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No relevant conflicts of interest to declare.

Several letters to the editor are presented in response to articles in previous issues including one by Françoise Chauvin in the June issue about the Carré Rive Gauche neighborhood in Paris, France, one concerning the exhibition "La Boîte de Pandore" at the Musée d'Art moderne de la Ville de Paris (Paris, France), and one regarding the closure of the Musée des Beaux-Arts (Dunkerque, France) in the April editorial.

Introduction Amiotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a prevalence rate of up to 7.4/100,000 and the overall risk of developing ALS over a lifetime is 1:400. Most patients die from respiratory failure following a course of progressive weakness. There is no effective therapy. Novel therapeutic strategies might be directed at replacing or repairing the damaged motor neurons; Cell therapy is emerging as a potential therapeutic option in ALS. The primary objective of our study was to verify the safety and tolerability of transplantation of human fetal neural stem cells (hNSCs) directly into the spinal cord of humans. The study was approved by the SuperiorNational Health Institute.Material and Methods 18 patients with definite ALS were recruited and treated. Patients were included if they had ALS of spinal onset with severe functional impairment of the lower limbs and mild functional impairment of the upper limbs without signs of respiratory failure. The patients were monitored by clinical evaluation which included the ALS-FRS scale, Norris score, bulbar score, and MRC strength scale. Respiratory assessment included clinical evaluation, pulmonary function tests, arterial blood gases analysis, and nocturnal cardio-respiratory monitoring. Neurophysiological assessments were made including EMG, and somatosensory evoked potentials. The neuroradiological assessment consisted of MRI of spinal cord and brain before and after Gadolinium DTA infusion. A clinical psychologist performed psychological evaluation including an interview and psychological tests. Human fetal brain tissue specimens, all derived from the forebrain, were routinely collected from fetuses at gestational ages greater than the 8th post-conceptional week. They were immediately dissected and used to generate hNSC lines under sterile conditions. Dissociation of brain tissue, primary culturing and cell propagation were performed according to the procedure described previously by Vescovi and colleagues. Six patients received hNSCs microinjections into the dorsal (T7-T9) cord tract (3 of them received unilateral hNSCs microinjection while the remaining ones received bilateral microinjections); the other twelve patients received hNSCs microinjections into the cervical (C5-C6) cord tract (3 of them received unilateral hNSCs microinjection while the remaining ones received bilateral microinjections).Results No patients manifested severe adverse events such as death, respiratory failure or permanent post-surgical neurological deficits. Minor adverse events were: intercostal pain (2 patients) which was reversible after a mean period of 3 days after surgery, arm and leg sensory dysesthesia (6 patients) which was reversible after a mean period of 6 weeks after surgery. No patient manifested bladder and bowel dysfunction, or arm and leg motor deficit. All patients showed a good acceptance of the procedure and no significant modifications of the psychological status or quality of life were observed.Conclusions Our results appear to demonstrate that the procedures of fetal stem cells transplantation into the spinal cord of humans are safe and well tolerated by ALS patients. The minimal side effects and the absence of detrimental effects on neurological function support further research in stem cell transplantation in carefully monitored patients with ALS.

Characterization of tissue surrounding glioblastoma (GBM) is a focus for translational research because tumor recurrence invariably occurs in this area. We investigated the expression of the progenitor/stem cell markers GD3 ganglioside and NG2 proteoglycan in GBM, peritumor tissue (brain adjacent to tumor, BAT) and cancer stem-like cells (CSCs) isolated from GBM (GCSCs) and BAT (PCSCs). GD3 and NG2 immunohistochemistry was performed in paired GBM and BAT specimens from 40 patients. Double-immunofluorescence was carried out to characterize NG2-positive cells of vessel walls. GD3 and NG2 expression was investigated in GCSCs and PCSCs whose tumorigenicity was also evaluated in Scid/bg mice. GD3 and NG2 expression was higher in tumor tissue than in BAT. NG2 decreased as the distance from tumor margin increased, regardless of the tumor cell presence, whereas GD3 correlated with neoplastic infiltration. In BAT, NG2 was coexpressed with α-smooth muscle actin (α-SMA) in pericytes and with nestin in the endothelium. Higher levels of NG2 mRNA and protein were found in GCSCs while GD3 synthase was expressed at similar levels in the 2 CSC populations. PCSCs had lower tumorigenicity than GCSCs. These data suggest the possible involvement of GD3 and NG2 in pre/pro-tumorigenic events occurring in the complex microenvironment of the tissue surrounding GBM.

A personal narrative is presented which explores the authors' experience in making multicolored, relief monotypes from a single block using Stanley Hayter's "multi-level" principles.

Central odontogenic fibroma is a very rare benign odontogenic tumour characterized by a fibrous mature stroma with variable strands or islands of inactive-looking odontogenic epithelium. Our aim is to report a case of a central odontogenic fibroma and describe the clinical usefulness of Er:YAG laser for the surgical treatment of this tumour. A 74-year-old woman presented with an expansive lesion located in a mandible with multilocular and mixed radiographic appearance. A conservative excision using Er:YAG laser was performed. Complete removal was obtained. There were no postoperative complications. The histopatologic features were consistent with the diagnosis of central odontogenic fibroma of rich-epithelium type. No recurrence was observed during follow-up.

Human herpesviruses may cause severe complications after allogeneic hematopoietic stem cell transplantation (HSCT) such as interstitial pneumonia, encephalitis, delayed engraftment and post-transplant lymphoproliferative disease. A prospective survey on the incidence of primary infection or reactivation and clinical features of the eight human herpesviruses after HSCT has not yet been performed in Brazilian patients. Additionally, the impact of most of these infections on the transplant outcome is still unclear.

Recent studies suggest that higher circulating dendritic cell counts after hematopoietic stem cell transplantation (HSCT) may be associated with lower risk of graft versus host disease (GVHD) and mortality. Plasmacytoid dendritic cells (pDC) have tolerogenic properties and may explain such results. However, only a few studies with conflicting results analyzed pDC counts in the allograft, mainly in the related HSCT setting.

Natural Killer Cells are innate immune system cells important in host defenses against viruses and tumor cells. Two subpopulations are well described: NK CD56bright CD16neg (NK56++16-, lower frequency on peripheral blood-PB, high cytokine production) and NK56dim16pos (NK56+16+, higher frequency on PB, high cytotoxic activity). They are activated through a balance between signals given from activating and inhibitory receptors (KAR and KIR, respectively). The ligands of KIRs are the MHC molecules and in the absence of compatible MHC, NK cells are activated. In the allogeneic hematopoietic stem cell transplantation (HSCT), recent studies showed that NK cells recovery is important on infection control and, in the presence of a KIR-MHC mismatch, they may be important on graft versus host disease (GVHD) and graft versus leukemia effects. However few studies evaluated NK subpopulations recovery and HSCT endpoints.

Natural Killer Cells are innate immune system cells important in host defenses against viruses and tumor cells. Two subpopulations are well described: NK CD56bright CD16neg (NK56++16-, lower frequency on peripheral blood-PB, high cytokine production) and NK56dim16pos (NK56+16+, higher frequency on PB, high cytotoxic activity). They are activated through a balance between signals given from activating and inhibitory receptors (KAR and KIR, respectively). The ligands of KIRs are the MHC molecules and in the absence of compatible MHC, NK cells are activated. In the allogeneic hematopoietic stem cell transplantation (HSCT), recent studies showed that NK cells recovery is important on infection control and, in the presence of a KIR-MHC mismatch, they may be important on graft versus host disease (GVHD) and graft versus leukemia effects. However few studies evaluated NK subpopulations recovery and HSCT endpoints.To evaluate the impact of NK subpopulations recovery on HSCT endpoints: relapse, GVHD, non-relapse mortality and overall survival.NK (CD3-, CD56+) subpopulations (NK56++16- and NK56+16+) were quantified by multiparametric flow cytometry at 9 sequential time points (before conditioning, at engraftment, and at days 3, 7, 14, 21, 60, 100 and 180 after engraftment). Overall, 111 patients, from 4 HSCT centers (65% male, median age 17 years, range 1-74), receiving bone marrow (BM, 46%), umbilical cord (UCB, 32%) or peripheral blood (PB, 22%) from unrelated (n=90) or related donors (n=21) were studied. The most common diagnosis was acute leukemia (AML 36%, ALL 31%, MDS 9%, CML 9%, Aplastic anemia 8%). Most patients received myeloablative conditioning (MAC) regimens (60%). Antithymocyte globulin (ATG) was used in 44 patients (40%) and total body irradiation (TBI) in 56 (51%). Median follow up time was 14 months (range 4-35).Eighty-six patients presented sustained allogeneic recovery (no differences among sources). Of these, median time to neutrophil engraftment was 18 days (range: 8-52). The cumulative incidence (CI) of non-relapse-related mortality (NRM) was significantly higher in those with lower counts of NK56++16– during first 3 weeks after HSCT (34% at 1 year for patients with less than 30 cells/uL at day 21 vs 11% for patients with higher counts, p=0.03). Overall survival was significantly worse in patients with lower counts of NK56++16- subpopulations in the day 21 after engraftment (86% at 1 year vs 54% for patients with less than 30 cells/uL – p=0.003). CI of grade II-IV acute GVHD and relapse were not significantly affected by NK counts. The number of NK56+16+ cells did not affect any endpoint studied. Cell source, age and conditioning regimen did not affect any of the NK subpopulations counts. In multivariate analysis, NK56++16- counts lower than 30 cells/uL at 21 and 60 days after engraftment remain an independent risk factor for non relapse mortality [HR: 4.8, CI (95%): 1.2-18.8].Low NK56++16- counts in the first weeks after HSCT are associated with increased non relapse related mortality, but not acute GVHD or relapse. The mechanisms that rules the NK56++16- role on immunity deserve further investigations.No relevant conflicts of interest to declare.

Although CD90 has been identified as a marker for various kinds of stem cells including liver cancer stem cells (CSCs) that are responsible for tumorigenesis, the potential role of CD90 as a marker for CSCs in gliomas has not been characterized. To address the issue, we investigated the expression of CD90 in tissue microarrays containing 15 glioblastoma multiformes (GBMs), 19 WHO grade III astrocytomas, 13 WHO grade II astrocytomas, 3 WHO grade I astrocytomas and 8 normal brain tissues. Immunohistochemical analysis showed that CD90 was expressed at a medium to high level in all tested high-grade gliomas (grade III and GBM) whereas it was barely detectable in low-grade gliomas (grade I and grade II) and normal brains. Double immunofluorescence staining for CD90 and CD133 in GBM tissues revealed that CD133+CSCs are a subpopulation of CD90+cells in GBMs in vivo. Flow cytometry analysis of the expression of CD90 and CD133 in GBM-derived stem-like neurospheres further confirmed the conclusion in vitro. The expression levels of both CD90 and CD133 were reduced along with the loss of stem cells after differentiation. Furthermore, the limiting dilution assay demonstrated that the sphere formation ability was comparable between the CD90+/CD133+and the CD90+/CD133−populations of GBM neurospheres, which is much higher than that of the CD90−/CD133−population. We also performed double staining for CD90 and a vascular endothelial cell marker CD31 in tissue microarrays which revealed that the CD90+cells were clustered around the tumor vasculatures in high-grade glioma tissues. These findings suggest that CD90 is not only a potential prognostic marker for high-grade gliomas but also a marker for CSCs within gliomas, and it resides within endothelial niche and may also play a critical role in the generation of tumor vasculatures via differentiation into endothelial cells.

The aim of this clinical study was to describe the possibility of using the Nd:YAG laser device utilized in the dental offices to weld metals intraorally. The authors, before applying this technique “in vivo” on human subjects, tested the “in vitro” metal welding efficacy of dental Nd:YAG device firstly by interferometry, SEM, and EDS and subsequently by thermal camera and thermocouples in order to record temperature changes during the welding process on bovine jaws. Four implants were inserted in the edentulous maxillary arch of a 67 years old male patient. Immediately after that, a bar previously made by the dental technician was intraorally welded to the abutments by Nd:YAG laser (Fidelis Plus III, Fotona, Slovenia) with these parameters: 9.90 mJ, 1 Hz, 15 msec, 0.6 mm spot. Then the prosthesis was connected to the bar with four OT Caps. This clinical study, even if preliminary, suggests that laser welding technique may be intraorally used without side effects.

Objective. The aim of this study was to assess the ability of Er:YAG laser to remove by excision torus mandibularis and to smooth torus palatinus exostosis. Materials and Methods. Torus mandibularis (TM) and torus palatinus (TP) were surgically eliminated via the Er:YAG laser using the following parameters: TM: output power ranging from 500 to 1000 mJ, frequency from 20 to 30 Hz, sapphire tips (diameter 0.8 mm), air-water spray (ratio 5/5), pulse duration 150 μsec, fluence ranging from 99592 J/cm2 to 199044,586 J/cm2. TP: a peeling technique was used to eliminate TP, as excision by slicing being impossible here. Results. TM: excision was obtained after 12730 pulses. TP: smoothing technique took more time compared with excision. Once peeling was considered to be accomplished, the use of a surgical rasp was necessary to eliminate bone spicules that could delay the wound to heal in good conditions. Conclusion. Er:YAG excision (TM) or Er:YAG peeling (TP) are safe clinical techniques easy to practice even if the time required for excision or surface smoothing is more than the time required with bony burs and high speed instruments.

The heterogeneous status of host immune defenses may influence the risk of infection and graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT). In such defense, dendritic cells (DC) which act as specialized antigen-presenting cells that bridge the innate and adaptive immune systems, and NK-cells, responsible for the innate defense against infections and residual tumor cells, are essential cell components.To monitor the recovery of different subsets of DC and NK cells after unrelated umbilical cord blood (UCB), bone marrow (BM), and peripheral blood (PBSC) HSCT and to evaluate the impact of the distribution of these cell subsets on the outcome of the transplant.Overall, 34 patients (median age 13y; range 1–63y) receiving a UCB (n=15), BM (n=14) or PBSC (n=5) unrelated HSCT were studied. The most common diagnosis was acute leukemia (ALL, 12 cases; AML, 10; CML, 5; aplastic anemia, 4; MDS, 2; Hodgkin lymphoma, 1; SCID, 1), a majority of patients were males (56%), and received myeloablative conditioning (MAC) regimens (73%). Antithymocyte globulin (ATG) was used in 38% and total body irraditation (TBI) in 41% of cases. Median time to neutrophil engraftment was 18 days (range: 12–45). T-cell (CD4+, CD8+, CD4−8−, CD4+8+), DC [CD123+ plasmacytoid(p)DC, CD11c+ myeloid(m)DC, and CD16+ monocytoid(mo)DC] and NK cell subsets (CD3−/CD19− 56++16− and 56+16++) were quantified by multiparametric flow cytometry at 7 sequential time points (pre-transplant, at engraftment, and at days 3, 7, 14, 21 and 60 after engraftment). Results: As compared to BM/PBSC, UCB was associated with a delayed neutrophil recovery (28 days vs. 17 days; p=0.01), and a trend to lower counts of all T-, NK- and pDC subsets, particularly for the CD4+ and CD4−/CD8− T-cells during the first 3 weeks after recovery. Conversely, no significant differences were observed between both groups as regards the distribution of mDC and moDC. The use of TBI, MAC or ATG were not associated with the reconstitution of the studied cell subsets. In contrast, patients who died from transplantation-related causes (TRM) had significantly lower counts of pDC and mDC during the first 3 weeks after HSCT. At day 21 after engraftment, the median number of pDC and mDC was 0.9 and 2.0/uL among patients who died from TRM vs. 7.1 (p=.006) and 8.4/uL (p=.01) in the remainder, respectively). Patients presenting grade II-IV acute GVHD also had significantly lower pDC counts at days 14 and 21. There was no significant association of both the hematopoietic stem cell source and the conditioning regimen on the risk of TRM or acute GVHD. Low pDC counts in the first weeks after unrelated HSCT are associated with an increased incidence of GVHD and mortality. The precise mechanisms that might explain the role of pDC on immunity early after HSCT deserve further investigations.No relevant conflicts of interest to declare.

The European Space Agency's Plancksatellite, launched on 14 May 2009, is the third-generation space experiment in the field of cosmic microwave background (CMB) research. It will image the anisotropies of the CMB over the whole sky, with unprecedented sensitivity (${{\Delta T}\over T}$~ 2 × 10-6) and angular resolution (~5 arcmin). Planckwill provide a major source of information relevant to many fundamental cosmological problems and will test current theories of the early evolution of the Universe and the origin of structure. It will also address a wide range of areas of astrophysical research related to the Milky Way as well as external galaxies and clusters of galaxies. The ability of Planckto measure polarization across a wide frequency range (30-350 GHz), with high precision and accuracy, and over the whole sky, will provide unique insight, not only into specific cosmological questions, but also into the properties of the interstellar medium. This paper is part of a series which describes the technical capabilities of the Planckscientific payload. It is based on the knowledge gathered during the on-ground calibration campaigns of the major subsystems, principally its telescope and its two scientific instruments, and of tests at fully integrated satellite level. It represents the best estimate before launch of the technical performance that the satellite and its payload will achieve in flight. In this paper, we summarise the main elements of the payload performance, which is described in detail in the accompanying papers. In addition, we describe the satellite performance elements which are most relevant for science, and provide an overview of the plans for scientific operations and data analysis.

No relevant conflicts of interest to declare.

Provides information on a study being conducted on neural cell replacement in treating central nervous system degenerative disorders. Reference to study by A.L. Vescovi and E.Y. Snyder published in the July 1999 issue of `Brain Pathology' journal; Definition of neural stem cell (NSC); Isolation and propagation of clones of NSC.

Incubation of plastids isolated from ripening tomato fruits (Lycopersicon esculentum) with [γ-32P]ATP resulted in the rapid phosphorylation of several polypeptides. The optimal substrate as Pi donor for the reaction was Mg2+-ATP, and the recovery of [32P]serine after acid hydrolysis indicated predominance of protein serine kinases. The endogenous phosphorylating patterns in chromoplasts isolated from ripe tomato fruits were distinguishable from those observed in green fruit plastids, which in turn were different from those found in leaf plastids. Dark-light transitions had no influence on the pattern of phosphorylation observed in these plastids. The overall results strongly indicate that plastid-specific protein phosphorylation systems are present at defined stages during fruit formation. We also found that dark/light transitions induce a clear stimulation on the phosphorylation in serine rather than in threonine residues in endogenous thylakoid polypeptides of chloroplasts from tomato leaves.