RETRACTED: Wiesinger et al. An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis. Pharmaceutics 2023, 15, 1565.

The journal retracts the article, An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis [...].

Bovine Udder Health: From Standard Diagnostic Methods to New Approaches-A Practical Investigation of Various Udder Health Parameters in Combination with 16S rRNA Sequencing.

Bovine udder health is an important factor for animal wellbeing and the dairy farm economy. Thus, researchers aim to understand factors causing mastitis. The gold standard for diagnosing mastitis in cows is the conventional culturing of milk samples. However, during the last few years, the use of molecular methods has increased. These methods, especially sequencing, provide a deeper insight into the diversity of the bacterial community. Yet, inconsistent results regarding the mammary microbiome have been published. This study aimed to evaluate the udder health of eight dairy cows at seven days postpartum with the standard methods in veterinary practice. Additionally, swabs from the teat canal and milk samples were analyzed using 16S rRNA gene amplicon sequencing. The sensitive low-biomass milk samples displayed only a few contaminations even though they were sampled in a field environment. In healthy udders, no bacterial communities were detected by the bacterial culture nor the 16S rRNA gene amplicons. The results from the standard examination of the cows, the cell count, and the bacteriological examination were comparable with the results from 16S rRNA gene amplicon sequencing when cows displayed subclinical or latent mastitis. Besides the pathogen detected in bacterial culturing, a second bacterial strain with low but significant abundance was detected by sequencing, which might aid in the understanding of mastitis incidence. In general, molecular biological approaches might lead to promising insights into pathological events in the udder and might help to understand the pathomechanism and infection source via epidemiological analyses.

An Innovative Tool for Evidence-Based, Personalized Treatment Trials in Mucopolysaccharidosis.

Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases associated with reduced life expectancy and a substantial unmet medical need. Immunomodulatory drugs could be a relevant treatment approach for MPS patients, although they are not licensed for this population. Therefore, we aim to provide evidence justifying fast access to innovative individual treatment trials (ITTs) with immunomodulators and a high-quality evaluation of drug effects by implementing a risk-benefit model for MPS. The iterative methodology of our developed decision analysis framework (DAF) consists of the following steps: (i) a comprehensive literature analysis on promising treatment targets and immunomodulators for MPS; (ii) a quantitative risk-benefit assessment (RBA) of selected molecules; and (iii) allocation phenotypic profiles and a quantitative assessment. These steps allow for the personalized use of the model and are in accordance with expert and patient representatives. The following four promising immunomodulators were identified: adalimumab, abatacept, anakinra, and cladribine. An improvement in mobility is most likely with adalimumab, while anakinra might be the treatment of choice for patients with neurocognitive involvement. Nevertheless, a RBA should always be completed on an individual basis. Our evidence-based DAF model for ITTs directly addresses the substantial unmet medical need in MPS and characterizes a first approach toward precision medicine with immunomodulatory drugs.

Individual Treatment Trials-Do Experts Know and Use This Option to Improve the Treatability of Mucopolysaccharidosis?

Mucopolysaccharidoses (MPS) are a group of rare, heterogeneous, lysosomal storage disorders. Patients show a broad spectrum of clinical features with a substantial unmet medical need. Individual treatment trials (ITTs) might be a valid, time- and cost-efficient way to facilitate personalized medicine in the sense of drug repurposing in MPS. However, this treatment option has so far hardly been used-at least hardly been reported or published. Therefore, we aimed to investigate the awareness and utilization of ITTs among MPS clinicians, as well as the potential challenges and innovative approaches to overcome key hurdles, by using an international expert survey on ITTs, namely, ESITT. Although 74% (20/27) were familiar with the concept of ITTs, only 37% (10/27) ever used it, and subsequently only 15% (2/16) published their results. The indicated hurdles of ITTs in MPS were mainly the lack of time and know-how. An evidence-based tool, which provides resources and expertise needed for high-quality ITTs, was highly appreciated by the vast majority (89%; 23/26). The ESITT highlights a serious deficiency of ITT implementation in MPS-a promising option to improve its treatability. Furthermore, we discuss the challenges and innovative approaches to overcome key barriers to ITTs in MPS.

The Development of the Bacterial Community of Brown Trout (Salmo trutta) during Ontogeny.

Brown trout (Salmo trutta) is an important aquaculture species in Germany, but its production faces challenges due to global warming and a high embryo mortality. Climate factors might influence the fish's bacterial community (BC) and thus increase embryo mortality. Yet, knowledge of the physiological BC during ontogeny in general is scarce. In this project, the BC of brown trout has been investigated in a period from unfertilized egg to 95 days post fertilization (dpf) using 16S rRNA gene amplicon sequencing. Developmental changes differed between early and late ontogeny and major differences in BC occurred especially during early developmental stages. Thus, analysis was conducted separately for 0 to 67 dpf and from 67 to 95 dpf. All analyzed stages were sampled in toto to avoid bias due to different sampling methods in different developmental stages. The most abundant phylum in the BC of all developmental stages was Pseudomonadota, while only two families (Comamonadaceae and Moraxellaceae) occurred in all developmental stages. The early developmental stages until 67 dpf displayed greater shifts in their BC regarding bacterial richness, microbial diversity, and taxonomic composition. Thereafter, in the fry stages, the BC seemed to stabilize and changes were moderate. In future studies, a reduction in the sampling time frames during early development, an increase in sampling numbers, and an attempt for biological reproduction in order to characterize the causes of these variations is recommended.

Revealing the Tick Microbiome: Insights into Midgut and Salivary Gland Microbiota of Female Ixodes ricinus Ticks.

The ectoparasite Ixodes ricinus is an important vector for many tick-borne diseases (TBD) in the northern hemisphere, such as Lyme borreliosis, rickettsiosis, human granulocytic anaplasmosis, or tick-borne encephalitis virus. As climate change will lead to rising temperatures in the next years, we expect an increase in tick activity, tick population, and thus in the spread of TBD. Consequently, it has never been more critical to understand relationships within the microbial communities in ticks that might contribute to the tick's fitness and the occurrence of TBD. Therefore, we analyzed the microbiota in different tick tissues such as midgut, salivary glands, and residual tick material, as well as the microbiota in complete Ixodes ricinus ticks using 16S rRNA gene amplicon sequencing. By using a newly developed DNA extraction protocol for tick tissue samples and a self-designed mock community, we were able to detect endosymbionts and pathogens that have been described in the literature previously. Further, this study displayed the usefulness of including a mock community during bioinformatic analysis to identify essential bacteria within the tick.

Detection of Borrelia burgdorferi Sensu-Lato-Specific Antibodies in Sera of Canine and Equine Origin-A Comparative Study with Two Line Immunoassays.

Lyme borreliosis is a vector-borne disease in humans and animals caused by bacteria from the Borrelia burgdorferi sensu lato complex (Bbsl). The possible transmission of Bbsl from companion animals to humans via ticks makes this disease important in terms of One Health approaches. Thus, early and accurate diagnosis and treatment are of utmost importance. Today's standard for the detection of specific antibodies against Bbsl is a two-tiered test system based on an ELISA for screening combined with a line immunoassay (LIA) for confirmation. In this study, 200 canine and 200 equine serum samples with known antibody status were tested with two different LIAs (A and B). Results were compared regarding sensitivity, specificity, the diagnostic outcome for dogs and horses, as well as operability of the test. The results for canine serum samples corresponded to 94.0%, making both LIAs a good choice for LB diagnostic in dogs. For equine serum samples, the agreement of both tests was 65.5%, displaying the challenge equine samples still provide in LB diagnostic. Major concerns were the interpretation of the OspA antigen (AG) signal and the use of unspecific (i.e., p100/p83) or too sensitive signals on the LIA. The operability of both LIAs was equally user-friendly. Regarding the tests' evaluation, the scanning process provided by LIA A was a major advantage considering the comparability of the tests.

The Inflammation in the Cytopathology of Patients With Mucopolysaccharidoses- Immunomodulatory Drugs as an Approach to Therapy.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases (LSDs), characterized by the accumulation of glycosaminoglycans (GAGs). GAG storage-induced inflammatory processes are a driver of cytopathology in MPS and pharmacological immunomodulation can bring improvements in brain, cartilage and bone pathology in rodent models. This manuscript reviews current knowledge with regard to inflammation in MPS patients and provides hypotheses for the therapeutic use of immunomodulators in MPS. Thus, we aim to set the foundation for a rational repurposing of the discussed molecules to minimize the clinical unmet needs still remaining despite enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT).