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In this paper, we document the pattern of unpaid domestic and care work, disaggregated on the basis of the type of work and the care recipient, and its partial correlation with subjective well-being as measured by reported life satisfaction. We explore gender-specific effects since domestic and unpaid work has an intrinsic relational dimension that, at least in the current Italian society, has an important gender-specific component. The data used come from the 2012 Survey on the Economic and Social Conditions in the Modena District (ICESmo3) which is a unique dataset that contains disaggregated data on unpaid work. In particular, this dataset allows us to look at the correlations between the different types of unpaid work and reported life satisfaction. The overall picture that emerges from the data is one where unpaid work within the household is more likely to be conducive of well-being if it is more likely to be genuinely voluntary and intrinsically motivated. Although we must admit that this conclusion is highly speculative, we think it is a good starting point for further analyses in this regard.

Background:The atherosclerotic plaque is a complex niche composed of immune cells including T cells and macrophages as well as vascular smooth muscle cells. How T cells interact with the plaque microenvironment is not well understood.Objective:To map the crosstalk between T cells, macrophages, and smooth muscle cells.Methods/Results:We performed single cell RNAseq using the 10x transcriptomics platform in coronary plaque samples from 12 patients, who underwent heart transplantation. We found a high proportion of macrophages as well as T cells, many of which display a memory phenotype that was confirmed by immunohistochemistry. Ligand-receptor computational analysis demonstrated significant cross talk between T cells, macrophages, and smooth muscle cells. One cytokine of interest is amphiregulin (AREG), which has been shown to mediate tissue healing and fibrosis. Of note, AREG expression appears to increase as coronary plaques progress from early lipid-rich stages to more advanced stages. To elucidate the effects of AREG on smooth muscle cells, we treated human coronary artery smooth muscle cells (hCASMCs) in vitro with recombinant AREG and found increased cell proliferation compared to control (P<0.001). Bulk RNAseq profiling of hCASMCs showed activation of pathways that promote inflammation, proliferation, and fibrosis (Figure 1).Conclusion:Taken together, our findings suggest that cross talk between T cells and smooth muscle cells, partially through AREG production by T cells, may contribute to plaque progression.

Background:Atherosclerosis is considered a chronic inflammatory disorder characterized by the presence of T cells and macrophages in the plaque. Given that T cells are the master regulators of the immune system, the possible role of T cells in mediating disease warrants further investigation.Objective:To map the T cell transcriptome in coronary artery plaque.Methods/Results:Using single cell RNAseq, we mapped the transcriptome of immune cells within the coronary atherosclerotic plaque in 12 patients with various disease stages. In addition to macrophages, we find an abundance of plaque T cells that appear to be enriched in plaque compared to blood (Figure 1A). Two plaque-enriched CD8 effector memory clusters (CD8 CTL Tem1 and CD8 CTL Tem2) display the highest proportion of activated cells (e.g., HLA-DRA+). These clusters are characterized by high expression of the pro-inflammatory cytokines (e.g., CCL3, CCL4, CCL5, and IFNG) and cytolytic markers (e.g.,GZMA, GZMH, GZMM, NKG7). CD8 CTL Tem1, however, has higher expression of GZMK, a cytolytic marker recently associated with inflammaging. CD8 CTL Tem2, on the other hand, has a higher expression of perforin and granulysin, two pore-forming proteins that mediate cell killing by enabling granzyme entry. Notably, CD8 CTL Tem2 appears to track with plaque progression, increasing as plaques mature from lipid-rich to more complex lesions then declining as plaques became more stable and calcified post-rupture. Specifically, this cluster displayed two-fold enrichment in complex plaques compared to other plaque phenotypes (12.1% vs. 6.9%, p=0.0069) (Figure 1B). This pro-inflammatory and cytolytic signature is also more apparent in the activated compared to nonactivated cells in this cluster.Conclusion:Taken together, our findings suggest that a pro-inflammatory CD8 T cell cluster characterized by a trifecta of cytolytic enzymes distinguishes complex plaque and deserves further investigation.

A measurement system designed for the characterisation of chemorestive sensors based on novel materials is described. The system allows to simultaneously test up to eight sensors. It exploits an ad hoc structure based on an alumina substrate equipped with electrodes, a heater and an accurate temperature sensor, on which the material under study can be easily deposited by screen printing, spin coating or dip coating. The system is designed to study the behaviour of the sensors by accurately setting the working conditions in terms of chemical environment composition, gas flow, humidity and temperature. In particular the temperature of each sensor under test can be individually set by a digital control loop to a constant value or can be forced to follow an arbitrary time profile. The control system measures the sensing film temperature with a resolution close to 0.1°C and sets it with an uncertainty close to 1°C. Both chemical transients and thermal transients can be studied. These features make this system suitable for determining the principal performance indexes of a gas sensing device (e.g., sensitivity, stability, selectivity, response/recovery times, etc.) as functions of various combinations of measurement conditions (e.g., gas concentrations, temperature, humidity, flow).

We developed an ex vivoapproach characterizing renal mesenchymal stem cell (MSC) adhesion to kidney sections. Specificity of MSC adhesion was confirmed by demonstrating a) 3T3 cells displayed 10-fold lower adhesion, and b) MSC adhesion was CXCR4/stromal-derived factor-1 (SDF-1)-dependent. MSC adhesion was asymmetrical, with postischemic sections exhibiting more than twofold higher adhesion than controls, and showed preference to perivascular areas. Pretreating kidney sections with cyclic arginine-glycine-aspartic acid peptide resulted in increased MSC adhesion (by displacing resident cells), whereas blockade of CXCR4 with AMD3100 and inhibition of α4β1(VLA4) integrin or vascular cellular adhesion molecule-1, reduced adhesion. The difference between adhered cells under cyclic arginine-glycine-aspartic acid peptide-treated and control conditions reflected prior occupancy of binding sites with endogenous cells. The AMD3100-inhibitable fraction of adhesion reflected CXCR4-dependent adhesion, whereas maximal adhesion was interpreted as kidney MSC-lodging capacity. MSC obtained from mice overexpressing caveolin-1 exhibited more robust adhesion than those obtained from knockout animals, consistent with CXCR4 dimerization in caveolae. These data demonstrate a) CXCR4/SDF-1-dependent adhesion increases in ischemia; b) CXCR4/SDF-1 activation is dependent on MSC surface caveolin-1; and c) occupancy of MSC binding sites is decreased, while d) capacity of MSC binding sites is expanded in postischemic kidneys. In conclusion, we developed a cell-bait strategy to unmask renal stem cell binding sites, which may potentially shed light on the MSC niche(s) and its characteristics.

Background: Acute kidney injury (AKI) following cardiac surgery with cardiopulmonary bypass (CPB) causes increased morbidity and mortality.Objective: To evaluate the plasma profile of biomarkers potentially involved in AKI development following CPB.Methods: In a nested case–control study, plasma levels of 27 biomarkers in 11 AKI cases were compared with 25 controls.Results: Pre-CPB, plasma levels of epidermal growth factor and macrophage inflammatory protein-1β, 2 h following CPB, soluble vascular cell adhesion molecule-1 (sVCAM-1), fractalkine and macrophage inflammatory protein-1α, and at later time points, sVCAM-1 and interleukin-6 were associated with AKI.Conclusion: Biomarkers associated with AKI following CPB may merit further study.

Primary and/or secondary injury of the renal microvascular endothelium is a common finding in various renal diseases. Besides well-known endothelial repair mechanisms, including endothelial cell (EC) proliferation and migration, homing of extrinsic cells such as endothelial progenitor cells (EPC) and hematopoietic stem cells (HSC) has been shown in various organs and may contribute to microvascular repair. However, these mechanisms have so far not been studied after selective microvascular injury in the kidney. The present study investigated the time course of EPC and HSC stimulation and homing following induction of selective EC injury in the mouse kidney along with various angiogenic factors potentially involved in EC repair and progenitor cell stimulation. Erythropoietin was used to stimulate progenitor cells in a therapeutic approach. We found that selective EC injury leads to a marked stimulation of EPCs, HSCs, and various angiogenic factors to orchestrate microvascular repair. Angiogenic factors started to increase as early as 30 min after disease induction. Progenitor cells could be first detected in the circulation and the spleen before they selectively homed to the diseased kidney. Injection of a high dose of erythropoietin 2 h after disease induction markedly attenuated vascular injury through nonhemodynamic mechanisms, possibly involving vascular endothelial growth factor release.

Adriamycin-associated nephropathy (AAN) remains poorly understood. We hypothesized that adriamycin affects endothelial progenitor cells (EPCs), leading to impaired regeneration. We analyzed renal hematopoietic stem cells (HSCs) and EPCs in mice with AAN and examined the potential contribution of adoptive transfer of intact EPCs to the repair processes. FACS analyses revealed that populations of HSCs and EPCs were scarcely represented in control kidneys and did not change numerically in kidneys obtained from mice with AAN. The observed defect in engraftment was attributable to the decreased viability and increased senescence of EPCs. Adoptive transfer of intact EPCs improved proteinuria and renal function, with a threefold decrease in mortality. Infusion of EPCs to adriamycin-treated mice reduced plasma levels of interleukin-1α and -β and granulocyte-colony stimulating factor as well as increased the level of vascular endothelial growth factor with concomitant improvement of vascular density and reduction of apoptosis. An additional mechanism of tissue repair is proposed based on tunneling nanotube formation between EPCs and endothelial cells exposed to adriamycin, leading to the multiple rounds of exchange between EPCs and mature cells. In conclusion, AAN is associated with development of EPC incompetence; adoptive transfer of intact EPCs blunts morphological and functional manifestations of AAN; and the proposed mechanisms of repair by EPCs include direct incorporation into blood vessels, paracrine signaling, and tunneling nanotube renewal of mitochondrial pool in endothelial cells.

The BCR-ABL1fusion gene defines the subgroup of acute lymphoblastic leukemia (ALL) with the worst clinical prognosis. To identify oncogenic lesions that combine with BCR-ABL1to cause ALL, we used Affymetrix Genome-Wide Human SNP arrays (250K NspI and SNP 6.0), fluorescence in situ hybridization, and genomic polymerase chain reaction to study 106 cases of adult BCR-ABL1–positive ALL. The most frequent somatic copy number alteration was a focal deletion on 7p12 of IKZF1, which encodes the transcription factor Ikaros and was identified in 80 (75%) of 106 patients. Different patterns of deletions occurred, but the most frequent were those characterized by a loss of exons 4 through 7 (Δ4-7) and by removal of exons 2 through 7 (Δ2-7). A variable number of nucleotides (patient specific) were inserted at the conjunction and maintained with fidelity at the time of relapse. The extent of the Δ4-7deletion correlated with the expression of a dominant-negative isoform with cytoplasmic localization and oncogenic activity, whereas the Δ2-7deletion resulted in a transcript lacking the translation start site. The IKZF1deletion also was identified in the progression of chronic myeloid leukemia to lymphoid blast crisis (66%) but never in myeloid blast crisis or chronic-phase chronic myeloid leukemia or in patients with acute myeloid leukemia. Known DNA sequences and structural features were mapped along the breakpoint cluster regions, including heptamer recombination signal sequences recognized by RAG enzymes during V(D)J recombination, suggesting that IKZF1deletions could arise from aberrant RAG-mediated recombination.

The BCR-ABL1 fusion gene defines the subgroup of acute lymphoblastic leukemia (ALL) with the worst clinical prognosis. To identify oncogenic lesions that combine with BCR-ABL1 to cause ALL, we used Affymetrix Genome-Wide Human SNP arrays (250K NspI and SNP 6.0), fluorescence in situ hybridization, and genomic polymerase chain reaction to study 106 cases of adult BCR-ABL1–positive ALL. The most frequent somatic copy number alteration was a focal deletion on 7p12 of IKZF1, which encodes the transcription factor Ikaros and was identified in 80 (75%) of 106 patients. Different patterns of deletions occurred, but the most frequent were those characterized by a loss of exons 4 through 7 (Δ4-7) and by removal of exons 2 through 7 (Δ2-7). A variable number of nucleotides (patient specific) were inserted at the conjunction and maintained with fidelity at the time of relapse. The extent of the Δ4-7 deletion correlated with the expression of a dominant-negative isoform with cytoplasmic localization and oncogenic activity, whereas the Δ2-7 deletion resulted in a transcript lacking the translation start site. The IKZF1 deletion also was identified in the progression of chronic myeloid leukemia to lymphoid blast crisis (66%) but never in myeloid blast crisis or chronic-phase chronic myeloid leukemia or in patients with acute myeloid leukemia. Known DNA sequences and structural features were mapped along the breakpoint cluster regions, including heptamer recombination signal sequences recognized by RAG enzymes during V(D)J recombination, suggesting that IKZF1 deletions could arise from aberrant RAG-mediated recombination.

There are conflicting data regarding the effects of transplantation of bone marrow-derived cells (BMDCs) on the severity of diabetes. We therefore inquired whether the competence of BMDCs is preserved on adoptive transfer into diabetic (db/db) mice and how the adoptive transfer of BMDCs affects vascular and metabolic abnormalities in these mice. Recipient db/dbmice received infusions of BMDCs prepared from either db/dbor non-diabetic heterozygout mice (db/m) mice and effects on endothelium-dependent relaxation, insulin sensitivity, and renal function were evaluated. Recipients of BMDCs from db/m, but not db/dbdonors showed better glucose control, exhibited striking improvement in endothelium-dependent relaxation in response to acetylcholine, and had partially restored renal function. Improved glucose control was due to enhanced insulin sensitivity, most likely secondary to improved vascular function. Enhanced apoptosis of endothelial progenitor cells under oxidative stress, as well as decreased endothelial progenitor cell numbers were responsible for the apparent functional incompetence of BMDCs from db/dbdonors. Treatment of db/dbmice with Ebselen restored the resistance of both BMDCs and endothelial progenitor cells to oxidative stress, improved acetylcholine-induced vasorelaxation, and reduced proteinuria in db/dbrecipients of BMDC transplantation. In conclusion, infusion of BMDCs obtained from db/mdonors to db/dbrecipient mice benefited macrovascular function, insulin sensitivity, and nephropathy. BMDCs obtained from db/dbmice were functionally incompetent secondary to the increased proportion of apoptotic cells on oxidative stress challenge; their competence was restored by Ebselen therapy.

Endothelial cell dysfunction is associated with bioavailable nitric oxide deficiency and an excessive generation of reactive oxygen species. We modeled this condition by chronically inhibiting nitric oxide generation with subpressor doses of NG-monomethyl-l-arginine (L-NMMA) in C57B6 and Tie-2/green fluorescent protein mouse strains. L-NMMA-treated mice exhibited a slight reduction in vasorelaxation ability, as well as detectable abnormalities in soluble adhesion molecules (soluble intercellular adhesion molecule-1 and vascular cellular adhesion molecule-1, and matrix metalloproteinase 9), which represent surrogate indicators of endothelial dysfunction. Proteomic analysis of the isolated microvasculature using 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy revealed abnormal expression of a cluster of mitochondrial enzymes, which was confirmed using immunodetection. Aconitase-2 and enoyl-CoA-hydratase-1 expression levels were decreased in L-NMMA-treated animals; this phenotype was absent in nitric oxide synthase-1 and -3 knockout mice. Depletion of aconitase-2 and enoyl-CoA-hydratase-1 resulted in the inhibition of the Krebs cycle and enhanced pyruvate shunting toward the glycolytic pathway. To assess mitochondrial mass in vivo, co-localization of green fluorescent protein and MitoTracker fluorescence was detected by intravital microscopy. Quantitative analysis of fluorescence intensity showed that L-NMMA-treated animals exhibited lower fluorescence of MitoTracker in microvascular endothelia as a result of reduced mitochondrial mass. These findings provide conclusive and unbiased evidence that mitochondriopathy represents an early manifestation of endothelial dysfunction, shifting cell metabolism toward “metabolic hypoxia” through the selective depletion of both aconitase-2 and enoyl-CoA-hydratase-1. These findings may contribute to an early preclinical diagnosis of endothelial dysfunction.

Deficiency of nitric oxide (NO) represents a consistent manifestation of endothelial dysfunction (ECD), and the accumulation of asymmetric dimethylarginine occurs early in renal disease. Here, we confirmed in vitro and in vivo the previous finding that a fragment of collagen XVIII, endostatin, was upregulated by chronic inhibition of NO production and sought to support a hypothesis that primary ECD contributes to nephrosclerosis in the absence of other profibrotic factors. To emulate more closely the indolent course of ECD, the study was expanded to an in vivo model with NG-monomethyl-l-arginine(l-NMMA; mimics effects of asymmetric dimethylarginine) administered to mice in the drinking water at subpressor doses of 0.3 and 0.8 mg/ml for 3–6 mo. This resulted in subtle but significant morphological alterations detected in kidneys of mice chronically treated with l-NMMA: 1) consistent perivascular expansion of interstitial matrix components at the inner stripe of the outer medulla and 2) collagen XVIII/endostatin abundance. Ultrastructural abnormalities were detected in l-NMMA-treated mice: 1) increased activity of the interstitial fibroblasts; 2) occasional detachment of endothelial cells from the basement membrane; 3) splitting of the vascular basement membrane; 4) focal fibrosis; and 5) accumulation of lipofuscin by interstitial fibroblasts. Preembedding labeling of microvasculature with anti-CD31 antibodies showed infiltrating leukocytes and agglomerating platelets attaching to the visibly intact or denuded capillaries. Collectively, the data indicate that the mouse model of subpressor chronic administration of l-NMMA is not a robust one (endothelial pathology visible only ultrastructurally), and yet it closely resembles the natural progression of endothelial dysfunction, microvascular abnormalities, and associated tubulointerstitial scarring.

Adiponectin, an abundant adipocyte-derived plasma protein that modulates vascular function in type 2 diabetes, has been shown to provide cytoprotection to both pancreatic and vascular systems in diabetes. Therefore, we examined whether up-regulation of heme oxygenase (HO)-1 ameliorates the levels of inflammatory cytokines and influences serum adiponectin in Zucker fat (ZF) rats. ZF rats displayed a decrease in both HO activity and HO-1 and HO-2 protein levels and an increase in tumor necrosis factor (TNF)-α and interleukin (IL)-6 compared with Zucker lean (ZL) rats. Treatment of ZF animals with 2 mg/kg cobalt protoporphyrin IX (CoPP) increased protein levels of HO-1 and HO activity, but HO-2 was unaffected. The increase in HO-1 was associated with a decrease in superoxide levels (p< 0.05) and an increase in plasma adiponectin (p< 0.005), compared with untreated ZF rats. CoPP treatment decreased visceral and s.c. fat content, and it reduced weight gain (p< 0.01). In addition, the inflammatory cytokines TNF-α and IL-6 were decreased (p< 0.04 and p< 0.008, respectively). Treatment of human bone marrow-derived adipocytes cultured with CoPP resulted in an increase in HO-1 and a decrease in superoxide levels. Up-regulation of HO-1 caused adipose remodeling, smaller adipocytes, and increased adiponectin secretion in the culture medium of human bone marrow-derived adipocytes. In summary, this study demonstrates that the antiobesity effect of HO-1 induction results in an increase in adiponectin secretion, in vivo and in vitro, a decrease in TNF-α and IL-6, and a reduction in weight gain. These findings highlight the pivotal role and symbiotic relationship of HO-1 and adiponectin in the modulation of the metabolic syndrome phenotype.

Adiponectin, an abundant adipocyte-derived plasma protein that modulates vascular function in type 2 diabetes, has been shown to provide cytoprotection to both pancreatic and vascular systems in diabetes. Therefore, we examined whether up-regulation of heme oxygenase (HO)-1 ameliorates the levels of inflammatory cytokines and influences serum adiponectin in Zucker fat (ZF) rats. ZF rats displayed a decrease in both HO activity and HO-1 and HO-2 protein levels and an increase in tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 compared with Zucker lean (ZL) rats. Treatment of ZF animals with 2 mg/kg cobalt protoporphyrin IX (CoPP) increased protein levels of HO-1 and HO activity, but HO-2 was unaffected. The increase in HO-1 was associated with a decrease in superoxide levels (p < 0.05) and an increase in plasma adiponectin (p < 0.005), compared with untreated ZF rats. CoPP treatment decreased visceral and s.c. fat content, and it reduced weight gain (p < 0.01). In addition, the inflammatory cytokines TNF-alpha and IL-6 were decreased (p < 0.04 and p < 0.008, respectively). Treatment of human bone marrow-derived adipocytes cultured with CoPP resulted in an increase in HO-1 and a decrease in superoxide levels. Up-regulation of HO-1 caused adipose remodeling, smaller adipocytes, and increased adiponectin secretion in the culture medium of human bone marrow-derived adipocytes. In summary, this study demonstrates that the antiobesity effect of HO-1 induction results in an increase in adiponectin secretion, in vivo and in vitro, a decrease in TNF-alpha and IL-6, and a reduction in weight gain. These findings highlight the pivotal role and symbiotic relationship of HO-1 and adiponectin in the modulation of the metabolic syndrome phenotype.

Effects of 5-week soil solarization, either alone or combined with dazomet or a chicken manure compost, on tomato and melon yield, root-knot nematode infestation and weeds were investigated along three crop cycles in a plastic greenhouse infested by Meloidogyne javanicain Southern Italy. Solarization treatment, either alone and combined with dazomet or organic amendment, always resulted in a significant increase of marketable crop yield, and its effect lasted up to two years from the treatment. Nematode population indices and number of root galls were always lower in solarized soil than in untreated control. Organic amendment alone suppressed soil nematode population only in the first two crop cycles, though less than solarization and with no significant reduction of gall formation. Dazomet alone resulted in a yield increase only in the first tomato crop, with no significant reduction of soil nematode density and root galls. Solarization treatment completely suppressed the emergence of all the annual and perennial weed species, though C. rotunduswas controlled only immediately after the treatment. Suppres- sivity of SOL on annual weeds and the perennial C. dactylonwas extended to the tomato and melon crop following the treatment, but persisted on D. sanguinalisand P. oleracea, also in the third crop. Combination of solarization with dazomet or chicken manure compost did not enhance the suppressive effect on weeds. Solarization confirmed to provide an effective suppression of root-knot nematodes and weeds in the greenhouse vegetable crop systems of warm climate regions, with no need to be combined with other control tools.

With the recent characterization of enzymes responsible for protein arginine methylation and demonstration that catabolic products of arginine methylation, such as asymmetric dimethylarginine (ADMA), are among the most powerful mechanisms of atherogenesis, developing endothelial dysfunction and cardiovascular complications in a variety of pathologic processes, the need for functional characterization of the methylation-demethylation processes becomes ever more urgent. Therefore, the aims of the present study were to refine the feedback regulation of protein arginine methylation using one of the heavily methylated proteins, an RNA-binding protein Sam68, as a prototype, to elucidate the relations between Sam68 methylation and tyrosine phosphorylation and the role of methylation in RNA binding and subcellular distribution, as well as the cellular consequences of reduced protein methylation. Screening pro-atherogenic substances known to induce endothelial dysfunction showed that ADMA did not affect the level of arginine methylation of Sam68, whereas peroxynitrite was a strong inhibitor of methylation. Adavanced glycation-modified collagen I, which accumulats in diabetes and induces formation of peroxynitrite and premature endothelial cell senescence, also inhibited arginine methylation of Sam68. When the level of arginine methylation of Sam68 was pharmacologically reduced, this did not affect its RNA binding or degree of tyrosine phosphorylation, but resulted in the predominantly nuclear hypomethylation pattern. Furthermore, protein hypomethylation resulted in the increased rate of apoptosis and premature senescence. This data may offer an additional explanation for the pro-apoptotic and senescence-accelerating action of peroxynitrite, a potent inhibitor of protein methylation.

This brief overview of the potential diagnostic, prognostic and pathophysiological value of studies into the urine proteome describes hypothesis-driven investigations of individual proteins and proteome-wide search for urinary biomarkers of various diseases and their progression. It is intended to illustrate the recent progress in the area of urine proteomics and proselytize for the promise of this centuries-old technique of uroscopy, yet to reveal its secrets, using modern approaches.

Total mercury and methylmercury concentrations were measured in the muscle tissue of different fish species from the Adriatic Sea to ascertain whether the concentrations exceeded the maximum level fixed by the European Commission. Large species-dependent variability was observed. The highest total mercury mean concentrations were in benthic (0.20-0.76 μg g-1 wet wt) and demersal fish (0.22-0.73 μg g-1 wet wt), while pelagic species showed the lowest levels (0.09-0.23 μg g-1 wet wt). In 15% of frost fish, in 42% of skate and in 30% of angler fish samples total mercury concentrations exceeded the maximum level fixed by the European Commission (Hg = 1 μg g-1 wet wt); for the species for which the maximum level was set to 0.5 μg g-1 wet wt, concentrations exceeding the prescribed legal limit were observed in 6.4% of bokkem, in 6.6% of pandora, in 20% of megrin, in 12.5% of four-spotted megrim, in 16% of striped mullet, in 5.0% of forkbeard and in 5.3% of picarel samples. In all the different species, mercury was present almost completely in the methylated form, with mean percentages between 70 and 100%. Weekly intake was estimated and compared with the provisional tolerable weekly intake recommended by the FAO/WHO Expert Committee on Food Additives. A high exposure was associated with the consumption of only skates, frost fish and angler fish, thought the consumption of the other species, such as, megrim, four spotted megrim, red fish striped mullet and forkbeard, resulted in a weekly intake slightly below the established provisional tolerable weekly intake.

The muscle tissue of different species of fish was analyzed for polychlorinated biphenyls (PCBs) in order to estimate the daily intake of these contaminants. Contamination levels among the different species varied between 108 and 678 ng/g lipid weight. Isomer-specific analysis in the muscle tissue of the various fish revealed a profile dominated by hexa- and pentachlorobiphenyls, followed by hepta- and tetrachlorobiphenyls. Other congeners, including those with fewer than four or more than nine chlorine atoms, were below the instrumental limit of detection in all samples. PCB dietary intake was below the range of 1 to 4 pg 2,3,7,8-tetrachloro-p-dioxin equivalents per kg body weight per day set by the World Health Organization. From a public health point of view, there is no indication of important risks associated with the consumption of these seafoods.

Two new species of the marine tardigrade family Stygarctidae, Parastygarctus mediterranicus and Pseudostygarctus rugosus, were recorded during an investigation of the meiofauna of two subtidal caves in San Domino Island (Tremiti Archipelago) in July and October 1997, July and October 1998 and May 1999. The description of the two species is given, and their phylogenetic relationships within the subfamily Stygarctinae are discussed. Bioecological information on the tardigrade fauna of the two caves are also supplied.

Available information about Mediterranean tardigrades regards mainly the insular and peninsular Italian coasts, but also Malta, the Alboran Sea, Spain, France, Albania, Morocco, Algeria, Tunisia, Cyprus, and Lebanon. The Mediterranean Tardigrades, more than 70 species, are Heterotardigrada, mainly the order Arthrotardigrada with several families, and the order Echiniscoidea with only the family Echiniscoididae. Coralligenous detritus seems to be the most favourable kind of sediment in which the highest values of biodiversity are reached. Halechiniscidae is the most important family in the subtidal zone, whereas Batillipedidae are more frequent in the intertidal zone. A study of 4 submarine cave populations has been carried out. Neoarctidae and Neostygarctidae, considered as the most ancient families, have only been found in the Mediterranean Sea to date. This could mean that Arthrotardigrada originated in the old Thetys Sea from which the basin of the Mediterranean Sea was formed.

Echiniscoides sigismundi verrucariae and E. sigismundi porphyrae, two new subspecies of Echiniscoides sigismundi sensu lato, from the intertidal zone of sub-Antarctic Macaroni Bay in Marion Island are described. The two subspecies show important peculiarities in cuticle structure, claw number, and male and female gonopores.

Scintigraphy with 111In-DTPA-octreotide (111In-octreotide) enables the localization of tumours with somatostatin receptors on their cell membranes, of which pituitary adenomas are an example. Trans-sphenoidal excision of such tumours is sometimes incomplete and the detection of post-surgical residues is a difficult diagnostic task. In this study, we used 111In-octeotide SPET to visualize pituitary adenomas and their minimal residues. In positive cases, the indirect demonstration of the presence of somatostatin receptors may be decisive for the planning of treatment. 111In-octreotide SPET was able to visualize adenomas in 21 of 27 patients (77.7) (10 GH-secreting, 10 PRL-secreting and 1 non-secreting). Repeat SPET after the recurrence of clinical symptoms and hormone hypersecretion revealed intense 111In-octreotide uptake by residues in 8 of 10 patients (4 GH-secreting and 6 PRL-secreting). Magnetic resonance imaging was positive in only 3 of these 10 patients. Our results suggest that 111In-octreotide SPET, in combination with other imaging modalities, is useful in the diagnosis and follow-up of pituitary adenomas. It ensures better selection of patients for treatment with somatostatin analogues, both pre- and postoperatively, and assists in the development of personalized treatment plans.

Brain 99Tcm-HMPAO single photon emission tomography (SPET) and 1H-MRS (proton magnetic resonance spectroscopy) were used to determine correlations between alterations in regional cerebral blood flow (rCBF) and changes in neuronal metabolites in 21 patients (28 examinations) with ischaemic cerebral infarction examined in different phases. rCBF was determined semi-quantitatively using Lassen's linearization algorithm. SPET provided evidence of the hypoperfused site of necrosis within a few hours after the acute event and alterations in rCBF were detected in both the infarcted and diaschistic areas at all stages. 1H-MRS was used to monitor the concentration of the following metabolites: N-acetyl-aspartate (NAA), creatine and phosphocreatine (CRPCr), compounds containing choline (Cho) and lactate (Lac). A significant correlation was found between reduction in rCBF and a fall in NAA and CrPCr in both the acute and chronic phases, but not during ‘luxury perfusion’ in the subacute phase. The presence of LAC in the infarcted area up to 9 months post-ictus was totally unexpected. Simultaneous SPET and 1H-MRS thus provides additional information regarding the physiopathogenesis of cerebral ictus by clarifying the relation between alterations in rCBF and biochemical neuronal changes. We believe that NAA and CrPCr concentrations are the best expression of agreement between flow and metabolism in infarcted areas, particularly with regard to hypoperfused areas not clearly detectable by magnetic resonance imaging in the early post-ictus stage.

The differential diagnosis among the diseases that may simulate retinoblastoma is supported by several techniques; however, none of them can give an undeniable answer. In the authors' opinion the tissue characterization by power spectrum analysis of the radiofrequency ultrasound data may play an important role in the backscattered signal spectrum while being sensitive to the spectral shift trend.In order to evaluate the patterns of regression and quiescence of retinoblastoma foci after conservative treatment the authors try to create a model of tissue characterization that provides information not available in conventional A & B scan ultrasonography about cell type, vascularization and necrosis.

Bone uptake of 99Tcm-MDP was evaluated 4 h after injection in 27 normal subjects aged 23–50 years by gamma camera measurement of the activity in whole skeleton regions of interest (ROIs) in anterior and posterior projection. The mean global skeletal uptake (GSU) ( of whole-body activity in both projections measured 30 s after injection) was 33.5 ± 4. The standard urinary excretion method (whole-body retention, WBR) gave a mean bone uptake value of 31.5 + 4. A significant correlation (r = 0.570; P<0.002) was found between GSU and WBR. The mean bone-to-soft tissue ratio (B/S index) was 3.0 ± 1.1. It is suggested that this direct, external counting method provides a way of obtaining both a qualitative and a semiquantitative evaluation of bone uptake with a single tracer administration in a routine bone scan. Investigation of its use in the assessment of bone involvement in low and high turnover bone diseases is now under way.

99Tcm-methylene diphosphonate (MDP) global skeletal uptake (4 h GSU) was determined by quantitative measurement of activity on bone scan images 4 h after injection in whole skeleton regions of interest (ROI) in 16 normal subjects, in five patients with hypertrophic pulmonary osteoarthropathy (HPO) and in 12 with Paget's disease. Values were correlated with those of whole body retention (24 h WBR), and serum bone gla protein (BGP), i.e. osteocalcin, alkaline phosphatase (AP) and type 1 procollagen (P1CP). They were 40 higher in HPO than in the normal controls, while in Paget's disease they increased more in polyostotic than in monostotic patients. A statistically significant difference was noted between 4 h GSU and 24 h WBR values in the two groups of patients compared with the controls. Of the bone metabolism markers, serum AP and P1CP were higher in the patients and positively correlated with their enhanced 4 h GSU values, whereas BGP was always within the normal range. This method may thus be regarded as a useful way of simultaneously determining bone 99Tcm-MDP uptake and altered bone turnover sites, especially in patients with systemic bone disease.

In a sample of coral sand from the intertidal zone of Asdhu Island, in the Male Nord Atoll of the Maldive Islands (Indian Ocean), three species of Florarctinae belonging to the two genera Florarctus and Wingstrandarctus were found. They are Florarctus hulingsi Renaud-Mornant, 1976, Florarctus pulcher n. sp., and Wingstrandarctus corallinus Kristensen, 1984.

The authors describe a case of primary central nervous system lymphoma In a 43-year-old male. Interest in this rare form of B-lymphocyte non-Hodgkin's lymphoma is due to its increasing incidence in the last decade, especially in immunodeficient patients. Extraneural involvement was excluded by staging examinations: bilateral bone marrow biopsy from the posterior iliac crest, bipedal lymphography, abdominal CT scan, skeletal, thoracic and gastrointestinal X-rays, spinal puncture, ORL and clinical examination. The peripheral immunologic state was particularly interesting: there was a substantial decrease in total circulating B-lymphocytes at diagnosis (4.4 % = 80/mmc; nv 13 ± 4 % = 287 ± 130/mmc) and a further decrease after 2 and 4 months of therapy (0.16% = 2/mmc). Three months after completion of therapy, the B-lymphocyte level returned to the base level at diagnosis (7 % = 88/mmc). At 10 months after diagnosis and 3 months after completion of chemotherapy, the patient is alive and in good health except for the after-effects of a left hemiparesis. The etiologic and possible pathogenic factors are considered.

The serum levels of Ceruloplasmin (CER), Properdin Factor B (PFB) and Copper (CU) were evaluated in a series of 40 patients with Hodgkin's Disease and 46 patients with non-Hodgkin's lymphoma. Concentrations of CER and PFB were determined by rate nephelometry and CU concentrations by the bathocuproine colorimetric method. The results obtained demonstrated that CER, together with the well documented CU, can be used for monitoring Hodgkin's Disease.

Halechinisats macroaphalus and H. paratuleari, two new species of marine Tardigrada (Heterotardigrada: Arthrotardigrada) are described from the Mediterranean. They display evident plesiomor-phic characteristics such as large unpaired medial cirrus, cephalic region deeply divided in lobes and evident lateral processes. Furthermore, H. paratuleari shows the same arrangement of the cephalic cirri as do Stygarctidae. All these elements confirm the close relationship between Halechiniscidae, mainly Halechiniscinae, and Stygarctidae.

Adaptive radiation which has occurred in marine Tardigrada is discussed on the basis of the wide variety of species. The establishment of a new family, Neostygarctidae, is proposed and the hypothesis that two evolutive lines started from it is advanced. The possible affinities with other phyla are also discussed.

Three new species of marine Heterotardigrada, Arthrotardigrada and Echiniscoidea from a sandy shore of the Island of Mauritius, are described. They are two species of Stygarctidae: Parastygarctus renaudae and Stygarctus lambertii, and a species of Echiniscoididae: Anisonyches mauritianus. The evolution of the cephalic plate in P. renaudae during post-embryonal development is somewhat peculiar. A. mauritianus has an evident medial cirrus and sense organs on the first three pairs of legs but both the clavae and the sense organs on the fourth pair of legs are indistinguishable.

As shown in experiments on the half life of radioiodinated serum in rabbits, trace-iodinated serum proteins are not directly desiodinated by the organism in the presence of excessive diiodotyrosine. iodide, or thyroxine. The half life of 131I-Serum proteins depends on the hormonal action of the thyroid rather than on a direct desiodination of 131I-proteins.

Whole body irradiation with lethal or sublethal X-ray doses caused more frequent and earlier deaths in hyperimmune rabbits than in non-sensitized controls.

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