Mammalian hydroxylation of microbiome-derived obesogen, delta-valerobetaine, to homocarnitine, a 5-carbon carnitine analog.

The recently discovered microbiome-generated obesogen, δ-valerobetaine (5-(trimethylammonio)pentanoate), is a 5-carbon structural analog of the carnitine precursor, γ-butyrobetaine. Here, we report that δ-valerobetaine is enzymatically hydroxylated by mammalian γ-butyrobetaine dioxygenase (BBOX) to form 3-hydroxy-5-(trimethylammonio)pentanoate, a 5-carbon analog of carnitine, which we term homocarnitine. Homocarnitine production by human liver extracts depends upon the required BBOX cofactors, 2-oxoglutarate, Fe, and ascorbate.

SMAC mimetics induce human macrophages to phagocytose live cancer cells.

Macrophages engulf apoptotic bodies and cellular debris as part of homeostasis, but they can also phagocytose live cells such as aged red blood cells. Pharmacologic reprogramming with the SMAC mimetic LCL161 in combination with T cell-derived cytokines can induce macrophages to phagocytose live cancer cells in mouse models. Here we extend these findings to encompass a wide range of monovalent and bivalent SMAC mimetic compounds, demonstrating that live cell phagocytosis is a class effect of these agents.

Hydrogel delivery of purinergic enzymes improves cardiac ischemia/reperfusion injury.

Rationale: The innate immune response contributes to cardiac injury in myocardial ischemia/reperfusion (MI/R). Neutrophils are an important early part of the innate immune response to MI/R. Adenosine, an endogenous purine, is a known innate immune modulator and inhibitor of neutrophil activation.

[Case-based learning can improve the teaching quality in trauma surgery education : A survey analysis among medical students].

Background: Medical education has always been challenging for students and teachers. Of growing importance is the promotion of knowledge of correlations and knowledge transfer from theoretical aspects into clinical practice. In order to achieve this aim, student-centered teaching concepts are increasingly being employed in the literature.

A Hydrogel Strategy to Augment Tissue Adenosine to Improve Hindlimb Perfusion.

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A novel internal fixation method for open book injuries of the pubic symphysis- A biomechanical analysis.

Background: Pelvic fractures in adults are common injuries and account for up to 3.64% of all fractures. Usually, the treatment of open book injuries (Types B1.

Stabilization of a Type B1.1 Injury in a Morbidly Obese Patient Using an Internal Fixator in a Minimally Invasive Technique: A Case Report.

Case: In this case report, we present a novel stabilization technique of the pubic symphysis using an internal spinal fixator in a 78-year-old morbidly obese woman having a pelvic disruption type B1.1 (AO classification). We treated the disruption using an internal fixator to reduce the extent of the incision and soft-tissue damage.

Cervical hyperaesthesia in dogs: an epidemiological retrospective study of 185 cases.

Objectives: To describe the prevalence, clinical findings and predictors of disease in dogs with cervical hyperaesthesia.

Materials And Methods: Medical records of dogs referred for neurological investigation of cervical hyperaesthesia between 2009 and 2013 were retrospectively reviewed. Dogs were assigned to one of the following groups according to the final diagnosis: Non-Neurologic, Brain, Cervical Spine, Multifocal, and Chiari-like Malformation/Syringomyelia.

Novel stepwise model of intervertebral disc degeneration with intact annulus fibrosus to test regeneration strategies.

Novel preclinical models that do not damage the annulus fibrosus (AF) of the intervertebral disc are required to study the efficacy of new regenerative strategies for the nucleus pulposus (NP). The aim of the study was to characterize a preclinical ovine model of intervertebral disc degeneration (IDD) induced by endplate (EP) damage and repair via the transpedicular approach, with or without partial nucleotomy, while keeping the AF intact. Twelve adult sheep were used.

Adenosine Production by Biomaterial-Supported Mesenchymal Stromal Cells Reduces the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury.

Background: During myocardial ischemia/reperfusion (MI/R) injury, there is extensive release of immunogenic metabolites that activate cells of the innate immune system. These include ATP and AMP, which upregulate chemotaxis, migration, and effector function of early infiltrating inflammatory cells. These cells subsequently drive further tissue devitalization.

Massa adiposa ligamenti falciformis or anterior abdominal fat pad - Its dimension and relation to body weight.

The anterior abdominal fat pad is associated with the falciform ligament in the upper middle/right abdomen and is frequently seen there in diagnostic imaging. It varies greatly in size and has often been described as an incidental finding in adults and has hitherto rarely been regarded as being illness-relevant. The aim of this study has been to assess whether the dimension of the corpus adiposum may be associated with body mass index.

Lumbosacral intraspinal extradural ganglion cyst in a cat.

Case Summary: A 16-year-old neutered female domestic shorthair cat was referred for chronic history of reluctance to jump, stiffness of the tail and lower back pain. Mild pelvic limb ataxia, reduced perianal reflex and lumbosacral discomfort were present on neurological examination. On magnetic resonance imaging, a well-defined rounded structure of 3 mm in diameter was identified on the right dorsal aspect of the epidural space at L7-S1, causing displacement of the cauda equina.

Reference Standardization for Mass Spectrometry and High-resolution Metabolomics Applications to Exposome Research.

The exposome is the cumulative measure of environmental influences and associated biological responses throughout the lifespan, including exposures from the environment, diet, behavior, and endogenous processes. A major challenge for exposome research lies in the development of robust and affordable analytic procedures to measure the broad range of exposures and associated biologic impacts occurring over a lifetime. Biomonitoring is an established approach to evaluate internal body burden of environmental exposures, but use of biomonitoring for exposome research is often limited by the high costs associated with quantification of individual chemicals.

Effect of Vitamin D Supplementation on Blood Pressure: A Systematic Review and Meta-analysis Incorporating Individual Patient Data.

Importance: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.

Objective: To systematically review whether supplementation with vitamin D or its analogues reduce BP.

Metabolome-wide association study of phenylalanine in plasma of common marmosets.

Little systematic knowledge exists concerning the impacts of cumulative lifelong exposure, termed the exposome, on requirements for nutrients. Phenylalanine (Phe) is an essential dietary amino acid with an aromatic ring structure similar to endogenous metabolites, dietary compounds and environmental agents. Excess plasma Phe in genetic disease or nutritional deficiency of Phe has adverse health consequences.

A facile and sensitive method for quantification of cyclic nucleotide monophosphates in mammalian organs: basal levels of eight cNMPs and identification of 2',3'-cIMP.

A sensitive, versatile and economical method to extract and quantify cyclic nucleotide monophosphates (cNMPs) using LC-MS/MS, including both 3',5'-cNMPs and 2',3'-cNMPs, in mammalian tissues and cellular systems has been developed. Problems, such as matrix effects from complex biological samples, are addressed and have been optimized. This protocol allows for comparison of multiple cNMPs in the same system and was used to examine the relationship between tissue levels of cNMPs in a panel of rat organs.

Mitochondrial metabolomics using high-resolution Fourier-transform mass spectrometry.

High-resolution Fourier-transform mass spectrometry (FTMS) provides important advantages in studies of metabolism because more than half of common intermediary metabolites can be measured in 10 min with minimal pre-detector separation and without ion dissociation. This capability allows unprecedented opportunity to study complex metabolic systems, such as mitochondria. Analysis of mouse liver mitochondria using FTMS with liquid chromatography shows that sex and genotypic differences in mitochondrial metabolism can be readily distinguished.

Trade as a structural driver of dietary risk factors for noncommunicable diseases in the Pacific: an analysis of household income and expenditure survey data.

Background: Noncommunicable diseases are a health and development challenge. Pacific Island countries are heavily affected by NCDs, with diabetes and obesity rates among the highest in the world. Trade is one of multiple structural drivers of NCDs in the Pacific, but country-level data linking trade, diets and NCD risk factors are scarce.

Effect of a randomised controlled vitamin D trial on insulin resistance and glucose metabolism in patients with type 2 diabetes mellitus.

The aim of our study was to investigate the influence of a 6-month vitamin D supplementation in patients with noninsulin-requiring type 2 diabetes mellitus. We included 86 patients in a placebo-controlled, randomised, double-blind study. During 6 months patients received Vigantol oil once a week corresponding to a daily dose of 1904 IU or placebo oil, followed by 6 months of follow-up.

Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum.

The transpedicular approach for the study of intervertebral disc regeneration strategies: in vivo characterization.

Purpose: To characterize in vivo the transpedicular approach (TA) as an alternative route to study intervertebral disc (IVD) regeneration strategies in a sheep model.

Methods: 48 IVD of 12 sheep were used. TA was performed under fluoroscopy, followed by nucleotomy (2-mm shaver resector).

Predicting network activity from high throughput metabolomics.

The functional interpretation of high throughput metabolomics by mass spectrometry is hindered by the identification of metabolites, a tedious and challenging task. We present a set of computational algorithms which, by leveraging the collective power of metabolic pathways and networks, predict functional activity directly from spectral feature tables without a priori identification of metabolites. The algorithms were experimentally validated on the activation of innate immune cells.

Cavernous sinus syndrome due to osteochondromatosis in a cat.

A 1-year-old sexually intact male Korat cat was referred for ophthalmological consultation due to anisocoria. Mydriasis with external ophthalmoplegia and absence of pupillary light responses in the right eye and nasofacial hypalgesia were seen. Cavernous sinus syndrome (CSS) was suspected.

High-performance metabolic profiling with dual chromatography-Fourier-transform mass spectrometry (DC-FTMS) for study of the exposome.

Studies of gene-environment (G × E) interactions require effective characterization of all environmental exposures from conception to death, termed the exposome. The exposome includes environmental exposures that impact health. Improved metabolic profiling methods are needed to characterize these exposures for use in personalized medicine.

xMSanalyzer: automated pipeline for improved feature detection and downstream analysis of large-scale, non-targeted metabolomics data.

Background: Detection of low abundance metabolites is important for de novo mapping of metabolic pathways related to diet, microbiome or environmental exposures. Multiple algorithms are available to extract m/z features from liquid chromatography-mass spectral data in a conservative manner, which tends to preclude detection of low abundance chemicals and chemicals found in small subsets of samples. The present study provides software to enhance such algorithms for feature detection, quality assessment, and annotation.