Patterns of genetic diversity and linkage disequilibrium in a highly structured Hordeum vulgare association-mapping population for the Mediterranean basin.

Population structure and genome-wide linkage disequilibrium (LD) were investigated in 192 Hordeum vulgare accessions providing a comprehensive coverage of past and present barley breeding in the Mediterranean basin, using 50 nuclear microsatellite and 1,130 DArT((R)) markers. Both clustering and principal coordinate analyses clearly sub-divided the sample into five distinct groups centred on key ancestors and regions of origin of the germplasm. For given genetic distances, large variation in LD values was observed, ranging from closely linked markers completely at equilibrium to marker pairs at 50 cM separation still showing significant LD. Mean LD values across the whole population sample decayed below r (2) of 0.15 after 3.2 cM. By assaying 1,130 genome-wide DArT((R)) markers, we demonstrated that, after accounting for population substructure, current genome coverage of 1 marker per 1.5 cM except for chromosome 4H with 1 marker per 3.62 cM is sufficient for whole genome association scans. We show, by identifying associations with powdery mildew that map in genomic regions known to have resistance loci, that associations can be detected in strongly stratified samples provided population structure is effectively controlled in the analysis. The population we describe is, therefore, shown to be a valuable resource, which can be used in basic and applied research in barley.

IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-kappaB and reduces the inflammatory response in myocardial ischemia-reperfusion injury.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) is a ubiquitous rapid response transcription factor involved in inflammatory reactions which exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. Oxidative stress causes NF-kappaB activation. IRFI 042 is a novel dual vitamin E-like antioxidant and we, therefore, investigated its ability to protect the heart from oxidative stress and to halt the inflammatory response in a model of myocardial ischaemia-reperfusion injury. METHODS: Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5-h reperfusion (MI/R). Sham myocardial ischaemia rats (sham-operated rats) were used as controls. Myocardial necrosis, cardiac output, cardiac and plasma vitamin E levels, myocardial malondialdehyde (MAL), cardiac SOD activity and elastase content (an index of leukocyte infiltration), hydroxyl radical (OH&z.ccirf;) formation, cardiac amount of mRNA codifying for ICAM-1 (evaluated by the means of reverse transcriptase polymerase chain reaction) and ICAM-1 immunostaining in the at-risk myocardium were investigated. NF-kappaB activation and the inhibitory protein of NF-kappaB, I-kappaBalpha, were also studied in at-risk myocardium by using electrophoretic mobility shift assay (EMSA) and Western blot analysis, respectively. RESULTS: The ischaemia-reperfusion model produced wide heart necrosis (area at risk-necrotic area=52+/-5%; necrotic area-left ventricle=28+/-3%), increased cardiac MAL, an index of lipid peroxidation (area at risk=62.5+/-3.9 nmol/g tissue; necrotic area=80.3+/-5.1 nmol/g tissue), induced tissue neutrophil infiltration, and caused a marked decrease in endogenous antioxidants. Furthermore, myocardial ischaemia plus reperfusion caused in the area at risk peak message for ICAM-1 at 3 h of reperfusion and increased cardiac ICAM-1 immunostaining at 5 h of reperfusion. NF-kappaB activation was also evident at 0.5 h of reperfusion and reached its maximum at 2 h of reperfusion. I-kappaBalpha was markedly decreased at 45 min of occlusion; peak reduction was observed at 1 h of reperfusion and thereafter it was gradually restored. Intraperitoneal administration of IRFI 042 (5, 10, 20 mg/kg, 5 min after reperfusion) reduced myocardial necrosis expressed as a percentage either of the area at risk (18+/-4%) or the total left ventricle (11+/-2%), and improved cardiac output. This treatment also limited membrane lipid peroxidation in the area at risk (MAL=14.3+/-2.5 nmol/g tissue) and in the necrotic area (MAL=26.5+/-3.7 nmol/g tissue), restored the endogenous antioxidants vitamin E and superoxide dismutase, and inhibited detrimental hydroxyl radical formation. Finally, IRFI 042 blocked the activation of NF-kappaB, reduced cardiac ICAM-1 expression, and blunted tissue elastase content, an index of leukocytes accumulation at the site of injury. CONCLUSIONS: Our data suggest that IRFI 042 is cardioprotective during myocardial infarction by limiting reperfusion-induced oxidative stress and by halting the inflammatory response.

Protection of low density lipoprotein oxidation by the antioxidant agent IRFI005, a new synthetic hydrophilic vitamin E analogue.

The oxidative modification of low density lipoprotein (LDL) is thought to be an important factor in the initiation and development of atherosclerosis. Antioxidants have been shown to protect LDL from oxidation and to inhibit atherosclerosis development in animals. Potent synthetic antioxidants are currently being tested, but they are not necessarily safe for human use. We here characterize the antioxidant activity of IRFI005, the active metabolite of Raxofelast (IRFI0016) that is a novel synthetic analog of vitamin E under clinical development, and demonstrate that it prevents oxidative modification of LDL. IFI005 inhibited the oxidative modification of LDL, measured through the generation of MDA, electrophoretic mobility and apo B100 fluorescence. During the oxidation process IRF1005 was consumed with the formation of the benzoquinone oxidation product. The powerful antioxidant activity of IRFI005 is at least in part mediated by a chain breaking mechanism as it is an efficient peroxyl radical scavenger with a rate constant k(IRFI005 + LOO(o)) of 1.8 X 10(6) M(-1)s(-1). 4. IRFI005 substantially preserved LDL-associated antioxidants, alpha-tocopherol and carotenoids, and when co-incubated with physiologic levels of ascorbate provoked a synergistic inhibition of LDL oxidation. Also the co-incubation of IRFI005 with Trolox caused a synergistic effect, and a lag phase in the formation of the trolox-benzoquinone oxidation product. A synergistic inhibition of lipid peroxidation was also demonstrated by co-incubating IRFI005 and alpha-tocopherol incorporated in linoleic acid micelles. These data strongly suggest that IRFI005 can operate by a recycling mechanism similar to the vitamin E/ascorbate sysem.

Synthesis and application of novel catalytically active polymers containing 1,4,7-triazacyclononanes.

New polymers containing 1,4,7-triazacyclononanes have been synthesised by means of ring opening metathesis polymerisation (ROMP); their complexes with Mn(II) catalyse the oxidation of simple olefins by hydrogen peroxide.

Reduction of carbon tetrachloride-induced rat liver injury by IRFI 042, a novel dual vitamin E-like antioxidant.

Carbon tetrachloride (CCl4 )-induced hepatotoxicity is likely the result of a CCl4 -induced free radical production which causes membrane lipid peroxidation and activation of transcription factors regulating both the TNF-alpha gene and the early-immediate genes involved in tissue regeneration. IRFI 042 is a novel vitamin E-like compound having a masked sulphydryl group in the aliphatic side chain. We studied the effect of IRFI 042 on CCl4 -induced liver injury. Liver damage was induced in male rats by an intraperitoneal injection of CCl4 (1 ml/kg in vegetal oil). Serum alanine aminotransferase (ALT) activity, liver malondialdehyde (MAL), hydroxyl radical formation (OH*), calculated indirectly by a trapping agent, hepatic reduced glutathione (GSH) concentration, plasma TNF-alpha, liver histology and hepatic mRNA levels for TNF-alpha were evaluated 48 h after CCl4 administration. Hepatic vitamin E (VE) levels were evaluated, in a separate group of animals, 2 h after CCl4 injection. A control group with vitamin E (100 mg/kg) was also treated in order to evaluate the differences versus the analogue treated groups. Intraperitoneal injection of carbon tetrachloride produced a marked increase in serum ALT activity (CCl4 = 404.61 +/- 10.33 U/L; Controls= 28.54 +/- 4.25 U/L), liver MAL (CCl4 = 0.67 +/- 0.16 nmol/mg protein; Controls= 0.13 +/- 0.06 nmol/mg protein), OH(7) levels assayed as 2,3-DHBA (CCl4 = 8.73 +/- 1.46 microM; Controls= 0.45 +/- 0.15 microM) and 2,5-DHBA (CCl4 = 24.61 +/- 3.32 microM; Controls= 2.75 +/- 0.93 microM), induced a severe depletion of GSH (CCl4 = 3.26 +/- 1.85 micromol/g protein; Controls= 17.82 +/- 3.13 micromol/g protein) and a marked decrease in VE levels (CCl4 = 5.67 +/- 1.22 nmol/g tissue; Controls= 13.47 +/- 3.21 nmol/g tissue), caused liver necrosis, increased plasma TNF-alpha levels (CCl4 = 57.36 +/- 13.24 IU/ml; Controls= 7.26 +/- 2.31 IU/ml) and enhanced hepatic mRNA for TNF-alpha (CCl4 = 19.22 +/- 4.38 a.u.; Controls= 0.76 +/- 0.36 a.u.). IRFI 042 (100 mg/kg, 30 min after CCl4 injection) blunted liver MAL (0.32 +/- 0.17 nmol/mg protein), decreased the serum levels of ALT (128.71 +/- 13.23 U/L), and restored the hepatic concentrations of VE (9.52 +/- 3.21 nmol/g tissue), inhibited OH* production (2,3-DHBA= 3.54 +/- 1.31 microM; 2,5-DHBA= 7.37 +/- 2.46 microM), restored the endogenous antioxidant GSH (12.77 +/- 3.73 mmol/g protein) and improved histology. Furthermore IRFI 042 treatment suppressed plasma TNF-alpha concentrations (31.47 +/- 18.25 IU/ml) and hepatic TNF-alpha mRNA levels (11.65 +/- 3.21 a.u.). The acute treatment with vitamin E failed to exert any protective effect against CCl4 -induced hepatotoxicity. These investigations suggest that IRFI 042 treatment may be of benefit during free radical-mediated liver injury.

Sodium d-fructose-1,6-diphosphate vs. sodium monohydrogen phosphate in total parenteral nutrition: a comparative in vitro assessment of calcium phosphate compatibility.

BACKGROUND: The supply of high amounts of calcium (Ca) and phosphorus (P) during total parenteral nutrition (TPN) is matter of concern because of the risk associated with calcium phosphate precipitation. The in vitro Ca-P compatibility in ready-for-use TPN solutions after the addition of different concentrations of inorganic phosphate or d-fructose-1,6-diphosphate (FDP) and calcium chloride was evaluated. METHODS: Four series of experiments for each Ca + P couple were carried out by varying amino acid concentrations (2% or 4%), temperature (25 degrees C or 37 degrees C), and pH. The extent of precipitation was estimated by visual inspection and particle count. The areas of maximal compatibility (ie, areas showing the complete absence of precipitates) were drawn from the precipitation curves. RESULTS: The precipitation extent was considerably higher in conditions mimicking body environment for both Ca + P couples. The compatibility area at 37 degrees C and 2% amino acid for CaCl2 + Na2HPO4 admixtures was included within 2.50 mmol/L CaCl2 and 2.22 mmol/L Na2HPO4, whereas that for CaCl2 + FDP was within 33.3 mmol/L CaCl2 and 10.0 mmol/L FDP (20 mEq/L of P). Unlike inorganic calcium phosphate, FDP dicalcium salt precipitation was kinetically delayed and was only minimally enhanced by decreasing amino acid concentration. CONCLUSIONS: Our data indicated that the use of FDP as the P source in parenteral nutrition solutions was effective in avoiding the life-threatening calcium phosphate precipitation. Thus, the addition of FDP to TPN admixtures represents a safe choice, allowing the simultaneous administration of high amounts of Ca and P in restricted fluid volumes, even at low amino acid concentrations.

Synthesis and A1-adenosine receptors affinities of purino[7,8-c]quinazoline-8,10(9H,11H)-diones as rigid analogues of 8-arylxanthines.

Title compounds were prepared by a cyclocondensation reaction between 8-(2-aminophenyl)xanthines and trialkyl orthoesters. Some of them showed activities as A1-adenosine receptor antagonists with binding values in the micromolar range. Results are discussed with reference to 1,3-dialkyl-8-arylxanthines. Considerations on the role played by both electronic and conformational factors are also reported.

[The replication of the educational activities of a course developed by the National Training Program for social health workers for controlling HIV infection]. / Replicazione dell'attività formativa di un corso previsto dal Piano nazionale di formazione per operatori socio-sanitari per la lotta alle infezioni da HIV.

A course for regional trainers was organized by the Working Group for HIV training (PFH) and held in Rome. This course has motivated the participants and has given them the ability to organize similar training activities at local level. The training methodology, the evaluation methods and the objectives used in the course are described. An investigation has been carried out by the Working Group of PFH to evaluate the training activity of the participants at the regional level. The results show that 17 out of the 25 participants have been able to organize a total number of 53 peripheral courses and train 2144 health workers. The training methodology and the evaluation method utilized at the different local levels have followed the ones used in the central course.

[Inhaled corticosteroids in asthma: which have the best tolerance?]. / Corticoïdes inhalés dans l'asthme: quelle tolérance en 2009?

Asthmatic syndrome, better definition of asthma, is an inflammatory chronic disease, probably the most frequent in pediatrics. An important characteristic of asthma is the bronchial inflammation with a complex network of cells and inflammatory mediators of pivotal importance in the pathogenesis. The long term control and treatment of this disease are cardinal points of the management of asthmatic syndrome. Inhaled corticosteroids (ICS) are the first-line treatment for persistent asthma in children of any age. The adverse events of the inhaled steroids on growth, bone mineralization, and hypothalamic-pituitary adrenal (HPA) axis function are the main concerns for the pediatricians. The long-term effects on growth and bone mineralization are actually reassuring. Good tolerance is achieved on hypothalamic-pituitary adrenal axis function with low to moderate doses in children. Scientific and clinical researches are pointed to find out molecules able to improve clinical efficacy of ICS with better tolerance and higher reduction of adverse events.