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River infrastructures such as weirs, hydropower stations or water reservoirs represent obstructions to migration for diadromous fish. Knowledge of accurate behaviour of fish in front of such structures is required to protect migrants from hazardous areas, guide them towards safe passage or adapt structure to improve the escapement. We developed and made available a method to process acoustic telemetry data based on Time Difference Of Arrival analysis to accurately locate tagged fish. Improved accuracy allows the detection of escape routes and description of dam‐crossing tactics. Sixteen tagged eels were tracked with high accuracy (1–2 m) and ~1 location min−1 frequency during their exploration period on reaching the dam. Two migration routes (spillways and bottom compensation flow pipe) were used by 77% and 23% of eels respectively. Spillways were the preferred route, but a median of 16 days were required to pass the dam versus 1.1 days via the compensation pipe. A minimal water crest of 40 cm was required for passage via spillways. Eels passing through the compensation pipe were exclusively nocturnal and mainly explored the bottom of the dam. Eels passing through spillways explored the whole dam area by night and day, and were not attracted to the compensation pipe entrance. With global warming, more frequent drought periods are expected, potentially leading to decreased opportunities for eels to migrate across safer dams by spillways. To conserve this endangered species, dam management strategies that account for expected hydrologic conditions and distinct exploration behaviours are needed. [ABSTRACT FROM AUTHOR]

The Bay of Aiguillon is a national French Nature Reserve of great importance for birds. Recently, the managers of the Reserve (ONCFS-LPO) paid attention to the influence of saltmarshes management on the nursery function for fish feeding in creeks at high tide. A study carried out from March to July 2012 aimed to evaluate the use of saltmarshes by fish juvenile fraction according to the mowing intensity in salt marshes surrounding creeks: ceased, irregular or annual mowing. This community approach was completed by a focus on the European sea bass Dicentrarchus labrax individual diet, vacuity index and growth, and the biomass of a main potential prey (the amphipod Orchestia gammarella). Whatever the mowing intensity, the juvenile fraction was very high for the main species, which were the grey mullet Liza ramada, the European sea bass, undetermined clupeid and the European flounder Platichthys flesus. Adult and subadult for these species were anecdotic or totally absent. Despite very different biomasses of amphipods between mown and natural sites, vacuity index, prey composition and their relative abundance in the diet of European sea bass juveniles were little different, contrary to their hypothetical growth (i.e. when assuming site fidelity), which appeared higher in non-mown site. The low distance between sampling sites could allow fish exchange over time between optimal and suboptimal creeks to feed on, as a hypothesis to explain such results. Because mowing was subsidized by European Union (EU) to favour open habitats for geese and maintain an economic activity, indirect impacts on nursery for fish called into question the appropriateness of such agro-environmental measure on natural habitats, and related fish nursery function. [ABSTRACT FROM AUTHOR]

Background Immunostimulating oligodeoxynucleotides containing unmethylated cytosine-guanosine motifs (CpG-ODN) have shown a promising efficacy in several cancer models when injected locally. A previous phase II study of CpG-ODN in patients with recurrent glioblastoma (GBM) has suggested some activity and has shown a limited toxicity. This multicentre single-blinded randomised phase II trial was designed to study the efficacy of a local treatment by CpG-ODN in patients with de novo glioblastomas. Patients and methods Patients with a newly diagnosed glioblastoma underwent large surgical resection and CpG-ODN was randomly administrated locally around the surgical cavity. The patients were then treated according to standard of care (SOC) with radiotherapy and temozolomide. The primary objective was 2-year survival. Secondary outcomes were progression free survival (PFS), and tolerance. Results Eighty-one (81) patients were randomly assigned to receive CpG-ODN plus SOC (39 patients) or SOC (42 patients). The 2-year overall survival was 31% (19%; 49%) in the CpG-ODN arm and 26% (16%; 44%) in the SOC arm. The median PFS was 9 months in the CpG-ODN arm and 8.5 months in the SOC arm. The incidence of adverse events was similar in both arms; although fever and post-operative haematoma were more frequent in the CpG-ODN arm. Conclusions Local immunotherapy with CpG-ODN injected into the surgical cavity after tumour removal and followed by SOC, although well tolerated, does not improve survival of patients with newly diagnosed GBM. [ABSTRACT FROM AUTHOR]

Intrapopulation variability, especially individual foraging specialization, has been investigated in many species. Nevertheless, the repeatability of foraging behaviour remains poorly understood. In particular, whether individuals differ in their respective degrees of repeatability still remains to be determined. Here, we estimated foraging behaviour repeatability in the great cormorant, at both the population and the individual levels, and assessed the effect of repeatability on individual foraging performance. At the population level, we found that some foraging variables were more repeatable (e.g. departure angle and trip duration) than others (e.g. time spent underwater per trip). At the individual level, we found differences in the degree of repeatability for each foraging variable, highlighting the presence of both highly flexible and highly consistent individuals in the population. The effect of repeatability on individual performance depended on the considered timescale: individual-level repeatability of time spent underwater per dive was negatively related to foraging efficiency while individual-level repeatability of time spent underwater per trip was positively related to foraging efficiency. Overall, our study demonstrates the importance of studying repeatability at the individual level and shows how both flexibility and consistency in animal behaviour shape their ability to extract energy from the environment. [ABSTRACT FROM AUTHOR]

A 37-year-old man with no medical history, apart from a lifelong horizontal diplopia, underwent brain magnetic resonance imaging, which revealed a curvilinear posterior pericallosal lipoma and a pineal cyst. Corpus callosum lipomas, with an incidence of 0.1%−0.5%, do not require neurosurgical treatment, except in rare cases of malformations causing epilepsy. The indications for surgery of pineal cysts, whose incidence is 0.6%, are controversial, except in case of hydrocephalus. In this case, ophthalmologic examination and magnetic resonance imaging were not consistent for a tectal plate compression and the findings were considered incidental. The association of these 2 abnormalities, which has not been described before, might reflect an interrelated embryologic development for pineal gland and midline lipomas, which derive from aberrant mesenchymal primitive meninx. [ABSTRACT FROM AUTHOR]

Attenuation of p53 activity appears to be a major step in Human T-lymphotropic virus type 1 (HTLV-1) Tax transformation. However, p53 genomic mutations are late and rather infrequent events in HTLV-1 induced Adult T cell leukemia (ATL). The paper by Zane et al. shows that a mediator of p53 activity, Wild-type p53-induced phosphatase 1 (Wip1), contributes to Tax-induced oncogenesis in a mouse model. Wip1 may therefore be a novel target for therapeutic approaches. [ABSTRACT FROM AUTHOR]

Many techniques are described to treat Chiari type I malformation. One of them is a splitting of the dura, removing its outer layer only to reduce the risks of cerebrospinal fluid (CSF) leak. We try to show the effectiveness of this technique from histological and biomechanical observations of dura mater. Study was performed on 25 posterior fossa dura mater specimens from fresh human cadavers. Dural composition and architecture was assessed on 47 transversal and sagittal sections. Uniaxial mechanical tests were performed on 22 dural samples (15 entire, 7 split) to focus on the dural macroscopic mechanical behavior comparing entire and split samples and also to understand deformation mechanisms. We finally created a model of volume expansion after splitting. Dura mater was composed of predominant collagen fibers with a few elastin fibers, cranio-caudally orientated. The classical description of two distinct layers remained inconstant. Biomechanical tests showed a significant difference between entire dura, which presents an elastic fragile behavior, with a small domain where deformation is reversible with stress, and split dura, which presents an elasto-plastic behavior with a large domain of permanent strain and a lower stress level. From these experimental results, the model showed a volume increase of approximately 50% below the split area. We demonstrated the capability of the split dura mater to enlarge for suitable stress conditions and we quantified it by biomechanical tests and experimental model. Thus, dural splitting decompression seems to have a real biomechanical substrate to envision the efficacy of this Chiari type I malformation surgical technique. [ABSTRACT FROM AUTHOR]

To restore the cerebrospinal fluid (CSF) flow at the craniocervical junction in Chiari I malformation (CM-I), most surgeons practice a suboccipital craniectomy with duraplasty. To reduce the risk of CSF leak, a dura splitting decompression is created removing only the dural outer layer. We report on a series of 11 patients with CM-I (five with syringomyelia) operated on between 2000 and 2007 using this technique. Neurological examination and cerebro-spinal MRI scan were performed before and after surgery. Symptoms improved completely in six patients. Headaches and cervicalgias disappeared for all patients. Dizziness and paresthesia in the upper limb remained unchanged for three and two patients, respectively. We observed no complications such as CSF leak, meningocele, or meningitis. Postoperative MRI scan showed a significant craniocervical decompression in ten patients. Four patients had a new cisterna magna. Two syringomyelias completely disappeared, two decreased, and one was stable. Dural splitting can be practiced to treat CM-I. Clinical results are similar to the other techniques with less complications. Radiological findings show satisfying posterior fossa decompression. [ABSTRACT FROM AUTHOR]

1. Freshwater communities are subject to various abrupt environmental disturbances and increasing pollution levels in their habitat. According to the nature and the periodicity of disturbances (i.e. punctuated, recurrent or continuous), one may expect different kinds of response of the target gastropod communities. 2. The gastropod community of a French lake has been investigated for 10 years to study its responses to three main environmental disturbances: supra-seasonal droughts, recurrent proliferations of cyanobacteria and parasitism by trematodes. The relationship between this latter factor, considered as a continuous stressor, and the gastropod community was a particular focus. 3. A total of 13 280 gastropods belonging to 17 species (mostly Pulmonata with Planorbidae as the dominant family) have been sampled in the lake over the 10-year time series. Species composition of the gastropod community varied strongly during the study period as did species richness (0–14, mean of 6.5 ± 0.4 species) and abundance of gastropods (0–4456, mean of 192 ± 72 individuals). Trematode larvae belonging to 11 morphotypes of cercariae were detected in 15 of the 17 species of gastropods and had a total prevalence of 2.9%. 4. Droughts (punctuated stressor) were responsible for the disappearance of nearly all gastropod species, and thus represent a severe environmental stressor for them. Nevertheless, the extent of this stressor was limited since the gastropod community was highly resilient. 5. Recurrent proliferations of toxic cyanobacteria (recurrent stressor) coincided with the large decline of the gastropod community, corresponding to a strong decrease in abundance and species richness. Intoxication of gastropods by toxic cyanobacteria was demonstrated by the bioaccumulation of microcystins in all gastropod tissues. 6. Trematode parasitism (continuous stressor) did not affect the gastropod community despite the possibly strong impact of parasites on some host species (those with monthly prevalence as high as 100% at some times). Indeed, abundance and species richness of gastropods were scarcely influenced by trematode prevalence or species richness. [ABSTRACT FROM AUTHOR]

In this study, we investigated the response of inland breeding cormorants Phalacrocorax carbo to a complex spatial configuration of feeding habitats in relation to social and individual feeding strategies. The numbers of feeding trips outside the colony site (Lake Grand-Lieu, western France), where only solitary fishing is used by cormorants, and the number of birds fishing on the lake where social fishing predominates were investigated during the breeding season and compared with the fledging period. From the investigation of feeding trip traffic, we identified three major habitats used by cormorants in the vicinity of the colony site (< 25 km around the colony site) that accounted for 94.1 of the IN flights and 92.0% of the OUT flights (n=1745 arrivals and 2404 departures respectively), and notably one area that accounted for 58% of total flights although it is the furthest away. No fundamental change in the relative significance of these feeding grounds for solitary fishing cormorants was found throughout the breeding season, even in a between-years comparison (1996–2001), in contrast to what has often been found elsewhere. Although the peak of foraging activity in the surrounding habitats and also within the lake waters largely coincided with the time when the majority of young had fledged, the index of cormorant numbers (ratio between bird numbers at a given time and that for a baseline date) on the lake remained at a high level until late August compared to movements outside the lake, as a result of regular social fishing (84.9±4.0% of fishing numbers). From these findings, we discuss factors governing the selection of feeding grounds throughout the breeding season in relation to energy considerations, feeding strategies and food resources. To cite this article: J.-M. Paillisson et al., C. R. Biologies 327 (2004). [Copyright &y& Elsevier]

This study describes the trends of a bitterling population in the Bourgneuf Marsh in relation to human activities. Although there were no bitterling during the period 1987–91, the species rapidly colonized the ditch network sampled (density reaching 61.7±47.0 individuals/100 m2 and frequency of occurrence around 70–75%) during a 5-year period (1997–2001). Clearance operations probably favoured the expansion of this vulnerable fish species because of positive associations of bitterling with large and deep ditches that had been cleared in the last 2–3 years and characterized by a small cover of submerged plants. Management recommendations are discussed for conserving the bitterling population. To cite this article: A. Carpentier et al., C. R. Biologies 326 (2003). [Copyright &y& Elsevier]

Introduction: Early mobilization is key in neurologically impaired persons, limiting complications and improving long-term recovery. Self-balanced exoskeletons are used in rehabilitation departments to help patients stand and walk. We report the first case series of exoskeleton use in acute neurosurgery and intensive care patients, evaluating safety, clinical feasibility and patients' satisfaction. Methods: We report a retrospective observational study including individuals hospitalized in the neurosurgical intensive care and neurosurgery departments. We included patients with a medical prescription for an exoskeleton session, and who met no contraindication. Patients benefited from standing sessions using a self-balanced exoskeleton (Atalante, Wandercraft, France). Patients and sessions data were collected. Safety, feasibility and adherence were evaluated. Results: Seventeen patients were scheduled for 70 standing sessions, of which 27 (39%) were completed. They were typically hospitalized for intracranial hemorrhage (74%) and presented with unilateral motor impairments, able to stand but with very insufficient weight shifting to the hemiplegic limb, requiring support (MRC 36.2 ± 3.70, SPB 2.0 ± 1.3, SPD 0.7 ± 0.5). The average duration of standing sessions was 16 ± 9 min. The only side effect was orthostatic hypotension (18.5%), which resolved with returning to seating position. The most frequent reason for not completing a session was understaffing (75%). All patients were satisfied and expressed a desire to repeat it. Conclusions: Physiotherapy using the exoskeleton is safe and feasible in the acute neurosurgery setting, although it requires adaptation from the staff to organize the sessions. An efficacy study is ongoing to evaluate the benefits for the patients. [ABSTRACT FROM AUTHOR]

Objective: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug‐resistant mesial temporal lobe epilepsy (MTLE). Methods: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow‐up. Patients were risk‐stratified by applying outcome‐relevant comorbidities, and benchmarks were calculated for low‐risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. Results: A total of 1119 patients with a mean age (range) of 36.7 (1–74) years and a male‐to‐female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in‐hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%–72.9% of cases per center and leaving 742 patients in the high‐risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow‐up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1‐year follow‐up) and ≥69.5% (mean follow‐up of 39.0 months). Significance: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques. [ABSTRACT FROM AUTHOR]

1. The drastic decline in European eel Anguilla anguilla stock is now widely recognized. However, while various causes for this decline have been identified, the relative importance of each cause remains unclear. 2. During the catadromous migration of silver eels, the negative impact of dams is frequently highlighted, but mainly for powered dams (with turbines) or where connectivity is completely ruptured. Mechanical impact due to turbine blades is often considered the most important cause of mortality of silver eels during downstream migration. Consequently, non-powered dams equipped with spillways are often considered safe for the passage of migrating silver eels. 3. We hypothesized that, to understand the negative impacts of dams, a much wider context must be considered than turbine mortality alone. Using an acoustic telemetry survey of silver eels, we demonstrated the negative effects of non-powered dams on downstream migration. 4. Five main impacts on eel populations were highlighted: (i) the attenuation or loss of triggering factors, leading to an absence of or delay in migration; (ii) extra delays and extra distances travelled when crossing the dam; (iii) extra energetic costs of the additional distance travelled as result of exploring the dam and the reservoir to find other escape passages; (iv) the selection of a more risky behavioral phenotype, i.e., bold eels; and (v) direct blocking once migration has started. Mortality was evaluated as a supplementary impact. Some of these effects (attenuation of triggers, extra delays to cross the dam) might be more important than the same effect from powered dams, probably due to the constant high water discharge required for turbines that facilitate the passage of eels. 5. As these "safe" dams are very widespread, they must be considered a potential threat to effective eel conservation. [ABSTRACT FROM AUTHOR]

• Use of fisheries-dependent data to undertake skate distribution models. • Broader scale skate spatio-temporal distributions than previously modelled. • Varying spatio-temporal distributions highlight differing skate vulnerability. • Use of skate life history distribution models for specific protection measures. • Use of fisheries dependent data to avoid bycatch. Elasmobranchs are k-strategy species with low reproduction rate and slow growth lending to increased anthropogenic vulnerability. Specific management measures to improve the conservation of elasmobranchs can be problematic due to insufficient information on their biology and ecology. Here, three sympatric skates occupying north-eastern Atlantic waters, which have differing conservation status were studied within ICES divisions 4.c, 7.d–e, 7.f–h and 8a–b and d. Fisheries-dependent data on skate bycatch and a series of environmental variables were used to model spatio-temporal differences in habitat use between the three species. Raja undulata , the undulate ray (IUCN red listed as 'Endangered') was observed to have a coastal distribution within the English Channel and the Bay of Biscay (ICES division 7.d–e and 8.a–b). Raja clavata, the thornback ray ('Near threatened'), had a broader distribution with higher presence in the eastern English Channel and the southern North Sea (ICES division 7.e and 4.c). Raja montagui , the spotted ray's probability of presence ('Least concerned') was higher off the coast of southern Ireland (ICES division 7.g). Seasonal and life-history trait differences were also observed. From the fisheries-dependent data, wider skate distributions than previously studied were modelled. Although the species do co-occur, spatio-temporal differences between these species were observed. This study contributes to a greater understanding of skate habitat during their different life history stages, and indicates reasons for R. undulata's increased vulnerability than R. clavata and R. montagui. Information from the distribution models could be used for specific spatio-temporal management measures. Better understanding of the distribution of species can also help reduce bycatch of protected species such as R. undulata. [ABSTRACT FROM AUTHOR]

Objectives: Brain imaging is particularly difficult to learn and to teach. This study aimed to evaluate the performance of teaching brain imaging through drawing method in medical faculty students.Methods: We conducted a prospective, interventional, randomized, single-blind study in third-year voluntary medical students between December 2016 and June 2019. Eighty medical students received a theoretical training on brain imaging interpretation and were subsequently randomized into two groups ("teaching through drawing" and "standard teaching"). An initial evaluation was carried out to assess the students' basic level. Three teaching and training sessions were spread over 2 months in each group. One month after the third teaching session, students were evaluated by an examiner who was blind to the student's group. The same comprehensive evaluation grid has been used for the initial and final students' evaluations to give an objective score out of 20 points. Students' scores were compared between groups using the t test and effect sizes were measured using Cohen's d.Results: Students' mean age was 21.1 years old. In total, 61.3% were female. Regarding initial evaluation, scores did not differ significantly between both groups (10.1 ± 2.0 versus 9.9 ± 1.9, p = 0.65), thus confirming the homogeneity of the students' basic level. The scores obtained from the final evaluation were significantly higher for the "teaching through drawing" students than for the "standard teaching" students (14.7 ± 2.7 vs 13.2 ± 2.0, p = 0.009, Cohen's d = 0.62).Conclusions: This study provides class II evidence that the method of drawing alone can improve brain imaging comprehension and analysis in medical faculty students.Key Points: • The method of drawing can improve brain imaging analysis in medical faculty students. • A large majority of students were satisfied by the method of brain imaging teaching through drawing. [ABSTRACT FROM AUTHOR]

While spatial distribution shifts have been documented in many marine fishes under global change, the responses of elasmobranchs have rarely been studied, which may have led to an underestimation of their potential additional threats. Given their irreplaceable role in ecosystems and their high extinction risk, we used a 24‐year time series (1997–2020) of scientific bottom trawl surveys to examine the effects of climate change on the spatial distribution of nine elasmobranch species within Northeast Atlantic waters. Using a hierarchical modeling of species communities, belonging to the joint species distribution models, we found that suitable habitats for four species increased on average by a factor of 1.6 and, for six species, shifted north‐eastwards and/or to deeper waters over the past two decades. By integrating species traits, we showed changes in habitat suitability led to changes in the elasmobranchs trait composition. Moreover, communities shifted to deeper waters and their mean trophic level decreased. We also note an increase in the mean community size at maturity concurrent with a decrease in fecundity. Because skates and sharks are functionally unique and dangerously vulnerable to both climate change and fishing, we advocate for urgent considerations of species traits in management measures. Their use would make it better to identify species whose loss could have irreversible impacts in face of the myriad of anthropogenic threats. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia. No treatments have led to clinically meaningful impacts. A major obstacle for peripherally administered therapeutics targeting the central nervous system is related to the blood–brain barrier (BBB). Ultrasounds associated with microbubbles have been shown to transiently and safely open the BBB. In AD mouse models, the sole BBB opening with no adjunct drugs may be sufficient to reduce lesions and mitigate cognitive decline. However, these therapeutic effects are for now mainly assessed in preclinical mouse models of amyloidosis and remain less documented in tau lesions. The aim of the present study was therefore to evaluate the effects of repeated BBB opening using low-intensity pulsed ultrasounds (LIPU) in tau transgenic P301S mice with two main readouts: tau-positive lesions and microglial cells. Our results show that LIPU-induced BBB opening does not decrease tau pathology and may even potentiate the accumulation of pathological tau in selected brain regions. In addition, LIPU-BBB opening in P301S mice strongly reduced microglia densities in brain parenchyma, suggesting an anti-inflammatory action. These results provide a baseline for future studies using LIPU-BBB opening, such as adjunct drug therapies, in animal models and in AD patients. [ABSTRACT FROM AUTHOR]

Aims: The distinction between CNS WHO grade 2 and grade 3 is instrumental in choosing between observational follow‐up and adjuvant treatment for resected astrocytomas IDH‐mutant. However, the criteria of CNS WHO grade 2 vs 3 have not been updated since the pre‐IDH era. Methods: Maximal mitotic activity in consecutive high‐power fields corresponding to 3 mm2 was examined for 118 lower‐grade astrocytomas IDH‐mutant. The prognostic value for time‐to‐treatment (TTT) and overall survival (OS) of mitotic activity and other putative prognostic factors (including age, performance status, pre‐surgical tumour volume, multilobar involvement, post‐surgical residual tumour volume and midline involvement) was assessed for tumours with ATRX loss and the absence of CDKN2A homozygous deletion or CDK4 amplification, contrast enhancement, histological necrosis and microvascular proliferation. Results: Seventy‐one per cent of the samples had <6 mitoses per 3 mm2. Mitotic activity, residual volume and multilobar involvement were independent prognostic factors of TTT. The threshold of ≥6 mitoses per 3 mm2 identified patients with a shorter TTT (median 18.5 months). A residual volume ≥1 cm3 also identified patients with a shorter TTT (median 24.5 months). The group defined by <6 mitoses per 3 mm2 and a residual volume <1 cm3 had the longest TTT (median 73 months) and OS (100% survival at 7 years). These findings were confirmed in a validation cohort of 52 tumours. Conclusions: Mitotic activity and post‐surgical residual volume can be combined to evaluate the prognosis for patients with resected astrocytomas IDH‐mutant. Patients with <6 mitoses per 3 mm2 and a residual volume <1 cm3 were the best candidates for observational follow‐up. [ABSTRACT FROM AUTHOR]

Systemic drugs can treat various retinal pathologies such as retinal cancers; however, their ocular diffusion may be limited by the blood–retina barrier (BRB). Sonication corresponds to the use of ultrasound (US) to increase the permeability of cell barriers including in the BRB. The objective was to study the efficacy and safety of sonication using microbubble-assisted low-intensity pulsed US in inducing a transient opening of the BRB. The eyes of C57/BL6J mice were sonicated at different acoustic pressures (0.10 to 0.50 MPa). Efficacy analyses consisted of fluorescein angiography (FA) performed at different timepoints and the size of the leaked molecules was assessed using FITC-marked dextrans. Tolerance was assessed by fundus photographs, optical coherence tomography, immunohistochemistry, RT-qPCR, and electroretinograms. Sonication at 0.15 MPa was the most suitable pressure for transient BRB permeabilization without altering the morphology or function of the retina. It did not increase the expression of inflammation or apoptosis markers in the retina, retinal pigment epithelium, or choroid. The dextran assay suggested that drugs up to 150 kDa in size can cross the BRB. Microbubble-assisted sonication at an optimized acoustic pressure of 0.15 MPa provides a non-invasive method to transiently open the BRB, increasing the retinal diffusion of systemic drugs without inducing any noticeable side-effect. [ABSTRACT FROM AUTHOR]

It is unknown whether ultrasound-induced blood–brain barrier (BBB) disruption can promote epileptogenesis and how BBB integrity changes over time after sonication. To gain more insight into the safety profile of ultrasound (US)-induced BBB opening, we determined BBB permeability as well as histological modifications in C57BL/6 adult control mice and in the kainate (KA) model for mesial temporal lobe epilepsy in mice after sonication with low-intensity pulsed ultrasound (LIPU). Microglial and astroglial changes in ipsilateral hippocampus were examined at different time points following BBB disruption by respectively analyzing Iba1 and glial fibrillary acidic protein immunoreactivity. Using intracerebral EEG recordings, we further studied the possible electrophysiological repercussions of a repeated disrupted BBB for seizure generation in nine non-epileptic mice. LIPU-induced BBB opening led to transient albumin extravasation and reversible mild astrogliosis, but not to microglial activation in the hippocampus of non-epileptic mice. In KA mice, the transient albumin extravasation into the hippocampus mediated by LIPU-induced BBB opening did not aggravate inflammatory processes and histologic changes that characterize the hippocampal sclerosis. Three LIPU-induced BBB opening did not induce epileptogenicity in non-epileptic mice implanted with depth EEG electrodes. Our experiments in mice provide persuasive evidence of the safety of LIPU-induced BBB opening as a therapeutic modality for neurological diseases. [ABSTRACT FROM AUTHOR]

Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood–brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma. We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m2, 80 mg/m2, 135 mg/m2, 175 mg/m2, 215 mg/m2, and 260 mg/m2) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood–brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov , NCT04528680 , and a phase 2 trial is currently open for accrual. 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12–12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40–215 mg/m2), and 12 patients were treated at dose level 6 (260 mg/m2). A total of 68 cycles of LIPU-MB-based blood–brain barrier opening were done (median 3 cycles per patient [range 2–6]). At a dose of 260 mg/m2, encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m2 in the case of the grade 3 encephalopathy, and to 215 mg/m2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood–brain barrier opening was most commonly associated with immediate yet transient grade 1–2 headache (12 [71%] of 17 patients). The most common grade 3–4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood–brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 μM [95% CI 0·022–0·063] in non-sonicated brain to 0·139 μM [0·083–0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 μM [0·562–1·747] in non-sonicated brain to 5·878 μM [3·462–9·980] μM in sonicated brain [5·9-times increase], p=0·0001). LIPU-MB using a skull-implantable ultrasound device transiently opens the blood–brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing. National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family. [ABSTRACT FROM AUTHOR]

Life-history traits of eels display a high level of phenotypic plasticity in response to large-scale biogeographical drivers, as well as local conditions encountered during the continental phase. Here, we provided a biogeographical snapshot of the variability of life-history traits of eels (Anguilla anguilla), across a large proportion of their natural distribution range. Silver eels (n = 99) were collected across eleven European catchments to investigate how life-history traits vary along geographical and saline habitats, as it was inferred from the Sr:Ca ratio in otoliths. Among 13 life-history traits tested, 3 of them such as total length, body or liver weight were related to geographical coordinates. Overall, eels grow faster in southern Europe and migrate earlier suggesting that the silvering process is related to the local growth conditions more than fish age. The salinity profiles revealed by the otoliths' Sr:Ca ratios indicate that eels with a brackish life-history generally grow faster, reach larger size-at-age, and have a better condition than eels living in freshwater. This observation associated with the lower abundance of the sanguivorous swimbladder nematode, Anguillicola crassus, confirms the importance of brackish areas for sustaining the eel production. A large proportion of the observed variation of life-history traits remained unexplained by the biogeographical trends and salinity condition, which suggests that other drivers act at the catchment scale. [ABSTRACT FROM AUTHOR]

Introduction: Refractory intracranial hypertension (rICH) is a severe complication among patients with severe traumatic brain injury (sTBI). Medical treatment may be insufficient, and in some cases, the only viable treatment option is decompressive hemicraniectomy. The assessment of a corticosteroid therapy against vasogenic edema secondary to severe brain injuries seems interesting to prevent this surgery in sTBI patients with rICH caused by contusional areas. Methods: This is a monocentric retrospective observational study including all consecutive sTBI patients with contusion injuries and a rICH requiring cerebrospinal fluid drainage with external ventricular drainage between November 2013 and January 2018. Patient inclusion criterium was a therapeutic index load (TIL; an indirect measure of TBI severity) > 7. Intracranial pressure (ICP) and TIL were assessed before and 48 h after corticosteroid therapy (CTC). Then, we divided the population into two groups according to the evolution of the TIL: responders and non-responders to corticosteroid therapy. Results: During the study period, 512 patients were hospitalized for sTBI, and among them, 44 (8.6%) with rICH were included. They received 240 mg per day [120 mg, 240 mg] of Solu-Medrol for 2 days [1; 3], 3 days after the sTBI. The average ICP in patients with rICH before the CTC bolus was 21 mmHg [19; 23]. After the CTC bolus, the ICP fell significantly to less than 15 mmHg (p < 0.0001) for at least 7 days. The TIL decreased significantly the day after the CTC bolus and until day 2. Among these 44 patients, 68% were included in the responder group (n = 30). Discussion: Short and systemic corticosteroid therapy in patients with refractory intracranial hypertension secondary to severe traumatic brain injury seems to be a potentially useful and efficient treatment for lowering intracranial pressure and decreasing the need for more invasive surgeries. [ABSTRACT FROM AUTHOR]

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood–brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A blood–brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10 µL/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly opened the BBB. BBB opening was confirmed visually and microscopically using Evans blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome in order to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain tumors account for over 20% of childhood cancers and are the biggest cancer killer in children and young adults. Several initiatives over the past 40 years have tried to identify more effective drug treatments, but with very limited success. This is largely due to the blood–brain barrier, which restricts the entry of many drugs into the brain. In this review, we describe the main techniques that are being developed to enhance brain tumor drug delivery and explore the preclinical brain tumor models that are essential for translational development of these techniques. We also identify existing approved drugs that, if coupled with an efficient delivery method, could have potential as brain tumor treatments. Bringing this information together is part of a funded initiative to highlight drug delivery as a research strategy to overcome the current challenges for children diagnosed with brain tumors. Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood–brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored. [ABSTRACT FROM AUTHOR]

Background: Little is known about incidence, time of onset, clinical presentation, and risk factors of epileptic seizure following brain arteriovenous malformation (bAVM) rupture. Methods: We performed a monocentric retrospective cohort study from January 2003 to March 2021. The main objective of this study was to determine the incidence of seizures after spontaneous bAVM rupture in nonepileptic adult patients and describe the corresponding clinical features. The secondary objective was to identify clinical, radiological, or biological predictors for the occurrence of de novo seizures after bAVM rupture. Results: Of the 296 cases of bAVM rupture registered during the study period, 247 nonepileptic patients (male 53%, median age 40) were included in the study. Fifty-nine patients (23.9%) had at least one seizure after bAVM rupture. The use of preventive antiepileptic drugs (10.3 [1.5–74.1]; P = 0.02) and decompressive craniectomy (15.4 [2.0–125]; P < 0.009) were independently associated with the occurrence of epilepsy after the bAVM rupture. The factors independently associated with the absence of any seizure after the rupture were isolated intraventricular hemorrhage (0.3 [0.1–0.99]; P = 0.04) and infratentorial location of the bAVM (0.2 [0.1–0.5]; P = 0.09). The first seizure occurred within the first year or within 5 years in, respectively, 83.1% and 98.3% of the patients. Conclusions: Epilepsy affects nearly a quarter of patients after bAVM rupture. Decompressive craniectomy represents an independent risk factor significantly associated with the occurrence of epilepsy after bAVM rupture. The introduction of preventive AEDs after rupture could be considered in these most severe patients who have a decompressive craniectomy. [ABSTRACT FROM AUTHOR]

• Fisheries-dependent data can fill gaps in knowledge of data-poor elasmobranch species. • L. fullonica is distributed within an area of high concentration where size segregation is present. • Its localized distribution is within an area subject to heavy fishing pressure. • L. fullonica is most susceptible to bycatch by bottom trawl fishing gear types. • Most of the L. fullonica individuals caught are immature. Little is still known about the biology and ecology of many elasmobranchs which often inhibits species specific management measures from being implemented. The primary aim of this study was to improve the knowledge on the distribution and habitat use of the threatened and data deficient shagreen ray, Leucoraja fullonica , using fisheries dependent data. To model its distribution, we used Bayesian hierarchical modelling, taking into consideration imperfect capture from the non-random nature of fishing gear type and spatial autocorrelation. Our second objective was to identify the potential functional role of the high occurrence area by analysing spatial length segregation using a generalised additive mixed model. From five environmental variables, depth, distance to coast, and seabed sediment type were used to model its habitat. L. fullonica was found to mainly inhabit an area of high concentration between the southern Celtic Seas and the northern Bay of Biscay. Within this area, smaller individuals were found in the deeper south-western part and larger individuals in shallower waters, closer to the coast, suggesting ontogenetic shift or spawning migration. L. fullonica were mainly caught by bottom trawl fishing gears. The isolated habitat occupancy of this species may increase its vulnerability, particularly since high fishing pressure has been observed in this area. These results highlight the importance of fisheries-dependent data for data-poor species and provide valuable new information on its ecology when considering management or conservation measures at a species level. [ABSTRACT FROM AUTHOR]

Different animal models have been proposed to investigate the mechanisms of Human T-lymphotropic Virus (HTLV)-induced pathogenesis: rats, transgenic and NOD-SCID/cnull (NOG) mice, rabbits, squirrel monkeys, baboons and macaques. These systems indeed provide useful information but have intrinsic limitations such as lack of disease relevance, species specificity or inadequate immune response. Another strategy based on a comparative virology approach is to characterize a related pathogen and to speculate on possible shared mechanisms. In this perspective, bovine leukemia virus (BLV), another member of the deltaretrovirus genus, is evolutionary related to HTLV-1. BLV induces lymphoproliferative disorders in ruminants providing useful information on the mechanisms of viral persistence, genetic determinants of pathogenesis and potential novel therapies. [ABSTRACT FROM AUTHOR]

Leptocephali are the poorly-understood transparent larvae of elopomorph fishes that live in the ocean surface layer throughout the world’s tropical and subtropical oceans. Their feeding ecology has been difficult to understand because they appear to primarily feed on particulate organic material (POM), which contains few identifiable objects, and there have been few studies on their diets or trophic positions. This study presents the first comparative results on the stable isotope ratios of 7 families of leptocephali in relation to the ratios of 30 taxa of other marine animals and POM samples. The carbon and nitrogen stable isotope ratios were analyzed using 50 specimens of leptocephali, 354 specimens of mesozooplankton, cephalopods, fishes, and POM collected west of the Mascarene Plateau in the western Indian Ocean. Nitrogen and carbon isotopic ratio analyses indicated that the 12 taxa of DNA barcoded leptocephali (⩾15 species) could be separated into 2 groups of species with either higher (Group 1: 9 taxa of 7 families, 25–91 mm) or lower (Group 2: 3 taxa of 2 families, 43–275 mm) δ 15 N ranges. Group 2 exclusively included species that reach much larger sizes of >150–200 mm ( Nemichthys and Avocettina , 3 species of Ariosoma -type), whereas Group 1 included Anguilla bicolor bicolor , Serrivomeridae, Muraenidae, Congridae (3 species), Chlopsidae, Ophichthidae (2 species), and Thalassenchelys . Differences in feeding depths, the types of POM ingested by preference or because of different jaw morphology, or the transport of larvae from other regions with different isotopic signatures are possible reasons for the differences between the two groups. The isotopic signatures of 14 taxa of copepods had higher but slightly overlapping δ 15 N and δ 13 C signatures compared to leptocephali and most crustaceans and other mezozooplankton, cephalopods and mesopelagic fish taxa had even higher values. The δ 15 N and δ 13 C signatures and composition of POM were variable spatially and with depth and may have been influenced by particulates originating from the shallow banks of the Mascarene Plateau. The two apparent isotopic groups of leptocephali should be examined in relation to their consumption of POM, which can include various proportions of prokaryotes, phytoplankton, protozoans, discarded appendicularian houses and other materials, by conducting further studies in different regions and using a variety of techniques. [ABSTRACT FROM AUTHOR]

In a 10-month experimental study, we assessed the combined impact of warming and acidification on critical life stages of small-spotted catshark (Scyliorhinus canicula). Using recently developed frameworks, we disentangled individual and group responses to two climate scenarios projected for 2100 (SSP2-4.5: Middle of the road and SSP5-8.5: Fossil-fueled Development). Seasonal temperature fluctuations revealed the acute vulnerability of embryos to summer temperatures, with hatching success ranging from 82% for the control and SSP2-4.5 treatments to only 11% for the SSP5-8.5 treatment. The death of embryos was preceded by distinct individual growth trajectories between the treatments, and also revealed inter-individual variations within treatments. Embryos with the lowest hatching success had lower yolk consumption rates, and growth rates associated with a lower energy assimilation, and almost all of them failed to transition to internal gills. Within 6 months after hatching, no additional mortality was observed due to cooler temperatures. • Summer temperatures revealed embryo vulnerability to seasonal fluctuations. • Hatching success ranged from 82% in control and SSP2-4.5 to 11% in SSP5-8.5. • The death of embryos was preceded by distinct individual growth trajectories. [ABSTRACT FROM AUTHOR]

Objectives: Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context.Design: Monocenter, retrospective, observational cohort study.Setting: A French tertiary center.Patients: All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients.Interventions: None.Measurements and Main Results: Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4-3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01-2.6]; p = 0.04).Conclusions: Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted. [ABSTRACT FROM AUTHOR]

Ecologists working with stable isotopes have to deal with complex datasets including temporal and spatial replication, which makes the analysis and the representation of patterns of change challenging, especially at high resolution. Due to the lack of a commonly accepted conceptual framework in stable isotope ecology, the analysis and the graphical representation of stable isotope spatial and temporal dynamics of stable isotope value at the organism or community scale remained in the past often descriptive and qualitative, impeding the quantitative detection of relevant functional patterns. The recent community trajectory analysis (CTA) framework provides more explicit perspectives for the analysis and the visualization of ecological trajectories. Building on CTA, we developed the Stable Isotope Trajectory Analysis (SITA) framework, to analyze the geometric properties of stable isotope trajectories on n‐dimensional (n ≥ 2) spaces of analysis defined analogously to the traditional multivariate spaces (Ω) used in community ecology. This approach provides new perspectives into the quantitative analysis of spatio‐temporal trajectories in stable isotope spaces (Ωδ) and derived structural and functional dynamics (Ωγ space). SITA allows the calculation of a set of trajectory metrics, based on either trajectory distances or directions, and new graphical representation solutions, both easily performable in an R environment. Here, we illustrate the use of our approach by reanalyzing previously published datasets from marine, terrestrial, and freshwater ecosystems. We highlight the insights provided by this new analytic framework at the individual, population, community, and ecosystems levels, and discuss applications, limitations, and development potential. [ABSTRACT FROM AUTHOR]

River fragmentation is expected to impact not only movement patterns and distribution of eels within catchment, but also their life-history traits. Here, we used otolith multi-elemental signatures to reconstruct life sequences of European silver eels within an obstructed catchment, just before the removal of hydropower dams. Beyond providing an initial state, we hypothesized that otolith signatures can provide crucial information on the way eels use the watershed. Indeed, their spatial distribution is expected to shape life-history traits, including condition coefficient, trophic level, growth rate, or infection by metazoan parasites. While Sr:Ca and Ba:Ca ratios were complementary in tracing fish movements between freshwater and estuary, the Ba:Ca variations allowed to discriminate three freshwater sectors. The eels assigned to the midstream sector were more mobile and exhibited lower growth rates, probably in response to higher competition at the vicinity of dams. While most eels are currently produced by downstream and midstream sectors, eels assigned to upper reaches of connected tributaries generally display higher richness in native parasite and higher body condition and lipid reserve, known to promote the success of migration and reproduction. In the near future, the dam removals will represent an outstanding experimental framework for evaluating impacts of catchment reconnection. [ABSTRACT FROM AUTHOR]

Abstract: Studying successional processes and related factors in salt marshes encompasses both fundamental (community structuration) and applied (biodiversity conservation and restoration) issues. Current managed realignment projects and sites where, in the past, large storm events led to breaches in embankments create unique experimental conditions for such challenges by re-instating tidal inundation and salt-marsh development. We conducted a pair-matched approach using natural and recreated (either accidentally or managed) salt marshes and studied changes in invertebrate communities over time during a field experiment (Essex, UK). Trophic guild was assigned to all invertebrates, and detailed analyzes conducted on most abundant (amphipods, Orchestia sp., 9666 individuals) and diversified (spiders, 43 species) groups. A total of 27,180 invertebrates (almost all arthropods: 99% of specimens) was collected in 2005. The conservation equivalency was achieved quickly (which was shown here with spider assemblages), but that did not translate into a complete functional equivalency. Indeed neither the structure of trophic guilds, nor the potential role of marine enrichment and fish nursery, estimated through the population size of amphipods, was achieved by managed realignments. We finally argue that the study of invertebrates brings information complementary to those brought by plants, and underline that functional and conservation equivalency have to be assessed separately. [Copyright &y& Elsevier]

Anterior fossa dural arteriovenous fistulas (AF-DAVF) usually display a cortical venous drainage and are therefore at risk for rupture. Microsurgery is traditionally considered in many centers as the first-line treatment since endovascular treatment (EVT) entails a lower cure rate and significant ophthalmic risks. The anterior interhemispheric approach (AIA), originally described by Mayfrank in 1996, seems to offer the effectiveness of microsurgery while limiting the risks related to subfrontal craniotomy. The objective of this study was to analyze the surgical outcomes of patients who underwent this surgical approach for the treatment of AF-DAVF. We hereby describe our 10 years' experience of patients treated for an AF-DAVF with this technique in our institution and retrospectively analyzed our results. In addition, we describe our operative technique and its specificities. Eleven patients with AF-DAVF were included in our study. The definitive cure of the fistula was confirmed in all cases with postoperative cerebral angiography. All patients had a good neurological outcome and no major complication occurred. Brain retractors were never used during surgery, the frontal sinus was never opened neither, and anosmia was never observed after surgery. Anterior interhemispheric approach seems to be safe and effective to treat AF-DAVF with lower risks than other surgical approaches. This technique could be more widely considered when facing such midline vascular lesion. [ABSTRACT FROM AUTHOR]

Background: Temporary disruption of the blood-brain barrier (BBB) using pulsed ultrasound leads to the clearance of both amyloid and tau from the brain, increased neurogenesis, and mitigation of cognitive decline in pre-clinical models of Alzheimer's disease (AD) while also increasing BBB penetration of therapeutic antibodies. The goal of this pilot clinical trial was to investigate the safety and efficacy of this approach in patients with mild AD using an implantable ultrasound device. Methods: An implantable, 1-MHz ultrasound device (SonoCloud-1) was implanted under local anesthesia in the skull (extradural) of 10 mild AD patients to target the left supra-marginal gyrus. Over 3.5 months, seven ultrasound sessions in combination with intravenous infusion of microbubbles were performed twice per month to temporarily disrupt the BBB. 18F-florbetapir and 18F-fluorodeoxyglucose positron emission tomography (PET) imaging were performed on a combined PET/MRI scanner at inclusion and at 4 and 8 months after the initiation of sonications to monitor the brain metabolism and amyloid levels along with cognitive evaluations. The evolution of cognitive and neuroimaging features was compared to that of a matched sample of control participants taken from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results: A total of 63 BBB opening procedures were performed in nine subjects. The procedure was well-tolerated. A non-significant decrease in amyloid accumulation at 4 months of − 6.6% (SD = 7.2%) on 18F-florbetapir PET imaging in the sonicated gray matter targeted by the ultrasound transducer was observed compared to baseline in six subjects that completed treatments and who had evaluable imaging scans. No differences in the longitudinal change in the glucose metabolism were observed compared to the neighboring or contralateral regions or to the change observed in the same region in ADNI participants. No significant effect on cognition evolution was observed in comparison with the ADNI participants as expected due to the small sample size and duration of the trial. Conclusions: These results demonstrate the safety of ultrasound-based BBB disruption and the potential of this technology to be used as a therapy for AD patients. Research of this technique in a larger clinical trial with a device designed to sonicate larger volumes of tissue and in combination with disease-modifying drugs may further enhance the effects observed. Trial registration: ClinicalTrials.gov, NCT03119961 [ABSTRACT FROM AUTHOR]

Outpatient neurosurgery is rising popularity leading to patients' satisfaction and cost-savings. Although several North-American teams have shown the safety of outpatient stereotactic brain biopsies, few data from other countries with different health care systems are available. We therefore conducted a feasibility and safety study on the outpatient stereotactic brain biopsies. We prospectively examined all the consecutive stereotactic brain biopsies performed in an outpatient setting at our tertiary medical center, between June 2018 and September 2020. Among the 437 patients who underwent stereotactic brain biopsy during the study period, 40 (9.2%) patients were enrolled for an outpatient management. The sex ratio was 1 and the median age on biopsy day was 55 [41–66] years. The median distance from patients' home to hospital was 17 km [3–47]. 95% of patients had pre-biopsy ASA score of 1 or 2 and mRs equal to 2 or less. The rate of same-day discharge was 100%. No patient experienced post-biopsy symptomatic complication necessitating readmission within the month following the biopsy. One patient (2.5%) resorted to an unplanned consultation. Histological findings obtained from brain biopsy led to a diagnosis in all patients; the most frequently found were neoplastic lesions (77.5%). Stereotactic brain biopsies can therefore be safely achieved on an outpatient setting in carefully selected patients. This process could be more widely adopted in other neurosurgical centers, without affecting the quality of patient's health care and safety. In this article, we propose management guidelines and pre-biopsy checklist for performing ambulatory stereotactic brain biopsies. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM), the most common primary brain tumor in adults, is usually rapidly fatal with median survival duration of only 15 months and a 3-year survival rate of <7 %. Temozolomide (TMZ) is the only anticancer drug that has improved survival in GBM when administered with concomitant radiotherapy. Irinotecan (CPT-11) has also shown efficacy in recurrent gliomas monotherapy with moderate response. As the efficacy of GBM treatments relies on their brain distribution through the blood-brain barrier (BBB), the aim of the present work was to study, on an in vivo model, the brain distribution of TMZ, CPT-11 and its active metabolite, SN-38. We have focussed on the role of ABCB1, the main efflux transporter at the BBB level, through pharmacokinetics studies in CF1 mdr1a (+/+) and mdr1a (−/−) mice. Our results show that TMZ, CPT-11 and SN-38 are transported by ABCB1 at the BBB level with brain/plasma ratios of 1.1, 2.1 and 2.3, respectively. [ABSTRACT FROM AUTHOR]

Despite the popularity of stable isotope analysis (Carbon and Nitrogen), the drivers of species isotopic niches and their consequences on food web functioning remained poorly described, especially in estuaries. Here, we hypothesised that species niche characteristics are influenced by ecosystem hydro-morphological features and the functional structure of fish assemblages. The trophic niches of four fish species (Dicentrarchus labrax, Pomatoschistus minutus, Sprattus and Platichthys flesus) and overlap between them were compared during two consecutive autumns in eight estuarine ecosystems of the northeast Atlantic Ocean. Our findings demonstrated a relative steadiness of trophic positions of fish in estuaries, despite a high level of interspecific variability. The seabass generally occupied the higher trophic position, followed by the sand goby, while the flounder and sprat were at the lowest position in the food web. Species isotopic niches and overlap were mediated by some estuarine features, including estuary size and intertidal extent, but also by biotic interactions at the intra- and inter-specific levels, as reflected by the influence of fish abundance and functional diversity metrics. Our results support the statement that the intertidal area is a pivotal factor in regulating trophic interactions, by promoting niche partitioning and diversification of trophic resources between species. Moreover, niche size and dietary divergence of species decreased with increasing regularity of trophic strategies within assemblages, suggesting that species occupied more restricted trophic niches when they were less subjected to competition for the same food resources. These findings emphasize the importance of local conditions and the functional composition of assemblages in modulating the trophic resources consumed by fish in estuarine environments. [Display omitted] • Trophic niches of four fishes were investigated across eight estuaries. • Species isotopic niches were influenced by functional diversity of assemblages. • Niche size and divergence decreased with functional divergence and evenness. • Intra- and inter-specific interactions affect species niches and overlap. • Intertidal area promote niche partitioning and diversification of trophic resources. [ABSTRACT FROM AUTHOR]

The temporal asynchronies in larvae production from different spawning areas are fundamental components for ensuring stability and resilience of marine metapopulations. Such a concept, named portfolio effect, supposes that diversifying larval dispersal histories should minimize the risk of recruitment failure by increasing the probability that at least some larvae successfully settle in nursery. Here, we used a reconstructive approach based on otolith chemistry to quantify the larval dispersal portfolio of the European seabass, Dicentrarchus labrax , across six estuarine nursery areas of the northeast Atlantic Ocean. The analysis of natal and trajectory signatures indicated that larvae hatch in distinct environments and then dispersed in water masses featured by contrasting chemical signatures. While some trace elements appeared affected by temporal changes (Mn and Sr), others varied spatially during the larval stage but remained poorly affected by temporal fluctuation and fish physiology (Ba, Cu, Rb and Zn). We then proposed two diversity metrics based on richness and variations of chemical signatures among populations to reflect spatio-temporal diversity in natal origins and larval trajectories (i.e., estimates of dispersal portfolio). Along the French coast, the diversity estimates were maximum in nurseries located at proximity of offshore spawning sites and featured by complex offshore hydrodynamic contexts, such as the Mont St-Michel bay. Finally, our findings indicate that the dispersal portfolio was positively related with the local abundance of seabass juveniles, supporting the assumption that heterogeneity in dispersal history contributes to promote recruitment success in nurseries. [Display omitted] • Larval dispersal portfolio of seabass was quantified based on otolith chemistry. • Otolith signatures reflect spatio-temporal changes of marine environment. • Larvae hatch and disperse in distinct environments between estuarine nurseries. • Diversity in natal origins and larval trajectories depends on hydrodynamic context. • Heterogeneity in dispersal history promotes juvenile abundance in fish nurseries. [ABSTRACT FROM AUTHOR]

Purpose: Focused ultrasound (FUS) is a promising tool to develop new modalities of therapeutic neurostimulation. The ability of FUS to stimulate the nervous system, in a noninvasive and spatiotemporally precise manner, has been demonstrated in animals and human subjects, but the underlying biomechanisms are not fully understood yet. The objective of the present study was to investigate the bioeffects involved in the generation of trains of action potentials (APs) by repetitive‐pulse FUS stimuli in a simple invertebrate neural model. Methods: The respective influences of different acoustic parameters on the neurostimulation success rate (NSR), defined as the rate of FUS stimuli capable of evoking at least one AP, were explored using the system of afferent nerves and giant fibers of Lumbricus terrestris as neural model. Each parameter was studied independently by administering random FUS sequences while keeping all but one FUS parameter constant. The NSR was evaluated as a function of (i) the spatial‐average pulse‐average intensity (Isapa); (ii) the pulse duration (PD); (iii) the pulse repetition frequency (PRF); iv) the number of cycles per pulse (Ncycles); (v) two ultrasound frequencies, f0 = 1.1 MHz and f3 = 3.3 MHz, corresponding to the fundamental and third‐harmonic resonant frequencies of the FUS transducer, respectively (spherical, radius of curvature: 50 mm); and (vi) levels of emerging stable cavitation and inertial cavitation. Results: The NSR associated to 1.1 MHz repetitive‐pulse FUS stimuli was found to increase as a function of increasing Isapa, PD, PRF, and Ncycles. When evaluating each parameter at f = 1.1 MHz, it was observed that NSRs close to 100% were achieved when sufficiently elevating their respective values. When computing the NSR as a function of the spatial‐average, temporal‐average intensity (Isata), defined as the product of PRF, PD, and Isapa, a significant elevation of the NSR from 0% to close to 100% was measured by increasing Isata from values approximate to 4 W/cm2 to values higher than 12 W/cm2. No clear and consistent trend was observed in trials aimed at exploring the effects of different levels of stable and inertial acoustic cavitation on the NSR. Finally, the feasibility of inducing neural responses with 3.3 MHz repetitive‐pulse FUS stimuli was also demonstrated with NSRs reaching up to 60%, in the range of FUS parameters studied. Conclusion: The time‐averaged value of the radiation force per unit volume of tissue is proportional to the acoustic intensity. As a result, the observations from this study suggest that the neural structure responding to the stimulus is sensitive to the mean radiation force carried by the FUS sequence, regardless of the combination of FUS parameters giving rise to such force. The results from this study further revealed the existence of a minimal activation threshold with regard to Isapa. [ABSTRACT FROM AUTHOR]

Abstract: Hepatotoxic microcystins (MCs) produced by cyanobacteria are known to accumulate in gastropods following grazing of toxic cyanobacteria and/or absorption of MCs dissolved in water, with adverse effects on life history traits demonstrated in the laboratory. In the field, such effects may vary depending on species, according to their relative sensitivity and ecology. The aims of this study were to i) establish how various intensities of MC-producing cyanobacteria proliferations alter the structure of gastropod community and ii) compare MC tissue concentration in gastropods in the field with those obtained in our previous laboratory experiments on the prosobranch Potamopyrgus antipodarum and the pulmonate Lymnaea stagnalis. We explored these questions through a one-year field study at three stations at Grand-Lieu Lake (France) affected by different intensities of cyanobacteria proliferations. A survey of the community structure and MC content of both cyanobacteria and gastropods was associated with a caging experiment involving P. antipodarum and L. stagnalis. In total, 2592 gastropods belonging to 7 prosobranch and 16 pulmonate species were collected. However, distribution among the stations was unequal with 62% vs 2% of gastropods sampled respectively at the stations with the lowest vs highest concentrations of MC. Irrespective of the station, pulmonates were always more diverse, more abundant and occurred at higher frequencies than prosobranchs. Only the pulmonate Physa acuta occurred at all stations, with abundance and MC tissue concentration (≤4.32µggDW−1) depending on the degrees of MC-producing cyanobacteria proliferations in the stations; therefore, P. acuta is proposed as a potential sentinel species. The caging experiment demonstrated a higher MC accumulation in L. stagnalis (≤0.36µggDW−1 for 71% of individuals) than in P. antipodarum (≤0.02µggDW−1 for 12%), corroborating previous laboratory observations. Results are discussed in terms of differential gastropod sensitivity and MC transfer through the food web. [Copyright &y& Elsevier]

The black bullhead (Ameiurus melas) is a North American species that has successfully established populations throughout Europe. The main management policy to regulate its population in France is systematic mass removal by fishers, but the efficiency of this measure has not been evaluated. In the Grande Briëre Motiërre marsh (northwest France), this species currently dominates the fish assemblage. We sampled this black bullhead population with trap nets and by electrofishing. The non-commercial fishery was also surveyed. Length-frequency distributions were significantly different between trapped individuals and those sampled by electrofishing, suggesting a size-selectivity of trap nets. Abundance of black bullhead was negatively correlated with the fishermen activity, measured at variable locations of the study site. The young-of-the-year / adult ratio was constant at each site, suggesting that black bullhead might not compensate for fishing mortality with increased recruitment. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) in patients with severe head injury allows comprehensive assessment of the primary insult thus providing an indicator of possible long term prognosis. Morphological images can now be coupled to metabolic analysis, thus providing a more precise assessment of brain lesions and opening a new exciting field of research. [ABSTRACT FROM AUTHOR]

Background: Cerebral cavernous malformations (CCMs) are common sporadic and inherited vascular malformations of the central nervous system. Although familial CCMs are linked to loss-of-function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood.Methods: We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis.Results: We found that in mice expressing one of two common genetic drivers of meningioma - Pik3caH1047R or AKT1E17K - in PGDS-positive cells, a spectrum of typical CCMs develops (in 22% and 11% of the mice, respectively) instead of meningiomas, which prompted us to analyze tissue samples from sporadic CCMs from 88 patients. We detected somatic activating PIK3CA and AKT1 mutations in 39% and 1%, respectively, of lesion tissue from the patients. Only 10% of lesions harbored mutations in the CCM genes. We analyzed lesions induced by the activating mutations Pik3caH1074R and AKT1E17K in mice and identified the PGDS-expressing pericyte as the probable cell of origin.Conclusions: In tissue samples from sporadic CCMs, mutations in PIK3CA were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.). [ABSTRACT FROM AUTHOR]

Mini: The incidence of spinal metastasis (SpM) is increasing, and life expectancy for patients with malignancy is also rising. The "elderly" represent a population with steady growth in SpM proportion. Bracing is associated with lower survival. We believe that surgery should be considered, regardless of the patient's age. [ABSTRACT FROM AUTHOR]

Previous studies reported interest in intraoperative shear-wave elastography (SWE) guidance for brain-tumor and epilepsy surgeries. Focal cortical dysplasia (FCD) surgery is one of the most appropriate indications for using SWE guidance. The aim of this study was to evaluate the efficacy of ultrasound SWE techniques for the intraoperative detection of FCDs. We retrospectively analyzed data from 18 adult patients with drug-resistant epilepsy associated with FCD who had undergone SWE-guided surgery. Conventional B-mode images detected FCD in 2 patients (11.1%), while SWE detected FCD in 14 patients (77.8%). The stiffness ratios between MRI-positive and -negative cases were significantly different (3.6 ± 0.4 vs. 2.2 ± 0.6, respectively; p < 0.001). FCDs were significantly more frequently detected by interoperative SWE in women (OR 4.7, 95% CI (1.7–12.7); p = 0.004) and in patients in whom FCD was visible on magnetic resonance imaging (MRI; OR 2.3, 95% CI (1.3–4.3); p = 0.04). At 1 year after surgery and at last follow-up (mean = 21 months), seizure outcome was good (International League Against Epilepsy (ILAE) Class 1 or 2) in 72.2% and 55.6% of patients, respectively. Despite some limitations, our study highlighted the potential of SWE as an intraoperative tool to detect FCD. Future technical developments should allow for optimizing intraoperative surgical-cavity evaluation from the perspective of complete FCD resection. Interobserver reliability of SWE measurements should also be assessed by further studies. [ABSTRACT FROM AUTHOR]