Metabarcoding analysis of gut microbiota of healthy individuals reveals impact of probiotic and maltodextrin consumption.

In a previously published double-blind, placebo-controlled study, we showed that probiotics intake exerted a positive effect on sleep quality and a general improvement across time in different aspects of the profile of mood state, like sadness, anger, and fatigue in 33 healthy individuals. The present work investigates the impact of the probiotic product, constituted of Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 (all former members of Lactobacillus genus), and Bifidobacterium longum 04, on the gut microbiota composition of the same cohort through a metabarcoding analysis. Both the placebo and probiotic treatments had a significant impact on the microbiota composition. Statistical analysis showed that the microbiota of the individuals could be clustered into three groups, or bacteriotypes, at the baseline, and, inherently, bacterial compositions were linked to different responses to probiotic and placebo intakes. Interestingly, L. rhamnosus and L. fermentum were retrieved in the probiotic-treated cohort, while a bifidogenic effect of maltodextrin, used as placebo, was observed. The present study shed light on the importance of defining bacteriotypes to assess the impact of interventions on the gut microbiota and allowed to reveal microbial components which could be related to positive effects (i.e. sleep quality improvement) to be verified in further studies.

Decrease in 14-3-3η protein levels is correlated with improvement in disease activity in patients with rheumatoid arthritis treated with Tofacitinib.

14-3-3η protein is a proinflammatory mediator that may represent a novel diagnostic and prognostic biomarker for rheumatoid arthritis (RA). We assessed the correlation between changes in serum 14-3-3η levels and changes in clinical disease activity measures in RA patients treated with Tofacitinib (TOF). Paired serum samples from 35 patients with RA were obtained at baseline and 5 months after the initiation of treatment with TOF. The levels of 14-3-3η were measured by JOINT stat 14-3-3η ELISA test kits (Augurex Life Sciences Corp.). The cut-off was defined as 0.19 ng/ml. 14-3-3η positivity was found in 57% of the patients at baseline and in 37% of the patients after 5 months of treatment. Mean ± SD baseline 14-3-3η levels [4.92 ± 8.86 ng/ml] were significantly higher (p < 0.005) than 14-3-3η levels following treatment [1.97 ± 4.59 ng/ml]. A statistically significant improvement (p < 0.001) of CDAI, SDAI, DAS4ESR and DAS4CRP was achieved after 5 month of treatment. Decrease in 14-3-3η protein levels was highly correlated with improvement in DAS4ESR (r = 0.50, p < 0.01), DAS4CRP (r = 0.46, p < 0.01) and ESR (r = 0.36, p = 0.03) and moderately correlated with improvement in CDAI (r = 0.32, p = 0.065) and SDAI (r = 0.33, p = 0.051). The correlation between decrease in 14-3-3η levels and improvement in DAS4ESR remained significant in a partial correlation analysis controlling for ESR (r = 0.39, p = 0.02). This study demonstrates that in RA patients who were treated with TOF, decrease in 14-3-3η levels is correlated with improvement in clinical disease activity parameters. The 14-3-3η protein may serve as an objective biomarker for monitoring of TOF therapy response.

The diagnostic value of 14-3-3η protein levels in patients with rheumatoid arthritis.

14-3-3η may represent a useful diagnostic biomarker for rheumatoid arthritis (RA). We assessed the prevalence and serum levels of 14-3-3η in patients with RA and in patients with other rheumatic diseases. Serum levels of 14-3-3η were measured in 96 patients with RA, in 101 patients with other rheumatic diseases, and in 66 healthy subjects. All of the sera samples were evaluated by JOINT stat 14-3-3η ELISA test kits (Augurex Life Sciences Corp.). Median (IQR) 14-3-3η levels were significantly higher in the early RA group [0.25 ng/ml (0.075-3.11)] and in patients with established RA [0.15 ng/ml (0.08-1.26)] than in healthy subjects [0 ng/ml (0-0)] and disease controls: SLE [0.01 ng/ml (0-0.055)], AS [0.05 ng/ml (0-0.255)], and PsA [0.01 ng/ml (0-0.065)]. The prevalence of 14-3-3η positivity in patients with early RA was 58%, significantly higher than that in disease controls and healthy subjects (p < 0.001). In patients with established RA, this prevalence was 43%, and it was significantly higher than that in patients with other rheumatic diseases and healthy subjects (p < 0.05), excluding the AS group (p = 0.054). In the early RA cohort, the positivity for 14-3-3η, RF, and anti-CCP was 58%, 67%, and 71%, respectively. Eighty-two percent of the patients in this cohort were positive for at least one of these biomarkers. The concentration of 14-3-3η protein may be used to distinguish between patients with early RA and patients with other rheumatic diseases.

14-3-3η: a novel biomarker platform for rheumatoid arthritis.

14-3-3 proteins are a conserved family of 7 isoforms with diverse cellular functions found predominantly intracellularly. The 14-3-3η isoform is expressed extracellularly in the joints of patients with rheumatoid arthritis (RA) and expression in both serum and joint fluid correlates strongly with expression of metalloproteinases. 14-3-3η activates proinflammatory signalling cascades and inflammatory mediators relevant to the pathogenesis of RA. A new ELISA based assay has diagnostic utility for RA with sensitivity of 63.6% and specificity of 92.6% using the optimal cut-off from ROC analysis of 0.19ng/ml. Adding 14-3-3η to anti-cyclic citrullinated peptide antibodies (ACPA) resulted in an identification rate of 72% compared to 59% for ACPA alone. Adding rheumatoid factor (RF) to ACPA increased diagnostic capture from 59% to 72% and this increased further to 78% when 14-3-3η was added. Positive 14-3-3η status is also significantly associated with radiographic progression in early RA at years 1, 3 and 5 indicating prognostic utility. Extracellular 14-3-3η elicits the production of autoantibodies to the native protein, which also possess diagnostic utility. These do not correlate with expression of the protein and have complementary diagnostic utility. The presence of either the protein or its autoantibodies is observed in 90% of patients with early RA. Together with RF and/or ACPA this may result in identification of 95% of patients with early RA.

Sol-gel processing of drug delivery materials and release kinetics.

Silica, calcium (5 mol%) silicate and silica/polycaprolactone hybrid inorganic/organic amorphous materials, all mixed with sodium ampicillin, a broad-spectrum antibiotic, have been synthesized by sol-gel method. The amorphous nature of the gels was ascertained by X-ray diffraction analysis. Release kinetics in a simulate body fluid (SBF) have been subsequently investigated. The amount of sodium ampicillin released has been detected by UV-Vis spectroscopy and SEM. The release kinetics seems to occur in more than one stage. Finally FTIR measurements and SEM micrograph showed the formation of a hydroxyapatite layer on the surface of the samples soaked in SBF. All data showed that these materials could be used as drug delivery bioactive systems.

Sol-gel synthesis, structure and bioactivity of polycaprolactone/CaO . SiO2 hybrid material.

A method has been developed to cast novel organic/inorganic polymer hybrids from multicomponent solutions containing tetramethyl orthosilicate, calcium nitrate tetrahydrate, polycaprolactone, water, and methylethyketone via sol-gel process. The existence of the hydrogen bonds between organic and inorganic components of the hybrid and hydroxyapatite formation on the surface was proved by Fourier transform infrared analysis. The morphology of the hybrid material was studied by scanning electron microscopy. The structure of a molecular level dispersion was disclosed by atomic force microscopy, pore size distribution, and surface measurements. The infrared spectra of the hybrid relative to sample soaked in a fluid simulating the composition of human blood plasma suggests that polycaprolactone/CaO * SiO(2) hybrid material synthesised via sol-gel process is bioactive as well as the CaO * SiO(2) gel glass.

Antibacterial and bioactive silver-containing Na2O x CaO x 2SiO2 glass prepared by sol-gel method.

The antibacterial effect of addition of silver oxide to Na2O x CaO x 2SiO2 glass have been studied. Silver containing and silver free Na2O x CaO x 2SiO2 glasses have been prepared by sol-gel synthesis using tetramethil orthosilicate, sodium ethoxide, calcium nitrate tetrahydrate and silver nitrate as starting materials and methyl ethyl ketone as solvent. The gel was examined by differential thermal analysis, thermo gravimetric analysis, FTIR spectroscopy and X-ray diffraction analysis. Antibacterial and bioactive tests on gel glass powders, obtained after a heat treatment of 2 h at 600 degrees C of the dried gel, were carried out. High antimicrobial effects of samples against Escherichia coli and Streptococcus mutans were found. FTIR measurements and SEM micrographs have ascertained the formation of a hydroxyapatite layer on the surface of samples soaked in a simulated body fluid for different times.

Characterisation of integrin-linked kinase signalling in sporadic human colon cancer.

The putative oncogene, integrin-linked kinase (ILK) is a protein serine/threonine kinase that has been reported to regulate a number of biological properties including anchorage-independent cell cycle progression, tumour cell invasion and apoptosis. Overexpression of ILK has been documented in a wide variety of human malignancies including Ewing's sarcoma (ES), primitive neural ectodermal tumours (PNETs) and prostate tumours (PT). We recently reported that ILK signalling was also dysregulated in patients with the genetic condition familial adenomatous polyposis (FAP), a precursor to colon cancer. In this study, we extended our previous work by investigating the ILK-signalling pathway in sporadic human colon cancer and representative lymph node metastases. The data indicate that the ILK protein is significantly hyperexpressed in malignant acini in relation to normal crypts. Moreover, overexpression of ILK not only coincided with increased MBP phosphotransferase activity but as well with effects on downstream targets like GSK3beta. Based upon the presented data, we propose that ILK signalling is dysregulated early during the development of human colon cancer, and that selective inhibition of this molecule alone or in combination with the standard therapeutic modality might be a more effective means of treating colon cancer.

Inadequate leptin level negatively affects body fat loss during a weight reduction programme for childhood obesity.

UNLABELLED: Obesity is a typical example of a complex multifactorial disease arising from behavioural, environmental and genetic factors that may affect individual responses to dietary intake and physical activity. Observational, longitudinal dietary interventional studies in obese patients present contrasting reports on the predictive value of baseline leptin levels. We report on the effect of a weight reduction programme in three different groups of obese children (82 patients in all) assembled on the basis of their baseline leptin levels adjusted for body mass index (BMI), gender and pubertal development. The effectiveness of this programme was decreased in patients with relative hyperleptinaemia or hypoleptinaemia compared to children with baseline leptin levels appropriate to BMI gender and pubertal development. CONCLUSION: Information gained from leptin assays could provide predictive insight into an individual's ability to lose body fat and may therefore have important implications for our approach to the treatment and prevention of childhood obesity.

Púrpura hipergammaglobulinémica asociada con cirrosis por hepatitis crónica por virus C / Hypergammaglobulinemic purpura associated with chronic hepatitis C and cirrhosis

Se presenta un paciente de 60 años, argentino, con antecedentes de púrpura hipergammaglobulinémica, afectando miembros inferiores y abdomen, desde hace 19 años, con vasculitis leucocitoclástica, factor reumatoideo positivo y crioglobulinemia, asociada con cirrosis por hepatitis crónica por virus C. Es posible que pacientes diagnosticados como púrpura crioglobulinémica estén afectados de hipergammaglobulinas séricas y ambas púrpuras representen una misma enfermedad

Púrpura hipergammaglobulinémica asociada con cirrosis por hepatitis crónica por virus C / Hypergammaglobulinemic purpura associated with chronic hepatitis C and cirrhosis

Se presenta un paciente de 60 años, argentino, con antecedentes de púrpura hipergammaglobulinémica, afectando miembros inferiores y abdomen, desde hace 19 años, con vasculitis leucocitoclástica, factor reumatoideo positivo y crioglobulinemia, asociada con cirrosis por hepatitis crónica por virus C. Es posible que pacientes diagnosticados como púrpura crioglobulinémica estén afectados de hipergammaglobulinas séricas y ambas púrpuras representen una misma enfermedad (AU)

Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells.

p53 undergoes phosphorylation on several residues in response to cellular stresses that include UV and ionizing radiation, however the influence of spindle damage on this parameter is relatively unclear. Consequently, the effect of nocodazole on serine 392 phosphorylation was examined in two epithelial cell lines. We show that this process is dependent upon the stepwise activation of p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase casein kinase 2 (CK2). Furthermore, this activation correlated with the biochemical regulation of the maturation-promoting factor (MPF, cdc2/cyclin B), as both DRB and antisense depletion of CK2, as well as SB203580 were associated with an inhibition of its activation in response to nocodazole. Strikingly, when the cell cycle characteristics of nocodazole treated cells were examined, we observed that depletion or inhibition of the catalytic subunit of CK2, in the presence of microtubule inhibitors, resulted in a compromise of the G2 arrest (spindle checkpoint). Furthermore, CK2-depleted, nocodazole treated cells demonstrated a dramatic reduction in the apoptotic cell fraction, confirming that these cells had been endowed with oncogenic properties. These changes were observed in both HeLa cells and HCT116 cells. We also show that this effect is dependent on the presence of functional wild-type p53, as this phenomenon is not apparent in HCT116 p53(-/-) cells. Collectively, our results indicate two novel roles for CK2 in the spindle checkpoint arrest, in concert with p53. Firstly, to maintain increased cyclinB/cdc2 kinase activity, as a component of G2 arrest, and secondly, a role in p53-mediated apoptosis. These findings may have implications for an improved understanding of abnormalities of the spindle checkpoint in human cancers, which is a prerequisite for defining future therapies.

Dysregulation of integrin-linked kinase (ILK) signaling in colonic polyposis.

Mutation of the adenomatous polyposis coli (APC) gene and the subsequent dysregulation of beta-catenin are well-documented abnormalities in familial adenomatous polyposis (FAP), as well as sporadic polyposis. Intriguingly, overexpression of the integrin-linked kinase (ILK) has been shown to modulate beta-catenin subcellular localization and function. However, the significance of this finding for human carcinogenesis remains unclear. Here, we report the increased biochemical activity and expression of ILK protein in polyps from FAP patients. Furthermore, dramatic increases in ILK immunoreactivity were observed in all abnormal crypts from sporadic polyps, when compared with the normal appearing crypts within the same resected specimens. As sulindac and aspirin are the two most important therapeutic/chemopreventative agents demonstrated in colorectal carcinogenesis, in both humans and animals, further investigation revealed that these non-steroidal anti-inflammatory drugs (NSAIDs) target ILK and ILK-mediated events in vivo. These include inhibition of, both the biochemical activation of ILK, inhibition of serine 9 GSK3beta phosphorylation and the enhancement of TCF-4 transcriptional activity. In conclusion, ILK protein hyperexpression appears to be an early event in colonic polyposis. Additionally, ILK signaling is shown to undergo modulation by sulindac (and aspirin) for the first time, indicating that it is likely to be one of the targets affected by these agents in vivo.

Investigation of the Mek-MAP kinase-Rsk pathway in human breast cancer.

BACKGROUND: Mitogenic signaling through the principal growth factor receptor tyrosine kinase (RTK) pathway, i.e. RTK-->Ras-->Raf-->Mek-->MAPK has been implicated in the pathogenesis of human cancer. However, biochemical characterization of this has not been adequately assessed in human cancers. MATERIALS AND METHODS: Using extracts from 23 human breast cancers and control tissue from the same resected specimens, the protein levels, phosphotransferase activities and subcellular locations of the mitogen-activated protein (MAP) kinase isoforms p42 Erk2 and p44 Erk1 were examined, together with their phosphotransferase activities towards myelin basic protein (MBP) and a peptide substrate patterned after the Thr-669 site in the epidermal growth factor receptor (EGFR T669) that is phosphorylated by MAP kinase. RESULTS: Overexpression of both Erk2 and Erk1 isoforms was evident using specific antibodies. A universal activation of MBP and EGFR T669 peptide phosphotransferase activities was also found (up to 3-fold). MonoQ fractionation resolved the bulk of the EGFR T669 peptide phosphorylation from elution of the MAP kinase protein. Erk1 and Erk2 activities determined by specific immunoprecipitation were increased by up to only 2.5-fold in only 50% of tumors overall. Immunohistochemical studies, using a monoclonal antibody specific for Erk2 demonstrated that the cellular distribution of this MAP kinase was similar in both control and tumor tissues, and Erk2 was largely confined to normal and malignant acini, whilst the intensity of staining was actually reduced in the tumor tissue. Mek1 and especially Mek2 protein expression, as well as MAP kinase kinase activity as determined by phosphorylation of kinase-inactive Erk [GST-K71A] were increased in cancer samples. CONCLUSIONS: a) This confirms that MAP kinase activity is increased in human breast cancer. However, the frequency and magnitude of this change is dependent upon the chosen methodology (i.e. crude lysate assays versus specific immunoprecipitation). b) A MAP-kinase-independent source of increased EGFR T669 phosphotransferase activity in tumor extracts has been demonstrated for the first time in human breast cancer. c) By immunohistochemistry, Erk2 protein was actually found to exhibit lower intensity in tumor samples; the increased expression was most likely due to its increased distribution. d) Increased Mek protein expression and activation have been demonstrated for the first time in human breast tumors.

Differential cyclin-dependent kinase expression and activation in human colon cancer.

BACKGROUND: Abnormalities of the cyclin-dependent protein kinase (CDK) machinery have been linked to cancer development. Hyperphosphorylation of the retinoblastoma (Rb) protein results in release from inhibition of progression through the G1 phase of the cell cycle. Hyperexpression of CDK1 and CDK2 may enable progression through late G1, S and the G2 phases of the cell cycle. METHODS/RESULTS: To investigate tumor-associated protein kinase activities, control and tumor samples were fractionated by MonoS chromatography and tested for their ability to phosphorylate histone H1. Two major peaks of histone H1 phosphotransferase activity were resolved. The first appeared in the flow through fractions, and occasionally showed enhanced activity in the tumor samples, whilst the second was consistently increased and eluted at approximately 0.4 M NaCl. Western immunoblotting with CDK1 and PSTAIRE antibodies confirmed the co-elution of CDK1 and CDK2 with the second peak. Next, the phosphotransferase activities (following specific immunoprecipitation) and protein levels of CDK1, 2, 4, and 6 were determined in human colon cancer samples and their respective controls. CDK4 activity was elevated in only 3 of 7 tumor samples (range 40-160%) relative to control samples from the same patients, whereas a significant increase in CDK6 activity was observed in the same group (p < 0.05). This contrasted sharply with the universal activations of CDK1 (up to 18-fold, p < 0.01, n = 12) and CDK2 (up to 17-fold, p < 0.05) in the same groups. CONCLUSIONS: CDK1 especially, and to a lesser extent CDK2 and CDK6 demonstrate the most consistent biochemical activation in human colon cancer and may represent targets for pharmacological intervention. Cellular proliferation as gauged by MIB1 was not directly correlated with the amplitude of activation.

Identification of kinase-phosphatase signaling modules composed of p70 S6 kinase-protein phosphatase 2A (PP2A) and p21-activated kinase-PP2A.

A growing body of evidence indicates that regulation of protein-serine/threonine phosphatase 2A (PP2A) involves its association with other cellular and viral proteins in multiprotein complexes. PP2A-containing protein complexes may exist that contribute to PP2A's important regulatory role in many cellular processes. To identify such protein complexes, PP2A was partially purified from rat brain soluble extracts following treatment with a reversible cross-linker to stabilize large molecular size forms of PP2A. Compared with native (uncross-linked) PP2A, cross-linked PP2A revealed an enrichment of p70 S6 kinase and two p21-activated kinases (PAK1 and PAK3) in the PP2A complex, indicating these kinases may associate with PP2A. The existence of protein kinase-PP2A complexes in rat brain soluble extracts was further substantiated by the following results: 1) independent immunoprecipitation of the kinases revealed that PP2A co-precipitated with p70 S6 kinase and the two PAK isoforms; 2) glutathione S-transferase fusion proteins of p70 S6 kinase and PAK3 each isolated PP2A; and 3) PAK3 and p70 S6 kinase bound to microcystin-Sepharose (an affinity resin for PP2A-PP1). Cumulatively, these findings provide evidence for association of PP2A with p70 S6 kinase, PAK1, and PAK3 in the context of the cellular environment. Moreover, together with the recent reports describing associations of PP2A with Ca2+/calmodulin-dependent protein kinase IV (Westphal, R. S., Anderson, K. A., Means, A. R., and Wadzinski, B. E. (1998) Science 280, 1258-1261) and casein kinase IIalpha (Heriche, J. K., Lebrin, F., Rabilloud, T., Leroy, D., Chambaz, E. M., and Goldberg, Y. (1997) Science 276, 952-955), the present data provide compelling evidence for the existence of protein kinase-PP2A signaling modules as a new paradigm for the control of various intracellular signaling cascades.

Epidemiological study of blood lead levels of children and adolescents living in Campania, Italy.

The aim of the present study is to evaluate blood levels (PbB) in a group of 500 (245 M, 255 F) children and adolescents of Campania (Italy) aged from 0.197 to 16.915 years, 269 (136 M, 133 F) of whom lived in urban zones and 231 (109 M, 122 F) in rural zones. PbB was assayed by electrothermal atomic absorption spectroscopy. The parents of the examined subjects children were interviewed about common risk factors for lead exposure using a standardized questionnaire. The PbB of children living in urban zones were significantly higher than the PbB of those living in rural zones (60.0 +/- 3.0 mg/L vs. 40.0 +/- 2.0 mg/L, p < 0.001). A PbB higher than 100 mg/L was found in 27 children (5.4%). We observed a significant correlation between age and PbB (p < 0.001, r = 0.529). Our data regarding children and adolescents demonstrate that the prevalence of PbB higher than 100 mg/L is greater in children living in urban areas (6.89%) than in subjects living in rural areas (3.89%). The findings can be explained by the higher presence of risk factors of Pb exposure in urban areas. Our data, if compared with those of previous studies concerning children of Campania, show a clear decrease of PbB. The correlation that we found between age and PbB indicates that long-term exposure at low doses more than a more intensive but short-term exposure seems to be important for the increase of blood lead levels.

Activation of phosphatidylinositol 3-kinase, protein kinase B, and p70 S6 kinases in lipopolysaccharide-stimulated Raw 264.7 cells: differential effects of rapamycin, Ly294002, and wortmannin on nitric oxide production.

Phosphatidylinositol 3-kinase (PI 3-kinase) and protein kinase B are critical players in cell proliferation and survival. Their downstream effector protein kinase, p70 S6 kinase, has an established role in protein translation. The mechanism by which bacterial LPS induces production of nitric oxide (NO) in murine macrophages is incompletely understood, and a role for PI 3-kinase/p70 S6 kinase pathway had not been previously investigated. In this study we demonstrate that LPS induced a fivefold activation of p70 S6 kinase and a twofold stimulation of PI 3-kinase. Pretreatment of Raw 264.7 cells with either rapamycin or Ly290042 completely blocked LPS-induced activation of p70 S6 kinase. Protein kinase B was also activated (twofold) by LPS and was only minimally affected by these inhibitors. PI 3-kinase activity was inhibited by both Ly294002 and wortmannin. The effects on NO production by these agents were strikingly different. While both rapamycin and Ly294002 resulted in almost complete inhibition of NO production, wortmannin was ineffective. Surprisingly, none of the inhibitors reduced the production of the inducible nitric oxide synthase protein (iNOS) as determined by immunoprecipitation. In vivo labeling studies revealed that the iNOS protein was phosphorylated in concordance with the production of NO. We conclude that LPS-mediated NO production occurs via a PI 3-kinase-independent, but FKBP12-rapamycin-associated protein-dependent, pathway in RAW cells by a mechanism probably involving phosphorylation of iNOS.

[Epidemiological study of blood lead levels in young subjects in the Campania region: preliminary data]. / Studio epidemiologico sui livelli di piombo ematico in soggetti in età evolutiva della regione Campania: dati preliminari.

Blood lead levels were assayed in 261 children (133 males and 128 females) living in Campania, 137 (63 females and 74 males) in urban areas and 124 (65 females and 59 males) in rural zones, aged between 0.197 and 16.863 years. Blood lead determination was carried out by electrothermal atomic absorption spectroscopy. All children were interviewed about common risk factors for lead exposure. PbB (median +/- SD) were significantly higher in the urban than in the rural population (6.0 +/- 0.31 vs 3.75 +/- 0.25 micrograms/100 ml; p < 0.001). The frequency of blood lead level above 10 micrograms/100 ml was 4.21% in our tested group, i.e., significantly lower than in previous studies. A significant direct correlation between blood lead levels and age was found (r = 0.47; p < 0.001). In agreement with the literature on this subject, our findings show a significant reduction with time, of blood lead levels of children and adolescents in our region. Time of exposure more than total dose seems to be important for the increase of blood lead level.

[Total quality: priority objective to improve the services of health facilities]. / Qualità totale: obiettivo prioritario per migliorare le prestazioni delle aziende sanitarie.

The increasing attention turned to the "total quality" inside health services is pointed out in the article. The development of this theme started in the United States and subsequently reached Europe. In Italy only since a few years we are noticing initiatives aiming both to the improvement of health services quality and to the relationship with clients. The main elements of the total quality management are pointed out: they are addressed to the satisfaction of clients expectations in an environment involving the whole health personnel towards the continuous quality improvement.