A primary consequence of plate tectonics is that basaltic oceanic crust subducts with lithospheric slabs into the mantle. Seismological studies extend this process to the lower mantle, and ...geochemical observations indicate return of oceanic crust to the upper mantle in plumes. There has been no direct petrologic evidence, however, of the return of subducted oceanic crustal components from the lower mantle. We analyzed superdeep diamonds from Juina-5 kimberlite, Brazil, which host inclusions with compositions comprising the entire phase assemblage expected to crystallize from basalt under lower-mantle conditions. The inclusion mineralogies require exhumation from the lower to upper mantle. Because the diamond hosts have carbon isotope signatures consistent with surface-derived carbon, we conclude that the deep carbon cycle extends into the lower mantle.
In vivo optical imaging shows that a fluorescent imaging probe, comprised of a near-infrared fluorophore attached to an affinity group containing two zinc(II)-dipicolylamine (Zn-DPA) units, targets ...prostate and mammary tumors in two different xenograft animal models. The tumor selectivity is absent with control fluorophores whose structures do not have appended Zn-DPA targeting ligands. Ex vivo biodistribution and histological analyses indicate that the probe is targeting the necrotic regions of the tumors, which is consistent with in vitro microscopy showing selective targeting of the anionic membrane surfaces of dead and dying cells.
Mitochondrial permeability transition is a phenomenon in which the mitochondrial permeability transition pore (PTP) abruptly opens, resulting in mitochondrial membrane potential (ΔΨm) dissipation, ...loss of ATP production, and cell death. Several genetic candidates have been proposed to form the PTP complex, however, the core component is unknown. We identified a necessary and conserved role for spastic paraplegia 7 (SPG7) in Ca2+- and ROS-induced PTP opening using RNAi-based screening. Loss of SPG7 resulted in higher mitochondrial Ca2+ retention, similar to cyclophilin D (CypD, PPIF) knockdown with sustained ΔΨm during both Ca2+ and ROS stress. Biochemical analyses revealed that the PTP is a heterooligomeric complex composed of VDAC, SPG7, and CypD. Silencing or disruption of SPG7-CypD binding prevented Ca2+- and ROS-induced ΔΨm depolarization and cell death. This study identifies an ubiquitously expressed IMM integral protein, SPG7, as a core component of the PTP at the OMM and IMM contact site.
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•Mitochondrial SPG7 is essential for the PTP complex formation in multiple cell types•SPG7 interacts with CypD and VDAC at the IMM and OMM contact site•C terminus of SPG7 and CsA-binding region of CypD are necessary for PTP formation•Loss of SPG7 protects mitochondria from Ca2+- and ROS-induced PTP-dependent necrosis
Using an RNAi-based screen, Shanmughapriya et al. identify mitochondrial spastic paraplegia 7 as essential for the PTP complex formation. They show that SPG7 interacts with CypD and VDAC1 at the IMM and OMM contact site, and loss of SPG7 protects mitochondria from Ca2+- and ROS-induced PTP-dependent necrosis.
Limited data exist regarding the natural history of proximal intracranial arterial occlusions. OBJECTIVE To investigate the outcomes of patients who had an acute ischemic stroke attributed to an ...anterior circulation proximal intracranial arterial occlusion.
A prospective cohort study at 2 university-based hospitals from 2003 to 2005 in which nonenhanced computed tomography scans and computed tomography angiograms were obtained at admission of all adult patients suspected of having an ischemic stroke in the first 24 hours of symptom onset.
Anterior circulation proximal intracranial arterial occlusion.
Frequency of good outcome (defined as a modified Rankin Scale score of ≤ 2) and mortality at 6 months.
A total of 126 patients with a unilateral complete occlusion of the intracranial internal carotid artery (ICA; 26 patients: median National Institutes of Health Stroke Scale NIHSS score, 11 interquartile range, 5-17), of the M1 segment of the middle cerebral artery (MCA; 52 patients: median NIHSS score, 13 interquartile range, 6-16), or of the M2 segment of the MCA (48 patients: median NIHSS score, 7 interquartile range, 4-15) were included. Of these 3 groups of patients, 10 (38.5%), 20 (38.5%), and 26 (54.2%) with ICA, MCA-M1, and MCA-M2 occlusions, respectively, achieved a modified Rankin Scale score of 2 or less, and 6 (23.1%), 12 (23.1%), and 10 (20.8%) were dead at 6 months. Worse outcomes were seen in patients with a baseline NIHSS score of 10 or higher, with a modified Rankin Scale score of 2 or less achieved in only 7.1% (1 of 14), 23.5% (8 of 34), and 22.7% (5 of 22) of patients and mortality rates of 35.7% (5 of 14), 32.4% (11 of 34), and 40.9% (9 of 22) among patients with ICA, MCA-M1, and MCA-M2 occlusions, respectively. Age (odds ratio, 0.94 95% CI, 0.91-0.98), NIHSS score (odds ratio, 0.73 95% CI, 0.64-0.83), and strength of leptomeningeal collaterals (odds ratio, 2.37 95% CI, 1.08-5.20) were independently associated with outcome, whereas the level of proximal intracranial arterial occlusion (ICA vs MCA-M1 vs MCA-M2) was not.
The natural history of proximal intracranial arterial occlusion is variable, with poor outcomes overall. Stroke severity and collateral flow appear to be more important than the level of proximal intracranial arterial occlusion in determining outcomes. Our results provide useful data for proper patient selection and sample size calculations in the design of new clinical trials aimed at recanalization therapies.
Despite the abundance of emerging multimodal imaging techniques in the field of stroke, there is a paucity of data demonstrating a strong correlation between imaging findings and clinical outcome. ...This study explored how proximal arterial occlusions alter flow in collateral vessels and whether occlusion or extent of collaterals correlates with prehospital symptoms of fluctuation and worsening since onset or predict in-hospital worsening.
Among 741 patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke, 134 cases with proximal middle cerebral artery occlusion and 235 control subjects with no occlusions were identified. CT angiography was used to identify occlusions and grade the extent of collateral vessels in the sylvian fissure and leptomeningeal convexity. History of symptom fluctuation or progressive worsening was obtained on admission.
Prehospital symptoms were unrelated to occlusion or collateral status. In cases, 37.5% imaged within 1 hour were found to have diminished collaterals versus 12.1% imaged at 12 to 24 hours (P=0.047). No difference in worsening was seen between cases and control subjects with adequate collaterals, but cases with diminished sylvian and leptomeningeal collaterals experienced greater risk of worsening compared with control subjects measured either by admission to discharge National Institutes of Health Stroke Scale increase > or =1 (55.6% versus 16.6%, P=0.001) or > or =4 (44.4% versus 6.4%, P<0.001).
Most patients with proximal middle cerebral artery occlusion rapidly recruit sufficient collaterals and follow a clinical course similar to patients with no occlusions, but a subset with diminished collaterals is at high risk for worsening.
Acute ischemic stroke due to large vessel occlusion (LVO)-vertebral, basilar, carotid terminus, middle and anterior cerebral arteries-likely portends a worse prognosis than stroke unassociated with ...LVO. Because little prospective angiographic data have been reported on a cohort of unselected patients with stroke and with transient ischemic attack, the clinical impact of LVO has been difficult to quantify.
The Screening Technology and Outcome Project in Stroke Study is a prospective imaging-based study of stroke outcomes performed at 2 academic medical centers. Patients with suspected acute stroke who presented within 24 hours of symptom onset and who underwent multimodality CT/CT angiography were approached for consent for collection of clinical data and 6-month assessment of outcome. Demographic and clinical variables and 6-month modified Rankin Scale scores were collected and combined with blinded interpretation of the CT angiography data. The OR of each variable, including occlusion of intracranial vascular segment in predicting good outcome and 6-month mortality, was calculated using univariate and multivariate logistic regression.
Over a 33-month period, 735 patients with suspected stroke were enrolled. Of these, 578 were adjudicated as stroke and 97 as transient ischemic attack. Among patients with stroke, 267 (46%) had LVO accounting for the stroke and 13 (13%) of patients with transient ischemic attack had LVO accounting for transient ischemic attack symptoms. LVO predicted 6-month mortality (OR, 4.5; 95% CI, 2.7 to 7.3; P<0.001). Six-month good outcome (modified Rankin Scale score <or=2) was negatively predicted by LVO (0.33; 0.24 to 0.45; P<0.001). Based on multivariate analysis, the presence of basilar and internal carotid terminus occlusions, in addition to National Institutes of Health Stroke Scale and age, independently predicted outcome.
Large vessel intracranial occlusion accounted for nearly half of acute ischemic strokes in unselected patients presenting to academic medical centers. In addition to age and baseline stroke severity, occlusion of either the basilar or internal carotid terminus segment is an independent predictor of outcome at 6 months.
Regular, evidence‐based assignment of patients to etiologic stroke categories is essential to enable valid comparison among studies. We designed an algorithm (SSS‐TOAST) that incorporated recent ...advances in stroke imaging and epidemiology to identify the most probable TOAST category in the presence of evidence for multiple mechanisms. Based on the weight of evidence, each TOAST subtype was subdivided into 3 subcategories as “evident”, “probable”, or “possible”. Classification into the subcategories was determined via predefined specific clinical and imaging criteria. These criteria included published risks of ischemic stroke from various mechanisms and published reports of the strength of associations between clinical and imaging features and particular stroke mechanisms. Two neurologists independently assessed 50 consecutively admitted patients with acute ischemic stroke through reviews of ed data from medical records. The number of patients classified as “undetermined‐unclassified” per the original TOAST system decreased from 38–40% to 4% using the SSS‐TOAST system. The kappa value for interexaminer reliability was 0.78 and 0.90 for the original TOAST and SSS‐TOAST respectively. The SSS‐TOAST system successfully classifies patients with acute ischemic stroke into determined etiologic categories without sacrificing reliabilty. The SSS‐TOAST is a dynamic algorithm that can accommodate modifications as new epidemiological data accumulate and diagnostic techniques advance. Ann Neurol 2005;58:688–697
Forty-one diamonds sourced from the Juina-5 kimberlite pipe in Southern Brazil, which contain optically identifiable inclusions, have been studied using an integrated approach. The diamonds contain ...<20 ppm nitrogen (N) that is fully aggregated as B centres. Internal structures in several diamonds revealed using cathodoluminescence (CL) are unlike those normally observed in lithospheric samples. The majority of the diamonds are composed of isotopically light carbon, and the collection has a unimodal distribution heavily skewed towards δ
13
C ~ −25 ‰. Individual diamonds can display large carbon isotope heterogeneity of up to ~15 ‰ and predominantly have isotopically lighter cores displaying blue CL, and heavier rims with green CL. The light carbon isotopic compositions are interpreted as evidence of diamond growth from abiotic organic carbon added to the oceanic crust during hydrothermal alteration. The bulk isotopic composition of the oceanic crust, carbonates plus organics, is equal to the composition of mantle carbon (−5 ‰), and we suggest that recycling/mixing of subducted material will replenish this reservoir over geological time. Several exposed, syngenetic inclusions have bulk compositions consistent with former eclogitic magnesium silicate perovskite, calcium silicate perovskite and NAL or CF phases that have re-equilibrated during their exhumation to the surface. There are multiple occurrences of majoritic garnet with pyroxene exsolution, coesite with and without kyanite exsolution, clinopyroxene, Fe or Fe-carbide and sulphide minerals alongside single occurrences of olivine and ferropericlase. As a group, the inclusions have eclogitic affinity and provide evidence for diamond formation at pressures extending to Earth’s deep transition zone and possibly the lower mantle. It is observed that the major element composition of inclusions and isotopic compositions of host Juina-5 diamonds are not correlated. The diamond and inclusion compositions are intimately related to subducted material and record a polybaric growth history across a depth interval stretching from the lower mantle to the base of the lithosphere. It is suggested that the interaction of slab-derived melts and mantle material combined with subsequent upward transport in channelised networks or a buoyant diapir explains the formation of Juina-5 diamonds. We conclude that these samples, despite originating at great mantle depths, do not provide direct information about the ambient mantle, instead, providing a snapshot of the Earth’s deep carbon cycle.
Patients with large vessel occlusion strokes (LVOS) may be better served by direct transfer to endovascular capable centers avoiding hazardous delays between primary and comprehensive stroke centers. ...However, accurate stroke field triage remains challenging. We aimed to develop a simple field scale to identify LVOS.
The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale was based on items of the National Institutes of Health Stroke Scale (NIHSS) with higher predictive value for LVOS and tested in the Screening Technology and Outcomes Project in Stroke (STOPStroke) cohort, in which patients underwent computed tomographic angiography within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the intracranial internal carotid artery, middle cerebral artery-M1, middle cerebral artery-2, or basilar arteries. Patients with partial, bihemispheric, and anterior+posterior circulation occlusions were excluded. Receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value of FAST-ED were compared with the NIHSS, Rapid Arterial Occlusion Evaluation (RACE) scale, and Cincinnati Prehospital Stroke Severity (CPSS) scale.
LVO was detected in 240 of the 727 qualifying patients (33%). FAST-ED had comparable accuracy to predict LVO to the NIHSS and higher accuracy than RACE and CPSS (area under the receiver operating characteristic curve: FAST-ED=0.81 as reference; NIHSS=0.80, P=0.28; RACE=0.77, P=0.02; and CPSS=0.75, P=0.002). A FAST-ED ≥4 had sensitivity of 0.60, specificity of 0.89, positive predictive value of 0.72, and negative predictive value of 0.82 versus RACE ≥5 of 0.55, 0.87, 0.68, and 0.79, and CPSS ≥2 of 0.56, 0.85, 0.65, and 0.78, respectively.
FAST-ED is a simple scale that if successfully validated in the field, it may be used by medical emergency professionals to identify LVOS in the prehospital setting enabling rapid triage of patients.
Partial melting in the Earth's mantle plays an important part in generating the geochemical and isotopic diversity observed in volcanic rocks at the surface. Identifying the composition of these ...primary melts in the mantle is crucial for establishing links between mantle geochemical 'reservoirs' and fundamental geodynamic processes. Mineral inclusions in natural diamonds have provided a unique window into such deep mantle processes. Here we provide experimental and geochemical evidence that silicate mineral inclusions in diamonds from Juina, Brazil, crystallized from primary and evolved carbonatite melts in the mantle transition zone and deep upper mantle. The incompatible trace element abundances calculated for a melt coexisting with a calcium-titanium-silicate perovskite inclusion indicate deep melting of carbonated oceanic crust, probably at transition-zone depths. Further to perovskite, calcic-majorite garnet inclusions record crystallization in the deep upper mantle from an evolved melt that closely resembles estimates of primitive carbonatite on the basis of volcanic rocks. Small-degree melts of subducted crust can be viewed as agents of chemical mass-transfer in the upper mantle and transition zone, leaving a chemical imprint of ocean crust that can possibly endure for billions of years.
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