58 research outputs found
SDF1 in the dorsal corticospinal tract promotes CXCR4+ cell migration after spinal cord injury
<p>Abstract</p> <p>Background</p> <p>Stromal cell-derived factor-1 (SDF1) and its major signaling receptor, CXCR4, were initially described in the immune system; however, they are also expressed in the nervous system, including the spinal cord. After spinal cord injury, the blood brain barrier is compromised, opening the way for chemokine signaling between these two systems. These experiments clarified prior contradictory findings on normal expression of SDF1 and CXCR4 as well as examined the resulting spinal cord responses resulting from this signaling.</p> <p>Methods</p> <p>These experiments examined the expression and function of SDF1 and CXCR4 in the normal and injured adult mouse spinal cord primarily using CXCR4-EGFP and SDF1-EGFP transgenic reporter mice.</p> <p>Results</p> <p>In the uninjured spinal cord, SDF1 was expressed in the dorsal corticospinal tract (dCST) as well as the meninges, whereas CXCR4 was found only in ependymal cells surrounding the central canal. After spinal cord injury (SCI), the pattern of SDF1 expression did not change rostral to the lesion but it disappeared from the degenerating dCST caudally. By contrast, CXCR4 expression changed dramatically after SCI. In addition to the CXCR4+ cells in the ependymal layer, numerous CXCR4+ cells appeared in the peripheral white matter and in the dorsal white matter localized between the dorsal corticospinal tract and the gray matter rostral to the lesion site. The non-ependymal CXCR4+ cells were found to be NG2+ and CD11b+ macrophages that presumably infiltrated through the broken blood-brain barrier. One population of macrophages appeared to be migrating towards the dCST that contains SDF1 rostral to the injury but not towards the caudal dCST in which SDF1 is no longer present. A second population of the CXCR4+ macrophages was present near the SDF1-expressing meningeal cells.</p> <p>Conclusions</p> <p>These observations suggest that attraction of CXCR4+ macrophages is part of a programmed response to injury and that modulation of the SDF1 signaling system may be important for regulating the inflammatory response after SCI.</p
Medical student changes in self-regulated learning during the transition to the clinical environment
Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study
Background
The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility.
Methods
We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates.
Findings
From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36â920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0¡7% [95% CI 0¡6â0¡8]) of 36â509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0¡56â0¡69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0¡38â0¡56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1¡35 (95% CI 1¡02â1¡69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant.
Interpretation
The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant.
Funding
Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society
Recommended from our members
Incidence of thrombus formation on the CardioSEAL and the Amplatzer interatrial closure devices.
Transcatheter closure for atrial septal defect (ASD) and patent foramen ovale (PFO) is a promising alternative to surgical closure or anticoagulant therapy. A potential complication is thrombus formation on the device after implantation. From February 2001 to June 2003, 66 patients with atrial communication were treated successfully with the Amplatzer device (16 septal and 20 PFO occluders) or the CardioSEAL device (30). Patients were discharged on antiplatelet medication (aspirin and clopidogrel) and/or anticoagulation. Fifty patients (76%) had transesophageal echocardiography (TEE) 1 month after device implantation (28 +/- 10 days). No patient experienced a thromboembolic episode during follow-up. TEE revealed that thrombus formation occurred more frequently on the CardioSEAL device (5 of 23 patients; 22%) than on the Amplatzer device (0 of 27 patients; 0%) (p = 0.02). Although thrombus disappeared or markedly diminished after additional anticoagulation therapy in 3 patients, 1 patient had surgical explantation of the device due to progressive increase in the size of thrombus with hypermobility despite intensive anticoagulation therapy. There was no variable associated with the presence of thrombus formation on the occluder other than the use of the CardioSEAL device. One month after insertion, the CardioSEAL device is more likely to have thrombus present than the Amplatzer device
Recommended from our members
Incidence of thrombus formation on the CardioSEAL and the Amplatzer interatrial closure devices.
Transcatheter closure for atrial septal defect (ASD) and patent foramen ovale (PFO) is a promising alternative to surgical closure or anticoagulant therapy. A potential complication is thrombus formation on the device after implantation. From February 2001 to June 2003, 66 patients with atrial communication were treated successfully with the Amplatzer device (16 septal and 20 PFO occluders) or the CardioSEAL device (30). Patients were discharged on antiplatelet medication (aspirin and clopidogrel) and/or anticoagulation. Fifty patients (76%) had transesophageal echocardiography (TEE) 1 month after device implantation (28 +/- 10 days). No patient experienced a thromboembolic episode during follow-up. TEE revealed that thrombus formation occurred more frequently on the CardioSEAL device (5 of 23 patients; 22%) than on the Amplatzer device (0 of 27 patients; 0%) (p = 0.02). Although thrombus disappeared or markedly diminished after additional anticoagulation therapy in 3 patients, 1 patient had surgical explantation of the device due to progressive increase in the size of thrombus with hypermobility despite intensive anticoagulation therapy. There was no variable associated with the presence of thrombus formation on the occluder other than the use of the CardioSEAL device. One month after insertion, the CardioSEAL device is more likely to have thrombus present than the Amplatzer device
- âŚ