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We review here work on two classes of compounds that have been promoted as potential hydrogen storage materials; alkali metal amides and borohydrides, highlighting how their crystal structure and chemical properties may be used to influence the key hydrogen absorption and desorption parameters in these materials. © 2008 Materials Research Society.

Studies in preclinical models have demonstrated the superior anti-tumor effect of CpG oligodeoxynucleotides (CpG-ODN) when administered at the tumor site rather than systemically. We evaluated the effect of aerosolized CpG-ODN on lung metastases in mice injected with immunogenic N202.1A mammary carcinoma cells or weakly immunogenic B16 melanoma cells. Upon reaching the bronchoalveolar space, aerosolized CpG-ODN activated a local immune response, as indicated by production of IL-12p40, IFN-γ and IL-1β and by recruitment and maturation of DC cells in bronchoalveolar lavage fluid of mice. Treatment with aerosolized CpG-ODN induced an expansion of CD4+ cells in lung and was more efficacious than systemic i.p. administration against experimental lung metastases of immunogenic N202.1A mammary carcinoma cells, whereas only i.p. delivery of CpG-ODN provided anti-tumor activity, which correlated with NK cell expansion in the lung, against lung metastases of the poorly immunogenic B16 melanoma. The inefficacy of aerosol therapy to induce NK expansion was related to the presence of immunosuppressive macrophages in B16 tumor-bearing lungs, as mice depleted of these cells by clodronate treatment responded to aerosol CpG-ODN through expansion of the NK cell population and significantly reduced numbers of lung metastases. Our results indicate that tumor immunogenicity and the tumor-induced immunosuppressive environment are critical factors to the success of CpG therapy in the lung, and point to the value of routine sampling of the lung immune environment in defining an optimal immunotherapeutic strategy.

The objective of this study was to investigate correlates of risk for having microalbuminuria in individuals with one or more cardiovascular risk factors.The study involved 1919 individuals who attended general practice settings, were aged 55 to 75 yr, and did not have a history of cardiovascular events or diabetes but had one or more cardiovascular risk factors. A tree-based regression technique and multivariate analysis were used to identify distinct, homogeneous subgroups of patients with different likelihood of having microalbuminuria; interaction between correlates of microalbuminuria and risk for microalbuminuria was also investigated.The prevalence of microalbuminuria was 5.9%. Patients who did not have hypertension and had postload glycemia140 mg/dl showed the lowest prevalence of microalbuminuria (1.9%) and represented the reference class. The likelihood of microalbuminuria was seven times higher in men with hypertension and homeostatic model assessment levels in the upper tertile and four times higher in women with the same characteristics. Individuals with hypertension and lower homeostatic model assessment levels and normotensive individuals with postload glycemiaor = 140 mg/dl had a more than three-fold increased likelihood of having microalbuminuria. Treatment with statins was associated with a 54% reduction in the likelihood of having microalbuminuria, whereas levels of triglycerides150 mg/dl and fibrinogen levels in the upper tertile were associated with a significantly higher risk for microalbuminuria.The likelihood of having microalbuminuria in a population-based study of elderly individuals is strongly related to the interaction between the components of the metabolic syndrome, particularly hypertension, insulin resistance, and impaired glucose tolerance.

BACKGROUND: Patients with acquired brain injury (ABI) often require long periods of having a tracheostomy tube for airway protection and prolonged mechanical ventilation. It has been recognized that fast and safe decannulation improves outcomes and facilitates the recovery process. Nevertheless, few studies have provided evidence for decannulation criteria, despite the high prevalence of ABI subjects with tracheostomies. The aim of our study was to assess which clinical parameters are the best predictors for decannulation in subjects with ABI. METHODS: In this cross-sectional study, we recruited 74 consecutive ABI subjects (mean age 51.52 ± 16.76) with tracheostomy tubes. First, the subjects underwent the original decannulation assessment for cannula removal. Second, they underwent our experimental decannulation protocol. The experimental protocol included: voluntary cough (cough peak flow >160 L/min), reflex cough, tracheostomy tube capping (>72 h), swallowing instrumental assessment (penetration aspiration scale 50%), saturation (SpO2 >95%), and level of consciousness evaluation (Glasgow coma scale >8). The reference standard was clinical removal of the tracheostomy tube within 48 h. RESULTS: Parameters showing the highest values of sensitivity and specificity, respectively, were tracheostomy tube capping (80%, 100%), endoscopy assessment of airway patency (100%, 30%), swallowing instrumental assessment (85%, 96%), and the blue dye test (65%, 85%). All these were combined in a clinical cluster parameter, which had higher sensitivity (100%) and specificity (82%). CONCLUSION: These results suggest that the best clinical prediction rule for decannulation in acquired brain injury subjects is a combination of the following assessments: (1) tracheostomy tube capping, (2) endoscopic assessment of patency of airways, (3) swallowing instrumental assessment, and (4) blue dye test.

The Li+ ion conductor Li0.3La0.567TiO 3 was synthesized as a metastable phase quenched in liquid N 2 from 1300°C, and it was studied by time-of-flight powder neutron diffraction at high-resolution (HRPD instrument, ISIS Facility, U.K.). At room temperature a tetragonal perovskite superstructure was found, with a √2ap × √2ap × 2ap unit cell (a = 5.48027(1), c = 7.75591(2) Å, and Z = 4), I4/mcm space group, and a0a0c- tilt system of the TiO6 octahedra. Superlattice hkl reflections with odd l were systematically weaker and broader. By Fourier difference maps, the Li atom was located in a disordered position inside the La vacancy hollow, close to the bottleneck site at the center of the Ti4O4 square window. The Rietveld refinement converged to Rp = 6.56%, RBragg(even l) = 3.26%, and RBragg(odd l) = 11.6%. A two-dimensional pathway of Li+ ion mobility inside the structure, based on the coupled ordering of lithium and lanthanum, is proposed. At about 600°C the unit cell transforms into a p × ap × ap, with a disappearance of superlattice reflections. A tetragonal pseudo-cubic P4/mmm structure (a = 3.89644(1), c = 3.89748(2) Å, and Z = 1) was found (T = 650°C) and Rietveld refined to Rp = 6.10% and RB = 4.86%. Lithium was located on the layer of Ti atoms rather than on that of La as in the room-temperature structure. © 2006 American Chemical Society.

Background Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis. Methods Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1. Intestinal mucosal epithelium integrity was assessed by histological analysis, cellular proliferation assays, real-time PCR gene expression assays and Western blot assays. Student’s t-test (paired two-tailed) and χ2 analyses were used for comparisons between groups. Differences were considered significant at p Results BLF501 administration in mice treated with DXR and/or 5-FU decreased the injuries to the mucosa in terms of epithelial integrity and cellular proliferative ability. Co-treatment with BLF501 led to a normal expression and distribution of both zonula occludens-1 (ZO-1) and beta-catenin, which were underexpressed after treatment with either chemotherapeutic agent alone. BLF501 administration also restored normal expression of caspase-3 and ezrin/radixin/moesin (ERM), which were overexpressed after treatment with DXR and 5-FU. In SGLT1-/- mice, BLF501 had no detectable effects. BLF501 administration in wild-type mice with growing A431 tumors did not modify antitumor activity of DXR. Conclusions BLF501-induced protection of the intestinal mucosa is a promising novel therapeutic approach to reducing the severity of chemotherapy-induced mucositis.

The sol-gel synthesis of TiO2 from TiCl4 assisted by the triblock copolymer EO20-PO70 -EO20 (EO = -CH2CH2O-, PO = -CH2 (CH3)CHO-) as templating agent was carried out by systematically changing H2O:Ti (rw) and HCl:Ti (ra) molar ratios. Mesoporous and nanocrystalline TiO2 samples with well-defined and controlled phase composition (anatase, rutile, and mixed phase) were obtained after calcination at 400 °C and characterized for the morphology, particle size, and shape using TEM, HRTEM, XRD, and surface area measurements. The role of rw and ra and influence of the copolymer in determining the phase composition was demonstrated. Rutile becomes the main phase by increasing rw. In fact, the decrease of Ti concentration slows down the condensation rate, favoring formation of rutile seeds in the gel. The photocatalytic activity of TiO2 in the UV photomineralization of phenol depends on the phase composition and oxidizing agent, H2O2 or O2. When the oxidation is performed by H2O2, rutile, formed by large crystalline rods with high aspect ratios (size 15-20 × 100-120 nm), shows higher catalytic activity with respect to the small, almost cubic, anatase particles (5-15 nm). If O2 is used, the catalytic activity generally decreases and the behavior of polymorphous species is reverse. EPR investigation of the paramagnetic charge carriers, formed under UV irradiation at 10 K, showed the resonance lines of holes trapped at O- lattice sites and electrons trapped at Ti3+ and O2- sites. The rutile crystalline rods present the largest quantity of O- and Ti3+ centers. The overall results suggest correlation between TiO2 particle size and shape and the photocatalytic activity and indicate that electron-hole recombination is the most probable rate-controlling process. © 2008 American Chemical Society.

Nanocrystalline TiO2catalysts based on pure rutile (R100) and a 30% of anatase and 70% of rutile (R70) were synthesized by the sol-gel method, using Pluronic PE 6400 as templating agent. Catalysts were characterized in terms of structural and morphological properties; moreover, the formation of paramagnetic charge carriers under UV irradiation was studied and related to the activity of TiO2in the photoinduced degradation of phenol. With respect to Degussa P25, the two sol-gel catalysts show lower surface area and a wider pore size distribution. The EPR spectra recorded under UV irradiation show enhanced charge separation in the sol-gel samples, with the O−species in higher amount than in Degussa P25. This result is in agreement with the high catalytic activity of R100 sample in the photoinduced degradation of phenol, very similar to that displayed by Degussa P25 and higher than that of R70 sample.

High-resolution time-of-flight neutron powder diffraction data (ISIS facility, Rutherford Appleton Laboratory, U. K.) were collected on sample I, prepared by slow cooling from 1300 °C, of the Li0.3La 0.567TiO3 (LLTO) lithium ion conductor, and on sample II quenched in liquid N2. Patterns were obtained at room temperature (RT), 400 and 700 °C on sample I, and at 550 °C on sample II, studied at RT in previous work. The structure was resolved and Rietveld refined in the tetragonal P4/nbm space group with √2ap × √2a p × 2ap unit-cell [a = 5.48162(1), c = 7.74646(1) Å at RT, Z = 4; ap is the cell edge of cubic perovskite] in all cases except 700 °C, where a P4/mmm (ap × ap × 2ap) structure was determined and refined [a = 3.89827(2), c = 7.8002(1) Å, Z = 2]. In both space groups lanthanum ordering over two La1 and La2 sites is present, but only in P4/nbm can an additional anti-phase octahedral tilting of type a0a0c- be observed, similar to what occurs in the I4/mcm RT metastable phase of the quenched sample. The two distortions are associated to hkl superlattice reflections with h + k even, l odd, and h + k odd, l odd, respectively. Lithium atoms were located in highly disordered sites within the less populated La1 hollows, with short Li-Li′ distances accounting for the high ionic mobility. Possible ordering schemes indicate a mainly (001) two-dimensional mechanism of ion hopping among Li sites. © The Royal Society of Chemistry 2007.

Purpose: Hyperprogression (HP), a paradoxical boost in tumor growth, was described in a subset of patients treated with immune checkpoint inhibitors (ICI). Neither clinicopathologic features nor biological mechanisms associated with HP have been identified. Experimental Design: Among 187 patients with non–small cell lung cancer (NSCLC) treated with ICI at our institute, cases with HP were identified according to clinical and radiologic criteria. Baseline histologic samples from patients treated with ICI were evaluated by IHC for myeloid and lymphoid markers. T-cell–deficient mice, injected with human lung cancer cells and patient-derived xenografts (PDX) belonging to specific mutational subsets, were assessed for tumor growth after treatment with antibodies against mouse and human programmed death receptor-1 (PD-1). The immune microenvironment was evaluated by flow cytometry and IHC. Results: Among 187 patients, 152 were evaluable for clinical response. We identified four categories: 32 cases were defined as responders (21%), 42 patients with stable disease (27.7%), 39 cases were defined as progressors (25.7%), and 39 patients with HP (25.7%). Pretreatment tissue samples from all patients with HP showed tumor infiltration by M2-like CD163+CD33+PD-L1+ clustered epithelioid macrophages. Enrichment by tumor-associated macrophages (TAM) was observed, even in tumor nodules from immunodeficient mice injected with human lung cancer cells and with PDXs. In these models, tumor growth was enhanced by treatment with anti–PD-1 but not anti–PD-1 F(ab)2 fragments. Conclusions: These results suggest a crucial role of TAM reprogramming, upon Fc receptor engagement by ICI, eventually inducing HP and provide clues on a distinctive immunophenotype potentially able to predict HP. See related commentary by Knorr and Ravetch, p. 904