Different Intestinal Microbiota Profile in Alcoholic Pancreatitis as Compared to Alcoholic Hepatitis

( Dragos Ciocan ),( Vinciane Rebours ),( Anne-marie Cassard ),( Laura Wrzosek ),( Cosmin Sebastian Voican ),( Virginie Puchois ),( Philippe Levy ),( Gabriel Perlemuter ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Chronic excessive alcohol consumption may cause alcoholic liver disease (ALD) or alcoholic pancreatitis (AP) in only a subset of patients. We have shown that individual susceptibility to ALD is substantially driven by intestinal microbiota (IM). However, factors related to tissue predilection (liver or pancreas) to alcohol toxicity are unknown. We aimed to characterize the IM profile in alcoholic patients according to the presence and the nature of the complication ie severe alcoholic hepatitis (sAH) or AP. Methods: Eighty-two alcoholic patients were included into 3 groups according to their complications: AP (N=24), sAH (N=13) and no complication despite a similar amount of alcohol consumption (alcoholic controls, N=45). IM was analyzed using high-throughput sequencing of the 16S Ribosomal RNA (16S RNA) gene. Results: Patients with AP had a reduced bacterial diversity (p=0.001) and a different global microbial composition as compared to alcoholic controls (p=0.001). 17 taxa at the genus level were different between the 2 groups; among them, 8 were increased in AP (Klebsiella, Enterococcus, Aquabacterium and Sphingomonas). When compared to sAH there was no difference in bacterial diversity between the 2 groups. However, 16 taxa were increased in sAH and 10 in AP. After adjusting for confounding factors (age, sex, BMI, alcohol intake, diabetes and proton-pump inhibitors) there was a marked increase in Haemophilus in sAH patients. Conclusions: Patients with AP have a specific dysbiosis as compared to alcoholic controls. Specific microbiome signatures are associated with AP and sAH.

A Tool for the Analysis of Robot Soccer Game

Drago Matko,Gregor Klan?ar,Marko Lepeti? 대한전기학회 2003 International Journal of Control, Automation, and Vol.1 No.2

Bile Acids and Intestinal Dysbiosis in Alcoholic Hepatitis

( Dragos Ciocan ),( Cosmin Sebastian Voican ),( Laura Wrzosek ),( Cindy Hugot ),( Gabriel Perlemuter ),( Anne-marie Cassard ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Alcoholic liver disease is associated with dysbiosis, impaired gut barrier and inflammation. Intestinal microbiota (IM) plays an important role in bile acids (BA) homeostasis and impact the gut barrier and promotes inflammation. The aim of our study was to study the structure of the IM and its function in BA homeostasis in alcoholic patients according to the severity of alcoholic liver disease. Methods: We included in a prospective study 4 groups of active alcoholic patients (N=97): two non-cirrhotic (nc) without or with alcoholic hepatitis (AH) (noAHnc, N=54 or AHnc N=14, respectively) and two cirrhotic groups without or with AH (noAHc, N=16 or sAHc, N=13, respectively). Serum and fecal BA profiles, as well as IM composition, using high-throughput 16s sequencing, were assessed. Results: In sAHc patients compared to noAHc patients, there was an increase in serum total BA, primary BA (total CA and total CDCA), conjugated BA and tauro-glycoconjugated ratio and a decrease in the UDCA/total BA and secondary/primary ratio. In feces, there was a decrease in total BA and an increase in secondary BA (total LCA and DCA). These 2 groups had a different IM structure. At the phyla level, there was an increase in Actinobacteria and a decrease in Bacteroidetes; 7 genera were increased and 4 were decreased. Moreover, in sAHc patients compared to noAHc patients, there was an increase in 4 and a decrease in 11 metabolic pathways (eg increase in glutathion and nucleotid metabolism, phosphotransferase system). In AHnc patients as compared to noAHnc, there was an increase in serum total conjugated BA. The IM of AHnc patients was characterized by an increase in Wolbachia and Dorea as compared to noAHnc. Conclusions: Disruption of BA homeostasis associated with alcoholic hepatitis is correlated to a specific IM signature that may lead to liver disease progression.

VEHICLES FRONTAL IMPACT ANALYSIS USING COMPUTER SIMULATION AND CRASH TEST

Dragos Sorin Dima,Dinu Covaciu 한국자동차공학회 2019 International journal of automotive technology Vol.20 No.4

Reconstruction of car accidents is a complex task, with many unknown variables. Among the parameters used to assess the accident severity, in case of a frontal collision between two vehicles, are the change in velocity (delta-v) and the Energy Equivalent Speed (EES). The EES is usually determined based on the deformations. Delta-v can be obtained from the crash pulse recorded with Event Data Recorders, or with crash loggers based on accelerometers, in case of crash tests. In this paper is presented a full scale crash test that involves two vehicles in a frontal collision. The results are obtained using different analysis methods: direct application of a model, processing the measured crash pulse, and computer simulation.

Evaluation of the new coastal protection scheme at Mamaia Bay in the nearshore of the Black Sea

Niculescu, Dragos M.,Rusu, Eugen V.C. Techno-Press 2018 Ocean systems engineering Vol.8 No.1

The target area of the proposed study, Mamaia beach, is a narrow stretch of sand barrier island that sits between the Siutghiol Lake and the Black Sea. In the northern part of the bay, is located the Midia Port, where between 1966 and 1971 a long extension of 5 km of the offshore was built. Because of this extension, the natural flow of sediments has been significantly changed. Thus, the southern part of the Mamaia Bay had less sand nourishment which meant that the coast was eroding and to prevent it a protection of six dikes was built. After approximately forty years of coastal erosion, the south of the Mamaia Bay had in 2016 a new protection scheme, which includes first of all the beach nourishment and a new dike structure (groins scheme for protection) to protect it. From this perspective, the objective of the proposed study is to evaluate the effectiveness of the old Master plan against the new one by modeling the outcome of the two scenarios and to perform a comparison with a third one, in which the protection dikes do not exist and only the artificial nourishment has been done. In order to assess the wave processes and the current patterns along the shoreline, a complex computational framework has been applied in the target area. This joins the SWAN spectral phase averaged model with the 1D surf model. Furthermore, new UAV technology was also used to map out, chart and validate the numerical model outputs within the target zone for a better evaluation of the trends expected in the shoreline dynamics.

OVERSAMPLED ∑-Δ A/D AND D/A CONVERTERS FOR LOW-POWER , LOW-VOLTAGE DIGITAL VOICE TERMINALS

Strle,Drago 대한전자공학회 1995 ICVC : International Conference on VLSI and CAD Vol.4 No.1

Design of oversampled ∑-△ A/D and D/A converters used in low-power, low-voltage digital voice terminal is presented in this article. The power consumption is reduced by reducing supply voltage down-to 4^*V_(TH) that is for 1㎛ CMOS process with V_(THn)= V_(THp) = 0.5V ague to V_(sup) ≥ 2.0V. The design of digital decimation and interpolation filters is based on the sine architecture with very careful logic and circuit design to avoid unnecessary transitions. The architecture of the analog sections are fully differential second order modulator and I bit D/A wish 2nd order Chebishev S-C filter. The achicved linearity is 13 bits and resolution of 14 bits at V_(sup)= 2.0V. The measured power consumption of a complete ∑-△ A/D and D/A wish oversampling frequency of 1MHz is 1.2mW. Area needed for the modulator and one bit D/A with 2nd order S-C filter is 1.7 ㎟.

Immunomodulatory Effects of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03, Alone and in Combination, on Peripheral Blood Mononuclear Cells of Allergic Asthmatics

Lorenzo Drago,Elena De Vecchi,Arianna Gabrieli,Roberta De Grandi,Marco Toscano 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.4

The aim of this study was to evaluate probiotic characteristics of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03 alone and in combination and their immunomodulatory activity in asthmatic subjects. Subjects affected by allergic asthma were recruited. Initially, LS01 and BR03 were analyzed for their growth compatibility by a broth compatibility assay. To study the antimicrobial activity of probiotic strains, an agar diffusion assay was performed. Finally, cytokine production by peripheral blood mononuclear cells (PBMCs) stimulated with LS01 and BR03 was determined by means of specific quantitative enzyme-linked immunosorbent assay (ELISA). The growth of some clinical pathogens were slightly inhibited by LS01 and LS01-BR03 co-culture supernatant not neutralized to pH 6.5, while only the growth of E. coli and S. aureus was inhibited by the supernatant of LS01 and LS01-BR03 neutralized to pH 6.5. Furthermore, LS01 and BR03 combination was able to decrease the secretion of proinflammatory cytokines by PBMCs, leading to an intense increase in IL-10 production. L. salivarius LS01 and B. breve BR03 showed promising probiotic properties and beneficial immunomodulatory activity that are increased when the 2 strains are used in combination in the same formulation.

CRY1 Variations Impacts on the Depressive Relapse Rate in a Sample of Bipolar Patients

Antonio Drago,Barbara Monti,Diana De Ronchi,Alessandro Serretti 대한신경정신의학회 2015 PSYCHIATRY INVESTIGATION Vol.12 No.1

ObjectiveaaA relevant part of the social and personal burden caused by Bipolar Disorder (BD) is related to depressive phases. Authors investigated the genetic impact of a set of variations located in CRY1, a gene involved in the control of the circadian rhythms, towards depressive episodes in a sample of bipolar patients from the STEP-BD sample. As a secondary analysis, CYR1 variations were analyzed as predictors of sleep disruption. Methodsaa654 bipolar patients were included in the analysis. Data were available genome-wide. The part of the genome coding for the CRY1 was imputed and pruned according to standards in the field. 7 SNPs were available for the analysis. A correction for multitesting was applied and we had sufficient power (0.80) to detect a small-medium effect size (0.22) between two allelic frequencies each one represented by at least 300 subjects. ResultsaaIntronic rs10861688 was associated with the number of depressive events corrected for the times patients were assessed during the period of observation. In particular, AA subjects (n=21) had 4.46±3.15 events, AG (n=141) had 3.08±3.17 and GG (n=342) 2.65±2.97 (p=0.0048, beta=-0.22). No other significant associations were reported. ConclusionaaWe bring further evidence that genes involved in the regulation of circadian rhythms may be relevant to depressive bipolar phases. Independent confirmation analyses are mandatory.

Macrolide Resistance and In Vitro Selection of Resistance to Antibiotics in Lactobacillus Isolates

Lorenzo Drago,Roberto Mattina,Lucia Nicola,Valentina Rodighiero,Elena De Vecchi 한국미생물학회 2011 The journal of microbiology Vol.49 No.4

Spreading of resistance to antibiotics is of great concern due to the increasing rate of isolation of multiresistant pathogens. Since commensal bacteria may transfer determinants of resistance to pathogens, studies on development of resistance should include also lactobacilli. Resistance to macrolides, penicillins and tetracycline was determined in 40 isolates of Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus crispatus,and Lactobacillus casei isolated from faeces of apparently healthy volunteers. Frequency of mutation and changes in susceptibility after serial exposure to these antibiotics at concentrations of 4× and 8× MIC were evaluated in susceptible isolates. Acquired resistance was defined as an increment in MIC values of at least four times in respect to the pre-selection values. Resistance to macrolides and/or tetracycline was identified in 14 and 4 isolates, respectively. ermB gene and A2058G mutation in 23S rRNA were detected in macrolide resistant isolates. Frequencies of mutation of susceptible isolates (n=26) were lower for ampicillin and erythromycin than for tetracycline. Serial exposure to antibiotics led to selection of resistant mutants. However,acquired resistance was rather unstable and was lost after subcultures in antibiotic-free medium in most mutants. Resistance to erythromycin was associated to a A2058G mutation in 23S rRNA. In conclusion,results indicate that resistance to macrolides and tetracycline is present among intestinal lactobacilli. Decrease in susceptibility following serial exposure to antibiotics might occur in lactobacilli, in a strain- and antibiotic-dependent way. Since lactobacilli are often used as probiotics, their ability to acquire resistance should be evaluated for isolates candidate to be included in probiotics based products.

Pharmacophore-based virtual screening.

Humana Press 2011 METHODS IN MOLECULAR BIOLOGY -CLIFTON THEN TOTOWA- Vol.672 No.-

<P>This chapter is a review of the most recent developments in the field of pharmacophore modeling, covering both methodology and application. Pharmacophore-based virtual screening is nowadays a mature technology, very well accepted in the medicinal chemistry laboratory. Nevertheless, like any empirical approach, it has specific limitations and efforts to improve the methodology are still ongoing. Fundamentally, the core idea of 'stripping' functional groups of their actual chemical nature in order to classify them into very few pharmacophore types, according to their dominant physico-chemical features, is both the main advantage and the main drawback of pharmacophore modeling. The advantage is the one of simplicity - the complex nature of noncovalent ligand binding interactions is rendered intuitive and comprehensible by the human mind. Although computers are much better suited for comparisons of pharmacophore patterns, a chemist's intuition is primarily scaffold-oriented. Its underlying simplifications render pharmacophore modeling unable to provide perfect predictions of ligand binding propensities - not even if all its subsisting technical problems would be solved. Each step in pharmacophore modeling and exploitation has specific drawbacks: from insufficient or inaccurate conformational sampling to ambiguities in pharmacophore typing (mainly due to uncertainty regarding the tautomeric/protonation status of compounds), to computer time limitations in complex molecular overlay calculations, and to the choice of inappropriate anchoring points in active sites when ligand cocrystals structures are not available. Yet, imperfections notwithstanding, the approach is accurate enough in order to be practically useful and actually is the most used virtual screening technique in medicinal chemistry - notably for 'scaffold hopping' approaches, allowing the discovery of new chemical classes carriers of a desired biological activity.</P>