Interrogation of the perturbed gut microbiota in gouty arthritis patients through in silico metabolic modeling

Recent studies have shown perturbed gut microbiota associated with gouty arthritis, a metabolic disease characterized by an imbalance between uric acid production and excretion. To mechanistically investigate altered microbiota metabolism associated with gout disease, 16S rRNA gene amplicon sequence data from stool samples of gout patients and healthy controls were computationally analyzed through bacterial community metabolic models. Patient-specific community models constructed with the metagenomics modeling pipeline, mgPipe, were used to perform k-means clustering of samples according to their metabolic capabilities. The clustering analysis generated statistically significant partitioning of samples into a Bacteroides-dominated, high gout cluster and a Faecalibacterium-elevated, low gout cluster. The high gout cluster was predicted to allow elevated synthesis of the amino acids D-alanine and L-alanine and byproducts of branched-chain amino acid catabolism, while the low gout cluster allowed higher production of butyrate, the sulfur-containing amino acids L-cysteine and L-methionine, and the L-cysteine catabolic product H2S. By expanding the capabilities of mgPipe to provide taxa-level resolution of metabolite exchange rates, acetate, D-lactate and succinate exchanged from Bacteroides to Faecalibacterium were predicted to enhance butyrate production in the low gout cluster. Model predictions suggested that sulfur-containing amino acid metabolism generally and H2S more specifically could be novel gout disease markers

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays

Аналіз впливу реклами на зміну виборчої поведінки споживачів (виборців) в Словацькій Республіці

У сучасному світі, де споживачі постійно піддаються впливу рекламних повідомлень та інформації, реклама має значущу роль у підвищенні ефективності політичного маркетингу. Вплив реклами на зміну поведінки виборців в Словацькій Республіці є питанням, яке заслуговує на увагу, оскільки політичні кампанії все більше використовують рекламні технології та засоби масової інформації для досягнення своїх цілей. Реклама під час виборів не є чимось новим, але її форма та обсяг істотно змінилися з приходом цифрової ери. Політичні діячі та партії вкладають значні кошти в рекламні кампанії, які охоплюють традиційні медіа, такі як телебачення, радіо та друковані видання, а також нові онлайн платформи та соціальні медіа. Метою статті є аналіз впливу реклами на зміну поведінки виборців та прийняття ними політичних рішень в Словацькій Республіці. Первинну інформацію отримано шляхом анкетування 362 респондентів. Об'єктом дослідження були виборці, які проживають в регіоні східної Словаччини. Отримані первинні дані оброблено статистичним програмним продуктами. Для перевірки висунутих гіпотез дослідження використано статистичний тест Пірсона і коефіцієнт Крамера. Результати дослідження дозволили підтвердити другу гіпотезу, що обґрунтовує наявність статистично значущого взаємозв’язку між засобами реклами та статусом респондентів. Результати дослідження можуть бути корисними для різних зацікавлених сторін. Політичні діячі та партії можуть використовувати отримані рекомендації щодо ефективного використання реклами під час передвиборчої кампаній. Крім того, менеджери засобів масової інформації можуть використовувати рекомендації при виборі релевантного каналу комунікації з урахуванням впливу політичних рекламних матеріалів на політичні рішення виборців. Отримані результати сприяють прозорості, інформованості та якості політичного процесу в Словацькій Республіці.In this day and age, where we are constantly exposed to advertising messages and information, it is not surprising that advertising also plays a significant role in the political sphere. The impact of advertising on changing voter behavior in the Slovak Republic is a matter that deserves attention as political campaigns increasingly use advertising techniques and media to achieve their objectives. Advertising in elections is nothing new, but its form and scope have changed significantly with the advent of the digital era. Candidates and political parties are investing heavily in advertising campaigns, which range from traditional media such as television, radio and print to new online platforms and social media. The aim of the paper is to summarize the issue of advertising, as well as to analyse the impact of advertising i on the change in voting behaviour and decision-making of Slovak consumers (voters). The primary information was obtained by actual collection. The sample consisted of 362 respondents. The subjects of the research were consumers living in the region of eastern Slovakia. The obtained primary data were then processed in the statistical program, and Pearson’s chi-squared test and Cramer’s V were used to confirm or reject the established hypotheses. The second hypothesis examined has also been confirmed and shows us that there is a significant relationship between the means of advertising and the gender of respondents. The results of our research can be of benefit to various stakeholders. Political actors and parties will gain valuable information on how to use advertising effectively during campaigns. The media will have a better understanding of the impact of political advertisements and how to improve their services. The public will have a better understanding of the impact of political ads on voter decisions, and the academic community will have new insights to study and research. Overall, these results contribute to the transparency, information and quality of the political process in the Slovak Republic

Elucidation of the causes of cobweb cracks on the surface of slab blanks

22.00; Translated from Czech (Hutn. Listy 1985 (12) p. 848-852)SIGLEAvailable from British Library Document Supply Centre- DSC:9022.06(BISI--25335)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Effects of AP39, a novel triphenylphosphonium derivatised anethole dithiolethione hydrogen sulfide donor, on rat haemodynamic parameters and chloride and calcium Cav3 and RyR2 channels.

Copyright © 2014 Elsevier Inc. All rights reserved.H2S donor molecules have the potential to be viable therapeutic agents. The aim of this current study was (i) to investigate the effects of a novel triphenylphosphonium derivatised dithiolethione (AP39), in the presence and absence of reduced nitric oxide bioavailability and (ii) to determine the effects of AP39 on myocardial membrane channels; CaV3, RyR2 and Cl(-). Normotensive, L-NAME- or phenylephrine-treated rats were administered Na2S, AP39 or control compounds (AP219 and ADT-OH) (0.25-1 µmol kg(-1)i.v.) and haemodynamic parameters measured. The involvement of membrane channels T-type Ca(2+) channels CaV3.1, CaV3.2 and CaV3.3 as well as Ca(2+) ryanodine (RyR2) and Cl(-) single channels derived from rat heart sarcoplasmic reticulum were also investigated. In anaesthetised Wistar rats, AP39 (0.25-1 µmol kg(-1) i.v) transiently decreased blood pressure, heart rate and pulse wave velocity, whereas AP219 and ADT-OH and Na2S had no significant effect. In L-NAME treated rats, AP39 significantly lowered systolic blood pressure for a prolonged period, decreased heart rate and arterial stiffness. In electrophysiological studies, AP39 significantly inhibited Ca(2+) current through all three CaV3 channels. AP39 decreased RyR2 channels activity and increased conductance and mean open time of Cl(-) channels. This study suggests that AP39 may offer a novel therapeutic opportunity in conditions whereby (•)NO and H2S bioavailability are deficient such as hypertension, and that CaV3, RyR2 and Cl(-) cardiac membrane channels might be involved in its biological actions.Slovak Research and Development AgencyBMBS COST Actio

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease