New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

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Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

The control of gene expression by microRNAs influences many cellular processes and has been implicated in the control of many (patho)physiological states. Recently, microRNAs have been detected in serum and plasma, and circulating microRNA profiles have now been associated with a range of different tumour types, diseases such as stroke and heart disease, as well as altered physiological states such as pregnancy. Here we review the disease-specific profiles of circulating microRNAs, and the methodologies used for their detection and quantification. We also discuss possible functions of circulating microRNAs and their potential as non-invasive biomarkers.

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Circulating microRNAs: Association with disease and potential use as biomarkers

Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples. We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies. The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases.

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A blood based 12-miRNA signature of Alzheimer disease patients

microRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases

MicroRNAs in common human diseases.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs) are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS) and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA) platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS.

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Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls

Since the outbreak of the COVID-19 pandemic, singing activities for children and young people have been strictly regulated with far-reaching consequences for music education in schools and ensemble and choir singing in some places. This is also due to the fact, that there has been no reliable data available on aerosol emissions from adolescents speaking, singing, and shouting. By utilizing a laser particle counter in cleanroom conditions we show, that adolescents emit fewer aerosol particles during singing than what has been known so far for adults. In our data, the emission rates ranged from 16 P/s to 267 P/s for speaking, 141 P/s to 1240 P/s for singing, and 683 P/s to 4332 P/s for shouting. The data advocate an adaptation of existing risk management strategies and rules of conduct for groups of singing adolescents, like gatherings in an educational context, e.g. singing lessons or choir rehearsals.

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Aerosol emission of adolescents voices during speaking, singing and shouting.

In this study, emission rates of aerosols emitted during singing are presented for professional singers. The results, measured with a laser particle counter, are compared with published data for breathing and speaking. In the investigated cohort of eight volunteers, the particle source strengths during singing are between 753.4 and 6093.14 P/s. The growth rates between singing and speaking are between 3.98 and 99.54. The present study contributes to a more precise assessment of a possible spread of SARS-CoV-2-viruses during singing. It should support the efforts to improve the risk management, especially for choir singing. Introduction The respiratory system is the main transmission route for SARS-CoV-2-viruses. (Asadi et al., 2020a; Morawska and Cao, 2020). Depending on particle size, a distinction can be made between droplets with a diameter greater than 5 μm and particles smaller than 5 μm (aerosols or droplet nuclei) (Couch et al., 1966; Tellier, 2006; Judson and Munster, 2019). Droplets and aerosols differ according to the influence of gravity. For example, droplets of a size of 100 μm sink to the ground within a short time and are transported up to a distance of 1.5 m (Kähler and Hain, 2020;Wei and Li, 2015). When aerosols are exhaled, the fluid component of the pathogen-containing particles evaporates more and more. They become lighter, can float in the air for longer periods and spread in closed rooms by air flow and diffusion (Stadnytskyi et al., 2020). As the basis of a possible aerogenic transmission of the SARS-CoV-2-virus, the spatial distribution of aerosols is dependent on several factors of the surrounding air, such as temperature and humidity (Morawska, 2006). Droplets and aerosols are also produced during speaking and singing, because the respiratory tract has a dual function: it is not only the main tool for ventilation, but also the source of voice and spoken language production. Particle formation in the pulmonary alveoli (Johnson and Morawska, 2009), flow effects of the vibrating vocal folds and adjustments of the articulation instruments are regarded as aerosol generating mechanisms (Johnson et al., 2011). In comparison to breathing, a stronger formation of aerosols is known for speaking, whereby also a dependence of the number of the arising particles on vocal loudness is described (Hartmann et al., 2020; Asadi et al., 2020b). For singing, a significantly higher aerosol production is assumed, probably due to the underlying physiological mechanisms and the greater continuity of voice production over time. This assumption is supported by reports of high infection rates during choir rehearsals in closed rooms (Hamner et al., 2020). Previous measurements focus on fluid mechanical aspects in the near-field plume of the mouth during singing (Anfinrud et al., 2020; Kähler and Hain, 2020). The spread of the emitted droplets is investigated, hence distance rules can be derived for protection against droplet infection. However, a risk assessment including the distribution of aerosols in larger rooms is not possible with this

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Aerosol emission is increased in professional singing

Infectious agents can be emitted into the room air via liquid particles (e.g. salivary droplets) during breathing, speaking and coughing and spread as aerosols over long distances. The source strength as well as the size distribution of these bioaerosols form the basis of their propagation behavior and are therefore the main value for the determination of the infection risk, which arises from human beings. This study presents emission rates of particle, which are emitted from mouth and nose during different activities: breathing, speaking and coughing.

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Emission rate and particle size of bioaerosols during breathing, speaking and coughing

In this study, emission rates of aerosols emitted by professional singers were measured with a laser particle counter under cleanroom conditions. The emission rates during singing varied between 753 and 6093 particles/sec with a median of 1537 particles/sec. Emission rates for singing were compared with data for breathing and speaking. Significantly higher emission rates were found for singing. The emission enhancements between singing and speaking were between 4.0 and 99.5 with a median of 17.4, largely due to higher sound pressure levels when singing. Further, significant effects of vocal loudness were found, whereas there were no significant differences between the investigated voice classifications. The present study supports the efforts to improve the risk management in cases of possible aerogenic virus transmission, especially for choir singing.

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Julia Lange

Papers

Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls

Aerosol emission of adolescents voices during speaking, singing and shouting.

Aerosol emission is increased in professional singing

Emission rate and particle size of bioaerosols during breathing, speaking and coughing

Aerosol emission in professional singing of classical music.