[The multidirectional effects of thrombin and the possibility of their control in neurology]. / Raznonapravlennye effekty trombina na protsessy gemokoagulyatsii i vozmozhnost' ikh kontrolya v nevrologii.

The review presents the main physiological functions of thrombin. The procoagulant and anticoagulant activities of the key serine protease are discussed in both physiological and pathological conditions of hemostasis. The involvement of thrombin in atherogenesis, as well as its role as a mediator of vascular dysfunction and inflammation in both the peripheral and central nervous system, is highlighted. A pronounced imbalance between the pro- and anticoagulant systems leads to an increase in thrombin formation and creates conditions for the development of thrombosis. Tests that allow direct or indirect assessment of thrombin's functional activity are presented. The potential applications of direct thrombin inhibitors and direct blockers of thrombin PAR receptors in vascular neurology are also considered.

A model of hope as a protective measure to lower burnout and secondary traumatic stress among employees working in developmental and intellectual disabilities services.

BACKGROUND: Burnout and secondary traumatic stress (STS) are problems for the workforce supporting people with developmental disabilities. This study investigated hope as a potential protective resource for burnout and STS among the developmental disability services workforce. METHOD: One hundred and fifty-two non-supervisor caseworkers from a state agency, developmental disabilities division were recruited to participate in an anonymous web-based survey. RESULTS: The analyses showed that hope was negatively associated with the three dimensions of STS (intrusion, avoidance, and arousal) and burnout. Controlling for tenure in the workforce and STS, the results of the hierarchical regression analyses showed that hope accounted for a significant incremental variance to burnout. CONCLUSION: These findings provide support for emerging literature showing hope as a protective resource to workforce burnout.

Context-aware deep network for coronary artery stenosis classification in coronary CT angiography.

Automatic coronary artery stenosis grading plays an important role in the diagnosis of coronary artery disease. Due to the difficulty of learning the informative features from varying grades of stenosis, it is still a challenging task to identify coronary artery stenosis from coronary CT angiography (CCTA). In this paper, we propose a context-aware deep network (CADN) for coronary artery stenosis classification. The proposed method integrates 3D CNN with Transformer to improve the feature representation of coronary artery stenosis in CCTA. We evaluate the proposed method on a multicenter dataset (APOLLO study with NCT05509010). Experimental results show that our proposed method can achieve the accuracy of 0.84, 0.83, and 0.86 for stenosis diagnosis on the lesion, artery, and patient levels, respectively.

Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters).

BACKGROUND: Evidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application. METHODS: The study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work. DISCUSSION: Successful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

Cutaneous manifestations, viral load, and prognosis among hospitalised patients with COVID-19: a cohort study.

INTRODUCTION: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes. METHODS: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed. RESULTS: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05). CONCLUSION: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored.

Evaluating Quality-of-Life, Length of Stay and Cost-Effectiveness of a Front-Door Geriatrics Program: An Exploratory Proof-of-Concept Study.

BACKGROUND: The Emergency Department Interventions for Frailty (EDIFY) program was developed to deliver early geriatric specialist interventions at the Emergency Department (ED). EDIFY has been successful in reducing acute admissions among older adults. OBJECTIVES: We aimed to examine the effectiveness of EDIFY in improving health-related quality-of-life (HRQOL) and length of stay (LOS), and evaluate EDIFY's cost-effectiveness. DESIGN: A quasi-experiment study. SETTING: The ED of a 1700-bed tertiary hospital. PARTICIPANTS: Patients (≥85 years) pending acute hospital admission and screened by the EDIFY team to be potentially suitable for discharge or transfer to low-acuity care areas. INTERVENTION: EDIFY versus standard-care. MEASUREMENTS: Data on demographics, comorbidities, premorbid function, and frailty status were gathered. HRQOL was measured using EQ-5D-5L over 6 months. We used a crosswalk methodology to compute Singapore-specific index scores from EQ-5D-5L responses and calculated quality-adjusted life-years (QALYs) gained. LOS and bills in Singapore-dollars (SGD) before subsidy from ED attendances (including admissions, if applicable) were obtained. We estimated average programmatic EDIFY cost and performed multiple imputation (MI) for missing data. QALYs gained, LOS and cost were compared. Potential uncertainties were also examined. RESULTS: Among 100 participants (EDIFY=43; standard-care=57), 61 provided complete data. For complete cases, there were significant QALYs gained at 3-month (coefficient=0.032, p=0.004) and overall (coefficient=0.096, p=0.002) for EDIFY, whilst treatment cost was similar between-groups. For MI, we observed only overall QALYs gained for EDIFY (coefficient=0.102, p=0.001). EDIFY reduced LOS by 17% (Incident risk ratio=0.83, p=0.015). In a deterministic sensitivity analysis, EDIFY's cost-threshold was SGD$2,500, and main conclusions were consistent in other uncertainty scenarios. Mean bills were: EDIFY=SGD$4562.70; standard-care=SGD$5530.90. EDIFY's average programmatic cost approximated SGD$469.30. CONCLUSIONS: This exploratory proof-of-concept study found that EDIFY benefits QALYs and LOS, with equivalent cost, and is potentially cost-effective. The program has now been established as standard-care for older adults attending the ED at our center.

Low intensity mechanical signals promote proliferation in a cell-specific manner: Tailoring a non-drug strategy to enhance biomanufacturing yields.

Biomanufacturing relies on living cells to produce biotechnology-based therapeutics, tissue engineering constructs, vaccines, and a vast range of agricultural and industrial products. With the escalating demand for these bio-based products, any process that could improve yields and shorten outcome timelines by accelerating cell proliferation would have a significant impact across the discipline. While these goals are primarily achieved using biological or chemical strategies, harnessing cell mechanosensitivity represents a promising - albeit less studied - physical pathway to promote bioprocessing endpoints, yet identifying which mechanical parameters influence cell activities has remained elusive. We tested the hypothesis that mechanical signals, delivered non-invasively using low-intensity vibration (LIV; <1g, 10-500Hz), will enhance cell expansion, and determined that any unique signal configuration was not equally influential across a range of cell types. Varying frequency, intensity, duration, refractory period, and daily doses of LIV increased proliferation in CHO-adherent cells (+79% in 96h) using a particular set of LIV parameters (0.2g, 500Hz, 3x30 min/d, 2h refractory period), yet this same mechanical input suppressed proliferation in CHO-suspension cells (-13%). Exposing these same CHO-suspension cells to distinct LIV parameters (30Hz, 0.7g, 2x60 min/d, 2h refractory period) increased proliferation by 210%. Particle image velocimetry combined with finite element modeling showed high transmissibility of these signals across fluids (>90%), and LIV effectively scaled up to T75 flasks. Ultimately, when LIV is tailored to the target cell population, its highly efficient transmission across media represents a means to non-invasively augment biomanufacturing endpoints for both adherent and suspended cells, and holds immediate applications, ranging from small-scale, patient-specific personalized medicine to large-scale commercial bio-centric production challenges.

Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

MR Imaging Findings in a Large Population of Autoimmune Encephalitis.

BACKGROUND AND PURPOSE: Autoimmune encephalitis is a rare condition in which autoantibodies attack neuronal tissue, causing neuropsychiatric disturbances. This study sought to evaluate MR imaging findings associated with subtypes and categories of autoimmune encephalitis. MATERIALS AND METHODS: Cases of autoimmune encephalitis with specific autoantibodies were identified from the medical record (2009-2019). Cases were excluded if no MR imaging of the brain was available, antibodies were associated with demyelinating disease, or >1 concurrent antibody was present. Demographics, CSF profile, antibody subtype and group (group 1 intracellular antigen or group 2 extracellular antigen), and MR imaging features at symptom onset were reviewed. Imaging and clinical features were compared across antibody groups using χ2 and Wilcoxon rank-sum tests. RESULTS: Eighty-five cases of autoimmune encephalitis constituting 16 distinct antibodies were reviewed. The most common antibodies were anti-N-methyl-D-aspartate (n = 41), anti-glutamic acid decarboxylase (n = 7), and anti-voltage-gated potassium channel (n = 6). Eighteen of 85 (21%) were group 1; and 67/85 (79%) were group 2. The median time between MR imaging and antibody diagnosis was 14 days (interquartile range, 4-26 days). MR imaging had normal findings in 33/85 (39%), and 20/33 (61%) patients with normal MRIs had anti-N-methyl-D-aspartate receptor antibodies. Signal abnormality was most common in the limbic system (28/85, 33%); 1/68 (1.5%) had susceptibility artifacts. Brainstem and cerebellar involvement were more common in group 1, while leptomeningeal enhancement was more common in group 2. CONCLUSIONS: Sixty-one percent of patients with autoimmune encephalitis had abnormal brain MR imaging findings at symptom onset, most commonly involving the limbic system. Susceptibility artifact is rare and makes autoimmune encephalitis less likely as a diagnosis. Brainstem and cerebellar involvement were more common in group 1, while leptomeningeal enhancement was more common in group 2.

Machine learning to predict myocardial injury and death after non-cardiac surgery.

Myocardial injury due to ischaemia within 30 days of non-cardiac surgery is prognostically relevant. We aimed to determine the discrimination, calibration, accuracy, sensitivity and specificity of single-layer and multiple-layer neural networks for myocardial injury and death within 30 postoperative days. We analysed data from 24,589 participants in the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation study. Validation was performed on a randomly selected subset of the study population. Discrimination for myocardial injury by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.70 (0.69-0.72) vs. 0.71 (0.70-0.73) with variables available before surgical referral, p < 0.001; 0.73 (0.72-0.75) vs. 0.75 (0.74-0.76) with additional variables available on admission, but before surgery, p < 0.001; and 0.76 (0.75-0.77) vs. 0.77 (0.76-0.78) with the addition of subsequent variables, p < 0.001. Discrimination for death by single-layer vs. multiple-layer models generated areas (95%CI) under the receiver operating characteristic curve of: 0.71 (0.66-0.76) vs. 0.74 (0.71-0.77) with variables available before surgical referral, p = 0.04; 0.78 (0.73-0.82) vs. 0.83 (0.79-0.86) with additional variables available on admission but before surgery, p = 0.01; and 0.87 (0.83-0.89) vs. 0.87 (0.85-0.90) with the addition of subsequent variables, p = 0.52. The accuracy of the multiple-layer model for myocardial injury and death with all variables was 70% and 89%, respectively.

Hope As a Buffer to Suicide Attempts Among Adolescents with Depression.

BACKGROUND: Suicide among adolescents has long been linked to symptoms of depression. However, limited research has examined the potential buffering effect of hope on the relationship between depression and suicide attempts. METHODS: To test the effect of hope on the positive relationship between depression and suicide attempts, we used data (N = 502 adolescents) from youth ages 12-18 collected as part of the 2018 Healthy Youth Survey in the State of Washington. Based on hope theory, we hypothesized a "buffering" form of moderation, with the presence of greater hope weakening the positive relationship between depression and suicide attempts. In other words, with higher hope, adolescents reporting depressive symptoms are less inclined to attempt suicide. RESULTS: Testing the moderating effect of hope via bootstrap resampling (N = 5000), the results indicated adolescents' hope levels indeed buffered the relationship between depressive symptoms and self-reported suicide attempts. To wit, when adolescents' hope was low, there was a significant, robust, and positive relationship between depressive symptoms and suicide attempts (b = 0.2644, 95% CI [0.1604, 0.3683], t = 5.0, p < .001). However, when adolescents' hope was high, there was no longer a significant relationship between depressive symptoms and suicide attempts (b = 0.0304, 95% CI [-0.997, 0.1605], t = 0.4590, p = .65). CONCLUSION: The buffering effect of hope was validated in a second, larger sample (n = 9308) of adolescents. This result suggests the potential utility of hope theory-based interventions to assist depressed adolescents reduce their likelihood of suicide.

Acute myocardial infarction and myocarditis following COVID-19 vaccination.

Emerging reports raise concerns on the potential association between the COVID-19 vaccines and cardiac manifestations. We sought to evaluate cardiac complications associated with COVID-19 vaccination in a pooled analysis from our institution's cohort study and systematic review. Consecutive patients admitted to a tertiary hospital in Singapore between 1 January 2021 and 31 March 2021, with the onset of cardiac manifestations within 14 days following COVID-19 vaccination, were studied. Furthermore, a systematic review was performed, with PubMed, Embase, Research Square, MedRxiv and LitCovid databases accessed from inception up to 29 June 2021. Relevant manuscripts reporting individual patient data on cardiac complications following COVID-19 vaccination were included. Thirty patients were included in the study cohort, with 29 diagnosed with acute myocardial infarction (AMI) and 1 with myocarditis. Five patients developed heart failure, two had cardiogenic shock, three intubated, and one had cardiovascular-related mortality. In the systematic review, 16 studies were included with 41 myocarditis and 6 AMI cases. In the pooled analysis of the study cohort and the systematic review, 35 patients had AMI and 42 had myocarditis. Majority were men, and myocarditis patients were younger than AMI patients. Myocarditis patients tended to present 72 h postvaccination, while AMI patients were older and typically presented 24 h postvaccination. Majority with AMI or myocarditis developed symptoms after the first and second vaccination dose, respectively. This pooled analysis of patients presenting with cardiac manifestations following COVID-19 vaccination highlights the differences between myocarditis and AMI presentations in temporal association with the vaccination.