A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Caracterización clínica, radiológica, pronóstica y del perfil de biomarcadores de los sujetos con ictus isquémico criptogénico no lacunar de mecanismo embólico

Introducció: L’interés per conèixer les característiques dels pacients amb ictus criptogènic no llacunar de mecanisme embòlic (de l’anglès ESUS) ha crescut últimament desde que es disposa de fàrmacs més segurs pel tractament preventiu. Ens planteguem que els ESUS presenten unes característiques clíniques, radiològiques, perfil de biomarcadors (BM) i pronòstic propis que difereixen de les altres etiologies. Metodologia: Analitzem dues cohorts. La primera cohort prospectiva analitza les característiques clíniques, de neuroimatge, ecocardiogràfiques, BM (NSE, IL-6, hs-CRP, troponina, NT-proBNP, fibrinogen, leucòcits, colesterol tradicional i no-tradicional) i recurrència. La segona cohort determina dades clíniques i de l’evolució intrahospitalaria. Ambdues van analitzar predictors de mal pronòstic en ESUS. Conclusions: Les característiques clíniques, radiològiques i perfil de BM que presenten els ESUS, els diferencien dels altres subtipus inclòs de la FA crònica i de novo. Això implicaria que no tots els ESUS regeixen el seu origen en una font cardioembòlica no detectada, establint diversos subtipus etiològics.Introducción: El interés por conocer las características de los sujetos con ictus criptogénico no lacunar de mecanismo embólico (del inglés ESUS) ha crecido últimamente tras disponer de fármacos más seguros para el tratamiento preventivo. Nos planteamos que los ESUS presentan características clínicas, radiológicas, perfil de biomarcadores (BM) y pronóstico propios que difieren de las otras etiologías. Metodología: Analizamos dos cohortes. La primera cohorte prospectiva analiza características clínicas, de neuroimagen, ecocardiográficos, BM (NSE, IL-6, hs-CRP, troponina, NT-proBNP, fibrinógeno, leucocitos, colesterol tradicional y no-tradicional) y recurrencia. La segunda cohorte determina datos de la clínica y evolución intrahospitalaria. Ambas analizaron predictores de mal pronóstico en ESUS. Conclusiones: Las características clínicas, radiológicas y perfil de BM que presentan los ESUS, los diferencia de los otros subtipos incluso de la FA crónica y de novo. Esto implicaría que no todos los ESUS rigen su origen en una fuente cardioembólica no detectada, pudiéndose establecer varios subtipos etiológicos.Introduction: The interest in knowing the characteristics of subjects with embolic source undetermined stroke (ESUS) has increased recently, following the release of safer drugs for preventive treatment. We propose that ESUS subjects exhibit specific clinical and radiological characteristics, biomarker (BK) patterns and a prognosis that differentiates them from other etiologies. Methodology: Two cohorts were analysed. The first prospective cohort analysed clinical, neuroimaging, echocardiography characteristics, BK (NSE, IL-6, hs-CRP, troponin, NT-proBNP, fibrinogen, leukocytes, traditional and non-traditional cholesterol) and recurrence. The second cohort established the clinical and intra-hospital evolution data. In both cohorts, the predictors of poor prognosis in ESUS were analysed. Conclusions: The clinical, radiological and BK profile characteristics of the ESUS differentiates them from the other subtypes, including chronic and the new diagnosis of AF. These results suggest that not all ESUS subjects originate from an undetected cardioembolic source, but in fact could establish several etiological subtypes

Depression and apathy after transient ischemic attack or minor stroke : prevalence, evolution and predictors

Few previous studies have focused on affective impairment after transient ischemic attack (TIA) and/or minor stroke. The aim was to establish the prevalence, evolution and predictors of post-stroke depression (PSD) and post-stroke apathy (PSA) over a 12-month follow-up period. We prospectively included TIA and minor stroke patients (NIHSS ≤4) who had undergone magnetic resonance imaging <7 days. PSD was diagnosed according to DSM-5 criteria and PSA was defined based on an Apathy Evaluation Scale (AES-C) score of ≥37. Clinical and neuroimaging variables (presence and patterns of lesion, cerebral bleeds and white matter disease) were analysed in order to find potential predictors for PSD and PSA. Follow-up was performed at 10 days and after 2, 6, 9 and 12 months. 82 patients were included (mean 66.4 [standard deviation11.0] years) of whom 70 completed the follow-up. At 10 days, 36 (43.9%) and 28 (34.1%) patients respectively were diagnosed with PSD and PSA. At 12 months, 25 of 70 (35.7%) patients still had PSA, but only 6 of 70 (8.6%) had PSD. Beck Depression Inventory-II score, mini mental state examination (MMSE) and a previous history of depression or anxiety were predictors for PSD. While MMSE score, The Montgomery Asberg Depression Rating Scale and having previously suffered a stroke were also risk factors for PSA. Acute basal ganglia lesion and periventricular leukoaraiosis were associated with PSA while deep leukorariosis with PSD. Despite the presence of few or only transient symptoms, PSD and PSA frequent appear early after TIA and minor stroke. Unlike PSD, apathy tends to persist during follow-up

Impairments in sleep and brain molecular clearance in people with cognitive deterioration and biological evidence of AD: a report of four cases

Abstract Background Recent evidence suggests that the failure of the glymphatic system – the brain’s waste clearance system, which is active during sleep – plays a key role in the pathophysiology of Alzheimer’s Disease (AD). Glymphatic function can be investigated using serial MRIs after intrathecal gadobutrol injection. This technique can reveal the health of the glymphatic system, but has not yet been used in participants with cognitive impairment due to AD. Case report This report describes the sleep and gadobutrol tracer clearance patterns of four participants diagnosed with mild to moderate cognitive impairment with evidence of AD pathology (pathological levels of Ab and p-tau in cerebrospinal fluid). We performed polysomnography and MRI studies before tracer injection and MRI scans at 1.5-2 h, 5–6 h, and 48 h after injection. Despite participants reporting no sleep problems, polysomnography revealed that all participants had moderate to severe sleep disturbances, including reduced sleep efficiency during the study and obstructive sleep apnea. Severe side-effects related to tracer administration were observed, impeding the completion of the protocol in two participants. Participants who finished the protocol displayed delayed and persistent tracer enrichment in the cortex and white matter, even 48 h after injection. These outcomes have not been observed in previous studies in participants without AD. Conclusion The findings suggest that brains with sleep impairment and AD pathology have poor glymphatic function, and therefore cannot clear the contrast tracer efficiently. This is likely to have caused the severe side effects in our participants, that have not been reported in healthy individuals. Our results may therefore represent the only available data acquired with this technique in participants with AD pathology

Metabolomics Predicts Neuroimaging Characteristics of Transient Ischemic Attack Patients

AbstractBackgroundNeuroimaging is essential for the diagnosis and prognosis of transient ischemic attack (TIA). The discovery of a plasmatic biomarker related to neuroimaging findings is of enormous interest because, despite its relevance, magnetic resonance diffusion weighted imaging (DWI) is not always available in all hospitals that attend to TIA patients.MethodsMetabolomic analyses were performed by liquid chromatography coupled to mass spectrometry in order to establish the metabolomic patterns of positive DWI, DWI patterns and acute ischemic lesion volumes. We used these methods with an initial TIA cohort of 129 patients and validated them with a 2nd independent cohort of 152 patients.FindingsPositive DWI was observed in 115 (40.9%) subjects and scattered pearls in one arterial territory was the most frequent lesion pattern (35.7%). The median acute ischemic lesion volume was 0.33 (0.15–1.90)cm3. We detected a specific metabolomic profile common to both cohorts for positive DWI (11 molecules including creatinine, threoninyl-threonine, N-acetyl-glucosamine, lyso phosphatidic acid and cholesterol-related molecules) and ischemic lesion volume (10 molecules including lysophosphatidylcholine, hypoxanthine/threonate, and leucines). Moreover lysophospholipids and creatinine clearly differed the subcortical DWI pattern from other patterns.InterpretationThere are specific metabolomic profiles associated with representative neuroimaging features in TIA patients. Our findings could allow the development of serum biomarkers related to acute ischemic lesions and specific acute ischemic patterns