Elucidating the Molecular Mechanisms by which Porous Polymer Networks Affect Structure, Aging Propensity, and Selectivity of Microporous Glassy Polymer Membranes using a Multiscale Approach.

Microporous glassy polymer membranes suffer from physical aging, which adversely affects their performance in the short time frame. We show that the aging propensity of a model microporous polymer, poly(1-trimethylsilyl-1-propyne) (PTMSP), can be effectively mitigated by blending with as little as 5 wt % porous polymer network (PPN) composed of triptycene and isatin. The aging behavior of these materials was monitored via N2 pure gas permeability measurements over the course of 3 weeks, showing a 14% decline in PTMSP blended with 5 wt % PPN vs a 41% decline in neat PTMSP. Noteworthy, PPNs are 2 orders of magnitude cheaper than the porous aromatic frameworks previously used to control PTMSP aging. A variety of experimental and computational techniques, such as Positron Annihilation Lifetime Spectroscopy (PALS), free volume measurements, cross-polarization/magic angle spinning (CP/MAS) 13C NMR, transport measurements and molecular dynamics (MD) simulations were used to uncover the molecular mechanisms leading to enhanced aging resistance. We show that partial PTMSP chain adsorption into the PPN porosity reduces the PTMSP local segmental mobility, leading to improved aging resistance. Permeability coefficients were broken into their elementary sorption and diffusion contributions, to elucidate the mechanism by which the reduced PTMSP local segmental mobility affects selectivity in gas separation applications. Finally, we demonstrate that in these systems, where both chemical and physical interactions take place, transport coefficients must be corrected for thermodynamic nonidealities to avoid erroneous interpretation of the results.

The antimicrobial resistance patterns and associated determinants in Streptococcus suis isolated from humans in southern Vietnam, 1997-2008.

BACKGROUND: Streptococcus suis is an emerging zoonotic pathogen and is the leading cause of bacterial meningitis in adults in Vietnam. Systematic data on the antimicrobial susceptibility profiles of S. suis strains isolated from human cases are lacking. We studied antimicrobial resistance and associated resistance determinants in S. suis isolated from patients with meningitis in southern Vietnam. METHODS: S. suis strains isolated between 1997 and 2008 were investigated for their susceptibility to six antimicrobial agents. Strains were screened for the presence and expression of tetracycline and erythromycin resistance determinants and the association of tet(M) genes with Tn916- like transposons. The localization of tetracycline resistance gene tet(L) was determined by pulse field gel electrophoresis and Southern blotting. RESULTS: We observed a significant increase in resistance to tetracycline and chloramphenicol, which was concurrent with an increase in multi-drug resistance. In tetracycline resistance strains, we identified tet(M), tet(O), tet(W) and tet(L) and confirmed their expression. All tet(M) genes were associated with a Tn916-like transposon. The co-expression of tet(L) and other tetracycline resistance gene(s) encoding for ribosomal protection protein(s) was only detected in strains with a minimum inhibitory concentration (MIC) of tetracycline of ≥ 64 mg/L. CONCLUSIONS: We demonstrated that multi-drug resistance in S. suis causing disease in humans in southern Vietnam has increased over the 11-year period studied. We report the presence and expression of tet(L) in S. suis strains and our data suggest that co-expression of multiple genes encoding distinct mechanism is required for an MIC ≥ 64 mg/L to tetracycline.

Obesity is an independent predictor of poor survival in metastatic breast cancer: retrospective analysis of a patient cohort whose treatment included high-dose chemotherapy and autologous stem cell support.

The purpose of the study was to identify predictors of long-term survival in metastatic breast cancer (MBC). A cohort of 96 patients, who received high-dose chemotherapy with autologous stem cell support (HD-ASCT) as part of their treatment, was analyzed. Percent long-term survival at 10 years was 24.5% (CI 17.2-34.9%) when metastasis was diagnosed and 14.4% (CI 8.7-23.9%) when MBC was diagnosed. Survival was impacted significantly by body mass index (BMI). Median overall survival from initial diagnosis or from time of metastasis for patients with BMIs ≤30 and >30 (obese) was 7.1 (CI 4.4-8.7) and 3.2 years (2.41-6.75), respectively, or 3.2 or 2.3 years (all P = 0.02). Also, obesity was the only independent patient-related predictor of time to metastasis and of survival. While obesity is linked with poor outcomes in earlier stages of breast cancer, this has not been previously reported for MBC.

Multiple cotunneling in large quantum dot arrays.

We investigate the effects of inelastic cotunneling on the electronic transport properties of gold nanoparticle multilayers and thick films at low applied bias, inside the Coulomb-blockade regime. We find that the zero-bias conductance, g(0)(T), in all systems exhibits Efros-Shklovskii-type variable range hopping transport. The resulting typical hopping distance, corresponding to the number of tunnel junctions participating in cotunneling events, is shown to be directly related to the power-law exponent in the measured current-voltage characteristics. We discuss the implications of these findings in light of models on cotunneling and hopping transport in mesoscopic, granular conductors.

Angiotensin gene polymorphism as a determinant of posttransplantation renal dysfunction and hypertension.

BACKGROUND: Polymorphism of the genes associated with angiotensin, including angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and the type 1 (AT1) and type 2 (AT2) angiotensin II receptors, has been implicated in the pathophysiology of hypertension, ischemic heart disease, and progression of chronic renal disease. METHODS: We investigated the impact of the ACE, AGT, AT1, and AT2 genotypes on renal allograft function in 148 patients (77 men, 71 women) who underwent transplantation over a 5-year period. Patients were genotyped using polymerase chain reaction sequence-specific primers and polymerase chain reaction followed by restriction fragment length polymorphism analysis. RESULTS: ACE (D) and AGT (A/A) genotypes were associated with poorer chronic renal transplant function and more rapid chronic progression, defined as an increase of serum creatinine level with time. In addition, mean diastolic blood pressure at 3 years was significantly (P<0.02) correlated with C gene dose of AT1 (A-->C, 1166), with levels of 79+/-10 mmHg, 82+/-8.6 mmHg, and 95+/-8.3 mmHg for the A/A, A/C, and C/C genotypes, respectively. An apparent AT2 homozygote disadvantage could be an epiphenomenon because AT2 maps to the X chromosome, and males are homozygous for just one of the AT2 alleles (A/- or G/-). CONCLUSIONS: Pretransplantation testing of the ACE, AGT, and AT1 genotypes may assist clinicians in identifying patients at risk for chronic renal transplant dysfunction and hypertension.

Severe and complicated malaria treated with artemisinin, artesunate or artemether in Viet Nam.

One hundred and seventy five Vietnamese adults with severe and complicated malaria admitted to a rural district hospital were entered into an open randomized comparative study to compare 4 treatment regimens based on artemisinin and its derivatives. The median time of defervescence was 48 h (95% confident interval [CI] 38-58 h) in those given intramuscular (i.m.) artemether, 42 h (95% CI 36-48 h) in those given artemisinin suppositories, 36 h (95% CI 30-42 h) in those receiving artesunate (i.m.) and 30 h (95% CI 18-42 h) in those receiving intravenous artesunate (P = 0.13). The respective median parasite clearance times were 30 h (95% CI 26-34 h), 30 h (95% CI 24-36 h), 24 h (95% CI 15-33 h), and 24 h (95% CI 15-33 h) (P = 0.30); the median times for recovery of consciousness were 47 h (95% CI 31-63 h), 24 h (95% CI 18-30 h), 30 h (95% CI 18-42 h), and 24 h (95% CI 4-44 h) (P = 0.18); and the mortality rates were 11.1%, 17.6%, 10.2% and 16.6%, respectively (P = 0.64). There was no significant difference in efficacy between the 4 treatments.

Cellular lipid and fatty acid compositions of Burkholderia pseudomallei strains isolated from human and environment in Viet Nam.

Viet nam is known as an endemic area of melioidosis but its etiologic agent originated in Viet nam was not extensively studied. For the first time, we analyzed the cellular lipid and fatty acid compositions of 15 Vietnamese isolates of Burkholderia pseudomallei, 10 from humans and 5 from the environment. Cellular lipid compositions were analyzed by two-dimensional thin-layer chromatography on silica gel G plates. Cellular fatty acid methyl esters were analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The major lipids in all the isolates were phosphatidylglycerol (PG), two forms of phosphatidylethanolamine (PE-1 and PE-2), and two forms of ornithine-containing lipid (OL-1 and OL-2). PE-1 contained non-hydroxy fatty acids at both sn-1 and -2 positions, while PE-2 possessed 2-hydroxy fatty acids and non-hydroxy fatty acids in a ratio of 1:1. Since snake venom phospholipase A2 digestion of PE-2 liberated 2-hydroxy fatty acids, it was confirmed that these acids are at the sn-2 position of glycerol moiety. In both OL-1 and OL-2, amide-linked fatty acid was 3-hydroxy palmitic acid (3-OH-C16:0), while ester-linked fatty acids were non-hydroxy acids in OL-1 and 2-hydroxy acids in OL-2. The total cellular fatty acid compositions of the test strains were characterized by the presence of 2-hydroxy palmitic (2-OH-C16:0), 2-hydroxy hexadecenoic (2-OH-C16:1), 2-hydroxy octadecenoic (2-OH-C18:1), 2-hydroxy methylene octadecanoic (2-OH-C19CPA), 3-hydroxy myristic (3-OH-C14:0) and 3-hydroxy palmitic (3-OH-C16:0) acids. There were significant differences in the concentration of hexadecenoic (C16:1), methylene hexadecanoic (C17CPA), octadecenoic (C18:1) and methylene octadecanoic (C19CPA) acids among the Vietnamese isolates of B. pseudomallei. However, no significant difference was observed in cellular lipid and fatty acid components between strains of human and environmental origins.

Apparent rates of glutathione turnover in rat tissues.

Apparent first-order rate constants for glutathione (GSH) turnover were determined for 14 tissues in male Fischer 344 rats after intravenous injection of [35S]cysteine ([35S]Cys). Rate constants for glutathione turnover were estimated by nonlinear least-squares iterative minimization from the decrease in GSH specific activity 1-102 hr after administration of [35S]Cys. Tissue nonprotein sulfhydryl concentrations were determined by Ellman's assay and compared with GSH and Cys levels detected by high-performance liquid chromatography equipped with an electrochemical detector. Additionally, total radiolabeled [35S]GSH was determined by high-performance liquid chromatography equipped with a flow-through radioactivity detector. There were substantial differences in the apparent rates of GSH turnover between the various tissues examined. For example, both the liver and the kidney had rapid turnover rates with half-lives of 1-5 hr, while those for heart, skeletal muscle, and blood were much slower with half-lives of 68-118 hr. Gastrointestinal tract tissues were shown to have intermediate turnover rates of the following order: glandular stomach = caecum > duodenum = small intestine = large intestine > colon > forestomach. [35S]GSH had a half-life in lung and skin of approximately 63 and 50 hr, respectively.

Rates of ethyl acrylate binding to glutathione and protein.

Ethyl acrylate is a monomer used extensively in polymer manufacturing. Although ethyl acrylate is toxic at high concentrations, it is metabolized and detoxified rapidly at low concentrations. In the current studies, in vitro experiments have demonstrated that [14C]ethyl acrylate reacts with both glutathione (GSH) and protein to give either [14C]3-(glutathion-S-yl)ethylpropionate or covalently bound protein adducts, respectively. The second-order rate constant for [14C]ethyl acrylate conjugation with GSH was determined by quantification of [14C]3-(glutathion-S-yl)ethylpropionate using an HPLC system equipped with a flow-through radioactive detector. The rate constant for conjugation was 32.8 M-1 min-1. Additionally, the apparent second-order rate constants were determined for [14C]ethyl acrylate binding to the protein fraction of 14 whole tissue homogenates. Estimation of total protein binding sites was performed by reacting tissue homogenates with high concentrations of [14C]ethyl acrylate, while rates of binding were determined by reacting tissue homogenates with 200 microM [14C]ethyl acrylate at 37 degrees C for various periods of time. Apparent second-order rate constants for ethyl acrylate binding to protein homogenates were similar to that observed for GSH reacting with ethyl acrylate. The role of GSH-transferase in catalyzing 3-(glutathion-S-yl)ethylpropionate formation also was evaluated with whole tissue homogenates. In most tissues, the GSH-transferases poorly catalyzed the conjugation reaction. However, a significant increase in 3-(glutathion-S-yl)ethylpropionate formation was observed with liver homogenate.