Characteristics of meiofauna in extreme marine ecosystems: a review

Extreme marine environments cover more than 50% of the Earth’s surface and offer many opportunities for investigating the biological responses and adaptations of organisms to stressful life conditions. Extreme marine environments are sometimes associated with ephemeral and unstable ecosystems, but can host abundant, often endemic and well-adapted meiofaunal species. In this review, we present an integrated view of the biodiversity, ecology and physiological responses of marine meiofauna inhabiting several extreme marine environments (mangroves, submarine caves, Polar ecosystems, hypersaline areas, hypoxic/anoxic environments, hydrothermal vents, cold seeps, carcasses/sunken woods, deep-sea canyons, deep hypersaline anoxic basins [DHABs] and hadal zones). Foraminiferans, nematodes and copepods are abundant in almost all of these habitats and are dominant in deep-sea ecosystems. The presence and dominance of some other taxa that are normally less common may be typical of certain extreme conditions. Kinorhynchs are particularly well adapted to cold seeps and other environments that experience drastic changes in salinity, rotifers are well represented in polar ecosystems and loriciferans seem to be the only metazoan able to survive multiple stressors in DHABs. As well as natural processes, human activities may generate stressful conditions, including deoxygenation, acidification and rises in temperature. The behaviour and physiology of different meiofaunal taxa, such as some foraminiferans, nematode and copepod species, can provide vital information on how organisms may respond to these challenges and can provide a warning signal of anthropogenic impacts. From an evolutionary perspective, the discovery of new meiofauna taxa from extreme environments very often sheds light on phylogenetic relationships, while understanding how meiofaunal organisms are able to survive or even flourish in these conditions can explain evolutionary pathways. Finally, there are multiple potential economic benefits to be gained from ecological, biological, physiological and evolutionary studies of meiofauna in extreme environments. Despite all the advantages offered by meiofauna studies from extreme environments, there is still an urgent need to foster meiofauna research in terms of composition, ecology, biology and physiology focusing on extreme environments

Poliovirus Induces Bax-Dependent Cell Death Mediated by c-Jun NH2-Terminal Kinase▿

Poliovirus (PV) is the causal agent of paralytic poliomyelitis, a disease that involves the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through an apoptotic process. However, mechanisms by which PV induces cell death in neuronal cells remain unclear. Here, we demonstrate that PV infection of neuronal IMR5 cells induces cytochrome c release from mitochondria and loss of mitochondrial transmembrane potential, both of which are evidence of mitochondrial outer membrane permeabilization. PV infection also activates Bax, a proapoptotic member of the Bcl-2 family; this activation involves its conformational change and its redistribution from the cytosol to mitochondria. Neutralization of Bax by vMIA protein expression prevents cytochrome c release, consistent with a contribution of PV-induced Bax activation to mitochondrial outer membrane permeabilization. Interestingly, we also found that c-Jun NH2-terminal kinase (JNK) is activated soon after PV infection and that the PV-cell receptor interaction alone is sufficient to induce JNK activation. Moreover, the pharmacological inhibition of JNK by SP600125 inhibits Bax activation and cytochrome c release. This is, to our knowledge, the first demonstration of JNK-mediated Bax-dependent apoptosis in PV-infected cells. Our findings contribute to our understanding of poliomyelitis pathogenesis at the cellular level

Impact of fiducial markers placement on the delineation of target volumes in radiation therapy for oesophageal cancer: FIDUCOR study

International audiencePurpose This prospective monocentric phase II study (FIDUCOR-study, NCT02526134) aimed to assess the impact of fiducial markers (FMs) implantation on conformal chemo-radiation therapy (CRT) planning in oesophageal carcinoma (EC) patients. Methods/materials Fifteen EC patients were enrolled in the study. Each patient underwent two simulation CT-scans before (CT1) and after (CT2) FMs implantation, in the same position. FMs (3 mm length gold markers, preloaded in a 22G needle) were implanted after sedation, under endoscopic ultrasound (EUS) and X-Ray guidance, and were placed at the tumor’s extremities, and in the visible lymph nodes. Target delineation and treatment plan were both performed first on CT1 with the assistance of diagnosis CT, gastroscopy and EUS details, and second on CT2 using FMs and CT-data. The value of FMs implantation was assessed by the difference of growth-tumor-volume (GTV) and clinical-target-volume (CTV) between CT1-based and CT2-based delineation. A significant difference was defined as a ≥5 mm-difference on axial(x) or coronal(y) slices, a ≥10mm-difference on sagittal slices, or a ≥20%-difference in GTV. The impact on dose distribution in organs at risk (OAR) (lung, heart, liver) was also studied. Results Between 09/2014 and 12/2015, 15 patients could achieve fiducial procedures, without any complication. One FM migration occurred. We observed a significant modification of the GTV-dimension in 100% of the cases (15/15, 95%CI: [78.2;100.0]), mainly due to a difference in sagittal dimension with a mean variation of 11.2 mm and a difference> 10 mm for 8/15 patients (53.3%). One patient had a significant isocenter displacement as high as 20 mm. The oesophagus tumor was not seen on the CT-scan in one patient due to its small size. One patient had a distant lymph node metastasis not visible on CT-scan. We observed no significant impact on OAR distribution. Conclusion In our study, FMs-implantation under EUS had a positive impact on accurate volume definition in EC-patients (modification of GTV in 15/15 patients). Close cooperation between gastroenterologist and radiation oncologist has the potential to improve local treatment of oesophageal carcinoma

Prognostic Risk Classification for Biochemical Relapse-Free Survival in Oligometastatic Recurrent Prostate Cancer Determined by Choline PET

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Multivariate normal tissue complication probability modeling of vaginal late toxicity after brachytherapy for cervical cancer

International audiencePURPOSE:To explore the best variables combination for a predictive model of vaginal toxicity in cervical cancer patients undergoing brachytherapy (BT).METHODS AND MATERIALS:Clinical and 3-dimensional dosimetric parameters were retrospectively extracted from an institutional database of consecutive patients undergoing intracavitary BT after external beam radiation therapy from 2006 to 2013 for a cervical cancer. A least absolute shrinkage and selection operator selection procedure in Cox's proportional hazards regression model was performed to select a set of relevant predictors for a multivariate normal tissue complication probability model of Grade ≥2 vaginal late toxicity. Outcomes reliability was internally assessed by bootstrap resampling method.RESULTS:One hundred sixty-nine women were included in the present study with a median followup time of 3.8 years (interquartile range [IQR], 1.9-5.6 years). The 2 years and 5 years cumulative incidence rates of Grade ≥2 late vaginal toxicity were 19.9% and 27.5%, respectively. Among 31 metrics and six clinical factors extracted, the optimal model included two dosimetric variables: V70Gy and D5% (the percentage volume that received a dose greater or equal to 70 Gy and the minimum dose given to the hottest 5% volume, respectively). Area under the ROC curve at 2 and 5 years of followup were 0.85 and 0.91, respectively. Regarding internal validation, median area under the ROC curve of bootstrap predictions was 0.83 (IQR, 0.78-0.88) and 0.89 (IQR, 0.85-0.93) at 2 and 5 years of followup, respectively.CONCLUSIONS:A multivariate normal tissue complication probability model for severe vaginal toxicity based on two dosimetric variables (V70Gy and D5%) provides reliable discrimination capability in a cohort of cervical cancer treated with external beam radiation therapy and BT

Incidence, clinical characteristics, and outcome after unexpected cardiac arrest among critically ill adults with COVID-19: insight from the multicenter prospective ACICOVID-19 registry

International audienceAbstract Background Initial reports have described the poor outcome of unexpected cardiac arrest (CA) in intensive care unit (ICU) among COVID-19 patients in China and the USA. However, there are scarce data on characteristics and outcomes of such CA patients in Europe. Methods Prospective registry in 35 French ICUs, including all in-ICU CA in COVID-19 adult patients with cardiopulmonary resuscitation (CPR) attempt. Favorable outcome was defined as modified Rankin scale ranging from 0 to 3 at day 90 after CA. Results Among the 2425 COVID-19 patients admitted to ICU from March to June 2020, 186 (8%) experienced in-ICU CA, of whom 146/186 (78%) received CPR. Among these 146 patients, 117 (80%) had sustained return of spontaneous circulation, 102 (70%) died in the ICU, including 48 dying within the first day after CA occurrence and 21 after withdrawal of life-sustaining therapy. Most of CA were non-shockable rhythm (90%). At CA occurrence, 132 patients (90%) were mechanically ventilated, 83 (57%) received vasopressors and 75 (51%) had almost three organ failures. Thirty patients (21%) had a favorable outcome. Sepsis-related organ failure assessment score > 9 before CA occurrence was the single parameter constantly associated with unfavorable outcome in multivariate analysis. Conclusions In-ICU CA incidence remains high among a large multicenter cohort of French critically ill adults with COVID-19. However, 21% of patients with CPR attempt remained alive at 3 months with good functional status. This contrasts with other recent reports showing poor outcome in such patients. Trial registration : This study was retrospectively registered in ClinicalTrials.gov (NTC04373759) in April 2020 ( https://www.clinicaltrials.gov/ct2/show/NCT04373759?term=acicovid&draw=2&rank=1 )

PIKHER2: A phase IB study evaluating buparlisib in combination with lapatinib in trastuzumab-resistant HER2-positive advanced breast cancer

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