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

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases MUTYH and hOGG1 in Colorectal Cancer Patients

Oxidative stress, oxidative DNA damage and resulting mutations play a role in colorectal carcinogenesis. Impaired equilibrium between DNA damage formation, antioxidant status, and DNA repair capacity is responsible for the accumulation of genetic mutations and genomic instability. The lesion-specific DNA glycosylases, e.g., hOGG1 and MUTYH, initiate the repair of oxidative DNA damage. Hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome) with germline mutations causing a loss-of-function in base excision repair glycosylases, serve as straight forward evidence on the role of oxidative DNA damage and its repair. Altered or inhibited function of above glycosylases result in an accumulation of oxidative DNA damage and contribute to the adenoma-adenocarcinoma transition. Oxidative DNA damage, unless repaired, often gives rise G:C > T:A mutations in tumor suppressor genes and proto-oncogenes with subsequent occurrence of chromosomal copy-neutral loss of heterozygosity. For instance, G>T transversions in position c.34 of a KRAS gene serves as a pre-screening tool for MUTYH-associated polyposis diagnosis. Since sporadic colorectal cancer represents more complex and heterogenous disease, the situation is more complicated. In the present study we focused on the roles of base excision repair glycosylases (hOGG1, MUTYH) in colorectal cancer patients by investigating tumor and adjacent mucosa tissues. Although we found downregulation of both glycosylases and significantly lower expression of hOGG1 in tumor tissues, accompanied with G>T mutations in KRAS gene, oxidative DNA damage and its repair cannot solely explain the onset of sporadic colorectal cancer. In this respect, other factors (especially microenvironment) per se or in combination with oxidative DNA damage warrant further attention. Base excision repair characteristics determined in colorectal cancer tissues and their association with disease prognosis have been discussed as well

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