Miniaturized and cost-efficient methods aiming at high throughput analysis of microbes are of great importance for the surveillance and control of infectious diseases and the related issue of ...antimicrobial resistance. Here we demonstrate a miniature nanosensor based on a honeycomb-patterned silicon nanowire field effect transistor (FET) capable of detection of bacterial growth and antibiotic response in microbiologically relevant nutrient media. We determine the growth kinetics and metabolic state of Escherichia coli cells in undiluted media via the quantification of changes in the source-drain current caused by varying pH values. Furthermore, by measuring the time dependent profile of pH change for bacterial cultures treated with antibiotics, we demonstrate for the first time the possibility of electrically distinguishing between bacteriostatic and bactericidal drug effects. We believe that the use of such nanoscopic FET devices enables addressing parameters that are not easily accessible by conventional optical methods in a label-free format, i.e. monitoring of microbial metabolic activity or stress response.
Abstract
Background
Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2–infected patients. Vitamin K activates both hepatic coagulation factors and ...extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease.
Methods
A total of 135 hospitalized COVID-19 patients were compared with 184 historic controls. Inactive vitamin K–dependent MGP (desphospho-uncarboxylated dp-uc MGP) and prothrombin (PIVKA-II) were measured inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed using computed tomography.
Results
dp-ucMGP was elevated in COVID-19 patients compared with controls (P < .001), with even higher dp-ucMGP in patients with poor outcomes (P < .001). PIVKA-II was normal in 82.1% of patients. dp-ucMGP was correlated with desmosine (P < .001) and with coronary artery (P = .002) and thoracic aortic (P < .001) calcification scores.
Conclusions
dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome; hepatic procoagulant factor II remained unaffected. These data suggest pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively.
Indirectly quantified extrahepatic vitamin K status is severely reduced in COVID-19. Data suggest pneumonia-induced vitamin K depletion leading to elastic fiber damage and thrombosis due to impaired vitamin K–dependent activation of matrix Gla protein and endothelial protein S, respectively.
Background: Stroke is not only an acute disease, but for the majority of patients, it also becomes a chronic condition. There is a major concern about the long-term follow-up with respect to ...activities of daily living (ADL) in stroke survivors. Some patients seem to be at risk for decline after a first-ever stroke. The purpose of this study was to determine the course of ADL from 3 months after the first-ever stroke and onward and identify factors associated with decline in ADL. Methods: A systematic literature search of 3 electronic databases through June 2015 was conducted. Longitudinal studies evaluating changes in ADL from 3 months post stroke onward were included. Cohorts including recurrent strokes and transient ischemic attacks were excluded. Regarding the course of ADL, a meta-analysis was performed using random-effects model. A best evidence synthesis was performed to identify factors associated with decline in ADL. Results: Out of 10,473 publications, 28 unique studies were included. A small but significant improvement in ADL was found from 3 to 12 months post stroke (standardized mean difference (SMD) 0.17 (0.04-0.30)), which mainly seemed to occur between 3 and 6 months post stroke (SMD 0.15 (0.05-0.26)). From 1 to 3 years post stroke, no significant change was found. Five studies found a decline in ADL status over time in 12-40% of patients. Nine factors were associated with ADL decline. There is moderate evidence for being dependent in ADL and impaired motor function of the leg. Limited evidence was found associated with insurance status, living alone, age ≥80, inactive state and having impaired cognitive function, depression and fatigue with decline in ADL. Conclusion: Although on an average patients do not seem to decline in ADL for up to 3 years, there is considerable variation within the population. Some modifiable factors associated with decline in ADL were identified. However, more research is needed before patients at risk of deterioration in ADL can be identified.
The live-attenuated yellow fever vaccine (YFV) is generally contraindicated in immunosuppressed patients. Our aim was to investigate if immunosuppressive therapy impairs the long-term protection ...against yellow fever virus in patients who had received YFV prior to the start of their immunosuppressive therapy.
Our study examined 35 healthy individuals and 40 immunosuppressed patients with autoimmune diseases or organ transplants. All individuals had received YFV prior to the onset of their immunosuppression. We analysed the long-term influence of the immunosuppressive therapy on the YFV protective immunity by measuring neutralising antibodies (NA) with the Plaque Reduction Neutralisation Test (PRNT). We assessed risk factors for a negative PRNT result (titre below 1: 10) and their influence on the magnitude of the NA.
A median time interval of 21.1 years (interquartile range 14.4–31.3 years) after the YFV in all patients, a total of 35 immunosuppressed patients (88%) were seropositive (PRNT ≥ 1:10) compared to 31 patients (89%) in the control group. The geometric mean titres of NA did not differ between the groups. The duration of an underlying rheumatic disease was the only risk factor found for a lower magnitude of NA. An insufficient level of NA was found in nine subjects (12%) who had received a single dose of YFV (in one subject, the number of YFV doses was unknown).
The use of an immunosuppressive drug started after the administration of the YFV did not affect long-term persistence of NA. A second dose of YFV may be necessary to secure long-term immunity.
Purpose: This study aims to (1) assess differences in participation restrictions between stroke survivors aged under and over 70 years and (2) identify predictors associated with favorable and ...unfavorable long-term participation in both age groups.
Methods: Prospective cohort study in which 326 patients were assessed at stroke onset, two months and one year after stroke. The Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-Participation) was used to measure participation restrictions one year after stroke. Bivariate and multivariate logistic regression analyses were performed including demographic factors, stroke-related factors, emotional functioning and comorbidity as possible predictors.
Results: Stroke survivors aged over 70 years perceived more participation restrictions in comparison to stroke survivors aged under 70 years one year after stroke. Independently significant predictors for unfavorable participation outcomes were advancing age, more severe stroke and anxiety symptoms in patients aged over 70 years, and female gender, more severe stroke, impaired cognition and depression symptoms in patients aged under 70 years. Lower age was the only independent predictor associated with favorable participation after one year in stroke survivors aged over 70 years.
Conclusions: This study emphasizes the need to pay more attention to participation restrictions in elderly stroke survivors.
Implications for rehabilitation
More attention in the rehabilitation process should be paid to restrictions in participation of stroke survivors aged older than 70 years, taking into account the different participation needs and predictors of older stroke survivors.
Early screening on the presence of anxiety symptoms could potentially prevent long-term restrictions in participation in stroke survivors aged over 70-year old.
Stroke survivors experience considerable restrictions in physical activity and mobility after one year, highlighting the need for the development of community-based exercise programs for stroke survivors.
In 3D topological insulators achieving a genuine bulk-insulating state is an important research topic. Recently, the material system (Bi,Sb)2(Te,Se)3 (BSTS) has been proposed as a topological ...insulator with high resistivity and a low carrier concentration (Ren et al 2011 Phys. Rev. B 84 165311). Here we present a study to further refine the bulk-insulating properties of BSTS. We have synthesized BSTS single crystals with compositions around x = 0.5 and y = 1.3. Resistance and Hall effect measurements show high resistivity and record low bulk carrier density for the composition Bi Sb Te Se . The analysis of the resistance measured for crystals with different thicknesses within a parallel resistor model shows that the surface contribution to the electrical transport amounts to 97% when the sample thickness is reduced to 1 m. The magnetoconductance of exfoliated BSTS nanoflakes shows 2D weak antilocalization with as expected for transport dominated by topological surface states.
Abstract
Background and Hypothesis
Social cognition training (SCT), an intervention for social cognition and social functioning, might be improved by using virtual reality (VR), because VR may offer ...better opportunities to practice in a potentially more realistic environment. To date, no controlled studies have investigated VR-SCT. This study investigated a VR-SCT, “DiSCoVR”. We hypothesized that DiSCoVR would improve social cognition and social functioning.
Study Design
Participants were randomized to DiSCoVR (n = 41) or VR relaxation (‘VRelax’, n = 40), an active control condition, and completed 16 twice-weekly sessions. Three assessments (baseline, posttreatment, and 3-month follow-up) were performed by blinded assessors. The primary outcome was social cognition (emotion perception and theory of mind). Secondary outcomes included social functioning (measured with an interview and experience sampling), psychiatric symptoms, information processing, and self-esteem. Data were analyzed using mixed-models regression analysis. Treatment effects were evaluated by the time by condition interaction terms.
Study Results
No significant time by condition interactions were found for any of the outcome variables, indicating an absence of treatment effects. Between-group effect sizes ranged from negligible to moderate (Cohen’s d < |0.53|). Main effects of time were found for several outcomes.
Conclusions
These results suggest that DiSCoVR was not effective, possibly because of inadequate simulation of emotional expressions in VR. This lack of efficacy may indicate that current SCT protocols are relatively unsuitable for improving social functioning. Previous studies showed small to moderate effects on higher order social cognition, but the SCT approach may need critical reevaluation, as it may not sufficiently lead to functional improvement.
Background and Purpose
The selection of the most suitable animal species and subsequent translation of the concentration-effect relationship to humans are critical steps for accurate assessment of ...the pro-arrhythmic risk of candidate molecules. The objective of this investigation was to assess quantitatively the differences in the QTc prolonging effects of moxifloxacin between cynomolgus monkeys, dogs and humans. The impact of interspecies differences is also illustrated for a new candidate molecule.
Experimental Approach
Pharmacokinetic data and ECG recordings from pre-clinical protocols in monkeys and dogs and from a phase I trial in healthy subjects were identified for the purpose of this analysis. A previously established Bayesian model describing the combined effect of heart rate, circadian variation and drug effect on the QT interval was used to describe the pharmacokinetic-pharmacodynamic relationships. The probability of a ≥10 ms increase in QT was derived as measure of the pro-arrhythmic effect.
Key Results
For moxifloxacin, the concentrations associated with a 50% probability of QT prolongation ≥10 ms (Cp
50
) varied from 20.3 to 6.4 and 2.6 μM in dogs, monkeys and humans, respectively. For NCE05, these values were 0.4 μM
vs
2.0 μM for monkeys and humans, respectively.
Conclusions and Implications
Our findings reveal significant interspecies differences in the QT-prolonging effect of moxifloxacin. In addition to the dissimilarity in pharmacokinetics across species, it is likely that differences in pharmacodynamics also play an important role. It appears that, regardless of the animal model used, a translation function is needed to predict concentration-effect relationships in humans.
To determine whether fatigue is associated with participation and health-related quality of life 5 years after perimesencephalic subarachnoid haemorrhage.
Multicentre cross-sectional study.
Forty-six ...patients with perimesencephalic subarachnoid haemorrhage.
Fatigue was assessed with the Fatigue Severity Scale, participation (frequency, restrictions, satisfaction) with the Utrecht Scale for Evaluation of Rehabilitation-Participation, healthrelated quality of life with the Stroke-Specific Quality of Life Scale-12, symptoms of depression and anxiety with the Hospital Anxiety and Depression Scale, and coping with the Coping Inventory for Stressful Situations.
A total of 46 patients were included (63% men, mean age 50.4 ± 9.4 years), with a mean time of 4.7 ± 1.6 years after perimesencephalic subarachnoid haemorrhage onset. Fatigued patients (33%) had worse participation (p < 0.01) and health-related quality of life (p < 0.001) than non-fatigued patients, and more often had hypertension, depression, anxiety and emotion-oriented coping (p < 0.05). Fatigue severity was inversely and independently (p < 0.005) associated with participation frequency (B = -3.62), satisfaction (B = -4.54), having restrictions (odds ratio = 2.48, 95% confidence interval 1.079-5.685), and health-related quality of life (B = -0.19), adjusted for depression, anxiety, and/or hypertension.
Five years after perimesencephalic subarachnoid haemorrhage, one-third of patients still reported fatigue, which was associated with worse participation and health-related quality of life. Future studies should examine whether these patients may benefit from rehabilitation aimed at fatigue.
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