Muc2-dependent microbial colonization of the jejunal mucus layer is diet sensitive and confers local resistance to enteric pathogen infection.

Intestinal mucus barriers normally prevent microbial infections but are sensitive to diet-dependent changes in the luminal environment. Here we demonstrate that mice fed a Western-style diet (WSD) suffer regiospecific failure of the mucus barrier in the small intestinal jejunum caused by diet-induced mucus aggregation. Mucus barrier disruption due to either WSD exposure or chromosomal Muc2 deletion results in collapse of the commensal jejunal microbiota, which in turn sensitizes mice to atypical jejunal colonization by the enteric pathogen Citrobacter rodentium.

Evaluation of therapeutic strategies targeting BCAA catabolism using a systems pharmacology model.

Abnormal branched-chained amino acids (BCAA) accumulation in cardiomyocytes is associated with cardiac remodeling in heart failure. Administration of branched-chain α-keto acid dehydrogenase (BCKD) kinase inhibitor BT2 has been shown to reduce cardiac BCAA levels and demonstrated positive effects on cardiac function in a preclinical setting. The current study is focused on evaluating the impact of BT2 on the systemic and cardiac levels of BCAA and their metabolites as well as activities of BCAA catabolic enzymes using a quantitative systems pharmacology model.

Corrigendum to "Use of the tau protein-to-peptide ratio in CSF to improve diagnostic classification of Alzheimer's disease" [Clin. Mass Spectrom. 14 (Part B) (2019) 74-82].

[This corrects the article DOI: 10.1016/j.clinms.

Use of the tau protein-to-peptide ratio in CSF to improve diagnostic classification of Alzheimer's disease.

Cerebrospinal fluid (CSF) tau and phospho-tau are well established biomarkers of Alzheimer's disease. While these measures are conventionally referred to as 'total tau' (T-tau) and 'phospho-tau' (P-tau), several truncated and modified tau forms exist that may relay additional diagnostic information. We evaluated the diagnostic performance of an endogenous tau peptide in CSF, tau 175-190, in the phosphorylated and non-phosphorylated state.

Paediatric haematohidrosis: an overview of a rare but clinically distinct condition.

Haematohidrosis is a rare and dramatic condition in which bleeding occurs spontaneously from intact skin. We report the case of a nine-year-old boy with a typical clinical presentation. The case highlights how challenging it can be for medical professionals to recognise and evaluate rare conditions.

Sample Preparation for Endopeptidomic Analysis in Human Cerebrospinal Fluid.

This protocol describes a method developed to identify endogenous peptides in human cerebrospinal fluid (CSF). For this purpose, a previously developed method based on molecular weight cut-off (MWCO) filtration and mass spectrometric analysis was combined with an offline high-pH reverse phase HPLC pre-fractionation step. Secretion into CSF is the main pathway for removal of molecules shed by cells of the central nervous system.

A novel quantification-driven proteomic strategy identifies an endogenous peptide of pleiotrophin as a new biomarker of Alzheimer's disease.

We present a new, quantification-driven proteomic approach to identifying biomarkers. In contrast to the identification-driven approach, limited in scope to peptides that are identified by database searching in the first step, all MS data are considered to select biomarker candidates. The endopeptidome of cerebrospinal fluid from 40 Alzheimer's disease (AD) patients, 40 subjects with mild cognitive impairment, and 40 controls with subjective cognitive decline was analyzed using multiplex isobaric labeling.

Expanding the cerebrospinal fluid endopeptidome.

Biomarkers of neurodegenerative disorders are needed to assist in diagnosis, to monitor disease progression and therapeutic interventions, and to provide insight into disease mechanisms. One route to identify such biomarkers is by proteomic and peptidomic analysis of cerebrospinal fluid (CSF). In the current study, we performed an in-depth analysis of the human CSF endopeptidome to establish an inventory that may serve as a basis for future targeted biomarker studies.

Comprehensive Quantitative Profiling of Tau and Phosphorylated Tau Peptides in Cerebrospinal Fluid by Mass Spectrometry Provides New Biomarker Candidates.

Aberrant tau phosphorylation is a hallmark in Alzheimer's disease (AD), believed to promote formation of paired helical filaments, the main constituent of neurofibrillary tangles in the brain. While cerebrospinal fluid (CSF) levels of total tau and tau phosphorylated at threonine residue 181 (pThr181) are established core biomarkers for AD, the value of alternative phosphorylation sites, which may have more direct relevance to pathology, for early diagnosis is not yet known, largely due to their low levels in CSF and lack of standardized detection methods. To overcome sensitivity limitations for analysis of phosphorylated tau in CSF, we have applied an innovative mass spectrometry (MS) workflow, TMTcalibratortrademark, to enrich and enhance the detection of phosphoproteome components of AD brain tissue in CSF, and enable the quantitation of these analytes.

Effects of different substituents on the crystal structures and antimicrobial activities of six Ag(I) quinoline compounds.

The syntheses and single crystal X-ray structures of [Ag(5-nitroquinoline)2]NO3 (1), [Ag(8-nitroquinoline)2]NO3·H2O (2), [Ag(6-methoxy-8-nitroquinoline)(NO3)]n (3), [Ag(3-quinolinecarbonitrile)(NO3)]n (4), [Ag(3-quinolinecarbonitrile)2]NO3 (5), and [Ag(6-quinolinecarboxylic acid)2]NO3 (6) are described. As an alternative to solution chemistry, solid-state grinding could be used to prepare compounds 1 and 3, but the preparation of 4 and 5 in this way failed. The Ag(I) ions in the monomeric compounds 1, 2, 5, and 6 are coordinated to two ligands via the nitrogen atoms of the quinoline rings, thereby forming a distorted linear coordination geometry with Ag-N bond distances of 2.

Integrated peripheral boost in preoperative radiotherapy for the locally most advanced non-resectable rectal cancer patients.

Background And Purpose: Few studies have explored the potential clinical advantages of dose escalation and integrated boosts for patients with non-resectable locally advanced rectal cancer. The possibility of escalating dose to non-resectable regions in these patients was the aim of this study.

Patients And Methods: Seven patients with locally very advanced rectal tumours (sacrum overgrowth or growth into pelvic side walls) were evaluated.

Delineation of gross tumor volume (GTV) for radiation treatment planning of locally advanced rectal cancer using information from MRI or FDG-PET/CT: a prospective study.

Purpose: Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV).

Distal femoral stem-bone anchorage of a cementless revision total hip arthroplasty: evaluation of 14 patients by CT.

Background And Purpose: According to the manual of the cementless Link MP reconstruction prosthesis, a distal femoral stem-bone anchorage of at least 80 mm is necessary to gain implant stability. There have been no in vivo studies showing that this distance is either achieved in clinical practice or needed for clinically satisfying results. Thus, we assessed the femoral stem-bone anchorage of the MP prosthesis using CT.

Significance of mesorectal volume in staging of rectal cancer with magnetic resonance imaging and the assessment of involvement of the mesorectal fascia.

The aim was to study the influence of mesorectal volume, as estimated by magnetic resonance imaging (MRI), that is to be removed during total mesorectal excision (TME), on the accuracy of the first preoperative MRI of rectal cancer compared to histopathology, and its correlation to locoregional prognostic factors. A total of 267 rectal cancer patients from a multinational study (MERCURY or MRI equivalence study) had their mesorectal volume retrospectively estimated by researchers without knowledge of the assessments made by the radiologist or the pathologist. The evaluations made by the pathologist and the radiologist were then compared, including T- and N-staging, assessment of extent of extramural tumor invasion (the largest portion of the tumor beyond the muscularis propria or EMI) and distance to mesorectal fascia; the discrepancies in the results were correlated to the mesorectal volume.