Parkinson's Disease Diagnosis Using miRNA Biomarkers and Deep Learning.

BACKGROUND: The current standard for Parkinson's disease (PD) diagnosis is often imprecise and expensive. However, the dysregulation patterns of microRNA (miRNA) hold potential as a reliable and effective non-invasive diagnosis of PD. METHODS: We use data mining to elucidate new miRNA biomarkers and then develop a machine-learning (ML) model to diagnose PD based on these biomarkers. RESULTS: The best-performing ML model, trained on filtered miRNA dysregulated in PD, was able to identify miRNA biomarkers with 95.65% accuracy. Through analysis of miRNA implicated in PD, thousands of descriptors reliant on gene targets were created that can be used to identify novel biomarkers and strengthen PD diagnosis. CONCLUSIONS: The developed ML model based on miRNAs and their genomic pathway descriptors achieved high accuracies for the prediction of PD.

Remote-Controlled and Pulse Pressure-Guided Fluid Treatment for Adult Patients with Viral Hemorrhagic Fevers.

Circulatory shock, caused by severe intravascular volume depletion resulting from gastrointestinal losses and profound capillary leak, is a common clinical feature of viral hemorrhagic fevers, including Ebola virus disease, Marburg hemorrhagic fever, and Lassa fever. These conditions are associated with high case fatality rates, and they carry a significant risk of infection for treating personnel. Optimized fluid therapy is the cornerstone of management of these diseases, but there are few data on the extent of fluid losses and the severity of the capillary leak in patients with VHFs, and no specific guidelines for fluid resuscitation and hemodynamic monitoring exist. We propose an innovative approach for monitoring VHF patients, in particular suited for low-resource settings, facilitating optimizing fluid therapy through remote-controlled and pulse pressure-guided fluid resuscitation. This strategy would increase the capacity for adequate supportive care, while decreasing the risk for virus transmission to health personnel.

Case Report: Severe Frostbite in Extreme Altitude Climbers-The Kathmandu Iloprost Experience.

Severe frostbite occurs frequently at extreme altitude in the Himalayas, often resulting in amputations. Recent advances in treatment of frostbite injuries with either intravenous or intra-arterial tissue plasminogen activator, or with iloprost, have improved outcomes in frostbite injuries, but only if the patient has access to these within 24 to 48 h postinjury, and ideally even sooner. Frostbitten Himalayan climbers are seldom able to reach medical care in this time frame. We wished to see if delayed iloprost use (up to 72 h) would help reduce tissue loss in grade 3 to 4 frostbite. In a series of 5 consecutive climbers with severe frostbite in whom we used iloprost, 4 of whom received treatment between 48 and 72 h from injury, 2 had excellent results with minimal tissue loss, and 2 had good results with tissue loss less than expected. The 1 patient with a poor outcome likely experienced a freeze-thaw-refreeze injury. This small series suggests that iloprost can be beneficial for severe frostbite, even after the standard 48-h window and perhaps for up to 72 h.

Human physiological and metabolic responses to an attempted winter crossing of Antarctica: the effects of prolonged hypobaric hypoxia.

An insufficient supply of oxygen to the tissues (hypoxia), as is experienced upon high-altitude exposure, elicits physiological acclimatization mechanisms alongside metabolic remodeling. Details of the integrative adaptive processes in response to chronic hypobaric hypoxic exposure remain to be sufficiently investigated. In this small applied field study, subjects (n = 5, male, age 28-54 years) undertook a 40 week Antarctica expedition in the winter months, which included 24 weeks residing above 2500 m. Measurements taken pre- and postexpedition revealed alterations to glucose and fatty acid resonances within the serum metabolic profile, a 7.8 (±3.6)% increase in respiratory exchange ratio measured during incremental exercise (area under curve, P > 0.01, mean ± SD) and a 2.1(±0.8) % decrease in fat tissue (P < 0.05) postexpedition. This was accompanied by an 11.6 (±1.9) % increase (P > 0.001) in VO2 max corrected to % lean mass postexpedition. In addition, spine bone mineral density and lung function measures were identified as novel parameters of interest. This study provides, an in-depth characterization of the responses to chronic hypobaric hypoxic exposure in one of the most hostile environments on Earth.

Ebola exposure, illness experience, and Ebola antibody prevalence in international responders to the West African Ebola epidemic 2014-2016: A cross-sectional study.

BACKGROUND: Healthcare and other front-line workers are at particular risk of infection with Ebola virus (EBOV). Despite the large-scale deployment of international responders, few cases of Ebola virus disease have been diagnosed in this group. Since asymptomatic or pauci-symptomatic infection has been described, it is plausible that infections have occurred in healthcare workers but have escaped being diagnosed. We aimed to assess the prevalence of asymptomatic or pauci-symptomatic infection, and of exposure events, among returned responders to the West African Ebola epidemic 2014-2016. METHODS AND FINDINGS: We used snowball sampling to identify responders who had returned to the UK or Ireland, and used an online consent and questionnaire to determine their exposure to EBOV and their experience of illness. Oral fluid collection devices were sent and returned by post, and samples were tested using an EBOV IgG capture assay that detects IgG to Ebola glycoprotein. Blood was collected from returnees with reactive samples for further testing. Unexposed UK controls were also recruited. In all, 300 individuals consented, of whom 268 (89.3%) returned an oral fluid sample (OFS). The majority had worked in Sierra Leone in clinical, laboratory, research, and other roles. Fifty-three UK controls consented and provided samples using the same method. Of the returnees, 47 (17.5%) reported that they had had a possible EBOV exposure. Based on their free-text descriptions, using a published risk assessment method, we classified 43 (16%) as having had incidents with risk of Ebola transmission, including five intermediate-risk and one high-risk exposure. Of the returnees, 57 (21%) reported a febrile or diarrhoeal illness in West Africa or within 1 mo of return, of whom 40 (70%) were not tested at the time for EBOV infection. Of the 268 OFSs, 266 were unreactive. Two returnees, who did not experience an illness in West Africa or on return, had OFSs that were reactive on the EBOV IgG capture assay, with similar results on plasma. One individual had no further positive test results; the other had a positive result on a double-antigen bridging assay but not on a competitive assay or on an indirect EBOV IgG ELISA. All 53 controls had non-reactive OFSs. While the participants were not a random sample of returnees, the number participating was high. CONCLUSIONS: This is the first study, to our knowledge, of the prevalence of EBOV infection in international responders. More than 99% had clear negative results. Sera from two individuals had discordant results on the different assays; both were negative on the competitive assay, suggesting that prior infection was unlikely. The finding that a significant proportion experienced "near miss" exposure events, and that most of those who experienced symptoms did not get tested for EBOV at the time, suggests a need to review and standardise protocols for the management of possible exposure to EBOV, and for the management of illness, across organisations that deploy staff to outbreaks.