Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort

Background: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. Objective: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. Design: In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate–controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. Results: Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. Conclusions: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans

Plasma pNfH levels differentiate SBMA from ALS

Spinal and bulbar muscular atrophy (SBMA), known as Kennedy disease (KD), is a slowly progressive adult-onset X-linked neuromuscular disorder with no effective treatment. It is characterised by progressive limb and bulbar muscle weakness, associated with metabolic and endocrine alterations.1 2 SBMA is caused by the expansion of a CAG repeat in exon 1 of the androgen receptor (AR) gene; more than 37 repeats are pathogenic.1 While the genetic test is diagnostic, biomarkers would aid the initial differential diagnosis, and furthermore, there is a strong need for disease activity and progression markers to inform effective clinical trials design. Neurofilaments (Nfs), both light and heavy chains, are now becoming a widely accepted marker of neuronal damage and a prognostic biomarker for amyotrophic lateral sclerosis (ALS) and other neurodegenerative disease.3–7 Recently, plasma neurofilament light chain (NfL) levels were unexpectedly found not to be raised in patients with SBMA.8 This finding supports other lines of evidence, including an increase in plasma muscle damage markers, myopathic changes in biopsies and a series of genetic experiments in mouse models, that point to a primary myopathic involvement in SBMA.2 9 10 We here used the highly sensitive single molecule array (SIMOA) platform to investigate plasma levels of phosphorylated neurofilament heavy chain (pNfH), another well-established marker of neuronal damage, in patients with SBMA and in a rodent model of disease

A review of assessment methods for river hydromorphology

The work leading to this paper has received funding for the EU’s FP7 under Grant Agreement No. 282656 (REFORM

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Geometric Mixing, Peristalsis, and the Geometric Phase of the Stomach

Mixing fluid in a container at low Reynolds number - in an inertialess environment - is not a trivial task. Reciprocating motions merely lead to cycles of mixing and unmixing, so continuous rotation, as used in many technological applications, would appear to be necessary. However, there is another solution: movement of the walls in a cyclical fashion to introduce a geometric phase. We show using journal-bearing flow as a model that such geometric mixing is a general tool for using deformable boundaries that return to the same position to mix fluid at low Reynolds number. We then simulate a biological example: we show that mixing in the stomach functions because of the "belly phase": peristaltic movement of the walls in a cyclical fashion introduces a geometric phase that avoids unmixing.Comment: Revised, published versio

Evaluation of the Re-entry Vulnerability Index to Predict Ventricular Tachycardia Circuits Using High Density Contact Mapping

BACKGROUND: Identifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The re-entry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for re-entrant arrhythmia initiation without inducing VT. OBJECTIVE: To provide the first assessment of RVI's capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate. METHODS: 18 VT ablation patients (16M, 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analysed off-line. Activation time (AT), activation-recovery interval (ARI), repolarization time (RT) were measured. Vulnerability to re-entry was mapped based on RVI and spatial distribution of AT, ARI and RT. The distance from sites identified as vulnerable to re-entry to the VT site of origin was measured, with distances 20 mm indicating accurate and inaccurate localization, respectively. RESULTS: The origin of 18 VTs was identified (n=6 entrainment, n=12 pace-mapping). RVI maps included 1012, 408-2098 (median, 1st-3rd quartiles) points/patient. RVI accurately localized 72.2% VT sites of origin, with median distance equal to 5.1, 3.2-10.1 mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%, OR=0.12, P=0.035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI, and non-significantly larger for sites showing highest AT and ARI gradients. CONCLUSION: RVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies

Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Gestational Valproate Alters BOLD Activation in Response to Complex Social and Primary Sensory Stimuli

Valproic acid (VPA) has been used clinically as an anticonvulsant medication during pregnancy; however, it poses a neurodevelopmental risk due to its high teratogenicity. We hypothesized that midgestational (GD) exposure to VPA will lead to lasting deficits in social behavior and the processing of social stimuli. To test this, animals were given a single IP injection of 600 mg/kg of VPA on GD 12.5. Starting on postnatal day 2 (PND2), animals were examined for physical and behavior abnormalities. Functional MRI studies were carried out after PND60. VPA and control animals were given vehicle or a central infusion of a V1a antagonist 90 minutes before imaging. During imaging sessions, rats were presented with a juvenile test male followed by a primary visual stimulus (2 Hz pulsed light) to examine the effects of prenatal VPA on neural processing. VPA rats showed greater increases in BOLD signal response to the social stimulus compared to controls in the temporal cortex, thalamus, midbrain and the hypothalamus. Blocking the V1a receptor reduced the BOLD response in VPA animals only. Neural responses to the visual stimulus, however, were lower in VPA animals. Blockade with the V1a antagonist did not revert this latter effect. Our data suggest that prenatal VPA affects the processing of social stimuli and perhaps social memory, partly through a mechanism that may involve vasopressin V1a neurotransmission

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit