Efficacy and tolerability of chitin-glucan combined with simethicone(GASTRAP^(■)DIRECT)in irritable bowel syndrome:A prospective,open-label,multicenter study

BACKGROUND Irritable bowel syndrome(IBS),defined according to the Rome IV diagnostic criteria,is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain related to altered bowel habits.First-line recommended treatments are limited to combining drugs targeting predominant symptoms,particularly pain(antispasmodics),constipation(laxatives),and diarrhea(loperamide),yielding only a limited therapeutic gain.GASTRAP^(■)DIRECT is a class IIa medical formulation composed of a combination of chitin-glucan and simethicone indicated for the symptomatic treatment of gas-related gastrointestinal disorders by combining different mechanisms of action.AIM To evaluate the efficacy,tolerability,and safety of 4-week GASTRAP^(■)DIRECT treatment in patients with IBS.METHODS In this prospective,multicenter,open-label trial,120 patients with IBS received three sticks of GASTRAP^(■)DIRECT(1.5 g/d of chitin-glucan and 0.75 mg/d of simethicone)per day for 4 weeks.The primary endpoint was the responder rate,defined as the number of patients whose abdominal pain score decreased by≥30%from baseline to week(W)4.The analysis was performed using the per-protocol set.Cardinal symptoms,impact of global symptoms on daily life,change in stool consistency,and improvement in defecatory disorders were evaluated.RESULTS Overall,100 patients were evaluated.At W4,67%(95%CI:57-75)showed improvement in abdominal pain(score:5.8±2.4 vs 2.9±2.0,P<0.0001).Similar improvements were observed for bloating[8.0±1.7 vs 4.7±2.9,P<0.0001;60%(95%CI:50-70)responders],abdominal distension[7.2±2.1 vs 4.4±3.1,P<0.0001;53%(95%CI:43-63)responders],and impact of global symptoms on daily life[7.1±2.0 vs 4.6±2.9,P<0.0001;54%(95%CI:44-64)responders].Stool consistency improved in most patients(90%and 57%for patients with liquid and hard stools,respectively).Overall,42%of patients with defecatory disorders reported very much/considerable improvements by W2.No severe adverse event occurred,and tolerability was rated“good”or“very good”by 93%of patients.CONCLUSION GASTRAP^(■)DIRECT is safe and well tolerated,alleviating IBS symptoms rapidly in 2 weeks.This open-label study suggests that the combination of chitin-glucan and simethicone could be beneficial in patients with IBS.

Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats

BACKGROUND Postoperative recurrence(POR)after ileocecal resection(ICR)affects most Crohn's disease patients within 3-5 years after surgery.Adherent-invasive Escherichia coli(AIEC)typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis.Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut.AIM To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic(TgB27)rat model.METHODS Sixty-four rats[strain F344,38 TgB27,26 control non-Tg(nTg)]underwent an ICR at the 12th wk(W12)of life and were sacrificed at the 18th wk(W18)of life.TgB27 rats were challenged daily with oral administration of LF82(109 colony forming units(CFUs)/day(d),n=8),PBS(n=5),CNCM I-3856(109 CFUs/d,n=7)or a combination of LF82 and CNCM I-3856(n=18).nTg rats receiving LF82(n=5),PBS(n=5),CNCM I-3856(n=7)or CNCM I-3856 and LF82(n=9)under the same conditions were used as controls.POR was analyzed using macroscopic(from 0 to 4)and histologic(from 0 to 6)scores.Luminal LF82 quantifications were performed weekly for each animal.Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18.Data are expressed as the median with the interquartile range.RESULTS nTg animals did not develop POR.A total of 7/8(87%)of the TgB27 rats receiving LF82 alone had POR(macroscopic score≥2),which was significantly prevented by CNCM I-3856 administration[6/18(33%)TgB27 rats,P=0.01].Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5(2-4).Seven out of 18 TgB27 rats(39%)receiving CNCM I-3856 and LF82 had no macroscopic lesions.Compared to untreated TgB27 animals receiving LF82 alone,coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic[3.5(2-4)vs 1(0-3),P=0.002]and histological lesions by more than 50%[4.5(3.3-5.8)vs 2(1.3-3),P=0.003].The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats(r=0.49,P=0.006),with a higher risk of POR in animals having high levels of luminal LF82(71.4%vs 25%,P=0.02).Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82,increased the production of interleukin(IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats.CONCLUSION In a reliable model of POR induced by LF82 in TgB27 rats,CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.

Pore pressure prediction in offshore Niger delta using data-driven approach: Implications on drilling and reservoir quality

Despite exploration and production success in Niger Delta,several failed wells have been encountered due to overpressures.Hence,it is very essential to understand the spatial distribution of pore pressure and the generating mechanisms in order to mitigate the pitfalls that might arise during drilling.This research provides estimates of pore pressure along three offshore wells using the Eaton's transit time method,multi-layer perceptron artificial neural network(MLP-ANN)and random forest regression(RFR)algorithms.Our results show that there are three pressure magnitude regimes:normal pressure zone(hydrostatic pressure),transition pressure zone(slightly above hydrostatic pressure),and over pressured zone(significantly above hydrostatic pressure).The top of the geopressured zone(2873 mbRT or 9425.853 ft)averagely marks the onset of overpressurization with the excess pore pressure above hydrostatic pressure(P∗)varying averagely along the three wells between 1.06−24.75 MPa.The results from the three methods are self-consistent with strong correlation between the Eaton's method and the two machine learning models.The models have high accuracy of about>97%,low mean absolute percentage error(MAPE<3%)and coefficient of determination(R2>0.98).Our results have also shown that the principal generating mechanisms responsible for high pore pressure in the offshore Niger Delta are disequilibrium compaction,unloading(fluid expansion)and shale diagenesis.

Defensins couple dysbiosis to primary immunodeficiency in Crohn's disease

Antimicrobial peptides,including defensins,are essential effectors in host defence and in the maintenance of immune homeostasis.Clinical studies have linked the defective expression of both α-and β-defensin to the reduced killing of certain microorganisms by the intestinal mucosa of patients suffering from ileal and colonic Crohn's disease(CD),respectively.Only recently have the events leading to defective expression of defensins in CD been further elucidated,and are discussed herein.These events may account for CD-associated alterations in the microbiome and may subsequently precipitate the development of granulomatous inflammatory lesions in genetically-predisposed patients.We also address how these discoveries may pave the way for the development of a molecular medicine aimed at restoring gut barrier function in CD.

Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract

Esophageal atresia(EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia(72%) and gastroesophageal reflux(GER)(67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.

中法老人基本心理需要满足对心理幸福感的影响:文化普遍性和差异性

目的:以自我决定理论为基础,并从跨文化的视角,来探讨中法两国老人的基本心理需要满足情况,及其对心理幸福感的影响。方法:对60~85岁的退休老人(n中=464,n法=129)施测基本心理需要满足量表,心理幸福感量表,主观健康和背景信息问卷。结果:(1)3个基本心理需要满足(自主、能力和关系)均显著正向预测中法老人的心理幸福感;(2)法国老人的自主需要满足水平显著高于中国老人(t=-2.42,P<0.05),但其对心理幸福感的预测力并不存在差异;中国老人的能力需要满足(t=2.86,P<0.01)及其对心理幸福感的预测力显著高于法国老人(Z=2.33,P<0.05)。结论:基本心理需要满足对老年人心理幸福感的影响既有跨文化的普遍性,同时也表现出了东西方背景下的文化差异性。

A novel approach for fabricating a CNT/AlSi composite with the self-aligned nacre-like architecture by cold spraying

A fully dense carbon nanotubes (CNTs) reinforced AlSi matrix composite with the multiscale nacre-like architecture was designed and successfully realized by flake powder metallurgy followed by cold spraying (CS). The nanolaminated and ultrafine-grained structure initially created in the CNT/AlSi flaky powder was perfectly conserved, due to the typical ‘cold’ feature of CS. As discussed based on finite element analysis and single splat observation, self-alignment behavior of the flaky powders during impact also allowed the formation of the microlaminated structure. Hence, the scalable CS technique opens a new avenue for bioinspired material design and fabrication with complex shape.

Validating the CorrectWearing of Protection Mask by Taking a Selfie:Design of a Mobile Application“CheckYourMask”to Limit the Spread of COVID-19

In a context of a virus that is transmissive by sputtering,wearing masks appear necessary to protect the wearer and to limit the propagation of the disease.Currently,we are facing the 2019-2020 coronavirus pandemic.Coronavirus disease 2019(COVID-19)is an infectious disease with first symptoms similar to the flu.The symptom of COVID-19 was reported first in China and very quickly spreads to the rest of the world.The COVID-19 contagiousness is known to be high by comparison with the flu.In this paper,we propose a design of a mobile application for permitting everyone having a smartphone and being able to take a picture to verify that his/her protection mask is correctly positioned on his/her face.Such application can be particularly useful for people using face protection mask for the first time and notably for children and old people.The designed method exploits Haar-like feature descriptors to detect key features of the face and a decision-making algorithm is applied.Experimental results show the potential of this method in the validation of the correct mask wearing.To the best of our knowledge,our work is the only one that currently proposes a mobile application design“CheckYourMask”for validating the correct wearing of protection mask.

HCV-specific immune responses induced by CIGB-230 in combination with IFN-α plus ribavirin

AIM:To analyze hepatitis C virus(HCV)-specific immune responses in chronically infected patients under triple therapy with interferon-α(IFN-α)plus ribavirin and CIGB-230.METHODS:CIGB-230 was administered in different schedules with respect to IFN-αplus ribavirin therapy.Paired serum and peripheral blood mononuclear cells(PBMC)samples from baseline and end of treatment were analyzed.The HCV-specific humoral response was tested by enzyme-linked immunosorbent assay,neutralizing antibodies were evaluated by cell culture HCV neutralization assays,PBMC proliferation was assayed by carboxyfluorescein succinimidyl ester staining and IFN-γsecretion was assessed by enzyme-linked immunospot.Data on virological and histological response and their association with immune variables are also provided.RESULTS:From week 12 to week 48,all groups of patients showed a significant reduction in mean leukocyte counts.Statistically significant reductions in antibody titers were frequent,but only individuals immunized with CIGB-230 as early add-on treatment sustained the core-IgG response,and the neutralizing antibody response was enhanced only in patients receiving CIGB-230.Cell-mediated immune responses also tended to decline,but significant reductions in IFN-γsecretion and total absence of core-specific lymphoproliferation were exclusive of the control group.Only CIGB-230-immunized individuals showed de novo induced lymphoproliferative responses against the structural antigens.Importantly,it was demonstrated that thequality of the CIGB-230-induced immune response depended on the number of doses and timing of administration in relation to the antiviral therapy.Specifically,the administration of 6 doses of CIGB-230 as late addon to therapy increased the neutralizing antibody activity and the de novo core-specific IFN-γsecretion,both of which were associated with the sustained virological response.CONCLUSION:CIGB-230,combined with IFN-α-based therapy,modifies the immune response in chronic patients.The study provides evidence for the design of more effective therapeutic vaccine interventions against HCV.

Preliminary Characterizations of a Carbohydrate from the Concentrated Culture Filtrate from <i>Fusarium solani</i>and Its Role in Benzo[a]Pyrene Solubilization

In order to investigate the mechanism of benzo[a]pyrene uptake by a filamentous fungus Fusarium solani, a biochemical characterization of its concentrated culture filtrate has been conducted. The preparation contained approximately (w/w): 50% of total carbohydrate, 6.5% of uronic acid and 6% protein, as determined by colorimetric tests. Gel filtration and anion-exchange chromatographic profiles indicated that the main product of the culture filtrate was a glycoprotein, which contained mannose, glucose and galactose in an approximate molar ratio of 1.5: 0.8: 1. The polysaccharide fraction of the culture filtrate was prepared by treatment with proteinase K, followed by gel-filtration chromatography. Its chemical structure was studied by methylation analysis, gas-liquid chromatography-mass spectrometry (GC-MS) and Nuclear Magnetic Resonance spectroscopy (NMR). The major carbohydrate was a polymer of β-(1 → 6)-linked galactofuranose units fully branched at positions O-2 by single residues of α-glucopyranose. The Fusarium concentrated culture filtrate increased 4-fold the BaP solubilization in comparison with its aqueous solubility and suggested that the carbohydrate present in this filtrate should probably be involved in this enhancement. Our findings point out the potential role of fungal glycoproteins in PAH microbial bioavaibility, an important step for PAH biodegradation.

Cue hierarchy in the foraging behaviour of the brackish cladoceran Daphniopsis australis

Zooplankton communities are an essential component of marine and freshwater food webs. However, there is still a relative lack of information on how these organisms behaviourally respond to a range of abiotic and biotic stressors. Specifically, the behaviour of the cladoceran D aphniopsis australis, a species endemic to South-eastern Australian saline lakes and ponds, is still unknown despite its potential role in the structure and function of inland water ecosystems. The swimming behaviour of males, parthenogenetic females and epiphial females was investigated under various conditions and combinations of food and conspecific cues. In the absence of cues, males displayed the most extensive swimming behaviour, exploring all areas of the container, and swimming in a series of relatively straight trajectories. In contrast, females typically exhibited a hop-and-sink motion characterised by the alternation between short bursts of swimming and sinking phases. Both females spent long periods near the bottom of the container, but epiphial females appeared to be more active than parthenogenetic ones that rarely made an excursion in the water column. In the presence of cues, males and females showed abilities to detect infochemicals from food and conspecifics, but exhibited specific behavioural strategies. Males essentially increased their swimming speed in the presence of food and/or conspecific infochemicals, and this increase was independent on the source of the cues, i.e. food, conspecific or a mixture of food and conspecifics. In contrast, females exhibited cue hierarchies that were related to their sexual status. Parthenogenetic females swam faster in the presence of food and a mixture of food and conspecific infochemicals than in the presence of cue from the opposite sex, which did not significantly differ from control observations conducted in the absence of cues. Epiphial females decreased their swimming speed in the presence of cues, with the most significant behavioural answers being driven by sex-related cues.

Cracking of S235JR Cold-Deformed Steel during Galvanizing—Developing a Test to Evaluate and Predict the Effect of the Zinc Alloy Composition

This paper presents a study on the cracking of steel pieces during their galvanization in alloyed liquid zinc. An experimental design was developed to show the effect of the amount of the various alloying elements (Sn, Bi, Pb) on this phenomenon. The characterization of the effect was obtained by 1) deformation by three-point bending of a piece of steel with different levels of deflection;2) galvanizing and 3) observation and measurement of the cracks. A model of the critical deflection (deflection for crack starting) with the amounts of Sn, Pb, and Bi is presented and the predictions are described.

Effect of Zirconium and Cerium Loadings on Aerogel Pd-Based Catalysts for Methane Combustion

Aerogel Pd/(Ce0.33Zr0.66O2)SiO2 catalysts (CeZry) were prepared with variable Ce and Zr loadings (molar ratio Ce/Zr = 1/2) by combining sol-gel and impregnation methods. First, N2-physisorption was used to investigate the texture evolution. Then, H2-chimisorption and TEM were performed to study the effect on particle dispersion. After, TPR was used to determine the catalyst reducibility. Furthermore, XPS characterization was done to identify the palladium oxidation state and to evaluate the Pd-support interaction. Finally, the prepared catalysts were tested in methane combustion to assess their catalytic activity. The obtained results showed that, when the Zr and Ce loadings are varied between 0% and 8% and between 0% and 6% respectively, the BET surface area was increased from 615 to 744 m2/g, the porosity diameter from 45.7 to 83.6 &#197;, the Pd particle diameter from 5.2 to 7.0 nm, the CeO2 and ZrO2 particle size from 0 to 68 nm, the reduction temperature shift reached 16°C, the Pd binding energy shift attained 0.6 eV, but an optimum amounts of Zr (4 wt.%) and Ce (3 wt.%) are needed to maximize the PdO reducibility and to enhance the catalytic activity. In effect, 100% conversion of methane was reached at around 415°C on the CeZr4 catalyst.

Oxidative dehydrogenation of propane under steady-state and transient regimes over alumina-supported catalysts prepared from mixed V_2W_4O_(19)^(4-) hexametalate precursors

An integrated approach combining the development of an innovative catalyst and the research of a set of adequate operating conditions for the propane oxidative dehydrogenation （ODH） is described.The experimental set-up,specially designed for steady-state and transient studies is presented.The preparation method,the characterization and the performances in steady-state and transient regimes of catalysts based on V2W4O194-Lindqvist isopolyanion used as a precursor and supported on alumina are reported.The influence of the preparation method of the catalyst and the role of water in the feed gas are more particularly discussed.

Hinokiflavone and Related C-O-C-Type Biflavonoids as Anti-cancer Compounds:Properties and Mechanism of Action

Biflavonoids are divided in two classes:C-C type compounds represented by the dimeric compound amentoflavone and C-O-C-type compounds typified by hinokiflavone(HNK)with an ether linkage between the two connected apigenin units.This later sub-group of bisflavonyl ethers includes HNK,ochnaflavone,delicaflavone and a few other dimeric compounds,found in a variety of plants,notably Selaginella species.A comprehensive review of the anticancer properties and mechanism of action of HNK is provided,to highlight the anti-proliferative and anti-metastatic activities of HNK and derivatives,and HNK-containing plant extracts.The anticancer effects rely on the capacity of HNK to interfere with the ERK1-2/p38/NFκB signaling pathway and the regulation of the expression of the matrix metalloproteinases MMP-2 and MMP-9(with a potential direct binding to MMP-9).In addition,HNK was found to function as a potent modulator of pre-mRNA splicing,inhibit-ing the SUMO-specific protease SENP1.As such,HNK represents a rare SENP1 inhibitor of natural origin and a scaffold to design synthetic compounds.Oral formulations of HNK have been elaborated to enhance its solubility,to facilitate the compound delivery and to enhance its anticancer efficacy.The review shed light on the anticancer potential of C-O-C-type biflavonoids and specifically on the pharmacological profile of HNK.This compound deserves further attention as a regu-lator of pre-mRNA splicing,useful to treat cancers(in particular hepatocellular carcinoma)and other human pathologies.

OTX2 signaling in retinal dysfunction,degeneration and regeneration

The protein OTX2 in the retina is necessary for the maintenance of normal physiologic processes,and may be a promising therapeutic agent for some ophthalmic diseases.In this Perspective,we first shortly introduce the organization of the retina and the importance of OTX2 expression.We then present an example of reduced OTX2 activity in the developed retina associated with structural and functional consequences.We next show that homeoproteins can have neuroprotective functions.We finally review several clear examples of OTX2 non-cell autonomous activity in the retina and the effects of diminishing or providing extracellular OTX2.

Performance comparison of chlorinated chiral stationary phases in supercritical fluid chromatography for separation of selected pyrrolidone derivatives

The effects of two chlorinated chiral stationary phases, namely, Lux Cellulose-2 and Lux i-Cellulose-5, flow-rate, percentage of co-solvent and chemical structures of the compounds on retention and resolution were studied within this article. In this work a backpressure of 150 bar, a temperature of 40 ℃ and 10% of methanol as co-solvent were chosen as operating conditions. The optimum flow-rate was 2 mL/min. The percentage of co-solvent was studied between 7.5% and 15%.We have observed that 15% of methanol gave the best results for most of the compounds. For all the derivatives, the Lux Cellulose-2 provided better resolutions going from 1.50 to 3.59 compared with Lux i-Cellulose-5.