A Protocol for Evaluating Digital Technology for Monitoring Sleep and Circadian Rhythms in Older People and People Living with Dementia in the Community.

Sleep and circadian rhythm disturbance are predictors of poor physical and mental health, including dementia. Long-term digital technology-enabled monitoring of sleep and circadian rhythms in the community has great potential for early diagnosis, monitoring of disease progression, and assessing the effectiveness of interventions. Before novel digital technology-based monitoring can be implemented at scale, its performance and acceptability need to be evaluated and compared to gold-standard methodology in relevant populations. Here, we describe our protocol for the evaluation of novel sleep and circadian technology which we have applied in cognitively intact older adults and are currently using in people living with dementia (PLWD). In this protocol, we test a range of technologies simultaneously at home (7-14 days) and subsequently in a clinical research facility in which gold standard methodology for assessing sleep and circadian physiology is implemented. We emphasize the importance of assessing both nocturnal and diurnal sleep (naps), valid markers of circadian physiology, and that evaluation of technology is best achieved in protocols in which sleep is mildly disturbed and in populations that are relevant to the intended use-case. We provide details on the design, implementation, challenges, and advantages of this protocol, along with examples of datasets.

Estimation of viral kinetics model parameters in young and aged SARS-CoV-2 infected macaques.

The SARS-CoV-2 virus disproportionately causes serious illness and death in older individuals. In order to have the greatest impact in decreasing the human toll caused by the virus, antiviral treatment should be targeted to older patients. For this, we need a better understanding of the differences in viral dynamics between SARS-CoV-2 infection in younger and older adults. In this study, we use previously published averaged viral titre measurements from the nose and throat of SARS-CoV-2 infection in young and aged cynomolgus macaques to parametrize a viral kinetics model. We find that all viral kinetics parameters differ between young and aged macaques in the nasal passages, but that there are fewer differences in parameter estimates from the throat. We further use our parametrized model to study the antiviral treatment of young and aged animals, finding that early antiviral treatment is more likely to lead to a lengthening of the infection in aged animals, but not in young animals.

Quantifying the effect of trypsin and elastase on in vitro SARS-CoV infections.

The SARS coronavirus (SARS-CoV) has the potential to cause serious disease that can spread rapidly around the world. Much of our understanding of SARS-CoV pathogenesis comes from in vitro experiments. Unfortunately, in vitro experiments cannot replicate all the complexity of the in vivo infection. For example, proteases in the respiratory tract cleave the SARS-CoV surface protein to facilitate viral entry, but these proteases are not present in vitro. Unfortunately, proteases might also have an effect on other parts of the replication cycle. Here, we use mathematical modeling to estimate parameters characterizing viral replication for SARS-CoV in the presence of trypsin or elastase, and in the absence of either. In addition to increasing the infection rate, the addition of trypsin and elastase causes lengthening of the eclipse phase duration and the infectious cell lifespan.

Síndrome de superposición de hepatitis autoinmune y colangitis biliar primaria asociada a trombosis de vena porta post COVID-19

Presentamos el caso de una mujer de 53 años con antecedentes de artritis reumatoide que, tras recuperarse de un cuadro de COVID-19grave, desarrolló hemorragia digestiva como manifestación de hipertensión portal e insuficiencia hepática progresiva. Basados en la serología y ecografía, se diagnosticó un síndrome overlap de hepatitis autoinmune y colangitis biliar primaria asociado a trombosis de vena porta. La respuesta a la corticoterapia y anticoagulación fue favorable. El compromiso hepático, inducido por el virus, está descrito en la COVID-19. Sin embargo, pueden desarrollarse enfermedades autoinmunes y fenómenos tromboembólicos, teniendo el hígado como órgano diana.

Investigating Different Mechanisms of Action in Combination Therapy for Influenza.

Combination therapy for influenza can have several benefits, from reducing the emergence of drug resistant virus strains to decreasing the cost of antivirals. However, there are currently only two classes of antivirals approved for use against influenza, limiting the possible combinations that can be considered for treatment. However, new antivirals are being developed that target different parts of the viral replication cycle, and their potential for use in combination therapy should be considered. The role of antiviral mechanism of action in the effectiveness of combination therapy has not yet been systematically investigated to determine whether certain antiviral mechanisms of action pair well in combination. Here, we use a mathematical model of influenza to model combination treatment with antivirals having different mechanisms of action to measure peak viral load, infection duration, and synergy of different drug combinations. We find that antivirals that lower the infection rate and antivirals that increase the duration of the eclipse phase perform poorly in combination with other antivirals.

A comparison of methods for extracting influenza viral titer characteristics.

Viral titer data collected in vitro or in vivo is often analyzed by extracting viral titer characteristics such as peak viral titer, time of viral peak and area under the curve (AUC). Researchers compare these characteristics in the absence and presence of various concentrations of antivirals in an attempt to quantify the effect of antivirals. Often these characteristics are estimated using only measured data points, although fitting of simple mathematical models to estimate these parameters is becoming more prevalent. In this article, our aim is to compare the estimates of different viral titer characteristics using three different approaches. The first approach is the traditional method that uses estimates based on experimentally measured data. The second approach relies on the use of a linear model to fit the viral titer data. The third approach uses an exponential model for the fitting process and the parameters of interest are extracted from there. The mathematical models are tested using in vivo and in vitro influenza infection data. Estimates of viral titer characteristics using either of the two fitting approaches were similar, but differed from estimates using the traditional method.