CRISPR/cas Loci of Type II Propionibacterium acnes Confer Immunity against Acquisition of Mobile Elements Present in Type I P. acnes

Propionibacterium acnes is a skin commensal that occasionally acts as an opportunistic pathogen. The population structure of this species shows three main lineages (I–III). While type I strains are mainly associated with sebaceous follicles of human skin and inflammatory acne, types II and III strains are more often associated with deep tissue infections. We investigated the occurrence and distribution of the clustered regularly interspaced short palindromic repeats (CRISPR) in P. acnes, assessed their immunological memory, and addressed the question if such a system could account for type-specific properties of the species. A collection of 108 clinical isolates covering all known phylotypes of P. acnes was screened for the existence of CRISPR/cas loci. We found that CRISPR loci are restricted to type II P. acnes strains. Sequence analyses of the CRISPR spacers revealed that the system confers immunity to P. acnes-specific phages and to two mobile genetic elements. These elements are found almost exclusively in type I P. acnes strains. Genome sequencing of a type I P. acnes isolate revealed that one element, 54 kb in size, encodes a putative secretion/tight adherence (TAD) system. Thus, CRISPR/cas loci in P. acnes recorded the exposure of type II strains to mobile genetic elements of type I strains. The CRISPR/cas locus is deleted in type I strains, which conceivably accounts for their ability to horizontally acquire fitness or virulence traits and might indicate that type I strains constitute a younger subpopulation of P. acnes

Tensor-Based Grading: A Novel Patch-Based Grading Approach for the Analysis of Deformation Fields in Huntington's Disease

The improvements in magnetic resonance imaging have led to the development of numerous techniques to better detect structural alterations caused by neurodegenerative diseases. Among these, the patch-based grading framework has been proposed to model local patterns of anatomical changes. This approach is attractive because of its low computational cost and its competitive performance. Other studies have proposed to analyze the deformations of brain structures using tensor-based morphometry, which is a highly interpretable approach. In this work, we propose to combine the advantages of these two approaches by extending the patch-based grading framework with a new tensor-based grading method that enables us to model patterns of local deformation using a log-Euclidean metric. We evaluate our new method in a study of the putamen for the classification of patients with pre-manifest Huntington's disease and healthy controls. Our experiments show a substantial increase in classification accuracy (87.5 $\pm$ 0.5 vs. 81.3 $\pm$ 0.6) compared to the existing patch-based grading methods, and a good complement to putamen volume, which is a primary imaging-based marker for the study of Huntington's disease

METHOD EVALUATION TO DETERMINE HYDRATION STATES OF TENDONS BY USING MRI

Due to the fact that water content is a determinant of the material properties of tendons and therefore might affect sports performance and the risk of injury, the purpose of this pilot study was to evaluate the reliabilityand sensitivity of a MRI based method to quantify content of a tendon. For this pilot study twenty porcine digital flexor tendons were chosen. All samples were examined on a MR scanner using three 3D ultra-short echo time sequences. With the applied sequences it was possible to determine a decrease in water content of the tendons. In addition, the methods showed a good inter session reliability. Further investigations are needed to improve the upper and lower limit of resolution regarding the physiological hydration state

Reduction of Femoral Fractures in Long-Term Care Facilities: The Bavarian Fracture Prevention Study

BACKGROUND: Hip fractures are a major public health burden. In industrialized countries about 20% of all femoral fractures occur in care dependent persons living in nursing care and assisted living facilities. Preventive strategies for these groups are needed as the access to medical services differs from independent home dwelling older persons at risk of osteoporotic fractures. It was the objective of the study to evaluate the effect of a fall and fracture prevention program on the incidence of femoral fracture in nursing homes in Bavaria, Germany. METHODS: In a translational intervention study a fall prevention program was introduced in 256 nursing homes with 13,653 residents. The control group consisted of 893 nursing homes with 31,668 residents. The intervention consisted of staff education on fall and fracture prevention strategies, progressive strength and balance training, and on institutional advice on environmental adaptations. Incident femoral fractures served as outcome measure. RESULTS: In the years before the intervention risk of a femoral fracture did not differ between the intervention group (IG) and control group (CG). During the one-year intervention period femoral fracture rates were 33.6 (IG) and 41.0/1000 person years (CG), respectively. The adjusted relative risk of a femoral fracture was 0.82 (95% CI 0.72-0.93) in residents exposed to the fall and fracture prevention program compared to residents from CG. CONCLUSIONS: The state-wide dissemination of a multi-factorial fall and fracture prevention program was able to reduce femoral fractures in residents of nursing homes

Reliability of NI-RADS criteria in the interpretation of contrast-enhanced magnetic resonance imaging considering the potential role of diffusion-weighted imaging

Objectives: To assess inter- and intrareader agreement of the Neck Imaging Reporting and Data System (NI-RADS) used in contrast-enhanced magnetic resonance imaging (MRI) including analysis of diffusion-weighted imaging (DWI), which is currently not part of the NI-RADS criteria. Methods: This retrospective study included anonymized surveillance contrast-enhanced MRI datasets of 104 patients treated for different head and neck cancers. Three radiologists experienced in head and neck imaging reported findings for the primary site and the neck using NI-RADS criteria in a first step and evaluated DWI sequences for the primary site in a second step. Thirty randomly selected imaging datasets were again presented to the readers. Kappa statistics and observed agreement (A(o)) were calculated. Results: Interreader agreement across all MRI datasets was moderate (kappa(Fleiss) = 0.53) for NI-RADS categories assigned to the primary site, substantial for NI-RADS categories of the neck (kappa(Fleiss) = 0.67), and almost perfect for DWI of the primary site (kappa(Fleiss) = 0.83). Interreader agreement for the primary site was particularly low in cases of cancer recurrence (kappa(Fleiss) = 0.35) and when categories 2a, 2b, and 3 were combined (kappa(Fleiss) = 0.30). Intrareader agreement was considerably lower for NI-RADS categories of the primary site (range A(o) = 53.3-70.0%) than for NI-RADS categories of the neck (range A(o) = 83.3-90.0%) and DWI of the primary site (range A(o) = 93.3-100.0%). Conclusion: Interreader agreement of NI-RADS for reporting contrast-enhanced MRI findings is acceptable for the neck but limited for the primary site. Here, DWI has the potential to serve as a reliable additional criterion

Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages : an opportunity for an in vitro drug screening assay

Infammatory bowel disease (IBD) is a widespread disease, afecting a growing demographic. The treatment of chronic infammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied. Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and limited in its throughput. Reliable and valid in vitro assays ofer the opportunity to overcome these limitations. We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the intestinal barrier and the immune response in IBD. The drug efcacy was analyzed by an LPS-infammation of the co-culture and drug exposure according to the IBD treatment pyramid. Efcacy was defned as the range between LPS control (0%) and untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α). The release of IL-6, IL-8, and TNF-α was identifed as an appropriate readout for a fast drug screening (“yes–no response”). TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine, and infiximab) with an R2 of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate establishing an “Efcacy Outcome Pathways (EOPs)” framework for drug efcacy assays. The in vitro assay ofers an easy and scalable method for IBD drug screening with a focus on human data, which requires further validation

Long-range, Seamless Traffic Density Monitoring using Fibre Optic Acoustic Sensing

Accurate real-time traffic sensing is of key importance, especially in the urban environment to be able to optimise traffic flow by intelligent traffic systems (ITS). Often the high density of traffic sensors, needed to achieve an accurate real-time monitoring of important arterial roads, is difficult to implement due to technical contraints or because of high installation cost. Furthermore, existing traffic sensing technology uses sensors that are only able to measure traffic flow on a cross-section of the road where they are installed (typically on a junction), giving no information on the situation in between. An alternative "seamless" measuring technology, is to use floating car data, with Google Maps being the most prominant example. This technology allows to derive traffic information over wide road sections, however it is unable to deliver real- time information, and it relies on the “cooperation” of the data providers (the fleet owner or the mobile phone users). Fiber optic acoustic sensing (FOAS) is a new alternative technology that allows a seamless, real-time monitoring of the road traffic situation over large distances of up to 50 km using the existing telecom fiber optic cable infrastructure. In our previous work we presented an algorithm and results for traffic flow and average speed computation from FOAS raw data at a specific location along a highway and compared it to reference traffic data [1],[2]. In this paper we demonstrate the potential of the seamless nature of the technique by evaluating the traffic density over a length of 25 km of the monitored highway for different days and times of the day

Interplay of superexchange and orbital degeneracy in Cr-doped LaMnO3

We report on structural, magnetic and Electron Spin Resonance (ESR) investigations in the manganite system LaMn_{1-x}Cr_{x}O_{3} (x<=0.5). Upon Cr-doping we observe a reduction of the Jahn-Teller distortion yielding less distorted orthorhombic structures. A transition from the Jahn-Teller distorted O' to the pseudocubic O phase occurs between 0.3<x<0.4. A clear connection between this transition and the doping dependence of the magnetic and ESR properties has been observed. The effective moments determined by ESR seem reduced with respect to the spin-only value of both Mn^{3+} and Cr^{3+} ions