The Effect of a Planetary Health Diet on the Human Gut Microbiome : A Descriptive Analysis

In 2019, researchers from the EAT-Lancet Commission developed the ‘Planetary Health (PH) diet’. Specifically, they provided recommendations pertaining to healthy diets derived from sustainable food systems. Thus far, it has not been analysed how such a diet affects the human intestinal microbiome, which is important for health and disease development. Here, we present longitudinal genome-wide metagenomic sequencing and mass spectrometry data on the gut microbiome of healthy volunteers adhering to the PH diet, as opposed to vegetarian or vegan (VV) and omnivorous (OV) diets. We obtained basic epidemiological information from 41 healthy volunteers and collected stool samples at inclusion and after 2, 4, and 12 weeks. Individuals opting to follow the PH diet received detailed instructions and recipes, whereas individuals in the control groups followed their habitual dietary pattern. Whole-genome DNA was extracted from stool specimens and subjected to shotgun metagenomic sequencing (~3 GB per patient). Conventional bacterial stool cultures were performed in parallel and bacterial species were identified with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. We analysed samples from 16 PH, 16 OV, and 9 VV diet patterns. The α-diversity remained relatively stable for all dietary groups. In the PH group, we observed a constant increase from 3.79% at inclusion to 4.9% after 12 weeks in relative abundance of Bifidobacterium adolescentis. Differential PH abundance analysis highlighted a non-significant increase in possible probiotics such as Paraprevotella xylaniphila and Bacteroides clarus. The highest abundance of these bacteria was observed in the VV group. Dietary modifications are associated with rapid alterations to the human gut microbiome, and the PH diet led to a slight increase in probiotic-associated bacteria at ≥4 weeks. Additional research is required to confirm these findings

Regulation of Gram-Positive Conjugation

Type IV Secretion Systems (T4SSs) are membrane-spanning multiprotein complexes dedicated to protein secretion or conjugative DNA transport (conjugation systems) in bacteria. The prototype and best-characterized T4SS is that of the Gram-negative soil bacterium Agrobacterium tumefaciens. For Gram-positive bacteria, only conjugative T4SSs have been characterized in some biochemical, structural, and mechanistic details. These conjugation systems are predominantly encoded by self-transmissible plasmids but are also increasingly detected on integrative and conjugative elements (ICEs) and transposons. Here, we report regulatory details of conjugation systems from Enterococcus model plasmids pIP501 and pCF10, Bacillus plasmid pLS1, Clostridium plasmid pCW3, and staphylococcal plasmid pSK41. In addition, regulation of conjugative processes of ICEs (ICEBs1, ICESt1, ICESt3) by master regulators belonging to diverse repressor families will be discussed. A special focus of this review lies on the comparison of regulatory mechanisms executed by proteins belonging to the RRNPP family. These regulators share a common fold and govern several essential bacterial processes, including conjugative transfer

A Systematic Review of International Clinical Guidelines for Rehabilitation of People With Neurological Conditions: What Recommendations Are Made for Upper Limb Assessment?

Conclusions: We present a comprehensive, critical, and original summary of current recommendations. Defining a core set of measures and agreed protocols requires international consensus between experts representing the diverse and multi-disciplinary field of neurorehabilitation including clinical researchers and practitioners, rehabilitation technology researchers, and commercial developers. Current lack of guidance may hold-back progress in understanding function and recovery. Together with a Delphi consensus study and an overview of systematic reviews of outcome measures it will contribute to the development of international guidelines for upper limb assessment in neurological conditions.This review formed part of the COST Action TD 1006A European Network on Robotics for Neurorehabilitation. It was an interdisciplinary EU-funded research network concentrating on the coordination of European research in the area of rehabilitation robotics

isomiRdb : microRNA expression at isoform resolution

A significant fraction of mature miRNA transcripts carries sequence and/or length variations, termed isomiRs. IsomiRs are differentially abundant in cell types, tissues, body fluids or patients’ samples. Not surprisingly, multiple studies describe a physiological and pathophysiological role. Despite their importance, systematically collected and annotated isomiR information available in databases remains limited. We thus developed isomiRdb, a comprehensive resource that compiles miRNA expression data at isomiR resolution from various sources. We processed 42 499 human miRNA-seq datasets (5.9 × 1011 sequencing reads) and consistently analyzed them using miRMaster and sRNAbench. Our database provides online access to the 90 483 most abundant isomiRs (>1 RPM in at least 1% of the samples) from 52 tissues and 188 cell types. Additionally, the full set of over 3 million detected isomiRs is available for download. Our resource can be queried at the sample, miRNA or isomiR level so users can quickly answer common questions about the presence/absence of a particular miRNA/isomiR in tissues of interest. Further, the database facilitates to identify whether a potentially interesting new isoform has been detected before and its frequency. In addition to expression tables, isomiRdb can generate multiple interactive visualisations including violin plots and heatmaps. isomiRdb is free to use and publicly available at: https://www.ccb.uni-saarland.de/isomirdb

Dynamic and static circulating cancer microRNA biomarkers : a validation study

For cancers and other pathologies, early diagnosis remains the most promising path to survival. Profiling of longitudinal cohorts facilitates insights into trajectories of biomarkers. We measured microRNA expression in 240 serum samples from patients with colon, lung, and breast cancer and from cancerfree controls. Each patient provided at least two serum samples, one prior to diagnosis and one following diagnosis. The median time interval between the samples was 11.6 years. Using computational models, we evaluated the circulating profiles of 21 microRNAs. The analysis yielded two sets of biomarkers, static ones that show an absolute difference between certain cancer types and controls and dynamic ones where the level over time provided higher diagnostic information content. In the first group, miR-99a-5p stands out for all three cancer types. In the second group, miR-155-5p allows to predict lung cancers and colon cancers. Classification in samples from cancer and non-cancer patients using gradient boosted trees reached an average accuracy of 79.9%. The results suggest that individual change over time or an absolute value at one time point may predict a disease with high specificity and sensitivity

ACEMg-mediated hearing preservation in cochlear implant patients receiving different electrode lengths (PROHEARING): study protocol for a randomized controlled trial

Abstract Background The indications for a cochlear implant (CI) have been extended to include patients with some residual hearing. Shorter and thinner atraumatic electrodes have been designed to preserve the residual hearing in the implanted ear. However, the insertion of the electrode array into the cochlea, with potential mechanical trauma and the presence of this foreign body inside the cochlea, may lead to free radical formation and reduced blood perfusion of the cochlea which can result in the loss of residual hearing. Methods/design In this single-center, randomized, placebo-controlled, double-blind phase II clinical trial the effect of free radical scavengers and a vasodilator on the residual hearing of 140 CI patients will be evaluated. The formulation is composed of β-carotene (vitamin A), ascorbic acid (vitamin C), dl-α-tocopherol acetate (vitamin E) and the vasodilator magnesium (Mg), or ACEMg. Medication is administered twice daily per os for approximately 3 months. The primary measure is based upon the reduction in postoperative low-frequency air-conducted pure-tone thresholds compared to preoperative thresholds in ACEMg-treated patients compared to those of a placebo group. Additionally, the effect of different electrode lengths (20, 24 and 28 mm) is analyzed. Study visits are scheduled 2 days before surgery, at first fitting, which is the adjustment and start of stimulation via CI 4 weeks after surgery and 3, 6, 9 and 12 months after first fitting. The primary endpoint is the air-conduction hearing loss at 500 Hz 3 months after first fitting. Additionally, speech recognition tests, hearing aid benefit in the implanted ear and electrophysiological measurements of implant function are assessed. Since this is a blinded clinical trial and recruitment is still ongoing, data continue to accrue and we cannot yet analyze the outcome of the ACEMg treatment. Discussion There is an unfulfilled need for new strategies to preserve acoustic hearing in CI patients. This study will provide first-in-man data on ACEMg-mediated protection of residual hearing in CI patients. Performing all surgeries and patient follow-up at one study site improves consistency in diagnosis and therapy and less variability in surgery, audiological test techniques and fitting. This approach will allow investigation of the influence of ACEMg on residual hearing in CI patients. Trial registration The German Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) application number 4039192, was registered on 6 December 2013 with protocol amendment version 3.0 from 19 August 2014. EudraCT number: 2012-005002-22 .http://deepblue.lib.umich.edu/bitstream/2027.42/134623/1/13063_2016_Article_1526.pd

Literary-theoretical Transformations of Social Models

This study investigates transformations of classical antiquity oikonomia and chrematistics from the Middle Ages to the present-day.From an ancient- historical, philosophical, literary and cultural-science perspective, it reconstructs exemplary acquisitions and reinterpretations of economic knowledge. The study argues that the modern economy has benefited from transformation relationships with the oikonomia of classical antiquity, which exhibit no unambiguously economic, efficient and profit-maximising character. For this reason, in addition to actual historical aspects, our interest also includes issues relating to the poetology of economic knowledge, the metaphorology and scenaristics of the house, the theoretical, narrative and literary representation economies and the promotion of ‘economy’ to an ordering category per se

Understanding health behaviours in context: A systematic review and meta-analysis of ecological momentary assessment studies of five key health behaviours

Ecological Momentary Assessment (EMA) involves repeated, real-time sampling of health behaviours in context. We present the state-of-knowledge in EMA research focused on five key health behaviours (physical activity and sedentary behaviour, dietary behaviour, alcohol consumption, tobacco smoking, sexual health), summarising theoretical (e.g., psychological and contextual predictors) and methodological aspects (e.g., study characteristics, EMA adherence). We searched Ovid MEDLINE, Embase, PsycINFO and Web of Science until February 2021. We included studies focused on any of the aforementioned health behaviours in adult, non-clinical populations that assessed ≥1 psychological/contextual predictor and reported a predictor-behaviour association. A narrative synthesis and random-effects meta-analyses of EMA adherence were conducted. We included 633 studies. The median study duration was 14 days. The most frequently assessed predictors were ‘negative feeling states’ (21%) and ‘motivation and goals’ (16.5%). The pooled percentage of EMA adherence was high at 81.4% (95% CI = 80.0%, 82.8%, k = 348) and did not differ by target behaviour but was somewhat higher in student (vs. general population) samples, when EMAs were delivered via mobile phones/smartphones (vs. handheld devices), and when event contingent (vs. fixed) sampling was used. This review showcases how the EMA method has been applied to improve understanding and prediction of health behaviours in context

Understanding health behaviours in context : A systematic review and meta-analysis of Ecological Momentary Assessment studies of five key health behaviours

Acknowledgments The review team would like to thank Dr. David Simons for his help with the R code, as well as Dr. Pierre Gerain, Sally Di Maio, Rike Panse, Noemi Lorbeer, Malte Stollwerck, Dr. Paul Gellert, and Dr. Ann DeSmet for their contributions to the data extraction. Funding Olga Perski and Dimitra Kale receive salary support from Cancer Research UK (C1417/A22962). Daniel Powell is funded by the Scottish Government’s Rural and Environment Science and Analytical Services (RESAS) and by the School of Medicine, Medical Sciences, and Nutrition (SMMSN) at the University of Aberdeen. Felix Naughton’s salary is covered by the Faculty of Medicine and Health Sciences at the University of East Anglia. Dominika Kwasnicka’s work is carried out within the HOMING program of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund (grant number POIR.04.04.00-00-5CF3/18-00; HOMING 5/2018) and she is also funded by the NHMRC CRE in Digital Technology to Transform Chronic Disease Outcomes, Australia.Peer reviewedPublisher PD

Machine Learning to Detect Alzheimer's Disease from Circulating Non-coding RNAs

Blood-borne small non-coding (sncRNAs) are among the prominent candidates for blood-based diagnostic tests. Often, high-throughput approaches are applied to discover biomarker signatures. These have to be validated in larger cohorts and evaluated by adequate statistical learning approaches. Previously, we published high-throughput sequencing based microRNA (miRNA) signatures in Alzheimer’s disease (AD) patients in the United States (US) and Germany. Here, we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by RT-qPCR. We computed models to assess the relation between miRNA expression and phenotypes, gender, age, or disease severity (Mini-Mental State Examination; MMSE). Of the 21 miRNAs, expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts. 18 miRNAs were significantly correlated with neurodegeneration (Benjamini-Hochberg adjusted P < 0.05) with highest significance for miR-532-5p (Benjamini-Hochberg adjusted P = 4.8 × 10−30). Machine learning models reached an area under the curve (AUC) value of 87.6% in differentiating AD patients from controls. Further, ten miRNAs were significantly correlated with MMSE, in particular miR-26a/26b-5p (adjusted P = 0.0002). Interestingly, the miRNAs with lower abundance in AD were enriched in monocytes and T-helper cells, while those up-regulated in AD were enriched in serum, exosomes, cytotoxic t-cells, and B-cells. Our study represents the next important step in translational research for a miRNA-based AD test