Alzheimer's disease (AD) is an irreversible neurodegenerative disease that affects more than 44 million people worldwide. The pathogenic mechanisms of AD still remain unclear. Currently, there are numerous studies investigating the microbiota-gut-brain axis in humans and rodents indicated that gut microbiota played a role in neurodegenerative diseases, including AD. However, the underlying relationship between the progress of AD disease and the dynamic distribution of gut microbiota is not well understood. In the present study, APPswe /PS1ΔE9 transgenic mice of different ages and sex were employed. After the evaluation of the AD mice model, gut metagenomic sequencing was conducted to reveal gut microbiota, moreover, probiotics intervention was treated in the AD mice. The results showed that (1) AD mice had reduced microbiota richness and a changed gut microbiota composition, and AD mice gut microbiota richness was correlated with cognitive performance. We have also found some potential AD-related microbes, for example, in AD-prone mice, the genus Mucispirillum was strongly associated with immune inflammation. (2) Probiotics intervention improved cognitive performance and changed gut microbiota richness and composition of AD mice. We revealed the dynamics distribution of gut microbiota and the effect of probiotics on AD in a mice model, which provides an important reference for the pathogenesis of AD, intestinal microbial markers associated with AD, and AD probiotic intervention.

The introduction of direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infected patients has greatly increased treatment success rates. However, viral response kinetics to DAA treatment may depend on pre-existing resistance-associated substitutions (RASs) in HCV. The aim of this study was to describe how pre-existing RASs affect DAA treatment-induced reduction in HCV RNA titers in HCV genotypes 1- and 3-infected individuals. Patients with HCV genotype 1 infection (N = 31) treated with either sofosbuvir/ledipasvir/ribavirin or paritaprevir/ombitasvir/ritonavir/dasabuvir/ribavirin and HCV genotype 3-infected patients (N = 16) treated with either sofosbuvir/daclatasvir/ribavirin or sofosbuvir/ribavirin were analyzed. HCV RNA levels were determined at baseline and frequently during treatment, and RAS profiles were obtained by deep sequencing at baseline. In total, 33/47 (70.2%) of the patients had baseline RASs. However, treatment-specific RASs were detected at baseline only in 12.9% and 18.8% of HCV genotypes 1- and 3-infected patients, respectively. In genotype 1-infected individuals, reduction in HCV RNA titer during the first week of treatment was not affected by evidence of either treatment-specific RASs or cirrhosis or treatment regimen. In genotype 3-infected individuals receiving sofosbuvir/daclatasvir/ribavirin, the presence of daclatasvir-specific NS5A RASs at baseline correlated with a reduced decline of HCV RNA in the first treatment week. For both genotypes 1- and 3-infected individuals, cirrhosis but not treatment-specific RAS were associated with the time of clearance of HCV RNA. It is, however, important to note that this study involves DAA regimens that were used only during the original introduction of interferon-free DAA-based treatments.

Multidrug resistance Candida auris is a dangerous fungal pathogen that is emerging at an alarming rate and posing serious threats to public health. C. auris is associated with nosocomial infections that cause invasive candidiasis in immunocompromised patients. Several antifungal drugs with distinct mechanisms of action are clinically approved for the treatment of fungal infections. The high rates of intrinsic and acquired drug resistance, particularly to azoles, reported in characterized clinical isolates of C. auris make treatment extremely problematic. In systemic infections, azoles are the first-line treatment for most Candida species; however, the increasing use of drugs results in the frequent emergence of drug resistance. More than 90% of the clinical isolates of C. auris is shown to be highly resistant to azole drugs especially fluconazole, with some strains (types) resistant to all three classes of commonly used antifungals. This presents a huge challenge for researchers in terms of completely understanding the molecular mechanism of azole resistance to develop more efficient drugs. Due to the scarcity of C. auris therapeutic alternatives, the development of successful drug combinations provides an alternative for clinical therapy. Taking advantage of various action mechanisms, such drugs in combination with azole are likely to have synergistic effects, improving treatment efficacy and overcoming C. auris azole drug resistance. In this review, we outline the current state of understanding about the mechanisms of azole resistance mainly fluconazole, and the current advancement in therapeutic approaches such as drug combinations toward C. auris infections.

APMISVolume 131, Issue 4 p. 133-134 Issue InformationFree Access Issue Information First published: 10 March 2023 https://doi.org/10.1111/apm.13238AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume131, Issue4April 2023Pages 133-134 RelatedInformation

This paper gives an account of the history of veterinary bacteriology including clinical veterinary bacteriology as well as the area of veterinary public health in Denmark from the 1880s to 2022. We describe key persons, including B. Bang, C.O. Jensen, K.A. Jensen and others who made important contributions to the development of these areas of microbiological expertise, and we discuss how challenges ranging from bovine tuberculosis to bacterial antimicrobial resistance have been met. Further, we describe progress in research on important bacterial pathogens both with regard to animal clinical aspects and zoonotic food-related aspects. Finally, we describe current issues in relation to One Health and research organization.

Høiby N. Louis Pasteur and the birth of microbiology in Denmark. APMIS 2022. Louis Pasteur's work initiated the birth of microbiology in Denmark. Carl Julius Salomonsen was the pioneer who inspired and taught Christian Gram, Thorvald Madsen and Bernhard Bang bacteriological techniques in his annual bacteriological course which he started in 1883 at the University of Copenhagen. These pioneers developed Danish human and veterinary microbiology and became world famous. Emil Chr. Hansen developed Danish technical/industrial microbiology in the Carlsberg Laboratory and purified yeast and designed equipment for the propagation of pure yeast which was used worldwide in beer brewing. He also became world famous. The fascinating birth and development of Danish microbiology is summarized in this article, which is dedicated to the 200thbirthday of Louis Pasteur, December 27, and 100thbirthday of the Danish Pasteur Society, October 25, 2022.