Discrimination between glioblastoma and solitary brain metastasis: a quantitative analysis based on FLAIR signal intensity.

OBJECTIVE: This study determined the diagnostic performance of fluid-attenuated inversion recovery (FLAIR) signal intensity (SI) in discriminating between glioblastoma (GBM) and solitary brain metastasis (SBM). PATIENTS AND METHODS: We recruited 40 patients with a histologically confirmed diagnosis of GBM or SBM who underwent conventional 3 Tesla magnetic resonance imaging before surgery or biopsy between August 2020 and January 2022. Three regions of interest were placed to assess FLAIR SI: the enhancing region (eFLAIR), the peritumoral region (pFLAIR), and the contralateral normal white matter (nFLAIR). The diagnostic performance of significantly different parameters between the two tumor entities was analyzed by receiver operating characteristic (ROC) curve analysis. RESULTS: The pFLAIR SI was significantly lower in GBM than in SBM (p < 0.05). The eFLAIR SI and the SI ratio eFLAIR and nFLAIR (e/nFLAIR) were significantly higher in GBM than in SBM (p < 0.05). On ROC curve analysis, the e/nFLAIR ratio provided the highest area under the curve value of 81%, with a sensitivity of 80.8% and a specificity of 85.7%, for distinguishing between the two tumor types. CONCLUSIONS: The eFLAIR, pFLAIR, and e/nFLAIR parameters are useful for differentiating between GBM and SBM.

Targeting a Cryptic Pocket in a Protein-Protein Contact by Disulfide-Induced Rupture of a Homodimeric Interface.

Interference with protein-protein interfaces represents an attractive as well as challenging option for therapeutic intervention and drug design. The enzyme tRNA-guanine transglycosylase, a target to fight Shigellosis, is only functional as a homodimer. Although we previously produced monomeric variants by site-directed mutagenesis, we only crystallized the functional dimer, simply because upon crystallization the local protein concentration increases and favors formation of the dimer interface, which represents an optimal and highly stable packing of the protein in the solid state. Unfortunately, this prevents access to structural information about the interface geometry in its monomeric state and complicates the development of modulators that can interfere with and prevent dimer formation. Here, we report on a cysteine-containing protein variant in which, under oxidizing conditions, a disulfide linkage is formed. This reinforces a novel packing geometry of the enzyme. In this captured quasi-monomeric state, the monomer units arrange in a completely different way and, thus, expose a loop-helix motif, originally embedded into the old interface, now to the surface. The motif adopts a geometry incompatible with the original dimer formation. Via the soaking of fragments into the crystals, we identified several hits accommodating a cryptic binding site next to the loop-helix motif and modulated its structural features. Our study demonstrates the druggability of the interface by breaking up the homodimeric protein using an introduced disulfide cross-link. By rational concepts, we increased the potency of these fragments to a level where we confirmed their binding by NMR to a nondisulfide-linked TGT variant. The idea of intermediately introducing a disulfide linkage may serve as a general concept of how to transform a homodimer interface into a quasi-monomeric state and give access to essential structural and design information.

Social media indicators of the food environment and state health outcomes.

OBJECTIVES: Contextual factors can influence health through exposures to health-promoting and risk-inducing factors. The aim of this study was to (1) build, from geotagged Twitter and Yelp data, a national food environment database and (2) to test associations between state food environment indicators and health outcomes. STUDY DESIGN: This is a cross-sectional study based upon secondary analyses of publicly available data. METHODS: Using Twitter's Streaming Application Programming Interface (API), we collected and processed 4,041,521 food-related, geotagged tweets between April 2015 and March 2016. Using Yelp's Search API, we collected data on 505,554 unique food-related businesses. In linear regression models, we examined associations between food environment characteristics and state-level health outcomes, controlling for state-level differences in age, percent non-Hispanic white, and median household income. RESULTS: A one standard deviation increase in caloric density of food tweets was related to higher all-cause mortality (+46.50 per 100,000), diabetes (+0.75%), obesity (+1.78%), high cholesterol (+1.40%), and fair/poor self-rated health (2.01%). More burger Yelp listings were related to higher prevalence of diabetes (+0.55%), obesity (1.35%), and fair/poor self-rated health (1.12%). More alcohol tweets and Yelp bars and pub listings were related to higher state-level binge drinking and heavy drinking, but lower mortality and lower percent reporting fair/poor self-rated health. Supplemental analyses with county-level social media indicators and county health outcomes resulted in finding similar but slightly attenuated associations compared to those found at the state level. CONCLUSIONS: Social media can be utilized to create indicators of the food environment that are associated with area-level mortality, health behaviors, and chronic conditions.

Biogas production from vietnamese animal manure, plant residues and organic waste: influence of biomass composition on methane yield.

Anaerobic digestion is an efficient and renewable energy technology that can produce biogas from a variety of biomasses such as animal manure, food waste and plant residues. In developing countries this technology is widely used for the production of biogas using local biomasses, but there is little information about the value of these biomasses for energy production. This study was therefore carried out with the objective of estimating the biogas production potential of typical Vietnamese biomasses such as animal manure, slaughterhouse waste and plant residues, and developing a model that relates methane (CH4) production to the chemical characteristics of the biomass. The biochemical methane potential (BMP) and biomass characteristics were measured. Results showed that piglet manure produced the highest CH4 yield of 443 normal litter (NL) CH4 kg(-1) volatile solids (VS) compared to 222 from cows, 177 from sows, 172 from rabbits, 169 from goats and 153 from buffaloes. Methane production from duckweed (Spirodela polyrrhiza) was higher than from lawn grass and water spinach at 340, 220, and 110.6 NL CH4 kg(-1) VS, respectively. The BMP experiment also demonstrated that the CH4 production was inhibited with chicken manure, slaughterhouse waste, cassava residue and shoe-making waste. Statistical analysis showed that lipid and lignin are the most significant predictors of BMP. The model was developed from knowledge that the BMP was related to biomass content of lipid, lignin and protein from manure and plant residues as a percentage of VS with coefficient of determination (R-square) at 0.95. This model was applied to calculate the CH4 yield for a household with 17 fattening pigs in the highlands and lowlands of northern Vietnam.

Microscopic observation of kinetic molecular sieving of hydrogen isotopes in a nanoporous material.

We report quasielastic neutron scattering studies of H2-D2 diffusion in a carbon molecular sieve, demonstrating remarkable quantum effects, with the heavier isotope diffusing faster below 100 K, confirming our recent predictions. Our transition state theory and molecular dynamics calculations show that while it is critical for this effect to have narrow windows of size comparable to the de Broglie wavelength, high flux requires that the energy barrier be reduced through small cages. Such materials will enable novel processes for kinetic molecular sieving of hydrogen isotopes.

On the strength of the hydrogen-carbon interaction as deduced from physisorption.

We deduce a new value for the potential well depth for the C-H2 interaction on the basis of experimental validations of isotherms of H2 and D2 predicted using independently characterized microstructural parameters. We use two carbons, one an activated carbon fiber whose structure has been recently characterized by us (Nguyen, T. X.; cohaut, N.; Bae, J.-S.; Bhatia, S. K. Langmuir 2008, 24, 7912) using hybrid reverse Monte Carlo simulation (HRMC) and the other the commercial Takeda 3A carbon molecular sieve whose pore size distribution is determined here from the 273 K CO2 adsorption isotherm. The conventional grand canonical Monte Carlo simulation technique incorporating a semiclassical Feynman and Hibbs (FH) potential approximation (FHGCMC) as well as path integral Monte Carlo calculations is employed to determine theoretical adsorption isotherms. It is found that curvature enhances the well depth for the LJ C-H2 interaction by a factor of 1.134 over that for a flat graphite surface, consistent with our recent study (Nguyen, T. X.; cohaut, N.; Bae, J.-S.; Bhatia, S. K. Langmuir 2008, 24, 7912). A value of the C-C well depth of 37.26 K, used for estimating the C-H2 well depth in conjunction with the Berthelot rules, with the Steele C-C well depth used for interaction with heavier gases (Ar, CO2 and CH4), leads to excellent agreement with experimental isotherms in all cases.

Characterization and adsorption modeling of silicon carbide-derived carbons.

We present characterization results of silicon carbide-derived carbons (Si-CDCs) prepared from both nano- and micron-sized betaSiC particles by oxidation in pure chlorine atmosphere at various synthesis temperatures (600-1000 degrees C). Subsequently, the adsorption modeling study of simple gases (CH4 and CO2) in these Si-CDC samples for a wide range of pressures and temperatures using our Finite Wall Thickness model [Nguyen, T. X.; Bhatia, S. K. Langmuir 2004, 20, 3532] was also carried out. In general, characterization results showed that the core of Si-CDC particles contains predominantly amorphous material while minor graphitization was also observed on the surface of these particles for all the investigated synthesis temperatures (600-1000 degrees C). Furthermore, postsynthetic heat treatment at 1000 degrees C for 3 days, as well as particle size of precursor (betaSiC) were shown to have slight impact on the graphitization. In spite of the highly disordered nature of Si-CDC samples, the adsorption modeling results revealed that the Finite Wall Thickness model provides reasonably good prediction of experimental adsorption data of CO2 and CH4 in all the investigated Si-CDC samples at the temperatures of 273 K, 313 K, and 333 K for a wide range of pressure up to 200 bar. Furthermore, the impact of the difference in molecular size and geometry between analysis and probing gases on the prediction of the experimental adsorption isotherm in a disordered carbon using the slit-pore model is also found. Finally, the correlation between compressibility of the Si-CDC samples under high pressure adsorption and their synthesis temperature was deduced from the adsorption modeling.

Polyethylene glycol-conjugated growth hormone-releasing hormone is long acting and stimulates GH in healthy young and elderly subjects.

OBJECTIVE: The clinical use of growth hormone-releasing hormone (GHRH) is limited by its short half-life. Polyethylene glycol-conjugated GHRH (PEG-GHRH) was developed to provide increased stability compared with the currently available GHRH(1-29). This study aimed to evaluate the safety, tolerability and pharmacodynamics of PEG-GHRH. DESIGN: PEG-GHRH was administered by subcutaneous injection to young healthy men (n = 12) and elderly men and women (aged > 60 years; n = 20). RESULTS: In both groups, administration of PEG-GHRH generated a clear increase in circulating GH compared with placebo. Following single-dose (0.25, 0.5, 2 or 4 mg) administration to young subjects, the effect persisted for 12 h, but a sustained increase was observed on repeated administration to the elderly. Serum insulin-like growth factor-I also increased in response to PEG-GHRH treatment. Injection-site reactions were more frequent with PEG-GHRH compared with placebo, but these were mild and transient; other adverse events were similar to those observed after placebo. Some impairment of glucose tolerance was observed in the elderly following repeated administration of PEG-GHRH. Antibodies to GHRH were not observed. CONCLUSIONS: PEG-GHRH offers the possibility of less frequent dosing compared with GHRH. This possibility deserves further clinical testing.

High-pressure adsorption capacity and structure of CO2 in carbon slit pores: theory and simulation.

We present new simulation results for the packing of single-center and three-center models of carbon dioxide at high pressure in carbon slit pores. The former shows a series of packing transitions that are well described by our density functional theory model developed earlier. In contrast, these transitions are absent for the three-center model. Analysis of the simulation results shows that alternations of flat-lying molecules and rotated molecules can occur as the pore width is increased. The presence or absence of quadrupoles has negligible effect on these high-density structures.

The expression of IL-2, IL-4 and interferon-gamma (IFN-gamma) mRNA using liver biopsies at different phases of acute exacerbation of chronic hepatitis B.

To investigate the hypothesis that Th1 phenotype cytokines are associated with the increasing activity of hepatitis and Th2 phenotype cytokines with decreasing activity in the liver of chronic viral hepatitis, expressions of the mRNA of the cytokines IL-2, IFN-gamma and IL-4 in the liver of 23 patients with chronic hepatitis B were investigated by reverse transcription polymerase chain reaction. Patients were divided into three groups according to the phase of acute exacerbation of hepatitis as increasing (n = 9), decreasing (n = 8), and stable phase (n = 6). Both IL-2 and IFN-gamma mRNA were preferentially expressed in increasing phase than in decreasing phase (P < 0.01, P < 0.05, respectively) and associated with the high serum alanine aminotransferase (ALT) level. On the other hand, IL-4 mRNA was detected in decreasing phase with significant frequency compared with increasing phase (P < 0.05). However, expression of IL-4 mRNA was not associated with serum ALT level. Our results suggest that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate the liver inflammation of chronic viral hepatitis.

Can Ca entry via Na-Ca exchange directly activate cardiac muscle contraction?

Developed twitch tension and action potentials were recorded in rabbit ventricular muscle in physiological saline at 30 degrees C stimulated at 0.5 Hz. Addition of 5 microM nifedipine to block Ca entry via Ca channels almost abolished twitches (to 2.5 +/- 0.7%, S.E.M., n = 10 of control). This suggests that under normal conditions Ca entry via Na-Ca exchange is insufficient to activate contractions. However, when muscles are first exposed to 4 microM acetylstrophanthidin to elevate [Na]i the same exposure to nifedipine only partially suppresses twitches (to 59 +/- 12% of the original control). This suggests that when [Na]i is elevated, Ca entry via the Na-Ca exchange may be adequate to partially activate contraction. From this result it is not clear whether Ca entry via Na-Ca exchange is sufficient to activate contraction directly or whether sarcoplasmic reticulum (SR) Ca release is required. When these experiments were carried out in the presence of 5 to 10 mM caffeine or 100 nM ryanodine similar results were obtained. That is, nifedipine still abolished contractions in the presence of caffeine or ryanodine (to 3.8 +/- 0.3% and 1.3 +/- 0.4%, respectively), but only partially inhibited contractions in the presence of caffeine + acetylstrophanthidin (to 21 +/- 5%) or ryanodine + acetylstrophanthidin (10 +/- 2%). Thus, it appears that even in the absence of a functional SR and with Ca current blocked, Na-Ca exchange might bring sufficient Ca into the cell to activate appreciable contractions, but only when [Na]i is elevated. Action potential duration is decreased by nifedipine and acetylstrophanthidin and is further decreased when nifedipine is added on top of acetylstrophanthidin. If this Ca entry is by an electrogenic 3 Na: 1 Ca exchange, Ca entry will be favored at more positive membrane potentials. If the action potential were not so abbreviated with these drugs, Na-Ca exchange might bring in more Ca and activate additional tension.

[Use of Doppler ultrasonic examination for per-operative checking of non surgical upper dorsal sympathectomy in the treatment of hyperhydrosis (author's transl)]. / Utilisation de l'effet Doppler en contrôle per-opératoire de la sympathectomie thoracique supérieure non chirurgicale dans le traitement de l'hyperhydrose des mains.

Doppler ultrasonic examination has been used as an indirect means of per-operative checking of sweat secretion after non surgical upper dorsal sympathectomy performed by percutaneous injection of hot saline into the upper dorsal sympathetic ganglions for the treatment of palmar hyperhydrosis. Their experience with pre, per and post-operative utilisation of Doppler effect in sixty cases has evidenced a full parallelism between the arterial vasodilation and the decrease in sweat secretion following the destruction of the sympathetic ganglions by hot saline. In the last series of thirty-five cases per-operative use of Doppler ultrasonic examination has spared them failures of the procedure. They consider Doppler ultrasonic examination as a precious help in classical open sympathectomy as well in their non surgical method.