European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010. They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.Fil: Arrossi, Silvina. Centro de Estudios de Estado y Sociedad; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: von Karsa, Lawrence. International Agency for Research on Cancer; FranciaFil: Patrick, J.. NHS Cancer Screening Programmes Sheffield; Reino Unido. University of Oxford; Reino UnidoFil: Segnan, N.. International Agency for Research on Cancer; Francia. AO Città della Salute e della Scienza di Torino; ItaliaFil: Atkin, W.. Imperial College London; Reino UnidoFil: Halloran, S.. University of Surrey; Reino UnidoFil: Saito, H.. National Cancer Centre; JapónFil: Sauvaget, C.. International Agency for Research on Cancer; FranciaFil: Scharpantgen, A.. Ministry of Health; LuxemburgoFil: Schmiegel, W.. Ruhr-Universität Bochum; AlemaniaFil: Senore, C.. AO Città della Salute e della Scienza di Torino; ItaliaFil: Siddiqi, M.. Cancer Foundation of India; IndiaFil: Sighoko, D.. University of Chicago; Estados Unidos. Formerly International Agency for Research on Cancer; FranciaFil: Smith, R.. American Cancer Society; Estados UnidosFil: Smith S.. University Hospitals Coventry & Warwickshire NHS Trust; Reino UnidoFil: Suchanek, S.. Charles University; República ChecaFil: Suonio, E.. International Agency for Research on Cancer; FranciaFil: Tong, W.. Chinese Academy of Sciences; República de ChinaFil: Törnberg, S.. Stockholm Gotland Regional Cancer Centre. Department of Cancer Screening; SueciaFil: Van Cutsem, E.. Katholikie Universiteit Leuven; BélgicaFil: Vignatelli, L.. Agenzia Sanitaria e Sociale Regionale; ItaliaFil: Villain, P.. University of Oxford; Reino UnidoFil: Voti, L.. Formerly International Agency for Research on Cancer; Francia. University of Miami; Estados UnidosFil: Watanabe, H.. Niigata University; JapónFil: Watson, J.. University of Oxford; Reino UnidoFil: Winawer, S.. Memorial Sloan–Kettering Cancer Center; Estados UnidosFil: Young, G.. Flinders University. Gastrointestinal Services; AustraliaFil: Zaksas, V.. State Patient Fund; LituaniaFil: Zappa, M.. Cancer Prevention and Research Institute; ItaliaFil: Valori, R.. NHS Endoscopy; Reino Unid

Prospects in Analytical Atomic Spectrometry

Tendencies in five main branches of atomic spectrometry (absorption, emission, mass, fluorescence and ionization spectrometry) are considered. The first three techniques are the most widespread and universal, with the best sensitivity attributed to atomic mass spectrometry. In the direct elemental analysis of solid samples, the leading roles are now conquered by laser-induced breakdown and laser ablation mass spectrometry, and the related techniques with transfer of the laser ablation products into inductively-coupled plasma. Advances in design of diode lasers and optical parametric oscillators promote developments in fluorescence and ionization spectrometry and also in absorption techniques where uses of optical cavities for increased effective absorption pathlength are expected to expand. Prospects for analytical instrumentation are seen in higher productivity, portability, miniaturization, incorporation of advanced software, automated sample preparation and transition to the multifunctional modular architecture. Steady progress and growth in applications of plasma- and laser-based methods are observed. An interest towards the absolute (standardless) analysis has revived, particularly in the emission spectrometry.Comment: Proofread copy with an added full reference list of 279 citations. A pdf version of the final published review may be requested from Alexander Bol'shakov <[email protected]

A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage. We highlight the current knowledge and describe how virological, animal, and clinical studies have shed light on the mechanisms driving the varied clinical diagnoses and observations of COVID-19 patients. Moreover, we describe how investigations into SARS-CoV-2 effects have informed the understanding of viral pathogenesis and provide innovative pathways for future research on the mechanisms of viral diseases

Short-Term Memory Trace in Rapidly Adapting Synapses of Inferior Temporal Cortex

Visual short-term memory tasks depend upon both the inferior temporal cortex (ITC) and the prefrontal cortex (PFC). Activity in some neurons persists after the first (sample) stimulus is shown. This delay-period activity has been proposed as an important mechanism for working memory. In ITC neurons, intervening (nonmatching) stimuli wipe out the delay-period activity; hence, the role of ITC in memory must depend upon a different mechanism. Here, we look for a possible mechanism by contrasting memory effects in two architectonically different parts of ITC: area TE and the perirhinal cortex. We found that a large proportion (80%) of stimulus-selective neurons in area TE of macaque ITCs exhibit a memory effect during the stimulus interval. During a sequential delayed matching-to-sample task (DMS), the noise in the neuronal response to the test image was correlated with the noise in the neuronal response to the sample image. Neurons in perirhinal cortex did not show this correlation. These results led us to hypothesize that area TE contributes to short-term memory by acting as a matched filter. When the sample image appears, each TE neuron captures a static copy of its inputs by rapidly adjusting its synaptic weights to match the strength of their individual inputs. Input signals from subsequent images are multiplied by those synaptic weights, thereby computing a measure of the correlation between the past and present inputs. The total activity in area TE is sufficient to quantify the similarity between the two images. This matched filter theory provides an explanation of what is remembered, where the trace is stored, and how comparison is done across time, all without requiring delay period activity. Simulations of a matched filter model match the experimental results, suggesting that area TE neurons store a synaptic memory trace during short-term visual memory

Neural Correlates of Visual Motion Prediction

Predicting the trajectories of moving objects in our surroundings is important for many life scenarios, such as driving, walking, reaching, hunting and combat. We determined human subjects’ performance and task-related brain activity in a motion trajectory prediction task. The task required spatial and motion working memory as well as the ability to extrapolate motion information in time to predict future object locations. We showed that the neural circuits associated with motion prediction included frontal, parietal and insular cortex, as well as the thalamus and the visual cortex. Interestingly, deactivation of many of these regions seemed to be more closely related to task performance. The differential activity during motion prediction vs. direct observation was also correlated with task performance. The neural networks involved in our visual motion prediction task are significantly different from those that underlie visual motion memory and imagery. Our results set the stage for the examination of the effects of deficiencies in these networks, such as those caused by aging and mental disorders, on visual motion prediction and its consequences on mobility related daily activities

Role of miR-2392 in driving SARS-CoV-2 infection

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans

Action observation activates neurons of the monkey ventrolateral prefrontal cortex

Prefrontal cortex is crucial for exploiting contextual information for the planning and guidance of behavioral responses. Among contextual cues, those provided by others' behavior are particularly important, in primates, for selecting appropriate reactions and suppressing the inappropriate ones. These latter functions deeply rely on the ability to understand others' actions. However, it is largely unknown whether prefrontal neurons are activated by action observation. To address this issue, we recorded the activity of ventrolateral prefrontal (VLPF) neurons of macaque monkeys during the observation of videos depicting biological movements performed by a monkey or a human agent, and object motion. Our results show that a population of VLPF neurons respond to the observation of biological movements, in particular those representing goal directed actions. Many of these neurons also show a preference for the agent performing the action. The neural response is present also when part of the observed movement is obscured, suggesting that these VLPF neurons code a high order representation of the observed action rather than a simple visual description of it

Mirror neurons in monkey area F5 do not adapt to the observation of repeated actions

Repetitive presentation of the same visual stimulus entails a response decrease in the action potential discharge of neurons in various areas of the monkey visual cortex. It is still unclear whether this repetition suppression effect is also present in single neurons in cortical premotor areas responding to visual stimuli, as suggested by the human functional magnetic resonance imaging literature. Here we report the responses of 'mirror neurons' in monkey area F5 to the repeated presentation of action movies. We find that most single neurons and the population at large do not show a significant decrease of the firing rate. On the other hand, simultaneously recorded local field potentials exhibit repetition suppression. As local field potentials are believed to be better linked to the blood-oxygen-level-dependent (BOLD) signal exploited by functional magnetic resonance imaging, these findings suggest caution when trying to derive conclusions on the spiking activity of neurons in a given area based on the observation of BOLD repetition suppression

Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. we analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)-encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1a to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. however, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. during early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. during the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. these data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology