French Defence Health Service

Neuroinflammation is central to temporal lobe epilepsy, yet the specific role of myeloid cells remains unclear. In status epilepticus (SE) models, circulating monocytes infiltrate the brain, although distinguishing them from microglia is challenging. Using a rat model, we traced infiltrating monocytes post-SE to investigate their persistence, phenotypic evolution during epileptogenesis and contribution to neuroinflammation. By tracking phagocytosed fluorescent nanoparticles and performing CD68 immunohistochemistry, we confirmed that monocytes entered the brain in significant numbers 24 hours post-SE, after the inflammatory peak occurred (7 hours). Their long-term presence and evolution into monocyte-macrophages (mo-mΦs) up to 7 weeks were monitored histologically using CD68. Distinct inflammatory profiles were further characterized after cell enrichment and fluorescence-activated cell sorting (FACS) distinguishing monocytes/mo-mΦs (CD11b+CD45hiCD11ahi) from microglia (CD11b+CD45loCD11alo). Microglia were the main drivers of the early pro-inflammatory response, with TNFα transcript levels nearly 14-fold higher in microglia than in monocytes 24h post-SE. In contrast, 24h post-SE, infiltrating monocytes transiently displayed an anti-inflammatory and neuroprotective phenotype, being the main source of IL-10, showing ~4-fold higher CD206, and expressing Arg1 absent in microglia. Tracked up to 7 weeks, these cells progressively adopted a microglia-like phenotype, contributed to the microglial scar and, although their expression of pro-inflammatory markers resembled nonactivated microglia, we hypothesize that their persistent presence might fuel the low-grade inflammation typical of chronic epilepsy. Importantly, since infiltrating monocytes initially engage in a transient anti-inflammatory response, strategies aiming to sustain or enhance this protective role in the context of epileptogenesis and epilepsy may open promising avenues for therapeutic intervention.

Background.The heartbeat evoked potential (HEP) is a brain response time-locked to the heartbeat and a potential marker of interoceptive processing. The insula and dorsal anterior cingulate cortex (dACC) are brain regions that may be involved in generating the HEP. Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique that can selectively target sub-regions of the insula and dACC to better understand their contributions to the HEP.Objective.Proof-of-concept study to determine whether LIFU modulation of the anterior insula (AI), posterior insula (PI), and dACC influences the HEP.Methods.In a within-subject, repeated-measures design, healthy human participants (n=16) received 10 minutes of stereotaxically targeted LIFU to the AI, PI, dACC or Sham at rest during continuous electroencephalography (EEG) and electrocardiography (ECG) recording on separate days. Primary outcome was change in HEP amplitudes. Relationships between LIFU pressure and HEP changes were examined using linear mixed modelling. Peripheral indices of visceromotor output including heart rate and heart rate variability (HRV) were explored between conditions.Results.Relative to sham, LIFU to the PI, but not AI or dACC, decreased HEP amplitudes; this was partially explained by increased LIFU pressure. LIFU did not affect time or frequency dependent measures of HRV.Conclusions.These results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions. Our findings have implications for the causal role of these areas in bottom-up heart-brain communication that could guide future work investigating the HEP as a marker of interoceptive processing in healthy and clinical populations.

Quantifying gait using inertial measurement units has gained increasing interest in recent years. Highly degraded gaits, especially in neurological impaired patients, challenge gait detection algorithms and require specific segmentation and analysis tools. Thus, the outcomes of these devices must be rigorously tested for both robustness and relevancy in order to recommend their routine use. In this study, we propose a multidimensional score to quantify and visualize gait, which can be used in neurological routine follow-up. We assessed the reliability and clinical coherence of this method in a group of severely disabled patients with progressive multiple sclerosis (pMS), who display highly degraded gait patterns, as well as in an age-matched healthy subjects (HS) group. Twenty-two participants with pMS and nineteen HS were included in this 18-month longitudinal follow-up study. During the follow-up period, all participants completed a 10-meter walk test with a U-turn and back, twice at M0, M6, M12, and M18. Average speed and seven clinical criteria (sturdiness, springiness, steadiness, stability, smoothness, synchronization, and symmetry) were evaluated using 17 gait parameters selected from the literature. The variation of these parameters from HS values was combined to generate a multidimensional visual tool, referred to as a semiogram. For both cohorts, all criteria showed moderate to very high test-retest reliability for intra-session measurements. Inter-session quantification was also moderate to highly reliable for all criteria except smoothness, which was not reliable for HS participants. All partial scores, except for the stability score, differed between the two populations. All partial scores were correlated with an objective but not subjective quantification of gait severity in the pMS population. A deficit in the pyramidal tract was associated with altered scores in all criteria, whereas deficits in cerebellar, sensitive, bulbar, and cognitive deficits were associated with decreased scores in only a subset of gait criteria. The proposed multidimensional gait quantification represents an innovative approach to monitoring gait disorders. It provides a reliable and informative biomarker for assessing the severity of gait impairments in individuals with pMS. Additionally, it holds the potential for discriminating between various underlying causes of gait alterations in pMS.

Here we trace the origin of travel-acquired microcephaly to Thailand, providing additional evidence that pre-American lineages of Zika virus can harm the fetus and highlighting that Zika virus constitutes a health threat even in a year of lower incidence.

Abstract BackgroundDuring the height of the COVID-19 pandemic in 2020, 11% of patients who were hospitalized in France were immediately admitted to intensive care. We aimed to identify and characterize the different types of primary care pathways of patients hospitalized for COVID-19 using patients’ self-reported experiences.MethodWe conducted a qualitative study using biographic interviews of patients who were hospitalized for COVID-19 between September 2020 and December 2021 in the infectious disease departments in Marseille and Nice. The biographical interviews used a life-events calendar approach to understand the sequences of clinical and care events prior to hospitalization.Results31 pathways were described. Short care pathways (i.e., admission to hospital ≤ 3 days after symptom onset) were more likely to be reported by older patients and those with comorbidities. These pathways were characterized by closer GP surveillance and by sudden symptom onset and rapid progression of the disease. Long care pathways (i.e., >10 days after system onset) were reported more by younger patients with no comorbidities. Multiple tests and medical consultations returning false-negatives had led this population to doubt they had COVID-19. They were more likely to present severe symptoms requiring intensive care. The study revealed key importance of patients’ loved ones in the process of their hospitalization.ConclusionThis study highlights that primary care management of COVID-19 patients needing hospitalization in France was particularly slow and detrimental to their health. It also underlines the need to improve the identification and monitoring of patients at risk of complications.

Abstract Background: While professionals working in chemical, biological, radiological, and nuclear (CBRN) environments have underlined the need to improve the psychological and operational safety of personnel, there are few data regarding the stress induced in responders who must wear CBRN equipment. These conditions are particularly restrictive, both due to the risk of exposure to life-threatening toxic agents, and the need to wear equipment that places demand on their psychological, cognitive, and physiological capacities. Inter-individual variability remains poorly understood. Current research recognizes that the activity of the parasympathetic system (PSS) can be used as an objective marker of stress adaptation, measured as heart rate variability (HRV). Methods:28 members of the Paris Fire Brigade medical team attended to three simulated scenarios requiring CBRN management of casualties. We examine: (i) anxiety, emotions, coping, body awareness, cognitive load, HRV, and exteroception impacts of working in CBRN environment; (ii) the role of PSS functioning in stress responses; and (iii) recovery. We recorded for three days: before the simulations (baseline), simulations’ day (pre- and post-training), and the following day. Results show: (i) a high level of anxiety at baseline (Median 51 [46;56]) which decreased between pre- and post-training (p = 0.02); (ii) a post-simulation decrease in negative affect (p = 0.03); (iii) a tendency to decrease in body awareness during simulation (p = 0.06), which returned to the initial level at follow-up (p = 0.07); and (iv) decrease in mean RR between baseline and post-simulation n°1 (p = 0.04), and between baseline and post-training (p= 0.01). Clustering analysis based on the post-training median RMSSD: (i.e., stress-adapted subject versus non-stress-adapted subject) shows that stress-adapted subject tends to have more positive affect (p=0.006), a higher mean RR (p = 0.014) and SDNN (p = 0.005). The autonomic nervous system (ANS) shows different kinetics: the PSS activity increases post simulation in stress-adapted subject, and collapse between baseline, pre- and post-training in non-stress-adapted subject (p = 0.002). The sympathetic activity tends to increase in stress-adapted subject between baseline, pre- and post-simulation and tend to decrease in non-stress-adapted subject. Conclusion: stress-adapted subject has a hardiness psycho-physiological response under CBRN stress.

Macrophages play a key role in the inflammatory phase of wound repair and foreign body reactions-two important processes in the Masquelet-induced membrane technique for extremity reconstruction. The macrophage response depends largely on the nature of the biomaterials implanted. However, little is known about the influence of the macrophage microenvironment on the osteogenic properties of the induced membrane or subsequent bone regeneration. We used metakaolin, an immunogenic material, as an alternative spacer to standard polymethylmethacrylate (PMMA) in a Masquelet model in rats. Four weeks after implantation, the PMMA- and metakaolin-induced membranes were harvested, and their osteogenic properties and macrophage microenvironments were investigated by histology, immunohistochemistry, mass spectroscopy and gene expression analysis. The metakaolin spacer induced membranes with higher levels of two potent pro-osteogenic factors, transforming growth factor-β (TGF-β) and bone morphogenic protein-2 (BMP-2). These alternative membranes thus had greater osteogenic activity, which was accompanied by a significant expansion of the total macrophage population, including both the M1-like and M2-like subtypes. Microcomputed tomographic analysis showed that metakaolin-induced membranes supported bone regeneration more effectively than PMMA-induced membranes through better callus properties (+58%), although this difference was not significant. This study provides the first evidence of the influence of the immune microenvironment on the osteogenic properties of the induced membranes.