Herein, we report a case of bullous dermatitis that occurred in a 61-year-old woman 5 days after beginning therapy with erlotinib for the treatment of stage IV pulmonary adenocarcinoma with metastases at the hypophyseal level. Skin reactions are the most common adverse drug reactions (ADRs) associated with epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors, and acneiform rash is the most frequently reported ADR in patients treated with erlotinib. To our knowledge, this is the first case of bullous dermatitis induced by erlotinib. This report highlights the need for additional research in the field of skin toxicity of EGFR-TK inhibitors.

The first 14 (3)Sigma(g)(+) and the first 15 (3)Sigma(u)(+) states of the H(2) molecule are computed with full configuration interaction both from Hartree-Fock molecular orbitals and Heitler-London atomic orbitals within the Born-Oppenheimer approximation, following recent studies for the (1)Sigma(g)(+) and (1)Sigma(u)(+) manifolds [Corongiu and Clementi, J. Chem. Phys. 131, 034301 (2009) and J. Phys. Chem.(in press)]. The basis sets utilized are extended and optimized Slater-type functions and spherical Gaussian functions. The states considered correspond to the configurations (1s(1)nl(1)) with n from 1 to 5; the internuclear separations sample the distances from 0.01 to 10 000 bohrs. For the first three (3)Sigma(g)(+) and (3)Sigma(u)(+) states and for the fourth and fifth (3)Sigma(g)(+) states, our computed energies at the equilibrium internuclear separation, when compared to the accurate values by Staszewska and Wolniewicz and by Kołos and Rychlewski, show deviations of about 0.006 kcal/mol, a test on the quality of our computations. Motivation for this work comes not only from obtaining potential energy curves for the high excited states of H(2) but also from characterizing the electronic density evolution from the united atom to dissociation to provide a detailed analysis of the energy contributions from selected basis subsets and to quantitatively decompose the state energies into covalent and ionic components. Furthermore, we discuss the origin of the seemingly irregular patterns in potential energy curves in the two manifolds, between 4 and 6-9 bohrs-there are two systems of states: the first, from the united atom to about 4 bohrs, is represented by functions with principal quantum number higher than the one needed at dissociation; this system interacts at around 4 bohrs with the second system, which is represented by functions with principal quantum number corresponding to one of the dissociation products.

BACKGROUND: Monitoring of residual gastric volume (RGV) to prevent aspiration is standard practice in mechanically ventilated patients receiving early enteral nutrition (EN). No data are available to support a correlation between RGV and adverse event rates. We evaluated whether not measuring RGV affected EN delivery, vomiting, or risk of nosocomial pneumonia. METHODS: Two hundred and five eligible patients with nasogastric feeding within 48 hours after intubation were included in a 7-day prospective before-after study. Continuous 24-hour nutrition was started at 25 mL/h then increased by 25 mL/h every 6 hours, to 85 mL/h. In both groups, intolerance was treated with erythromycin (250 mg IV/6 h) and a delivery rate decrease to the previously well-tolerated rate. RGV monitoring was used during the first study period (n = 102), but not during the subsequent intervention period (n = 103). Intolerance was defined as RGV >250 mL/6 h or vomiting in the standard-practice group and as vomiting in the intervention group. RESULTS: Groups were similar for baseline characteristics. Median daily volume of enteral feeding was higher in the intervention group (1489; interquartile range [IQR], 1349-1647) than in the controls (1381; IQR, 1151-1591; P =.002). Intolerance occurred in 47 (46.1%) controls and 27 (26.2%) intervention patients (P =.004). The vomiting rate did not differ between controls and intervention group patients (24.5% vs 26.2%, respectively; P =.34), and neither was a difference found for ventilator-associated pneumonia (19.6% vs 18.4%; P =.86). Conclusion: Early EN without RGV monitoring in mechanically ventilated patients improves the delivery of enteral feeding and may not increase vomiting or ventilator-associated pneumonia.(JPEN J Parenter Enteral Nutr.XXXX;xx:xx-xx).

Summary Bacterial symbionts of insects have been proposed for blocking transmission of vector-borne pathogens. However, in many vector models the ecology of symbionts and their capability of cross-colonizing different hosts, an important feature in the symbiotic control approach, is poorly known. Here we show that the acetic acid bacterium Asaia, previously found in the malaria mosquito vector Anopheles stephensi, is also present in, and capable of cross-colonizing other sugar-feeding insects of phylogenetically distant genera and orders. PCR, real-time PCR and in situ hybridization experiments showed Asaia in the body of the mosquito Aedes aegypti and the leafhopper Scaphoideus titanus, vectors of human viruses and a grapevine phytoplasma respectively. Cross-colonization patterns of the body of Ae. aegypti, An. stephensi and S. titanus have been documented with Asaia strains isolated from An. stephensi or Ae. aegypti, and labelled with plasmid- or chromosome-encoded fluorescent proteins (Gfp and DsRed respectively). Fluorescence and confocal microscopy showed that Asaia, administered with the sugar meal, efficiently colonized guts, male and female reproductive systems and the salivary glands. The ability in cross-colonizing insects of phylogenetically distant orders indicated that Asaia adopts body invasion mechanisms independent from host-specific biological characteristics. This versatility is an important property for the development of symbiont-based control of different vector-borne diseases.

BACKGROUNDS & AIMS: To evaluate an intervention for improving the delivery of early enteral nutrition (EN) in patients receiving mechanical ventilation with prone positioning (PP). METHODS: Eligible patients receiving EN and mechanical ventilation in PP were included within 48h after intubation in a before-after study. Patients were semi-recumbent when supine. Intolerance to EN was defined as residual gastric volume greater than 250ml/6h or vomiting. In the before group (n=34), the EN rate was increased by 500ml every 24h up to 2000ml/24h; patients were flat when prone and received erythromycin (250mgIV/6h) to treat intolerance. In the intervention group (n=38), the EN rate was increased by 25ml/h every 6h to 85ml/h, 25 degrees head elevation was used in PP, and prophylactic erythromycin was started at the first turn. RESULTS: Compared to the before group, larger feeding volumes were delivered in the intervention group (median volume per day with PP, 774ml [IQR 513-925] vs. 1170ml [IQR 736-1417]; P<0.001) without increases in residual gastric volume, vomiting, or ventilator-associated pneumonia. CONCLUSION: An intervention including PP with 25 degrees elevation, an increased acceleration to target rate of EN, and erythromycin improved EN delivery.

An increasing number of novel molecular markers based on nanomaterials for tumor diagnostics have been developed in recent years. Many efforts have focused on the achievement of site-targeted bioconjugated nanoparticles. In contrast, the mechanisms of toxicity, endocytosis, and degradation pathways are still poorly understood, despite their primary importance for clinical translation. In this study, three different model nanoscale magnetofluorescent particle systems (MFNs) are designed and fabricated. These nanoparticles are evaluated in terms of size, morphology, zeta potential, fluorescence efficiency, capability of enhancing T(2) relaxivity of water protons, and stability. Accordingly, two are developed and the mechanism of internalization, the intracellular fate, and the toxicity in MCF-7 adenocarcinoma cells are studied. Besides the well-documented size effect, the anionic charge seems to be a crucial factor for particle internalization, as MFN penetration through the cell membrane could be modulated by surface charge. Ultrastructural analysis of transmission electron micrographs combined with evidence from confocal microscopy reveals that MFNs are internalized by clathrin-mediated endocytosis and macropinocytosis. Moreover, MFNs are found in EEA1-positive endosomes and in lysosomes, indicating that they follow a physiological pathway of endocytosis. Magnetorelaxometric analysis demonstrates that MFNs enable the detection of 5 x 10(5) cells mL(-1) after treatment with particle dosages as low as 30 microg mL(-1). Hence, MFNs appear to be a valuable and safe bimodal contrast agent that can be developed for the noninvasive diagnosis of breast cancer.

The first 15 (1)Sigma(g)(+) states of the H(2) molecule are computed with full configuration interaction (CI) both from Hartree-Fock molecular orbitals and Heitler-London atomic orbitals; the computations are correlated with a comprehensive analysis. The basis sets utilized are extended and optimized Slater-type functions [Slater-type orbital (STO)] and spherical Gaussian functions [Gaussian-type orbital (GTO)]. The full CI computations cover the internuclear distances from 0.01 to 10,000 bohr. The available accurate data by Wolniewicz and co-workers for the first five excited states verify the quality of our computations. We focus on the characterization of the orbitals in the wave functions, on the electronic density evolution from the united atom to dissociation, on quantitative decomposition of the total energy into covalent and ionic components, and on detailed analyses of energy contributions to the total state energy from selected STO and GTO subsets. These analyses lead to study (with full CI) the H(-) negative ion with a proton and the H(+)H(-) ion pair systems. The ground and excited states for the He and H atoms and for the H(-) ion are computed to discuss the united atom and the dissociation products H(1s)+H(nl) of the n state manifolds. With the exception of n=1, each manifold has one state, specifically the EF, H, 7, and 11, whose second minimum has strong ionic character; state 11 dissociates as H(+)H(-).

Ataxia with oculomotor apraxia (AOA) type 2 (AOA2 MIM 606002) is a recessive subtype of AOA characterized by cerebellar atrophy, oculomotor apraxia, early loss of reflexes, and peripheral neuropathy. Various mutations either in homozygous or compound heterozygous condition were so far identified in the associated gene SETX (MIM 608465). SETX encodes a large protein called senataxin with a DNA-RNA helicase domain and a putative N-terminus protein interaction domain. Here, we report the identification of two novel homozygous mutations in SETX gene, c.340_342delCTT (p.L114Del) and c.1669C > T (p.R557X), in two AOA2 families. The characterization of the mutant lymphoblastoid cell lines for sensitivity to oxidative DNA-damaging agents indicates that the p.L114Del deletion confers an increased sensitivity to H(2)O(2), camptothecin, and mitomycin C, previously found to induce death in lymphoblasts harbouring other SETX mutations; the cells carrying the nonsense mutation display instead values within the normal range. Further analysis of a neuronal cell model SKNBE, transfected with the mutant senataxin proteins, reveals increased sensitivity also to staurosporine and excitotoxicity associated with the p.L114Del mutant only. We also demonstrate that the sensitizing effect of p.L114Del on apoptosis can be reversed by senataxin silencing. The ability of a single amino acid deletion to sensitize cells to death by different agents, compared to the lack of effect of a whole protein deletion, seems to exclude a protective role played by the native protein while suggesting that a specific mutation confers to the protein the ability to enhance the toxic effect of various cell damaging agents.