Evaluation of lockdown effect on SARS-CoV-2 dynamics through viral genome quantification in waste water,Greater Paris,France, 5 March to 23 April 2020

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease (COVID-19). People infected with SARS-CoV-2 may exhibit no or mild non-specific symptoms; thus, they may contribute to silent circulation of the virus among humans. Since SARS-CoV-2 RNA can be detected in stool samples, monitoring SARS-CoV-2 RNA in waste water (WW) has been proposed as a complementary tool to investigate virus circulation in human populations.AimTo test if the quantification of SARS-CoV-2 genomes in WW correlates with the number of symptomatic or non-symptomatic carriers.MethodWe performed a time-course quantitative analysis of SARS-CoV-2 by RT-qPCR in raw WW samples collected from several major WW treatment plants in Greater Paris. The study period was 5 March to 23 April 2020, including the lockdown period in France (from 17 March).ResultsWe showed that the increase of genome units in raw WW accurately followed the increase of human COVID-19 cases observed at the regional level. Of note, the viral genome could be detected before the epidemic grew massively (around 8 March). Equally importantly, a marked decrease in the quantities of genome units was observed concomitantly with the reduction in the number of new COVID-19 cases, 29 days following the lockdown.ConclusionThis work suggests that a quantitative monitoring of SARS-CoV-2 genomes in WW could generate important additional information for improved monitoring of SARS-CoV-2 circulation at local or regional levels and emphasises the role of WW-based epidemiology.     

The Sequential Relation Between Changes in Catastrophizing and Changes in Posttraumatic Stress Disorder Symptom Severity

Catastrophizing has been discussed as a cognitive precursor to the emergence of posttraumatic stress disorder (PTSD) symptoms following the experience of stressful events. Implicit in cognitive models of PTSD is that treatment-related reductions in catastrophizing should yield reductions in PTSD symptoms. The tenability of this prediction has yet to be tested. The present study investigated the sequential relation between changes in a specific form of catastrophizing—symptom catastrophizing—and changes in PTSD symptom severity in a sample of 73 work-disabled individuals enrolled in a 10-week behavioral activation intervention. Measures of symptom catastrophizing and PTSD symptom severity were completed at pre-, mid-, and posttreatment assessment points. Cross-sectional analyses of pretreatment data revealed that symptom catastrophizing accounted for significant variance in PTSD symptom severity, β = .40, p < .001, sr = .28 (medium effect size), even when controlling for known correlates of symptom catastrophizing, such as pain and depression. Significant reductions in symptom catastrophizing and PTSD symptoms were observed during treatment, with large effect sizes, ds = 1.42 and 0.94, respectively, ps < .001. Cross-lagged analyses revealed that early change in symptom catastrophizing predicted later change in PTSD symptoms; early changes in PTSD symptom severity did not predict later change in symptom catastrophizing. These findings are consistent with the conceptual models that posit a causal relation between catastrophizing and PTSD symptom severity. The clinical implications of the findings are discussed.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody

Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.