Automatic measurement of departing times in smartphone alerting systems: A pilot study

Aim Smartphone alerting systems (SAS) alert volunteers in close vicinity of suspected out-of-hospital cardiac arrest. Some systems use sophisticated algorithms to select those who will probably arrive first. Precise estimation of departing times and travel times may help to further improve algorithms. We developed a global positioning system (GPS) based method for automatic measurements of departing times. The aim of this pilot study was to evaluate feasibility and precision of the method. Methods Region of Lifesavers alerting app (iOS/ Android, version 3.0, FirstAED ApS, Denmark) was used in this study. 27 experiments were performed with 9 students, who were instructed to stay in their flats during the study days. A geofence was set for each alarm in the alerting system with a radius of 10 m (8 cases), 15 m (10 cases), and 20 m (9 cases) around the GPS position at which the alarm was accepted in the app. The system logged responders as being departed when the smartphone position was registered outside the geofence. The students were instructed to manually start a stopwatch at the time of the alert and to stop the stopwatch once they had entered the street in front of their flat. Results The median difference between automatically and manually retrieved times were −16 seconds [interquartile range IQR 50 seconds] (geofence 10 m), 30 seconds [IQR 25 seconds] (15 m), and 20 seconds [IQR 13 seconds] (20 m), respectively. The 20 m geofence was associated with the smallest interquartile range. Conclusion Departing times of volunteer responders in SAS can be retrieved automatically using GPS and a geofence

Whole genome assessment of the retinal response to diabetes reveals a progressive neurovascular inflammatory response

<p>Abstract</p> <p>Background</p> <p>Despite advances in the understanding of diabetic retinopathy, the nature and time course of molecular changes in the retina with diabetes are incompletely described. This study characterized the functional and molecular phenotype of the retina with increasing durations of diabetes.</p> <p>Results</p> <p>Using the streptozotocin-induced rat model of diabetes, levels of retinal permeability, caspase activity, and gene expression were examined after 1 and 3 months of diabetes. Gene expression changes were identified by whole genome microarray and confirmed by qPCR in the same set of animals as used in the microarray analyses and subsequently validated in independent sets of animals. Increased levels of vascular permeability and caspase-3 activity were observed at 3 months of diabetes, but not 1 month. Significantly more and larger magnitude gene expression changes were observed after 3 months than after 1 month of diabetes. Quantitative PCR validation of selected genes related to inflammation, microvasculature and neuronal function confirmed gene expression changes in multiple independent sets of animals.</p> <p>Conclusion</p> <p>These changes in permeability, apoptosis, and gene expression provide further evidence of progressive retinal malfunction with increasing duration of diabetes. The specific gene expression changes confirmed in multiple sets of animals indicate that pro-inflammatory, anti-vascular barrier, and neurodegenerative changes occur in tandem with functional increases in apoptosis and vascular permeability. These responses are shared with the clinically documented inflammatory response in diabetic retinopathy suggesting that this model may be used to test anti-inflammatory therapeutics.</p

Th17-skewed immune response and cluster of differentiation 40 ligand expression in canine steroid-responsive meningitis-arteritis, a large animal model for neutrophilic meningitis

Background: Steroid-responsive meningitis-arteritis (SRMA) is an immune-mediated disorder characterized by neutrophilic pleocytosis and an arteritis particularly in the cervical leptomeninges. Previous studies of the disease have shown increased levels of IL-6 and TGF-beta(1) in cerebrospinal fluid (CSF). In the presence of these cytokines, naive CD4+ cells differentiate into Th17 lymphocytes which synthesize interleukin 17 (IL-17). It has been shown that IL-17 plays an active role in autoimmune diseases, it induces and mediates inflammatory responses and has an important role in recruitment of neutrophils. The hypothesis of a Th17-skewed immune response in SRMA should be supported by evaluating IL-17 and CD40L, inducing the vasculitis. Methods: An enzyme-linked immunosorbent assay (ELISA) was performed to measure IL-17 and CD40L in serum and CSF from a total of 79 dogs. Measurements of patients suffering from SRMA in the acute state (SRMA A) were compared with levels of patients under treatment with steroids (SRMA T), recurrence of the disease (SRMA R), other neurological disorders, and healthy dogs, using the two-part test. Additionally, secretion of IL-17 and interferon gamma (IFN-gamma) from the peripheral blood mononuclear cells (PBMCs) was confirmed by an enzyme-linked immunospot (ELISpot) assay. Results: Significant higher levels of IL-17 were found in CSF of dogs with SRMA A compared with SRMA T, other neurological disorders and healthy dogs (p < 0.0001). In addition, levels of CD40L in CSF in dogs with SRMA A and SRMA R were significantly higher than in those with SRMA T (p = 0.0004) and healthy controls (p = 0.014). Furthermore, CSF concentrations of IL-17 and CD40L showed a strong positive correlation among each other (rSpear = 0.6601;p < 0.0001) and with the degree of pleocytosis (rSpear = 0.8842;p < 0.0001 and rSpear = 0.6649;p < 0.0001, respectively). IL-17 synthesis from PBMCs in SRMA patients was confirmed;however, IL-17 is mainly intrathecally produced. Conclusions: These results imply that Th17 cells are inducing the autoimmune response in SRMA and are involved in the severe neutrophilic pleocytosis and disruption of the blood-brain barrier (BBB). CD-40L intrathecal synthesis might be involved in the striking vasculitis. The investigation of the role of IL-17 in SRMA might elucidate important pathomechanism and open new therapeutic strategies

Automatic measurement of departing times in smartphone alerting systems: A pilot study

Aim: Smartphone alerting systems (SAS) alert volunteers in close vicinity of suspected out-of-hospital cardiac arrest. Some systems use sophisticated algorithms to select those who will probably arrive first. Precise estimation of departing times and travel times may help to further improve algorithms. We developed a global positioning system (GPS) based method for automatic measurements of departing times. The aim of this pilot study was to evaluate feasibility and precision of the method. Methods: Region of Lifesavers alerting app (iOS/ Android, version 3.0, FirstAED ApS, Denmark) was used in this study. 27 experiments were performed with 9 students, who were instructed to stay in their flats during the study days. A geofence was set for each alarm in the alerting system with a radius of 10 m (8 cases), 15 m (10 cases), and 20 m (9 cases) around the GPS position at which the alarm was accepted in the app. The system logged responders as being departed when the smartphone position was registered outside the geofence. The students were instructed to manually start a stopwatch at the time of the alert and to stop the stopwatch once they had entered the street in front of their flat. Results: The median difference between automatically and manually retrieved times were −16 seconds [interquartile range IQR 50 seconds] (geofence 10 m), 30 seconds [IQR 25 seconds] (15 m), and 20 seconds [IQR 13 seconds] (20 m), respectively. The 20 m geofence was associated with the smallest interquartile range. Conclusion: Departing times of volunteer responders in SAS can be retrieved automatically using GPS and a geofence

Neuropilin-1 modulates vascular endothelial growth factor-induced poly(ADP-ribose)-polymerase leading to reduced cerebrovascular apoptosis

Cerebral ischemia is encompassed by cerebrovascular apoptosis, yet the mechanisms behind apoptosis regulation are not fully understood. We previously demonstrated inhibition of endothelial apoptosis by vascular endothelial growth factor (VEGF) through upregulation of poly(ADP-ribose)-polymerase (PARP) expression. However, PARP overactivation through oxidative stress can lead to necrosis. This study tested the hypothesis that neuropilin-1 (NP-1), an alternative VEGF receptor, regulates the response to cerebral ischemia by modulating PARP expression and, in turn, apoptosis inhibition by VEGF. In endothelial cell culture, NP-1 colocalized with VEGF receptor-2 (VEGFR-2) and acted as its coreceptor. This significantly enhanced VEGF-induced PARP mRNA and protein expression demonstrated by receptor-specific inhibitors and VEGF-A isoforms. NP-1 augmented the inhibitory effect of VEGF/VEGFR-2 interaction on apoptosis induced by adhesion inhibition through the αV-integrin inhibitor cRGDfV. NP-1/VEGFR-2 signal transduction involved JNK and Akt. In rat models of permanent and temporary middle cerebral artery occlusion, the ischemic cerebral hemispheres displayed endothelial and neuronal apoptosis next to increased endothelial NP-1 and VEGFR-2 expression compared to non-ischemic cerebral hemispheres, sham-operated or untreated controls. Increased vascular superoxide dismutase-1 and catalase expression as well as decreased glycogen reserves indicated oxidative stress in the ischemic brain. Of note, protein levels of intact PARP remained stable despite pro-apoptotic conditions through increased PARP mRNA production during cerebral ischemia. In conclusion, NP-1 is upregulated in conditions of imminent cerebrovascular apoptosis to reinforce apoptosis inhibition and modulate VEGF-dependent PARP expression and activation. We propose that NP-1 is a key modulator of VEGF maintaining cerebrovascular integrity during ischemia. Modulating the function of NP-1 to target PARP could help to prevent cellular damage in cerebrovascular disease