Regional brain atrophy in gray and white matter is associated with cognitive impairment in Myotonic Dystrophy type 1

Background: Myotonic Dystrophy type 1 (DM1) is a slowly progressive myopathy characterized by varying multisystemic involvement. Several cerebral features such as brain atrophy, ventricular enlargement, and white matter lesions (WMLs) have frequently been described. The aim of this study is to investigate the structural organization of the brain that defines the disease through multimodal imaging analysis, and to analyze the relation between structural cerebral changes and DM1 clinical and neuropsychological profiles. Method: 31 DM1 patients and 57 healthy controls underwent an MRI scan protocol, including T1, T2 and DTI. Global gray matter (GM), global white matter (WM), and voxel-level Voxel Based Morphometry (VBM) and voxel-level microstructural WM abnormalities through Diffusion Tensor Imaging (DTI) were assessed through group comparisons and linear regression analysis with age, degree of muscular impairment (MIRS score), CTG expansion size and neuropsychological outcomes from a comprehensive assessment. Results: Compared with healthy controls, DM1 patients showed a reduction in both global GM and WM volume; and further regional GM decrease in specific primary sensory, multi-sensory and association cortical regions. Fractional anisotropy (FA) was reduced in both total brain and regional analysis, being most marked in frontal, paralimbic, temporal cortex, and subcortical regions. Higher ratings on muscular impairment and longer CTG expansion sizes predicted a greater volume decrease in GM and lower FA values. Age predicted global GM reduction, specifically in parietal regions. At the cognitive level, the DM1 group showed significant negative correlations between IQ estimate, visuoconstructive and executive neuropsychological scores and both global and regional volume decrease, mainly distributed in the frontal, parietal and subcortical regions. Conclusions: In this study, we describe the structural brain signatures that delineate the involvement of the CNS in DM1. We show that specific sensory and multi-sensory — as well as frontal cortical areas — display potential vulnerability associated with the hypothesized neurodegenerative nature of DM1 brain abnormalities

Neurodegeneration trajectory in pediatric and adult/late DM1: A follow‐up MRI study across a decade

Objective: To characterize the progression of brain structural abnormalities in adults with pediatric and adult/late onset DM1, as well as to examine the potential predictive markers of such progression. Methods: 21 DM1 patients (pediatric onset: N = 9; adult/late onset: N = 12) and 18 healthy controls (HC) were assessed longitudinally over 9.17 years through brain MRI. Additionally, patients underwent neuropsychological, genetic, and muscular impairment assessment. Inter-group comparisons of total and voxel-level regional brain volume were conducted through Voxel Based Morphometry (VBM); cross-sectionally and longitudinally, analyzing the associations between brain changes and demographic, clinical, and cognitive outcomes. Results: The percentage of GM loss did not significantly differ in any of the groups compared with HC and when assessed independently, adult/late DM1 patients and their HC group suffered a significant loss in WM volume. Regional VBM analyses revealed subcortical GM damage in both DM1 groups, evolving to frontal regions in the pediatric onset patients. Muscular impairment and the outcomes of certain neuropsychological tests were significantly associated with follow-up GM damage, while visuoconstruction, attention, and executive function tests showed sensitivity to WM degeneration over time. Interpretation: Distinct patterns of brain atrophy and its progression over time in pediatric and adult/late onset DM1 patients are suggested. Results indicate a possible neurodevelopmental origin of the brain abnormalities in DM1, along with the possible existence of an additional neurodegenerative process. Fronto-subcortical networks appear to be involved in the disease progression at young adulthood in pediatric onset DM1 patients. The involvement of a multimodal integration network in DM1 is discussed.CIBERNED609 Eusko JaurlaritzaPRE_ 2016_1_0187PRE_2019_1_0070SAIO08- PE08BF01 Institute of Health Carlos III cofounded by Fondo Europeo de Desarrollo Regional-FEDERPI17/01231 PI17/0184

Transcriptional signatures of synaptic vesicle genes define myotonic dystrophy type I neurodegeneration

Aim: To delineate the neurogenetic profiles of brain degeneration patterns in myotonic dystrophy type I (DM1). Methods: In two cohorts of DM1 patients, brain maps of volume loss (VL) and neuropsychological deficits (NDs) were intersected to large-scale transcriptome maps provided by the Allen Human Brain Atlas (AHBA). For validation, neuropathological and RNA analyses were performed in a small series of DM1 brain samples. Results: Twofold: (1) From a list of preselected hypothesis-driven genes, confirmatory analyses found that three genes play a major role in brain degeneration: dystrophin (DMD), alpha-synuclein (SNCA) and the microtubule-associated protein tau (MAPT). Neuropathological analyses confirmed a highly heterogeneous Tau-pathology in DM1, different to the one in Alzheimer's disease. (2) Exploratory analyses revealed gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. RNA analyses confirmed synaptic vesicle dysfunction. Conclusions: The combination of large-scale transcriptome interactions with brain imaging and cognitive function sheds light on the neurobiological mechanisms of brain degeneration in DM1 that might help define future therapeutic strategies and research into this condition

Components of a Neanderthal gut microbiome recovered from fecal sediments from El Salt

A comprehensive view of our evolutionary history cannot ignore the ancestral features of our gut microbiota. To provide some glimpse into the past, we searched for human gut microbiome components in ancient DNA from 14 archeological sediments spanning four stratigraphic units of El Salt Middle Paleolithic site (Spain), including layers of unit X, which has yielded well-preserved Neanderthal occupation deposits dating around 50 kya. According to our findings, bacterial genera belonging to families known to be part of the modern human gut microbiome are abundantly represented only across unit X samples, showing that well-known beneficial gut commensals, such as Blautia, Dorea, Roseburia, Ruminococcus, Faecalibacterium and Bifidobacterium already populated the intestinal microbiome of Homo since as far back as the last common ancestor between humans and Neanderthals.Results and discussion - Ancient DNA sequencing and damage assessment. - Detection of ancient human mitochondrial DNA. - Profiling of ancient prokaryotic DNA. - Putative components of the Neanderthal gut microbiome. Methods - Site and sampling. - Ancient DNA extraction. - Library preparation and sequencing. - Bioinformatics analysis. - Independent validation of taxonomic assignments. - mtDNA analysis and contamination estimate. - Statistics and reproducibility

Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 2)

Head and neck cancer is one of the most frequent malignances worldwide. Despite the site-specific multimodality therapy, up to half of the patients will develop recurrence. Treatment selection based on a multidisciplinary tumor board represents the cornerstone of head and neck cancer, as it is essential for achieving the best results, not only in terms of outcome, but also in terms of organ-function preservation and quality of life. Evidence-based international and national clinical practice guidelines for head and neck cancer not always provide answers in terms of decision-making that specialists have to deal with in their daily practice. This is the first Expert Consensus on the Multidisciplinary Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It offers a number of specific recommendations based on the available evidence and the expertise of our specialists to facilitate decision-making of all health-care specialists involved.Also, special thanks to Ainhoa Torres and the Merck Health Foundation for funding and promoting the project and development of the Article.Peer Reviewe

Inferring fish escape behaviour in trawls based on catch comparison data: Model development and evaluation based on data from Skagerrak, Denmark

During the fishing process, fish react to a trawl with a series of behaviours that often are species and size specific. Thus, a thorough understanding of fish behaviour in relation to fishing gear and a scientific understanding of the ability of different gear designs to utilize or stimulate various behavioural patterns during the catching process are essential for developing more efficient, selective, and environmentally friendly trawls. Although many behavioural studies using optical and acoustic observation systems have been conducted, harsh observation conditions on the fishing grounds often hamper the ability to directly observe fish behaviour in relation to fishing gear. As an alternative to optical and acoustic methods, we developed and applied a new mathematical model to catch data to extract detailed and quantitative information about species- and size-dependent escape behaviour in towed fishing gear such as trawls. We used catch comparison data collected with a twin trawl setup; the only difference between the two trawls was that a 12 m long upper section was replaced with 800 mm diamond meshes in one of them. We investigated the length-based escape behaviour of cod (Gadus morhua), haddock (Melanogrammus aeglefinus), saithe (Pollachius virens), witch flounder (Glyptocephalus cynoglossus), and lemon sole (Microstomus kitt) and quantified the extent to which behavioural responses set limits for the large mesh panel's selective efficiency. Around 85% of saithe, 80% of haddock, 44% of witch flounder, 55% of lemon sole, and 55% of cod (below 68 cm) contacted the large mesh panel and escaped. We also demonstrated the need to account for potential selectivity in the trawl body, as it can bias the assessment of length-based escape behaviour. Our indirect assessment of fish behaviour was in agreement with the direct observations made for the same species in a similar section of the trawl body reported in the literature

The Human Parahippocampal Region: I. Temporal Pole Cytoarchitectonic and MRI Correlation

The temporal pole (TP) is the rostralmost portion of the human temporal lobe. Characteristically, it is only present in human and nonhuman primates. TP has been implicated in different cognitive functions such as emotion, attention, behavior, and memory, based on functional studies performed in healthy controls and patients with neurodegenerative diseases through its anatomical connections (amygdala, pulvinar, orbitofrontal cortex). TP was originally described as a single uniform area by Brodmann area 38, and von Economo (area TG of von Economo and Koskinas), and little information on its cytoarchitectonics is known in humans. We hypothesize that 1) TP is not a homogenous area and we aim first at fixating the precise extent and limits of temporopolar cortex (TPC) with adjacent fields and 2) its structure can be correlated with structural magnetic resonance images. We describe here the macroscopic characteristics and cytoarchitecture as two subfields, a medial and a lateral area, that constitute TPC also noticeable in 2D and 3D reconstructions. Our findings suggest that the human TP is a heterogeneous region formed exclusively by TPC for about 7 mm of the temporal tip, and that becomes progressively restricted to the medial and ventral sides of the TP. This cortical area presents topographical and structural features in common with nonhuman primates, which suggests an evolutionary development in human species