The local microenvironment drives activation of neutrophils in human brain tumors.

Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors in substantial numbers. However, their precise functions in different cancer types remain incompletely understood, including in the brain microenvironment. We therefore investigated neutrophils in tumor tissue of glioma and brain metastasis patients, with matched peripheral blood, and herein describe the first in-depth analysis of neutrophil phenotypes and functions in these tissues. Orthogonal profiling strategies in humans and mice revealed that brain tumor-associated neutrophils (TANs) differ significantly from blood neutrophils and have a prolonged lifespan and immune-suppressive and pro-angiogenic capacity. TANs exhibit a distinct inflammatory signature, driven by a combination of soluble inflammatory mediators including tumor necrosis factor alpha (TNF-ɑ) and Ceruloplasmin, which is more pronounced in TANs from brain metastasis versus glioma. Myeloid cells, including tumor-associated macrophages, emerge at the core of this network of pro-inflammatory mediators, supporting the concept of a critical myeloid niche regulating overall immune suppression in human brain tumors.

Fine motor control improves in older adults after 1 year of piano lessons: Analysis of individual development and its coupling with cognition and brain structure.

Musical training can improve fine motor skills and cognitive abilities and induce macrostructural brain changes. However, it is not clear whether the changes in motor skills occur simultaneously with changes in cognitive and neurophysiological parameters. In this study, 156 healthy, musically naïve and right-handed older adults were recruited and randomly assigned to a piano training or a music listening group. Before, after 6 and 12 months, participants were scanned using MRI and assessed for fine motor skills, auditory working memory and processing speed. A Bayesian multilevel modelling approach was used to examine behavioural and neurophysiological group differences. The relationships between motor and cognitive and between motor and neurophysiological parameters were determined using latent change score models. Compared with music listening, practicing piano resulted in greater improvement in fine motor skills and probably working memory. Only in the piano group, unimanual fine motor skills and grey matter volume of the contralateral M1 changed together during the 6-12-month period. Additionally, M1 co-developed with ipsilateral putamen and thalamus. Playing piano induced more prevalent coupling between the motor and cognitive domains. However, there is little evidence that fine motor control develops concurrently with cognitive functions. Playing an instrument promotes motor, cognitive and neural development into older age. During the learning process, the consolidation of piano skills appears to take place in sensorimotor networks, enabling musicians to perform untrained motor tasks with higher acuity. Relationships between the development of motor acuity and cognition were bidirectional and can be explained by a common cause as well as by shared resources with compensatory mechanisms.

Early non-invasive ventilation and high-flow nasal oxygen therapy for preventing endotracheal intubation in hypoxemic blunt chest trauma patients: the OptiTHO randomized trial.

BACKGROUND: The benefit-risk ratio of prophylactic non-invasive ventilation (NIV) and high-flow nasal oxygen therapy (HFNC-O2) during the early stage of blunt chest trauma remains controversial because of limited data. The main objective of this study was to compare the rate of endotracheal intubation between two NIV strategies in high-risk blunt chest trauma patients. METHODS: The OptiTHO trial was a randomized, open-label, multicenter trial over a two-year period. Every adult patients admitted in intensive care unit within 48 h after a high-risk blunt chest trauma (Thoracic Trauma Severity Score ≥ 8), an estimated PaO2/FiO2 ratio < 300 and no evidence of acute respiratory failure were eligible for study enrollment (Clinical Trial Registration: NCT03943914). The primary objective was to compare the rate of endotracheal intubation for delayed respiratory failure between two NIV strategies: i) a prompt association of HFNC-O2 and "early" NIV in every patient for at least 48 h with vs. ii) the standard of care associating COT and "late" NIV, indicated in patients with respiratory deterioration and/or PaO2/FiO2 ratio ≤ 200 mmHg. Secondary outcomes were the occurrence of chest trauma-related complications (pulmonary infection, delayed hemothorax or moderate-to-severe ARDS). RESULTS: Study enrollment was stopped for futility after a 2-year study period and randomization of 141 patients. Overall, 11 patients (7.8%) required endotracheal intubation for delayed respiratory failure. The rate of endotracheal intubation was not significantly lower in patients treated with the experimental strategy (7% [5/71]) when compared to the control group (8.6% [6/70]), with an adjusted OR = 0.72 (95%IC: 0.20-2.43), p = 0.60. The occurrence of pulmonary infection, delayed hemothorax or delayed ARDS was not significantly lower in patients treated by the experimental strategy (adjusted OR = 1.99 [95%IC: 0.73-5.89], p = 0.18, 0.85 [95%IC: 0.33-2.20], p = 0.74 and 2.14 [95%IC: 0.36-20.77], p = 0.41, respectively). CONCLUSION: A prompt association of HFNC-O2 with preventive NIV did not reduce the rate of endotracheal intubation or secondary respiratory complications when compared to COT and late NIV in high-risk blunt chest trauma patients with non-severe hypoxemia and no sign of acute respiratory failure. CLINICAL TRIAL REGISTRATION: NCT03943914, Registered 7 May 2019.

Train the brain with music (TBM): brain plasticity and cognitive benefits induced by musical training in elderly people in Germany and Switzerland, a study protocol for an RCT comparing musical instrumental practice to sensitization to music.

BACKGROUND: Recent data suggest that musical practice prevents age-related cognitive decline. But experimental evidence remains sparse and no concise information on the neurophysiological bases exists, although cognitive decline represents a major impediment to healthy aging. A challenge in the field of aging is developing training regimens that stimulate neuroplasticity and delay or reverse symptoms of cognitive and cerebral decline. To be successful, these regimens should be easily integrated in daily life and intrinsically motivating. This study combines for the first-time protocolled music practice in elderly with cutting-edge neuroimaging and behavioral approaches, comparing two types of musical education. METHODS: We conduct a two-site Hannover-Geneva randomized intervention study in altogether 155 retired healthy elderly (64-78) years, (63 in Geneva, 92 in Hannover), offering either piano instruction (experimental group) or musical listening awareness (control group). Over 12 months all participants receive weekly training for 1 hour, and exercise at home for ~ 30 min daily. Both groups study different music styles. Participants are tested at 4 time points (0, 6, and 12 months & post-training (18 months)) on cognitive and perceptual-motor aptitudes as well as via wide-ranging functional and structural neuroimaging and blood sampling. DISCUSSION: We aim to demonstrate positive transfer effects for faculties traditionally described to decline with age, particularly in the piano group: executive functions, working memory, processing speed, abstract thinking and fine motor skills. Benefits in both groups may show for verbal memory, hearing in noise and subjective well-being. In association with these behavioral benefits we anticipate functional and structural brain plasticity in temporal (medial and lateral), prefrontal and parietal areas and the basal ganglia. We intend exhibiting for the first time that musical activities can provoke important societal impacts by diminishing cognitive and perceptual-motor decline supported by functional and structural brain plasticity. TRIAL REGISTRATION: The Ethikkomission of the Leibniz Universität Hannover approved the protocol on 14.08.17 (no. 3604-2017), the neuroimaging part and blood sampling was approved by the Hannover Medical School on 07.03.18. The full protocol was approved by the Commission cantonale d'éthique de la recherche de Genève (no. 2016-02224) on 27.02.18 and registered at clinicaltrials.gov on 17.09.18 ( NCT03674931 , no. 81185).

Acute respiratory failure: nonintubation assist methods for the acutely deteriorating patient.

PURPOSE OF REVIEW: Noninvasive ventilation is strongly recommended in acute hypercapnic respiratory failure, whereas high-flow nasal oxygen therapy could be an alternative in de novo respiratory failure. RECENT FINDINGS: High-flow nasal oxygen may improve the outcome of patients de novo respiratory failure as compared with standard oxygen. Its success within 2 h after initiation is well predicted by a ROX index (ratio of SpO2/FiO2 to respiratory rate) greater than 4.88, as failure when less than 3.85 at 12 h after initiation. However, the superiority of high-flow nasal oxygen to standard oxygen has not been confirmed in immunocompromised patients. Although noninvasive ventilation may be deleterious through barotrauma in patients with de novo respiratory failure, its use seems to be an optimal strategy for preoxygenation before intubation in preventing severe hypoxemia in most hypoxemic patients. In mild hypoxemic patient, high-flow nasal oxygen may be more efficient than bag-valve mask in preventing severe adverse events. After anesthetic induction further positive-pressure ventilation can better secure intubation procedure than absence of ventilation. SUMMARY: Despite the growing use of high-flow nasal oxygen, new studies are needed to confirm its superiority to standard oxygen in de novo respiratory failure and others causes of acute respiratory failure in place of standard oxygen.

Left Brain Asymmetry of the Planum Temporale in a Nonhominid Primate: Redefining the Origin of Brain Specialization for Language.

The planum temporale (PT) is a critical region of the language functional network in the human brain showing a striking size asymmetry toward the left hemisphere. Historically considered as a structural landmark of the left-brain specialization for language, a similar anatomical bias has been described in great apes but never in monkeys-indicating that this brain landmark might be unique to Hominidae evolution. In the present in vivo magnetic resonance imaging study, we show clearly for the first time in a nonhominid primate species, an Old World monkey, a left size predominance of the PT among 96 olive baboons (Papio anubis), using manual delineation of this region in each individual hemisphere. This asymmetric distribution was quasi-identical to that found originally in humans. Such a finding questions the relationship between PT asymmetry and the emergence of language, indicating that the origin of this cerebral specialization could be much older than previously thought, dating back, not to the Hominidae, but rather to the Catarrhini evolution at the common ancestor of humans, great apes and Old World monkeys, 30-40 million years ago.

Impact of sleep alterations on weaning duration in mechanically ventilated patients: a prospective study.

Sleep is markedly altered in intensive care unit (ICU) patients and may alter respiratory performance. Our objective was to assess the impact of sleep alterations on weaning duration.We conducted a prospective physiological study at a French teaching hospital. ICU patients intubated for at least 24 h and difficult to wean were included. Complete polysomnography (PSG) was performed after the first spontaneous breathing trial failure. Presence of atypical sleep, duration of sleep stages, particularly rapid eye movement (REM) sleep, and electroencephalogram (EEG) reactivity at eyes opening were assessed by a neurologist.20 out of 45 patients studied (44%) had atypical sleep that could not be classified according to the standard criteria. Duration of weaning between PSG and extubation was significantly longer in patients with atypical sleep (median (interquartile range) 5 (2-8) versus 2 (1-2) days; p=0.001) and in those with no REM sleep compared with the others. Using multivariate logistic regression analysis, atypical sleep remained independently associated with prolonged weaning (>48 h after PSG). Altered EEG reactivity at eyes opening was a good predictor of atypical sleep.Our results suggest for the first time that brain dysfunction may have an influence on the ability to breathe spontaneously.

The average baboon brain: MRI templates and tissue probability maps from 89 individuals.

The baboon (Papio) brain is a remarkable model for investigating the brain. The current work aimed at creating a population-average baboon (Papio anubis) brain template and its left/right hemisphere symmetric version from a large sample of T1-weighted magnetic resonance images collected from 89 individuals. Averaging the prior probability maps output during the segmentation of each individual also produced the first baboon brain tissue probability maps for gray matter, white matter and cerebrospinal fluid. The templates and the tissue probability maps were created using state-of-the-art, freely available software tools and are being made freely and publicly available: http://www.nitrc.org/projects/haiko89/ or http://lpc.univ-amu.fr/spip.php?article589. It is hoped that these images will aid neuroimaging research of the baboon by, for example, providing a modern, high quality normalization target and accompanying standardized coordinate system as well as probabilistic priors that can be used during tissue segmentation.

Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.

Objective: Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma. Methods: Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals. Results: The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma. Conclusions: MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.

Planum temporale asymmetry in newborn monkeys predicts the future development of gestural communication's handedness.

The planum temporale (PT), a key language area, is specialized in the left hemisphere in prelinguistic infants and considered as a marker of the pre-wired language-ready brain. However, studies have reported a similar structural PT left-asymmetry not only in various adult non-human primates, but also in newborn baboons. Its shared functional links with language are not fully understood. Here we demonstrate using previously obtained MRI data that early detection of PT left-asymmetry among 27 newborn baboons (Papio anubis, age range of 4 days to 2 months) predicts the future development of right-hand preference for communicative gestures but not for non-communicative actions. Specifically, only newborns with a larger left-than-right PT were more likely to develop a right-handed communication once juvenile, a contralateral brain-gesture link which is maintained in a group of 70 mature baboons. This finding suggests that early PT asymmetry may be a common inherited prewiring of the primate brain for the ontogeny of ancient lateralised properties shared between monkey gesture and human language.

Impact of Radial Arterial Location on Catheter Lifetime in ICU Surgical Intensive Care.

The use of arterial catheters is frequent in intensive care for hemodynamic monitoring of patients and for blood sampling, but they are often removed because of dysfunction. The primary objective is to compare the prevalence of radial arterial catheter dysfunction according to location in relation to the radiocarpal joint in intensive care patients. DESIGN: Prospective randomized, controlled, single-center study. SETTING: The surgical ICU of the university hospital of Poitiers in France. PATIENTS: From January 2016 to April 2017, all patients over 18 years old admitted to the surgical ICU and requiring an arterial catheter were included. INTERVENTIONS: Randomization into two groups: catheter placed near the wrist (within 4 cm of the radiocarpal joint) and catheter placed away the wrist. The primary endpoint was the prevalence of dysfunction. We also compared the prevalence of infection and colonization. MEASUREMENTS AND MAIN RESULTS: One hundred seven catheters were analyzed (14 failed placements with no difference between the two groups, and 16 catheters excluded for missing data), with 58 catheters in near the wrist group and 49 in away the wrist group. We did not find any significant difference in the number of catheter dysfunctions between the two groups (p = 0.56). The prevalence density of catheter dysfunction was 30.5 of 1,000 catheter days for near the wrist group versus 26.7 of 1,000 catheter days for away the wrist group. However, we observed a significant difference in terms of catheter-related infection in favor of away the wrist group (p = 0.04). In addition, distal positioning of the catheter was judged easier by the physicians. CONCLUSIONS: The distal or proximal position of the arterial catheter in the radial position has no influence on the occurrence of dysfunction. However, there may be an association with the prevalence of infections.

Increased functional connectivity in the right dorsal auditory stream after a full year of piano training in healthy older adults.

Learning to play an instrument at an advanced age may help to counteract or slow down age-related cognitive decline. However, studies investigating the neural underpinnings of these effects are still scarce. One way to investigate the effects of brain plasticity is using resting-state functional connectivity (FC). The current study compared the effects of learning to play the piano (PP) against participating in music listening/musical culture (MC) lessons on FC in 109 healthy older adults. Participants underwent resting-state functional magnetic resonance imaging at three time points: at baseline, and after 6 and 12 months of interventions. Analyses revealed piano training-specific FC changes after 12 months of training. These include FC increase between right Heschl's gyrus (HG), and other right dorsal auditory stream regions. In addition, PP showed an increased anticorrelation between right HG and dorsal posterior cingulate cortex and FC increase between the right motor hand area and a bilateral network of predominantly motor-related brain regions, which positively correlated with fine motor dexterity improvements. We suggest to interpret those results as increased network efficiency for auditory-motor integration. The fact that functional neuroplasticity can be induced by piano training in healthy older adults opens new pathways to countervail age related decline.

Sleep Assessment in Critically Ill Patients With Acute Hypoxemic Respiratory Failure.

BACKGROUND: Sleep deprivation alters respiratory muscle performance and may precipitate respiratory failure. This study aimed to assess sleep in subjects admitted to ICU for acute hypoxemic respiratory failure and its role in the risk of intubation. METHODS: This was a prospective observational single-center cohort study including subjects admitted to ICU for de novo acute hypoxemic respiratory failure defined as breathing frequency ≥ 25 breaths/min or clinical signs of respiratory distress and PaO2 /FIO2 < 300 mm Hg while receiving high-flow nasal oxygen. Subjects with altered consciousness, central nervous or psychiatric disorders, continuous sedation or neuroleptic medication, or were uncooperative were excluded. Sleep was assessed by complete polysomnography (PSG) the night following ICU admission. The main outcome was to assess sleep among subjects with acute hypoxemic respiratory failure and to compare sleep between subjects who eventually required intubation to those who did not. RESULTS: Over a 24-month inclusion period, 34 subjects had complete PSG, among whom 5 (15%) required intubation in the ICU. Total sleep time was 4.2 h in median (interquartile range 2.9-6.8); deep-sleep duration was 70 min (34-127), and rapid eye movement (REM) sleep duration was 9 min (0-28). Among them, 13 subjects (38%) had no REM sleep. Total sleep time and duration of deep and REM sleep stages did not differ between subjects who required intubation and those successfully treated with high-flow nasal oxygen. CONCLUSIONS: Whereas total sleep time remained relatively preserved in critically ill subjects with acute hypoxemic respiratory failure, REM sleep time was uncommon or completely absent in a large number of subjects. Sleep did not differ between subjects who required intubation and those who did not. However, given a trend toward an increased risk of intubation in subjects with a complete absence of REM sleep, further studies are needed to better explore the impact of REM sleep on the risk of intubation.

Broca's cerebral asymmetry reflects gestural communication's lateralisation in monkeys (Papio anubis).

Manual gestures and speech recruit a common neural network, involving Broca's area in the left hemisphere. Such speech-gesture integration gave rise to theories on the critical role of manual gesturing in the origin of language. Within this evolutionary framework, research on gestural communication in our closer primate relatives has received renewed attention for investigating its potential language-like features. Here, using in vivo anatomical MRI in 50 baboons, we found that communicative gesturing is related to Broca homologue's marker in monkeys, namely the ventral portion of the Inferior Arcuate sulcus (IA sulcus). In fact, both direction and degree of gestural communication's handedness - but not handedness for object manipulation are associated and correlated with contralateral depth asymmetry at this exact IA sulcus portion. In other words, baboons that prefer to communicate with their right hand have a deeper left-than-right IA sulcus, than those preferring to communicate with their left hand and vice versa. Interestingly, in contrast to handedness for object manipulation, gestural communication's lateralisation is not associated to the Central sulcus depth asymmetry, suggesting a double dissociation of handedness' types between manipulative action and gestural communication. It is thus not excluded that this specific gestural lateralisation signature within the baboons' frontal cortex might reflect a phylogenetical continuity with language-related Broca lateralisation in humans.

Evidence of cortical thickness increases in bilateral auditory brain structures following piano learning in older adults.

Morphological differences in the auditory brain of musicians compared to nonmusicians are often associated with life-long musical activity. Cross-sectional studies, however, do not allow for any causal inferences, and most experimental studies testing music-driven adaptations investigated children. Although the importance of the age at which musical training begins is widely recognized to impact neuroplasticity, there have been few longitudinal studies examining music-related changes in the brains of older adults. Using magnetic resonance imaging, we measured cortical thickness (CT) of 12 auditory-related regions of interest before and after 6 months of musical instruction in 134 healthy, right-handed, normal-hearing, musically-naive older adults (64-76 years old). Prior to the study, all participants were randomly assigned to either piano training or to a musical culture/music listening group. In five regions-left Heschl's gyrus, left planum polare, bilateral superior temporal sulcus, and right Heschl's sulcus-we found an increase in CT in the piano training group compared with the musical culture group. Furthermore, CT of the right Heschl's gyrus could be identified as a morphological substrate supporting speech in noise perception. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults.

Six Months of Piano Training in Healthy Elderly Stabilizes White Matter Microstructure in the Fornix, Compared to an Active Control Group.

While aging is characterized by neurodegeneration, musical training is associated with experience-driven brain plasticity and protection against age-related cognitive decline. However, evidence for the positive effects of musical training mostly comes from cross-sectional studies while randomized controlled trials with larger sample sizes are rare. The current study compares the influence of six months of piano training with music listening/musical culture lessons in 121 musically naïve healthy elderly individuals with regard to white matter properties using fixel-based analysis. Analyses revealed a significant fiber density decline in the music listening/musical culture group (but not in the piano group), after six months, in the fornix, which is a white matter tract that naturally declines with age. In addition, these changes in fiber density positively correlated to episodic memory task performances and the amount of weekly piano training. These findings not only provide further evidence for the involvement of the fornix in episodic memory encoding but also more importantly show that learning to play the piano at an advanced age may stabilize white matter microstructure of the fornix.

Role of sleep on respiratory failure after extubation in the ICU.

BACKGROUND: Sleep had never been assessed immediately after extubation in patients still in the ICU. However, sleep deprivation may alter respiratory function and may promote respiratory failure. We hypothesized that sleep alterations after extubation could be associated with an increased risk of post-extubation respiratory failure and reintubation. We conducted a prospective observational cohort study performed at the medical ICU of the university hospital of Poitiers in France. Patients at high-risk of extubation failure (> 65 years, with any underlying cardiac or lung disease, or intubated > 7 days) were included. Patients intubated less than 24 h, with central nervous or psychiatric disorders, continuous sedation, neuroleptic medication, or uncooperative were excluded. Sleep was assessed by complete polysomnography just following extubation including the night. The main objective was to compare sleep between patients who developed post-extubation respiratory failure or required reintubation and the others. RESULTS: Over a 3-year period, 52 patients had complete polysomnography among whom 12 (23%) developed post-extubation respiratory failure and 8 (15%) required reintubation. Among them, 10 (19%) had atypical sleep, 15 (29%) had no deep sleep, and 33 (63%) had no rapid eye movement (REM) sleep. Total sleep time was 3.2 h in median [interquartile range, 2.0-4.4] in patients who developed post-extubation respiratory failure vs. 2.0 [1.1-3.8] in those who were successfully extubated (p = 0.34). Total sleep time, and durations of deep and REM sleep stages did not differ between patients who required reintubation and the others. Reintubation rates were 21% (7/33) in patients with no REM sleep and 5% (1/19) in patients with REM sleep (difference, - 16% [95% CI - 33% to 6%]; p = 0.23). CONCLUSIONS: Sleep assessment by polysomnography after extubation showed a dramatically low total, deep and REM sleep time. Sleep did not differ between patients who were successfully extubated and those who developed post-extubation respiratory failure or required reintubation.

Improved Speech in Noise Perception in the Elderly After 6 Months of Musical Instruction.

Understanding speech in background noise poses a challenge in daily communication, which is a particular problem among the elderly. Although musical expertise has often been suggested to be a contributor to speech intelligibility, the associations are mostly correlative. In the present multisite study conducted in Germany and Switzerland, 156 healthy, normal-hearing elderly were randomly assigned to either piano playing or music listening/musical culture groups. The speech reception threshold was assessed using the International Matrix Test before and after a 6 month intervention. Bayesian multilevel modeling revealed an improvement of both groups over time under binaural conditions. Additionally, the speech reception threshold of the piano group decreased during stimuli presentation to the left ear. A right ear improvement only occurred in the German piano group. Furthermore, improvements were predominantly found in women. These findings are discussed in the light of current neuroscientific theories on hemispheric lateralization and biological sex differences. The study indicates a positive transfer from musical training to speech processing, probably supported by the enhancement of auditory processing and improvement of general cognitive functions.