Objective
In a previous magnetic resonance imaging (MRI) study, we found a significant increase in hippocampal volume immediately after electroconvulsive therapy (ECT) in patients with depression. ...The aim of this study was to evaluate hippocampal volume up to 1 year after ECT and investigate its possible relation to clinical and cognitive outcome.
Method
Clinical and cognitive outcome in 12 in‐patients with depression receiving antidepressive pharmacological treatment referred for ECT were investigated with the Montgomery–Asberg Depression Rating Scale (MADRS) and a broad neuropsychological test battery within 1 week before and after ECT. The assessments were repeated 6 and 12 months after baseline in 10 and seven of these patients, respectively. Hippocampal volumes were measured on all four occasions with 3 Tesla MRI.
Results
Hippocampal volume returned to baseline during the follow‐up period of 6 months. Neither the significant antidepressant effect nor the significant transient decrease in executive and verbal episodic memory tests after ECT could be related to changes in hippocampal volume. No persistent cognitive side effects were observed 1 year after ECT.
Conclusion
The immediate increase in hippocampal volume after ECT is reversible and is not related to clinical or cognitive outcome.
The normal intestinal microbiota inhabits the colon mucus without triggering an inflammatory response. The reason for this and how the intestinal mucus of the colon is organized have begun to be ...unraveled. The mucus is organized in two layers: an inner, stratified mucus layer that is firmly adherent to the epithelial cells and approximately 50 μm thick; and an outer, nonattached layer that is usually approximately 100 μm thick as measured in mouse. These mucus layers are organized around the highly glycosylated MUC2 mucin, forming a large, net-like polymer that is secreted by the goblet cells. The inner mucus layer is dense and does not allow bacteria to penetrate, thus keeping the epithelial cell surface free from bacteria. The inner mucus layer is converted into the outer layer, which is the habitat of the commensal flora. The outer mucus layer has an expanded volume due to proteolytic activities provided by the host but probably also caused by commensal bacterial proteases and glycosidases. The numerous O-glycans on the MUC2 mucin not only serve as nutrients for the bacteria but also as attachment sites and, as such, probably contribute to the selection of the species-specific colon flora. This observation that normal human individuals carry a uniform MUC2 mucin glycan array in colon may indicate such a specific selection.
La Commission internationale de protection radiologique (CIPR) a initié un examen et une révision du système de radioprotection afin de mettre à jour les recommandations générales de 2007 dans la
...Publication 103
de la CIPR. Il s’agit du début d’un processus de plusieurs années qui nécessite une collaboration ouverte et transparente avec les organismes et les personnes du monde entier. Bien que le système soit robuste et efficace, il convient de l’adapter à l’évolution des connaissances scientifiques et de la société afin de demeurer adapté aux besoins. Le présent document vise à encourager les discussions sur les domaines du système qui pourraient bénéficier le plus d’un examen, et à engager des initiatives de collaboration. Le renforcement de la clarté et de la cohérence constitue une priorité. Plus le degré de compréhension du système est élevé, plus il est possible de l’appliquer efficacement, ce qui se traduit par une amélioration de la protection et une harmonisation accrue. De nombreux domaines pourraient faire l’objet d’un examen, notamment : la classification des effets, avec un accent particulier sur les réactions tissulaires ; la reformulation du détriment radiologique, qui pourrait inclure les maladies non cancéreuses ; la réévaluation de la relation entre le détriment et la dose efficace, et la possibilité de définir des détriments pour les hommes et les femmes et différentes classes d’âge ; la variation de la réponse individuelle à l’exposition aux rayonnements ; les effets héréditaires ; les effets et risques pour le biote non humain et les écosystèmes. Certains des concepts de base sont également examinés, notamment le cadre permettant de réunir la protection des personnes et de l’environnement, les améliorations progressives des principes fondamentaux de justification et d’optimisation, une approche plus large de la protection des personnes et la clarification des situations d’exposition introduites en 2007. En outre, la CIPR envisage de déterminer dans quels cas l’incorporation explicite des fondements éthiques dans le système présenterait un avantage, comment mieux refléter l’importance des échanges et de l’implication des parties prenantes, et de donner des conseils supplémentaires sur l’éducation et la formation. La CIPR invite à répondre à ces questions et à d’autres liées à l’examen du système de radioprotection.
The International Commission on Radiological Protection (ICRP) has embarked on a review and revision of the system of Radiological Protection that will update the 2007 general recommendations in ICRP Publication 103. This is the beginning of a process that will take several years, involving open and transparent engagement with organisations and individuals around the world. While the system is robust and has performed well, it must adapt to address changes in science and society to remain fit for purpose. The aim of this paper is to encourage discussions on which areas of the system might gain the greatest benefit from review, and to initiate collaborative efforts. Increased clarity and consistency are high priorities. The better the system is understood, the more effectively it can be applied, resulting in improved protection and increased harmonisation. Many areas are identified for potential review including: classification of effects, with particular focus on tissue reactions; reformulation of detriment, potentially including non-cancer diseases; re-evaluation of the relationship between detriment and effective dose, and the possibility of defining detriments for males and females of different ages; individual variation in the response to radiation exposure; heritable effects; and effects and risks in nonhuman biota and ecosystems. Some of the basic concepts are also being considered, including the framework for bringing together protection of people and the environment, incremental improvements to the fundamental principles of justification and optimisation, a broader approach to protection of individuals, and clarification of the exposure situations introduced in 2007. In addition, ICRP is considering identifying where explicit incorporation of the ethical basis of the system would be beneficial, how to better reflect the importance of communications and stakeholder involvement, and further advice on education and training. ICRP invites responses on these and other areas relating to the review of the System of Radiological Protection.
Large-scale sequencing of RNA from individual cells can reveal patterns of gene, isoform and allelic expression across cell types and states
. However, current short-read single-cell RNA-sequencing ...methods have limited ability to count RNAs at allele and isoform resolution, and long-read sequencing techniques lack the depth required for large-scale applications across cells
. Here we introduce Smart-seq3, which combines full-length transcriptome coverage with a 5' unique molecular identifier RNA counting strategy that enables in silico reconstruction of thousands of RNA molecules per cell. Of the counted and reconstructed molecules, 60% could be directly assigned to allelic origin and 30-50% to specific isoforms, and we identified substantial differences in isoform usage in different mouse strains and human cell types. Smart-seq3 greatly increased sensitivity compared to Smart-seq2, typically detecting thousands more transcripts per cell. We expect that Smart-seq3 will enable large-scale characterization of cell types and states across tissues and organisms.
Background and purpose
Despite the important role of imaging in diagnosing idiopathic normal‐pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The ...purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms.
Methods
In this prospective, population‐based study of iNPH, 168 individuals (93 females) mean age 75 (range 66–92) years underwent computed tomography of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters, i.e. Evans’ index, callosal angle, size of temporal horns, narrow high‐convexity sulci, dilated Sylvian fissures, focally dilated sulci, peri‐ventricular hypodensities and bulging of the lateral ventricular roof.
Results
In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, P < 0.001) between the total iNPH Radscale score and clinical symptoms. The inter‐rater agreement for the included radiological parameters was high (intraclass correlation, 0.74–0.97).
Conclusion
The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms should raise suspicion of iNPH, motivating further evaluation for shunt surgery.
Mammalian gene expression is inherently stochastic
, and results in discrete bursts of RNA molecules that are synthesized from each allele
. Although transcription is known to be regulated by ...promoters and enhancers, it is unclear how cis-regulatory sequences encode transcriptional burst kinetics. Characterization of transcriptional bursting, including the burst size and frequency, has mainly relied on live-cell
or single-molecule RNA fluorescence in situ hybridization
recordings of selected loci. Here we determine transcriptome-wide burst frequencies and sizes for endogenous mouse and human genes using allele-sensitive single-cell RNA sequencing. We show that core promoter elements affect burst size and uncover synergistic effects between TATA and initiator elements, which were masked at mean expression levels. Notably, we provide transcriptome-wide evidence that enhancers control burst frequencies, and demonstrate that cell-type-specific gene expression is primarily shaped by changes in burst frequencies. Together, our data show that burst frequency is primarily encoded in enhancers and burst size in core promoters, and that allelic single-cell RNA sequencing is a powerful model for investigating transcriptional kinetics.
Background
Magnetic resonance imaging (MRI) of the brain including diffusion‐weighted imaging (DWI) is reported to have high prognostic accuracy in unconscious post‐cardiac arrest (CA) patients. We ...documented acute MRI findings in the brain in both conscious and unconscious post‐CA patients treated with target temperature management (TTM) at 32–34°C for 24 h as well as the relation to patients’ neurological outcome after 6 months.
Methods
A prospective observational study with MRI was performed regardless of the level of consciousness in post‐CA patients treated with TTM. Neurological outcome was assessed using the Cerebral Performance Categories scale and dichotomized into good and poor outcome.
Results
Forty‐six patients underwent MRI at 3–5 days post‐CA. Patients with good outcome had minor, mainly frontal and parietal, lesions. Acute hypoxic/ischemic lesions on MRI including DWI were more common in patients with poor outcome (P = 0.007). These lesions affected mostly gray matter (deep or cortical), with or without involvement of the underlying white matter. Lesions in the occipital and temporal lobes, deep gray matter and cerebellum showed strongest associations with poor outcome. Decreased apparent diffusion coefficient, was more common in patients with poor outcome.
Conclusions
Extensive acute hypoxic/ischemic MRI lesions in the cortical regions, deep gray matter and cerebellum detected by visual analysis as well as low apparent diffusion coefficient values from quantitative measurements were associated with poor outcome. Patients with good outcome had minor hypoxic/ischemic changes, mainly in the frontal and parietal lobes.
CNS lymphoma consists of 2 major subtypes: secondary CNS involvement by systemic lymphoma and PCNSL. Contrast-enhanced MR imaging is the method of choice for detecting CNS lymphoma. In leptomeningeal ...CNS lymphoma, representing two-thirds of secondary CNS lymphomas, imaging typically shows leptomeningeal, subependymal, dural, or cranial nerve enhancement. Single or multiple periventricular and/or superficial contrast-enhancing lesions are characteristic of parenchymal CNS lymphoma, representing one-third of secondary CNS lymphomas and almost 100% of PCNSLs. New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions. Advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis. Furthermore, these imaging techniques may play a pivotal role in planning targeted therapies, prognostication, and monitoring treatment response.
Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the ...consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination. A national workshop to discuss these issues was held in Stockholm, Sweden, in August 2015, which resulted in a Swedish consensus statement regarding the use of MRI in the care of individuals with MS. The aim of this consensus statement is to provide practical advice for the use of MRI in this setting. The recommendations are based on a review of relevant literature and the clinical experience of workshop attendees. It is our hope that these recommendations will benefit individuals with MS and guide healthcare professionals responsible for their care.
Olfactory perception has implications for human chemosensory communication and in a broader context, it affects well-being. However, most of the studies investigating the consequences of olfactory ...loss have recruited patients who have already been categorized as having a dysfunctional sense of smell and sought help in an ENT clinic. We revisit these findings by distinguishing subjects with olfactory impairment from a group of subjects who all declared a normal sense of smell when enrolling for this study. In the initial sample of 203 individuals, we found 59 to have impaired olfaction and four with marginal olfactory performance, not useful in daily life. Interestingly, we found a significant between-group difference in cognitive functioning, further supporting the notion of the relationship between cognition and olfactory performance. However, their chemosensory communication and well-being appeared not to be different from subjects with normosmia. Impaired olfactory function certainly has a severe impact on daily life but more so in individuals who are bothered with it and decide to seek treatment. The limited-to-no olfactory perception in the fraction of subjects who neither complain about it nor seek help in ENT clinics does not seem to have a major effect on their social, cognitive, emotional and health functioning. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.
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