Structural transformations in Sc/Si multilayers irradiated by EUVlasers

Multilayer mirrors for the extreme ultraviolet (EUV) are keyelements for numerous applications of coherent EUV sources such as newtabletop lasers and free-electron lasers. However the field ofapplications is limited by the radiation and thermal stability of themultilayers. Taking into account the growing power of EUV sources thestability of the optics becomes crucial. To overcome this problem it isnecessary to study the degradation of multilayers and try to increasetheir temporal and thermal stability. In this paper we report the resultsof detailed study of structural changes in Sc/Simultilayers when exposedto intense EUV laser pulses. Various types of surface damage such asmelting, boiling, shockwave creation and ablation were observed asirradiation fluencies increase. Cross-sectional TEM study revealed thatthe layer structure was completely destroyed in the upper part ofmultilayer, but still survived below. The layers adjacent tothe substrateremained intact even through the multilayer surface melted down, thoughthe structure of the layers beneath the molten zone was noticeablychanged. The layer structure in this thermally affected zone is similarto that of isothermally annealed samples. All stages of scandium silicideformation such as interdiffusion, solid-state amorphization, silicidecrystallization, etc., are present in the thermally affected zone. Itindicates a thermal nature of the damage mechanism. The tungstendiffusion barriers were applied to the scandium/silicon interfaces. Itwas shown that the barriers inhibited interdiffusion and increased thethermal stability of Sc/Si mirrors

COVID-19 Pandemic and IBS. Results of the All-Russian Observational Non-interventional Program to Study the Effectiveness of the Drug Kolofort® in Real Clinical Practice in Patients with Irritable Bowel Syndrome After a New Coronavirus Infection (VESNA)

Aim: to study the effectiveness and safety of using the drug Kolofort® in outpatients with irritable bowel syndrome (IBS) after a new coronavirus infection.Materials and methods. An observational non-interventional program was conducted in patients with exacerbation of IBS symptoms after a new coronavirus infection. One hundred forty-one patients took part in the study. The final efficacy analysis included data from 127 study participants. All patients complained of increased/appearing gastrointestinal symptoms that appeared within 1–6 months after the infection (all patients had a history of COVID-19 infection). To assess the presence and severity of symptoms of the disease, the “7 × 7” questionnaire was used before the start of treatment and three months after the start of treatment.Results. At the stage of inclusion in the program, the average total score on the “7 × 7” questionnaire was 17.36, which corresponded to a moderately severe disorder. During the treatment period, the average total score decreased to 6.14, which corresponded to borderline disorder. In addition, significant improvement was observed for each symptom separately. After three months of therapy, doctors rated the overall impression of the treatment on a 5-point Likert scale from “very effective” to “ineffective”. The average score was 4.24. In addition, no serious adverse events were identified while taking the drug.Conclusion. In real clinical practice, the drug Kolofort® demonstrated high clinical efficacy in the treatment of patients with IBS after COVID-19 infection

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Features of treatment of patients with constipation in irritable bowel syndrome

The article presents a classification of functional bowel pathology; the reader's attention is drawn to the problem of functional constipation in irritable bowel syndrome, describes modern approaches to treatment of adult patients

Why treat non-alcoholic fatty liver disease?

The article considers the problem of non-alcoholic fatty liver disease, analyzes the main etiopathogenic aspects and risk factors such as obesity, insulin resistance and other. The treatment regimen with pathogenically relevant drugs, including the new generation hepatorpotectors, is discussed

Probiotics in the Modern World

Aim of review. The review highlights modern concepts of the role of microbiome in sustaining the human body, the place of probiotics in treatment and prevention of pathologies related to disorders in healthy microbiota.Key points. Microbiome is a unique panorganismal system normally maintaining self-equilibrium and possessing a vast and diverse functionality. Imbalance in normal microbiota can be assisted by probiotics, i.e. living microorganisms that sustain health of the host when being supplied in adequate amounts. Alike normal microflora, probiotic strains incorporate into general metabolism by mediating a spectrum of functions, e.g. maintaining colonisation resistance, nutrient metabolism, supplying the host with vital metabolites, regulation of local and adaptive immune responses, enhancing the intestinal barrier. Probiotics are applied in various diseases associated with general imbalances of the organism. Modern probiotic preparations are characterised by acid- and antibiotic-resistivity and safety, thus being suitable for treating gut microbiome-associated disorders in various age groups.Conclusion. Probiotic strains, as well as medications designed on their basis, are widely applied and show good promise. Further research into their properties will advance the prospects of probiotic treatment

Ustekinumab as induction and maintenance therapy for ulcerative colitis

BACKGROUND The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. METHODS We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range\u2013based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of 642 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). RESULTS The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P=0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo. CONCLUSIONS Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis