DNA damage in workers exposed to pigment grade titanium dioxide (TiO2) and association with biomarkers of oxidative stress and inflammation.

The present study was aimed at investigating DNA damage, micronuclei frequency and meta-nuclear alterations in buccal cells of workers involved in pigment-grade TiO2 production (15 exposed and 20 not-exposed). We also assessed associations of genotoxicity biomarkers with oxidative stress/inflammatory biomarkers in urine and exhaled breath condensate (EBC), as well as possible associations between biomarkers and reported respiratory symptoms. In spite of compliance with TiO2 Occupational Exposure Limits, results showed increased direct/oxidative DNA damage and micronuclei frequency in exposed workers. Genotoxicity parameters were associated with oxidative stress/inflammation biomarkers in urine and EBC, thus confirming that TiO2 exposure can affect the oxidative balance. Workers with higher genotoxic/oxidative stress biomarkers levels reported early respiratory symptoms suggesting that molecular alterations can be predictive of early health dysfunctions. These findings suggest the need to assess early health impairment in health surveillance programs and to address properly safety issues in workplaces where TiO2 is handled.

Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral circulation in brain-dead adults.

BACKGROUND: Near-infrared spectroscopy, a non-invasive technique for monitoring cerebral oxygenation, is widely used, but its accuracy is questioned because of the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods. We investigated UT-NIRS in healthy volunteers and in brain-dead patients. METHODS: We studied 20 healthy volunteers and 20 brain-dead patients with two UT-NIRS devices, CerOx™ and c-FLOW™ (Ornim Medical, Kfar Saba, Israel), which measure cerebral flow index (CFI), a parameter related to changes in cerebral blood flow (CBF). Monitoring started after the patients had been declared brain dead for a median of 34 (range: 11-300) min. In 11 cases, we obtained further demonstration of absent CBF. RESULTS: In healthy volunteers, CFI was markedly different in the two hemispheres in the same subject, with wide variability amongst subjects. In brain-dead patients (median age: 64 yr old, 45% female; 20% traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial haemorrhage), the median (inter-quartile range) CFI was 41 (36-47), significantly higher than in volunteers (33; 27-36). CONCLUSIONS: In brain-dead patients, where CBF is absent, the UT-NIRS findings can indicate an apparently perfused brain. This might reflect an insufficient separation of signals from extra-cranial structures from a genuine appraisal of cerebral perfusion. For non-invasive assessment of CBF-related parameters, the near-infrared spectroscopy still needs substantial improvement.

Renopancreatic Transplantation: Evaluation of 15 Years in 131 Patients.

BACKGROUND: The most common multiple-organ transplant is the simultaneous pancreas-kidney transplantation (SPK). It is usually offered to patients who have insulin-dependent diabetes mellitus and those with diabetic nephropathy and renal failure that has already been established. In this study we present the results of 15 years of SPK in a transplant hospital center in Paraná, Brazil, and evaluated survival, immunosuppression, and transplant-related problems. METHODS: This study was a retrospective analysis of 131 SPK transplants performed at the Angelina Caron Hospital between January 2001 and December 2015. RESULTS: The mean age of SPK recipients was 34 years, with slight a predominance of males (50.4%). Mean graft ischemia time was 11 hours. Exocrine drainage was predominantly vesical, but this approach was abandoned after 2011. As for immunosuppression, induction was performed with basiliximab or thymoglobulin and maintained with prednisone, mycophenolate mofetil, tacrolimus, and/or sirolimus. Patient survival increased from 68.1% in 2001 to 2005 to 77.6% in 2011 to 2015. Graft survival at the end of the period was 85.7% for kidney and 75.5% for pancreas. The main surgery-derived problems for pancreas and kidney was thrombosis (15% and 6%, respectively). The main clinical problems were rejection of the pancreas (18.3%) and urinary infection of the kidney (33.3%). The main cause of death was intra-abdominal sepsis (11.4%). CONCLUSION: There was an improvement in survival rates over the time frame observed, but it remains necessary to adopt measures to reduce transplant-derived problems, including review of the antibiotic therapy protocol and measures to avoid graft thrombosis.

Comparative molecular analysis of bacterial species associated with periodontal disease.

Periodontal disease is an inflammatory disorder affecting the supporting teeth structures, including gingiva, periodontal ligament and alveolar bone, causing loss of connective tissue, reabsorption of alveolar bone and formation of periodontal pockets. The aim of this study is to find a correlation between bacterial growth and periodontal disease. Fifty-seven patients aged between 21 and 65 years, median age 46 years, were enrolled. According to gingival pocket depth, ranging from 3 to 7 mm, patients were divided into two groups: the first (30 patients, 53%) with deep pockets ³ 5 mm and the second (27 patients, 47%) less than 5 mm. The samples taken were processed for microbiological analysis by absolute quantitative real-time Taq-Man technique. Patients affected by periodontal disease were 32 (56%) and patients with gingival bleeding were 35 (61%). This data showed that the presence, the type and the bacterial load in gingival pockets were strongly correlated with gingival depth, periodontal disease and gingival bleeding. Quantitative microbiological analysis is a key point to improve patient compliance, allowing to choose the specific antibiotic treatment. avoiding antibiotic resistance and ensuring the successful outcome of therapy for periodontal disease.

Arterial endofibrosis in professional cyclists.

External Iliac Artery Endofibrosis (EIAE) is an uncommon disease usually affecting young, otherwise healthy, patients. It usually involves cyclists but cases have been reported in other groups of endurance athletes. The external iliac artery is the most affected anatomical site but other locations are described too. The precise pathophysiology and long-term evolution of the disease still remain unknown. The diagnosis may be challenging and delayed as the patients usually present symptoms only in extreme conditions and physical and instrumental examinations may be normal at rest. We present two cases of young professional cyclists who suffered of exercise-induced leg pain which led them to reduce running. Both patients were firstly treated with balloon angioplasty that rapidly failed to improve their symptoms. The successive open surgery with endofibrosectomy and autologous saphenous vein closure patch completely resolved physical limitations. EIAE is a rare disease that can induce arterial stenosis, thrombosis, dissection and secondary atheroma. After-exercise ankle-brachial index represents a useful diagnostic criterion. Careful observation of angio-CT may strengthen the suspect. Knowledge of the these features allows a better pre-operative assessment and an early effective treatment. Surgical revascularization remains the gold standard approach.

Human leucocytes in asthenozoospermic patients: endothelial nitric oxide synthase expression.

In a basic study at the Andrology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy, we evaluated the pattern of mRNA endothelial nitric oxide synthase (eNOS) expression in human blood leucocytes isolated from normozoospermic fertile and asthenozoospermic infertile men to elucidate any pathogenic involvement in sperm cell motility. Forty infertile men with idiopathic asthenozoospermia and 45 normozoospermic fertile donors, age-matched, were included. Semen parameters were evaluated, and expression analysis of mRNA was performed in human leucocytes using reverse transcription polymerase chain reaction. Sperm volume, count, motility and morphology were determined, and eNOS expression and Western blotting analyses were performed. A positive correlation was observed between the concentrations of NO and the percentage of immotile spermatozoa. The mRNA of eNOS was more expressed in peripheral blood leucocytes isolated from asthenozoospermic infertile men versus those of fertile normozoospermic men (7.46 ± 0.38 versus 7.06 ± 0.56, P = 0.0355). A significant up-regulation of eNOS gene in peripheral blood leucocytes was 1.52-fold higher than that of fertile donors. It is concluded that eNOS expression and activity are enhanced in blood leucocytes in men with idiopathic asthenozoospermia.

Luminosity-independent measurement of the proton-proton total cross section at √s=8 TeV.

The TOTEM collaboration has measured the proton-proton total cross section at √s=8 TeV using a luminosity-independent method. In LHC fills with dedicated beam optics, the Roman pots have been inserted very close to the beam allowing the detection of ~90% of the nuclear elastic scattering events. Simultaneously the inelastic scattering rate has been measured by the T1 and T2 telescopes. By applying the optical theorem, the total proton-proton cross section of (101.7±2.9) mb has been determined, well in agreement with the extrapolation from lower energies. This method also allows one to derive the luminosity-independent elastic and inelastic cross sections: σ(el)=(27.1±1.4) mb; σ(inel)=(74.7±1.7) mb.

Double diffractive cross-section measurement in the forward region at the LHC.

The first double diffractive cross-section measurement in the very forward region has been carried out by the TOTEM experiment at the LHC with a center-of-mass energy of sqrt[s]=7 TeV. By utilizing the very forward TOTEM tracking detectors T1 and T2, which extend up to |η|=6.5, a clean sample of double diffractive pp events was extracted. From these events, we determined the cross section σDD=(116±25) µb for events where both diffractive systems have 4.7<|η|min<6.5.

One hundred pancreas transplants performed in a Brazilian institution.

After decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for selected patients with type 1 diabetes mellitus. Between January 2001 and January 2008, 100 patients underwent pancreatic transplantation at our center: 88 simultaneous pancreas-kidney transplantation and 12 pancreas transplantations alone. Pancreas graft management of the exocrine drainage technique involved enteric drainage in 8 (all simultaneous pancreas-kidney) and the bladder in 92 cases. The recipient systemic venous system was used for the pancreas graft venous effluent in all cases. Our overall results have shown that the number of functioning pancreatic grafts was 64 of 100. Graft losses were: rejection (n = 8), venous thrombosis (n = 9), arterial thrombosis (n = 1), or surgical complications such as anastomotic leak (n = 3), perigraft infection (n = 10), pancreatitis of the graft (n = 5). Most cases of pancreatitis (80%) had preservation times exceeding 18 hours. Despite surgical and immunosuppressive complications, our impression was that pancreas transplantation was a highly effective therapy for diabetes mellitus. After 7 years of the program and 100 transplantations, we believe that there is a major role for transplantation in diabetes management.

Celsior versus Wisconsin solution in pancreas transplantation.

Celsior solution (CS), which has recently become available, that might theoretically offer a new means for improving graft preservation quality. The present prospective, randomized study was designed to evaluate the efficacy of CS compared with University of Wisconsin (UW) for pancreas allografts. Between January 2001 and January 2007, 88 patients underwent pancreatic transplantation, including the last 30 consecutive simultaneous pancreas kidney patients who were randomly assigned to either CS or UW. There was no case of graft thrombosis in either group. There were 2 cases of pancreatitis in the UW group compared with 1 in the CS group. No case of primary nonfunction occurred in either group. There were 2 cases of early duodenal stump fistulae in the CS group that required transplantectomy, whereas this complication was not observed in the UW group. Relaparotomy in the UW group was required in 3 cases due to infection and treated by close drainage that which, progressed to fatal sepsis in 1 patient. In the UW group with 6 months of follow-up, there were 12 patients insulin free. In the CS group, 6 patients underwent relaparotomy, 3 for transplantectomy and the others for intra-abdominal infection, which was fatal in 2 cases. In the CS group with 6 months of follow-up, there were 10 patients insulin free. Two patients died with functioning grafts. These results provided indirect evidence that CS solution is at least as safe as UW to mitigate postreperfusion graft edema and pancreatitis, as well as graft thrombosis.

Temporally controlled modulation of antihydrogen production and the temperature scaling of antiproton-positron recombination.

We demonstrate temporally controlled modulation of cold antihydrogen production by periodic RF heating of a positron plasma during antiproton-positron mixing in a Penning trap. Our observations have established a pulsed source of atomic antimatter, with a rise time of about 1 s, and a pulse length ranging from 3 to 100 s. Time-sensitive antihydrogen detection and positron plasma diagnostics, both capabilities of the ATHENA apparatus, allowed detailed studies of the pulsing behavior, which in turn gave information on the dependence of the antihydrogen production process on the positron temperature T. Our data are consistent with power law scaling T (-1.1+/-0.5) for the production rate in the high temperature regime from approximately 100 meV up to 1.5 eV. This is not in accord with the behavior accepted for conventional three-body recombination.

Application of automated ribotyping to support the evaluation of Listeria monocytogenes sources in a Taleggio cheese producing plant.

In March 2005, Listeria monocytogenes was detected on the rinds of Taleggio cheeses produced in an Italian plant. To identify the pathogen source, 154 rinds of cheeses that had been manually and automatically salinated and 52 environmental swabs collected from salting equipment, ripening cloths, and ripening boxes were tested for L. monocytogenes. Twenty-seven strains isolated from cheese samples and 16 strains isolated from environmental samples were genotyped by EcoRI and PvuII automated ribotyping. The microbiological results revealed a significant incidence of contamination of cheeses that were automatically salinated and contamination on the salting equipment, ripening cloths, and boxes. All cheese and environmental strains had the same EcoRI and PvuII ribotyping profiles, designated 153-204-S5 and 153-210-S-2, respectively. The only exception were three Taleggio strains, isolated from the same lot of product, that had EcoRI and PvuII ribotyping profiles designated 153-289-S6 and 153-214-S-5, respectively. Strains with EcoRI profile 153-204-S5 were classified as DUP-ID 1045 and serotype 1/2a, whereas strains with EcoRI profile 153-289-S6 were classified as DUP-ID 1034 and serotype 1/2b. The microbiological and molecular typing data collected in this study suggest that the source of the L. monocytogenes contamination in the Taleggio plant under study was the automated salting equipment. The isolate DUP-IDs were used to trace the introduction of potentially dangerous strains, such as those characterized as DUP-ID 1034, in the processing plant.

Evidence for the production of slow antiprotonic hydrogen in vacuum.

We present evidence showing how antiprotonic hydrogen, the quasistable antiproton (p)-proton bound system, has been synthesized following the interaction of antiprotons with the molecular ion H2+ in a nested Penning trap environment. From a careful analysis of the spatial distributions of antiproton annihilation events, evidence is presented for antiprotonic hydrogen production with sub-eV kinetic energies in states around n=70, and with low angular momenta. The slow antiprotonic hydrogen may be studied using laser spectroscopic techniques.

Search for laser-induced formation of antihydrogen atoms.

Antihydrogen can be synthesized by mixing antiprotons and positrons in a Penning trap environment. Here an experiment to stimulate the formation of antihydrogen in the n = 11 quantum state by the introduction of light from a CO2 continuous wave laser is described. An overall upper limit of 0.8% with 90% C.L. on the laser-induced enhancement of the recombination has been found. This result strongly suggests that radiative recombination contributes negligibly to the antihydrogen formed in the experimental conditions used by the ATHENA Collaboration.

Regional changes in the metabolite profile after long-term hypoxia-ischemia in brains of young and aged rats: a quantitative proton MRS study.

Quantitative proton magnetic resonance spectroscopy (MRS) was used to determine region-specific metabolic changes in young and aged animals subjected to a long-term hypoxic-ischemic injury. Focal ischemia, which was studied as an experimental stroke model, was induced in 3- and 24-month-old rats by unilateral common carotid artery occlusion associated with 24 h of hypoxia. Eight metabolites were quantified from extracts in three different brain regions (hippocampus, frontoparietal and occipital cortices) from both the ipsilateral and contralateral sides. Our findings showed significant differences in lactate and myo-inositol concentration values in the hippocampus of the aged rats as compared to the same area of the young adult group under normoxic conditions. After hypoxia-ischemia (HI), the most relevant changes in metabolite concentrations were found in the hippocampal region of both young and aged groups as compared to their age-matched controls. Of the three brain areas under investigation, the hippocampus proved to be particularly susceptible to the prolonged hypoxia-ischemia perturbation. The effects were more evident in the aged animals.

New source of dense, cryogenic positron plasmas.

We have developed a new method, based on the ballistic transfer of preaccumulated plasmas, to obtain large and dense positron plasmas in a cryogenic environment. The method involves transferring plasmas emanating from a region with a low magnetic field (0.14 T) and relatively high pressure (10(-9) mbar) into a 15 K Penning-Malmberg trap immersed in a 3 T magnetic field with a base pressure better than 10(-13) mbar. The achieved positron accumulation rate in the high field cryogenic trap is more than one and a half orders of magnitude higher than the previous most efficient UHV compatible scheme. Subsequent stacking resulted in a plasma containing more than 1.2 x 10(9) positrons, which is a factor 4 higher than previously reported. Using a rotating wall electric field, plasmas containing about 20 x 10(6) positrons were compressed to a density of 2.6 x 10(10) cm(-3). This is a factor of 6 improvement over earlier measurements.

Differential expression and cytoplasm/membrane distribution of endoglin (CD105) in human tumour cell lines: Implications in the modulation of cell proliferation.

Endoglin (CD105, an accessory component of the TGF-beta receptor complex) expression and distribution on different human tumour cells and its role in cellular proliferation were evaluated. We examined: 1) sixteen human carcinoma cell lines, 2) eight human sarcoma cell lines, 3) five miscellaneous tumour cell lines. HECV (endothelial cells) were employed as a positive control for endoglin expression. Normal Human Dermal Fibroblasts (NHDF) and 293 cells (epithelial kidney cells) were used as normal controls for connective and epithelial tissues, respectively. The results showed that CD105 was poorly expressed in the majority of human carcinoma cells (10/16), whereas it was highly expressed in most human sarcoma cells (7/8), and differently expressed by miscellaneous tumour cell lines. These data reflect endoglin expression by the normal counterparts of tumour cell lines, i.e. NHDF and 293 cells. However, CD105 levels in sarcoma cell lines, even though consistently lower than in NHDF, were significantly higher than those observed in carcinoma cells. Interestingly, CD105 presented a strong expression in the cytoplasm of MDA-MB-453 (breast carcinoma), NPA (papillary thyroid carcinoma), COLO-853 (melanoma) and SaOS-2 (osteosarcoma), but was weakly expressed on their cell membrane. This differential expression in the cytoplasm and on the membrane of some tumour cells, suggests a complex mechanism of translocation for this protein. The analysis of clonal growth in soft agar of some cell lines, characterized by high CD105 expression, showed an increased colony formation potential that was antagonized by the addition of anti-CD105 blocking mAb. The results indicated that endoglin is differentially expressed in human carcinoma and sarcoma cells and its overexpression modulates the proliferative rate of human solid tumour cells. Moreover, these data suggest that CD105 is involved in the regulation of TGF-beta effects in human solid malignancies, and therefore it could play an important role in tumour diagnosis and treatment.

Spatial distribution of cold antihydrogen formation.

Antihydrogen is formed when antiprotons are mixed with cold positrons in a nested Penning trap. We present experimental evidence, obtained using our antihydrogen annihilation detector, that the spatial distribution of the emerging antihydrogen atoms is independent of the positron temperature and axially enhanced. This indicates that antihydrogen is formed before the antiprotons are in thermal equilibrium with the positron plasma. This result has important implications for the trapping and spectroscopy of antihydrogen.

Three-dimensional annihilation imaging of trapped antiprotons.

We demonstrate three-dimensional imaging of antiprotons in a Penning trap, by reconstructing annihilation vertices from the trajectories of the charged annihilation products. The unique capability of antiparticle imaging has allowed, for the first time, the observation of the spatial distribution of the particle loss in a Penning trap. The radial loss of antiprotons on the trap wall is localized to small spots, strongly breaking the azimuthal symmetry expected for an ideal trap. Our observations have important implications for detection of antihydrogen annihilations.