Vagus nerve stimulation for depression: efficacy and safety in a European study

Background Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression. Method An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically. Results The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%). Conclusions VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European stud

Multi-objective optimization of genome-scale metabolic models: the case of ethanol production

Ethanol is among the largest fermentation product used worldwide, accounting for more than 90% of all biofuel produced in the last decade. However current production methods of ethanol are unable to meet the requirements of increasing global demand, because of low yields on glucose sources. In this work, we present an in silico multi-objective optimization and analyses of eight genome-scale metabolic networks for the overproduction of ethanol within the engineered cell. We introduce MOME (multi-objective metabolic engineering) algorithm, that models both gene knockouts and enzymes up and down regulation using the Redirector framework. In a multi-step approach, MOME tackles the multi-objective optimization of biomass and ethanol production in the engineered strain; and performs genetic design and clustering analyses on the optimization results. We find in silico E. coli Pareto optimal strains with a knockout cost of 14 characterized by an ethanol production up to 19.74mmolgDW−1h−1 (+832.88% with respect to wild-type) and biomass production of 0.02h−1 (−98.06% ). The analyses on E. coli highlighted a single knockout strategy producing 16.49mmolgDW−1h−1 (+679.29% ) ethanol, with biomass equals to 0.23h−1 (−77.45% ). We also discuss results obtained by applying MOME to metabolic models of: (i) S. aureus; (ii) S. enterica; (iii) Y. pestis; (iv) S. cerevisiae; (v) C. reinhardtii; (vi) Y. lipolytica. We finally present a set of simulations in which constrains over essential genes and minimum allowable biomass were included. A bound over the maximum allowable biomass was also added, along with other settings representing rich media compositions. In the same conditions the maximum improvement in ethanol production is +195.24%

VARIATION OF DISTRIBUTION COEFFICIENT OF CAFFEINE BETWEEN WATER AND ETHYL ACETATE/CHLOROFORM MIXTURE DEPENDING ON THE MEDIUM ACIDITY

Kafein, ülkemizde önemli bir tarımsal ürün olan ve büyük miktarlarda üretilen çayın enönemli bileşenidir. Kafein, çok yaygın ve farklı alanlardaki kullanımı nedeniyle büyük ticarideğer taşımaktadır. Bu nedenle, ekonomik üretim proseslerinin geliştirilmesi son dereceönemlidir.Bu çalışmanın amacı, kafeinin su ve etil asetat/kloroform karışımı arasındaki dağılmakatsayılarının pH\'a bağlı olarak değişiminin incelenmesidir. Çalışmada organik çözücükarışımı etil asetat/kloroformun beş farklı oranı kullanılmıştır. Bu oranlar %20, %40, %50,%60 ve %80 kloroform içerecek şekilde seçilmiştir. Ayrıca dağılma katsayısının pH\'yabağımlılığının incelenmesi için denemeler beş farklı pH\'da yapılmıştır. Bu pH değerleri 5.65,5.90, 6.25, 7.10 ve 7.90\'dır. Deneysel çalışmada hazırlanan % 1\'lik (hacimsel) kafeinçözeltisinden belirli miktar alınarak çözücü karışımı ile ekstrakt edilmiş ve iyodometriyöntemiyle kafein analizi yapılmıştır. Yapılan deneysel çalışmalar sonucunda, pH değerininyükselmesiyle dağılma katsayısının arttığı tespit edilmiştir.Caffeine is a main component of tea, which is an important agricultural product in ourcountry. It has a great economical value because of its different and extensive industrialapplications.The aim of this study is to investigate the variation of the distribution coefficients ofcaffeine between water and ethyl acetate/chloroform mixture depending on pH. Ethylacetate/chloroform mixture was used in five different ratios. These ratios were selected as tocontain 20%, 40%, 50%, 60% and 80% chloroform. Also five different pH were selected toinvestigate the distribution coefficient depending on pH. These pH values were 5.65, 5.90,6.25, 7.10 and 7.90.In experimental investigations, 1% aqueous solution of caffeine was used. Caffeinecontent was analysed by means of Iodometry method.It was seen that the distribution coefficient of caffeine between water and solvent mixturewas increased with increasing pH

VARIATION OF DISTRIBUTION COEFFICIENT OF CAFFEINE BETWEEN WATER AND ETHYL ACETATE/CHLOROFORM MIXTURE DEPENDING ON THE MEDIUM ACIDITY

Kafein, ülkemizde önemli bir tarımsal ürün olan ve büyük miktarlarda üretilen çayın enönemli bileşenidir. Kafein, çok yaygın ve farklı alanlardaki kullanımı nedeniyle büyük ticarideğer taşımaktadır. Bu nedenle, ekonomik üretim proseslerinin geliştirilmesi son dereceönemlidir.Bu çalışmanın amacı, kafeinin su ve etil asetat/kloroform karışımı arasındaki dağılmakatsayılarının pH\'a bağlı olarak değişiminin incelenmesidir. Çalışmada organik çözücükarışımı etil asetat/kloroformun beş farklı oranı kullanılmıştır. Bu oranlar %20, %40, %50,%60 ve %80 kloroform içerecek şekilde seçilmiştir. Ayrıca dağılma katsayısının pH\'yabağımlılığının incelenmesi için denemeler beş farklı pH\'da yapılmıştır. Bu pH değerleri 5.65,5.90, 6.25, 7.10 ve 7.90\'dır. Deneysel çalışmada hazırlanan % 1\'lik (hacimsel) kafeinçözeltisinden belirli miktar alınarak çözücü karışımı ile ekstrakt edilmiş ve iyodometriyöntemiyle kafein analizi yapılmıştır. Yapılan deneysel çalışmalar sonucunda, pH değerininyükselmesiyle dağılma katsayısının arttığı tespit edilmiştir.Caffeine is a main component of tea, which is an important agricultural product in ourcountry. It has a great economical value because of its different and extensive industrialapplications.The aim of this study is to investigate the variation of the distribution coefficients ofcaffeine between water and ethyl acetate/chloroform mixture depending on pH. Ethylacetate/chloroform mixture was used in five different ratios. These ratios were selected as tocontain 20%, 40%, 50%, 60% and 80% chloroform. Also five different pH were selected toinvestigate the distribution coefficient depending on pH. These pH values were 5.65, 5.90,6.25, 7.10 and 7.90.In experimental investigations, 1% aqueous solution of caffeine was used. Caffeinecontent was analysed by means of Iodometry method.It was seen that the distribution coefficient of caffeine between water and solvent mixturewas increased with increasing pH

How β-Lactam Antibiotics Enter Bacteria: A Dialogue with the Porins

BACKGROUND:Multi-drug resistant (MDR) infections have become a major concern in hospitals worldwide. This study investigates membrane translocation, which is the first step required for drug action on internal bacterial targets. beta-lactams, a major antibiotic class, use porins to pass through the outer membrane barrier of Gram-negative bacteria. Clinical reports have linked the MDR phenotype to altered membrane permeability including porin modification and efflux pump expression. METHODOLOGY/PRINCIPAL FINDINGS: Here influx of beta-lactams through the major Enterobacter aerogenes porin Omp36 is characterized. Conductance measurements through a single Omp36 trimer reconstituted into a planar lipid bilayer allowed us to count the passage of single beta-lactam molecules. Statistical analysis of each transport event yielded the kinetic parameters of antibiotic travel through Omp36 and distinguishable translocation properties of beta-lactams were quantified for ertapenem and cefepime. Expression of Omp36 in an otherwise porin-null bacterial strain is shown to confer increases in the killing rate of these antibiotics and in the corresponding bacterial susceptibility. CONCLUSIONS/SIGNIFICANCE: We propose the idea of a molecular "passport" that allows rapid transport of substrates through porins. Deciphering antibiotic translocation provides new insights for the design of novel drugs that may be highly effective at passing through the porin constriction zone. Such data may hold the key for the next generation of antibiotics capable of rapid intracellular accumulation to circumvent the further development MDR infections

Vagus nerve stimulation for depression: efficacy and safety in a European study

Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression

A Genome-Wide RNAi Screen Identifies Regulators of Cholesterol-Modified Hedgehog Secretion in Drosophila

Hedgehog (Hh) proteins are secreted molecules that function as organizers in animal development. In addition to being palmitoylated, Hh is the only metazoan protein known to possess a covalently-linked cholesterol moiety. The absence of either modification severely disrupts the organization of numerous tissues during development. It is currently not known how lipid-modified Hh is secreted and released from producing cells. We have performed a genome-wide RNAi screen in Drosophila melanogaster cells to identify regulators of Hh secretion. We found that cholesterol-modified Hh secretion is strongly dependent on coat protein complex I (COPI) but not COPII vesicles, suggesting that cholesterol modification alters the movement of Hh through the early secretory pathway. We provide evidence that both proteolysis and cholesterol modification are necessary for the efficient trafficking of Hh through the ER and Golgi. Finally, we identified several putative regulators of protein secretion and demonstrate a role for some of these genes in Hh and Wingless (Wg) morphogen secretion in vivo. These data open new perspectives for studying how morphogen secretion is regulated, as well as provide insight into regulation of lipid-modified protein secretion

The Drosophila melanogaster host model

The deleterious and sometimes fatal outcomes of bacterial infectious diseases are the net result of the interactions between the pathogen and the host, and the genetically tractable fruit fly, Drosophila melanogaster, has emerged as a valuable tool for modeling the pathogen–host interactions of a wide variety of bacteria. These studies have revealed that there is a remarkable conservation of bacterial pathogenesis and host defence mechanisms between higher host organisms and Drosophila. This review presents an in-depth discussion of the Drosophila immune response, the Drosophila killing model, and the use of the model to examine bacterial–host interactions. The recent introduction of the Drosophila model into the oral microbiology field is discussed, specifically the use of the model to examine Porphyromonas gingivalis–host interactions, and finally the potential uses of this powerful model system to further elucidate oral bacterial-host interactions are addressed

Adsorptive removal of biophenols from olive mill wastewaters (OMW) by activated carbon: mass transfer, equilibrium and kinetic studies

In this study, the removal of biophenols from olive mill wastewater by activated carbon of different particle sizes has been carried out using the batch adsorption technique. The effects of the sorbent specific surface area and concentration, temperature, initial biophenols concentration, and contact time on the adsorption efficiency have been analyzed independently. The sorbent yields higher removal efficiency of biophenols as its specific surface area increases. When increasing the sorbent concentration from 10 to 50 g L-1, the sorbent uptake capacity increases from 20% to 41%, and it reaches a maximum value of 65 mg g(-1) at 298.2 K. Adsorption of olive mill wastewater biophenols is moderately rapid, being about 38% to 40% of the initial phenolic content after 120 min. Kinetic analysis shows that the adsorption process can be approximated by a pseudo-second-order model for which pore diffusion is the essential rate-controlling step. Equilibrium modeling by linearized adsorption isotherms reveals that a Langmuir-type isotherm with a preferable monolayer sorption would likely proceed. Calculated thermodynamic parameters such as Gibbs energy, enthalpy, entropy, activation energy, and sticking probability indicate that adsorption is a typical endothermic yet spontaneous process with a preferable physisorption mechanism. An external mass transfer coefficient model has been developed to determine the rate of adsorption controlled initially by the boundary layer film, with particular focus on its predictive performance. Copyright (C) 2016 Curtin University of Technology and John Wiley & Sons, Ltd