Transcriptional signature in microglia isolated from an Alzheimers disease mouse model treated with scanning ultrasound

Rationale: Intracranial scanning ultrasound combined with intravenously injected microbubbles (SUS+MB) transiently opens the blood-brain barrier and reduces amyloid-beta (Abeta) pathology in the APP23 mouse model of Alzheimer disease (AD). This has been accomplished, at least in part, through the activation of microglial cells; however, their response to the SUS treatment is only incompletely understood. Methods: Wild-type (WT) and APP23 mice were subjected to SUS+MB, using non-SUS+MB-treated mice as sham controls. After 48 hours, the APP23 mice were injected with methoxy-XO4 to label Abeta aggregates, followed by microglial isolation into XO4+ and XO4- populations using flow cytometry. Both XO4+ and XO4- cells were subjected to RNA sequencing and their transcriptome was analyzed through a bioinformatics pipeline. Results: The transcriptomic analysis of the microglial cells revealed a clear segregation depending on genotype (AD model versus WT mice), as well as treatment (SUS+MB versus sham) and Abeta internalization (XO4+ versus XO4- microglia). Differential gene expression analysis detected 278 genes that were significantly changed by SUS+MB in the XO4+ cells (248 up/30 down) and 242 in XO- cells (225 up/17 down). Not surprisingly given previous findings of increased phagocytosis of plaques following SUS+MB, the pathway analysis highlighted that the treatment induced an enrichment in genes related to the phagosome pathway in XO4+ microglia; however, when comparing SUS+MB to sham, the analysis revealed an enrichment in genes involved in the cell cycle in both the XO4+ and XO4- microglial population. Conclusion: Our data provide a comprehensive analysis of microglia in an AD mouse model subjected to ultrasound treatment as a function of Abeta internalization, one of the defining hallmarks of AD. Several differentially expressed genes are highlighted, pointing to an ultrasound-induced activation of cell cycle mechanisms in microglial cells isolated from APP23 mice treated with SUS+MB.

Reynolds Model versus JFO Theory in Steadily Loaded Journal Bearings

Cavitation has a potential effect on the performance of full circle journal bearings. This paper studied the effects of cavitation on steadily loaded journal bearings, with the purpose of analyzing the necessity of adopting a mass-conserving model for ordinary journal bearings. The Christopherson’s method and Elrod cavitation algorithm were implemented to represent the non-mass-conserving Reynolds model and the mass-conserving Jakobsson-Floberg-Olsson (JFO) theory, respectively. The difference in the oil film reformation boundaries predicted by the two methods was focused on. The typical performance parameters including oil film pressure, load-carrying capacity, attitude angle, friction force, and leakage were comprehensively compared. The results show that the load-carrying capacity is improved by the decrease in cavitation pressure, and the effect is significant in lightly loaded cavitated bearings. In non-cavitated cases and the cavitated cases with intermediate and heavy loads, the difference between the Reynolds model and the JFO theory can be effectively ignored, but the accuracy of the leakage predicted using the Reynolds model should be carefully evaluated.

Cost and Potential Savings of Electronic Consultation and Its Relationship with Reduction in Atmospheric Pollution

Background: Telemedicine has been incorporated into daily clinical practice. The purpose of this paper is to evaluate the economic impact of electronic consultation as a means of referring patients between Primary Care (PC) services and the referral Cardiology Service (CS) of a tertiary hospital, in particular, the cost of reduced air pollution. Methods: The direct and indirect costs associated with all the interconsultations between PC and a CS of a tertiary hospital were analyzed under a universal single act model versus a prior e-consultation model that selected patients who would later attend the single-act consultation. The cost of pollution from private motor vehicle travel by road has been analyzed with a Cobb–Douglas cost function. Results: The total cost per patient, including the costs associated with death, represented a saving in the model with e-consultation of 25.6%. The economic value for the reduction of contamination would be EUR 12.86 per patient. Conclusions: The introduction of e-consultation in the outpatient management of patients referred from PC to a CS, helps to reduce direct and indirect costs for the patient and the Health Care System. The cost of pollution associated with the trips explains the total cost to a greater extent, except for the first face-to-face consultation.

SEIRDQ: A COVID-19 case projection modeling framework using ANN to model quarantine

We propose and implement a novel approach to model the evolution of COVID-19 pandemic and predict the daily COVID-19 cases (infected, recovered and dead). Our model builds on the classical SEIR-based framework by adding additional compartments to capture recovered, dead and quarantined cases. Quarantine impacts are modeled using an Artificial Neural Network (ANN), leveraging alternative data sources such as the Google mobility reports. Since our model captures the impact of lockdown policies through the quarantine functions we designed, it is able to model and predict future waves of COVID-19 cases. We also benchmark out-of-sample predictions from our model versus those from other popular COVID-19 case projection models.

Comparing the effect of a consult model versus an integrated palliative care and medical oncology co-rounding model on health care utilization in an acute hospital – an open-label stepped-wedge cluster-randomized trial

Background: The benefit of specialist palliative care for cancer inpatients is established, but the best method to deliver specialist palliative care is unknown. Aim: To compare a consult model versus a co-rounding model; both provide the same content of specialist palliative care to individual patients but differ in the level of integration between palliative care and oncology clinicians. Design: An open-label, cluster-randomized trial with stepped-wedge design. The primary outcome was hospital length of stay; secondary outcomes were 30-day readmissions and access to specialist palliative care. ClinicalTrials.gov number NCT03330509. Setting/participants: Cancer patients admitted to the oncology inpatient service of an acute hospital in Singapore. Results: A total of 5681 admissions from December 2017 to July 2019 were included, of which 5295 involved stage 3-4 cancer and 1221 received specialist palliative care review. Admissions in the co-rounding model had a shorter hospital length of stay than those in the consult model by 0.70 days (95%CI −0.04 to 1.45, p = 0.065) for all admissions. In the sub-group of stage 3-4 cancer patients, the length of stay was 0.85 days shorter (95%CI 0.05–1.65, p = 0.038). In the sub-group of admissions that received specialist palliative care review, the length of stay was 2.62 days shorter (95%CI 0.63–4.61, p = 0.010). Hospital readmission within 30 days (OR1.03, 95%CI 0.79–1.35, p = 0.822) and access to specialist palliative care (OR1.19, 95%CI 0.90–1.58, p = 0.215) were similar between the consult and co-rounding models. Conclusions: The co-rounding model was associated with a shorter hospital length of stay. Readmissions within 30 days and access to specialist palliative care were similar.