Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Pratos e mais pratos: louças domésticas, divisões culturais e limites sociais no Rio de Janeiro, século XIX

Reply to ten comments on a paper published in the last issue of this journal. The discussion follows along six main lines: History museums, identity, ideology and the category of nation; the need of material collections and their modalities: patrimonial, operational, virtual; theater versus laboratory; visitors and their ambiguities; Public History: the museum and the academy.Resposta aos comentários de dez especialistas que contribuíram no debate de texto publicado no último número desta revista. A discussão orientou-se segundo seis tópicos principais: museus históricos, identidade, ideologia e a categoria de nação; a necessidade de acervos materiais e suas modalidades: acervo patrimonial, operacional, virtual; teatro versus laboratório; o público e suas ambigüidades; História Pública: o museu e a Academia

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Reperfusion and Clinical Outcomes in Acute Ischemic Stroke: Systematic Review and Meta-Analysis of the Stent-Retriever-Based, Early Window Endovascular Stroke Trials

Objective: To explore the effects of reperfusion grade rates on clinical outcomes in the setting of stent-retriever-based reperfusion therapy for anterior circulation stroke in early time windows. Methods: Systematic searching of Medline and Embase databases was performed to identify stroke trials of stent-retriever-based therapy versus standard care. Mixed effects meta-regression was used to analyze the trial-level association between reperfusion rates and clinical outcomes. Results: A total of five trials met the inclusion criteria (n = 1,287). Rates of successful reperfusion [modified thrombolysis in cerebral ischemia grade 2b/3] demonstrated strong evidence for an association with good functional outcomes [modified Rankin scale score (mRS) 0-2] OR 1.59 (95% CI 1.16, 2.19) p = 0.019 and very strong evidence for an association with excellent functional outcomes (mRS 0-1) OR 2.10 (95% CI 1.46, 3.01) p = 0.007. In addition, there was weak evidence for an association with symptomatic intracranial hemorrhage OR 0.54 (95% CI 0.28, 1.04) p = 0.057 and mortality OR 0.69 (95% CI 0.69, 1.01) p = 0.053. Conclusion: In early, stent-retriever-based acute ischemic stroke treatment, reperfusion appears to be a major predictor of outcomes. Every 10% increase in the rates of successful reperfusion is associated with an 11% increase in the probability of achieving good and 17% increase in the probability of achieving excellent outcomes. Symptomatic intracranial hemorrhage and mortality may be decreased as reperfusion rates are improved

data_sheet_3_Reperfusion and Clinical Outcomes in Acute Ischemic Stroke: Systematic Review and Meta-Analysis of the Stent-Retriever-Based, Early Window Endovascular Stroke Trials.DOC

Objective<p>To explore the effects of reperfusion grade rates on clinical outcomes in the setting of stent-retriever-based reperfusion therapy for anterior circulation stroke in early time windows.</p>Methods<p>Systematic searching of Medline and Embase databases was performed to identify stroke trials of stent-retriever-based therapy versus standard care. Mixed effects meta-regression was used to analyze the trial-level association between reperfusion rates and clinical outcomes.</p>Results<p>A total of five trials met the inclusion criteria (n = 1,287). Rates of successful reperfusion [modified thrombolysis in cerebral ischemia grade 2b/3] demonstrated strong evidence for an association with good functional outcomes [modified Rankin scale score (mRS) 0–2] OR 1.59 (95% CI 1.16, 2.19) p = 0.019 and very strong evidence for an association with excellent functional outcomes (mRS 0–1) OR 2.10 (95% CI 1.46, 3.01) p = 0.007. In addition, there was weak evidence for an association with symptomatic intracranial hemorrhage OR 0.54 (95% CI 0.28, 1.04) p = 0.057 and mortality OR 0.69 (95% CI 0.69, 1.01) p = 0.053.</p>Conclusion<p>In early, stent-retriever-based acute ischemic stroke treatment, reperfusion appears to be a major predictor of outcomes. Every 10% increase in the rates of successful reperfusion is associated with an 11% increase in the probability of achieving good and 17% increase in the probability of achieving excellent outcomes. Symptomatic intracranial hemorrhage and mortality may be decreased as reperfusion rates are improved.</p

data_sheet_1_Reperfusion and Clinical Outcomes in Acute Ischemic Stroke: Systematic Review and Meta-Analysis of the Stent-Retriever-Based, Early Window Endovascular Stroke Trials.DOCX

Objective<p>To explore the effects of reperfusion grade rates on clinical outcomes in the setting of stent-retriever-based reperfusion therapy for anterior circulation stroke in early time windows.</p>Methods<p>Systematic searching of Medline and Embase databases was performed to identify stroke trials of stent-retriever-based therapy versus standard care. Mixed effects meta-regression was used to analyze the trial-level association between reperfusion rates and clinical outcomes.</p>Results<p>A total of five trials met the inclusion criteria (n = 1,287). Rates of successful reperfusion [modified thrombolysis in cerebral ischemia grade 2b/3] demonstrated strong evidence for an association with good functional outcomes [modified Rankin scale score (mRS) 0–2] OR 1.59 (95% CI 1.16, 2.19) p = 0.019 and very strong evidence for an association with excellent functional outcomes (mRS 0–1) OR 2.10 (95% CI 1.46, 3.01) p = 0.007. In addition, there was weak evidence for an association with symptomatic intracranial hemorrhage OR 0.54 (95% CI 0.28, 1.04) p = 0.057 and mortality OR 0.69 (95% CI 0.69, 1.01) p = 0.053.</p>Conclusion<p>In early, stent-retriever-based acute ischemic stroke treatment, reperfusion appears to be a major predictor of outcomes. Every 10% increase in the rates of successful reperfusion is associated with an 11% increase in the probability of achieving good and 17% increase in the probability of achieving excellent outcomes. Symptomatic intracranial hemorrhage and mortality may be decreased as reperfusion rates are improved.</p

data_sheet_2_Reperfusion and Clinical Outcomes in Acute Ischemic Stroke: Systematic Review and Meta-Analysis of the Stent-Retriever-Based, Early Window Endovascular Stroke Trials.DOC

Objective<p>To explore the effects of reperfusion grade rates on clinical outcomes in the setting of stent-retriever-based reperfusion therapy for anterior circulation stroke in early time windows.</p>Methods<p>Systematic searching of Medline and Embase databases was performed to identify stroke trials of stent-retriever-based therapy versus standard care. Mixed effects meta-regression was used to analyze the trial-level association between reperfusion rates and clinical outcomes.</p>Results<p>A total of five trials met the inclusion criteria (n = 1,287). Rates of successful reperfusion [modified thrombolysis in cerebral ischemia grade 2b/3] demonstrated strong evidence for an association with good functional outcomes [modified Rankin scale score (mRS) 0–2] OR 1.59 (95% CI 1.16, 2.19) p = 0.019 and very strong evidence for an association with excellent functional outcomes (mRS 0–1) OR 2.10 (95% CI 1.46, 3.01) p = 0.007. In addition, there was weak evidence for an association with symptomatic intracranial hemorrhage OR 0.54 (95% CI 0.28, 1.04) p = 0.057 and mortality OR 0.69 (95% CI 0.69, 1.01) p = 0.053.</p>Conclusion<p>In early, stent-retriever-based acute ischemic stroke treatment, reperfusion appears to be a major predictor of outcomes. Every 10% increase in the rates of successful reperfusion is associated with an 11% increase in the probability of achieving good and 17% increase in the probability of achieving excellent outcomes. Symptomatic intracranial hemorrhage and mortality may be decreased as reperfusion rates are improved.</p

Reperfusion and Clinical Outcomes in Acute Ischemic Stroke: Systematic Review and Meta-Analysis of the Stent-Retriever-Based, Early Window Endovascular Stroke Trials

ObjectiveTo explore the effects of reperfusion grade rates on clinical outcomes in the setting of stent-retriever-based reperfusion therapy for anterior circulation stroke in early time windows.MethodsSystematic searching of Medline and Embase databases was performed to identify stroke trials of stent-retriever-based therapy versus standard care. Mixed effects meta-regression was used to analyze the trial-level association between reperfusion rates and clinical outcomes.ResultsA total of five trials met the inclusion criteria (n = 1,287). Rates of successful reperfusion [modified thrombolysis in cerebral ischemia grade 2b/3] demonstrated strong evidence for an association with good functional outcomes [modified Rankin scale score (mRS) 0–2] OR 1.59 (95% CI 1.16, 2.19) p = 0.019 and very strong evidence for an association with excellent functional outcomes (mRS 0–1) OR 2.10 (95% CI 1.46, 3.01) p = 0.007. In addition, there was weak evidence for an association with symptomatic intracranial hemorrhage OR 0.54 (95% CI 0.28, 1.04) p = 0.057 and mortality OR 0.69 (95% CI 0.69, 1.01) p = 0.053.ConclusionIn early, stent-retriever-based acute ischemic stroke treatment, reperfusion appears to be a major predictor of outcomes. Every 10% increase in the rates of successful reperfusion is associated with an 11% increase in the probability of achieving good and 17% increase in the probability of achieving excellent outcomes. Symptomatic intracranial hemorrhage and mortality may be decreased as reperfusion rates are improved

HFE p.C282Y homozygosity predisposes to rapid serum ferritin rise after menopause: A genotype‐stratified cohort study of hemochromatosis in Australian women

Background and aimWomen who are homozygous for the p.C282Y mutation in the HFE gene are at much lower risk of iron overload-related disease than p.C282Y homozygous men, presumably because of the iron-depleting effects of menstruation and pregnancy. We used data from a population cohort study to model the impact of menstruation cessation at menopause on serum ferritin (SF) levels in female p.C282Y homozygotes, with p.C282Y/p.H63D simple or compound heterozygotes and those with neither p.C282Y nor p.H63D mutations (HFE wild types) as comparison groups.MethodsA sample of the Melbourne Collaborative Cohort Study was selected for the "HealthIron" study (n&nbsp;=&nbsp;1438) including all HFE p.C282Y homozygotes plus a random sample stratified by HFE-genotype (p.C282Y and p.H63D). The relationship between the natural logarithm of SF and time since menopause was examined using linear mixed models incorporating spline smoothing.ResultsFor p.C282Y homozygotes, SF increased by a factor of 3.6 (95% CI (1.8, 7.0), P&nbsp;&lt;&nbsp;0.001) during the first 10&nbsp;years postmenopause, after which SF continued to increase but at less than half the previous rate. In contrast, SF profiles for other HFE genotype groups increase more gradually and did not show a distinction between premenopausal and postmenopausal SF levels. Only p.C282Y homozygotes had predicted SF exceeding 200&nbsp;μg/L postmenopause, but the projected SF did not increase the risk of iron overload-related disease.ConclusionsThese data provide the first documented evidence that physiological blood loss is a major factor in determining the marked gender difference in expression of p.C282Y homozygosity