Slow breathing and hypoxic challenge: cardiorespiratory consequences and their central neural substrates

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge

Chlamydia trachomatis-associated respiratory disease in the very early neonatal period

Of 103 preterm neonates admitted consecutively to the neonatal intensive care unit soon after birth for respiratory distress, 8 were found to be Chlamydia trachomatis-positive as early as within the first 24 h of life. All these patients required mechanical ventilation and supplemental oxygen. Six infants had evidence on chest radiographs of hyaline membrane disease, one of pneumonia, and one of slight bilateral parenchymal changes. Our results suggest that the presence of C. trachomatis in preterm infants with neonatal respiratory distress is probably not an infrequent event

Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints : a 3-year follow-up study

Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer's disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE epsilon 4 allele, comorbidities, brain amyloid-beta (A beta) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE epsilon 4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of A beta deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood

Identification and Characterization of Human Observational Studies in Nutritional Epidemiology on Gut Microbiomics for Joint Data Analysis

In any research field, data access and data integration are major challenges that even large, well-established consortia face. Although data sharing initiatives are increasing, joint data analyses on nutrition and microbiomics in health and disease are still scarce. We aimed to identify observational studies with data on nutrition and gut microbiome composition from the Intestinal Microbiomics (INTIMIC) Knowledge Platform following the findable, accessible, interoperable, and reusable (FAIR) principles. An adapted template from the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) consortium was used to collect microbiome-specific information and other related factors. In total, 23 studies (17 longitudinal and 6 cross-sectional) were identified from Italy (7), Germany (6), Netherlands (3), Spain (2), Belgium (1), and France (1) or multiple countries (3). Of these, 21 studies collected information on both dietary intake (24 h dietary recall, food frequency questionnaire (FFQ), or Food Records) and gut microbiome. All studies collected stool samples. The most often used sequencing platform was Illumina MiSeq, and the preferred hypervariable regions of the 16S rRNA gene were V3-V4 or V4. The combination of datasets will allow for sufficiently powered investigations to increase the knowledge and understanding of the relationship between food and gut microbiome in health and disease

Revolution of Resting-State Functional Neuroimaging Genetics in Alzheimer’s Disease

for the Alzheimer Precision Medicine Initiative (APMI)International audienceThe quest to comprehend genetic, biological, and symptomatic heterogeneity underlying Alzheimer’s disease (AD) requires a deep understanding of mechanisms affecting complex brain systems. Neuroimaging genetics is an emerging field that provides a powerful way to analyze and characterize intermediate biological phenotypes of AD. Here, we describe recent studies showing the differential effect of genetic risk factors for AD on brain functional connectivity in cognitively normal, preclinical, prodromal, and AD dementia individuals. Functional neuroimaging genetics holds particular promise for the characterization of preclinical populations; target populations for disease prevention and modification trials. To this end, we emphasize the need for a paradigm shift towards integrative disease modeling and neuroimaging biomarker-guided precision medicine for AD and other neurodegenerative diseases

Pancreatic Tumors in Children and Adolescents: The Italian TREP Project Experience

INTRODUCTION: Malignant pancreatic tumors are exceedingly rare in pediatric age and their clinical features and treatment usually go unappreciated by most pediatric oncologists and surgeons. METHODS: From January 2000 to July 2009, 21 patients <18 years old with pancreatic tumors were prospectively registered in the Italian cooperative TREP project dedicated to very rare pediatric tumors. RESULTS: Tumor types were 4 pancreatoblastomas, 2 pancreatic carcinomas, 3 neoplasms of the endocrine pancreas, and 12 solid pseudopapillary tumors. Three of the four patients with pancreatoblastoma had advanced disease at diagnosis and were given chemotherapy; at the time of this report, three patients were alive in first remission, while one died due to treatment toxicity. Both the cases of pancreatic carcinoma had the acinar cell subtype and successfully underwent pancreaticoduodenectomy with complete tumor resection, remaining without evidence of disease at the time of this analysis. The histological diagnoses of the three endocrine tumors were a malignant islet cell tumor, a gastrinoma, and a well-differentiated tumor. All 12 patients with solid pseudopapillary tumors underwent complete tumor resection and were given no adjuvant treatment; 11 were alive in first remission, while one experienced a local and distant relapse 5 years after diagnosis. CONCLUSIONS: Surgery remains the keystone of treatment for pancreatic tumors in pediatric age as in adults. The TREP project shows that prospective cooperative studies are feasible even for such very rare tumors as these and may serve as a model for developing international cooperative schemes

Focal activity within insula cortex correlating with physiological changes.

<p>Sagittal and horizontal sections from a standard template brain presented to highlight the location of activity changes within insula cortex associated with task-induced changes in physiological regressors. Of note are the deep insula components of signal change associated with heart rate decrease, merging with a marked engagement of basal ganglia, mirroring striatocortical activation previously observed in relation to expectancy-related heart rate deceleration [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127082#pone.0127082.ref022" target="_blank">22</a>]. The broadly distributed signal change, associated with this particular analysis arguably appears to carry most artefact, beyond what was controlled for by including movement, global and arterial O₂ / end tidalCo₂ regressors as confounding covariates within the analyses. Ventilation (VT) evoked predominantly right hemispheric changes in parietal and insula cortices and basal ganglia. Increases in end tidal CO₂ was associated with enhanced activation within posterior ‘primary interoceptive’ insula, but did not impact global signal at threshold significance. Heart rate variability, blood pressure increases and blood pressure variability were associated with focal activation of distinct subregions of anterior and mid insula consistent with viscerotopography [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127082#pone.0127082.ref023" target="_blank">23</a>]. Data is illustrated at a significance of P<0.05 corrected, determined from the combination of voxel-wise significance and a cluster extent thresholds (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127082#sec002" target="_blank">Methods</a>).</p

Focal brainstem activity correlating with physiological changes.

<p>Selected illustration of activity correlated with physiological changes. Data is illustrated at a voxel-wise threshold significance of P<0.001 uncorrected). <b>A)</b> within medulla, where the same locus reflects blood pressure increases and heart rate variability increases consistent with a neural substrate for the baroreflex mediating adjustments to hypoxic challenge. <b>B)</b> within pons and midbrain, where adjacent nuclei demonstrate relationships with decreases in heart rate and increases in tidal volume, putatively representing human homologues of brainstem centres supporting cardiorespiratory coupling as identified in experimental animals.</p

Physiological data acquisition, illustrating experimental design.

<p>The figure shows data recording (CED Spike software, Cambridge) during the experiment in which participants breathed normoxic and hypoxic air mixtures over periods of approximately 5 minutes at their natural spontaneous rate (unpaced) and at paced rates approximating to a regular rate (paced normal rate: 9.9 breaths per minute) and at a slow rate (paced slow rate 5.5 breaths per minute). These task conditions were counterbalanced within and between participants and for hypoxia periods were preceded by a 1.5 minute ‘wash-in’ period and followed by a 1 minute ‘wash-out’ period. During the experiment, volume changes associated with breathing were recorded directly using pneumotachography alongside measurement of expired CO_2, and through pulse oximetry, arterial oxygen saturation, pulse volume and pulse rate. The experiment entailed repetitions of task conditions in hypoxia and normoxia. For a subset of participants, beat-to-beat blood pressure was also recorded.</p