The temporal dynamics of the tracheal microbiome in tracheostomised patients with and without lower respiratory infections

Background: Airway microbiota dynamics during lower respiratory infection (LRI) are still poorly understood due, in part, to insufficient longitudinal studies and lack of uncontaminated lower airways samples. Furthermore, the similarity between upper and lower airway microbiomes is still under debate. Here we compare the diversity and temporal dynamics of microbiotas directly sampled from the trachea via tracheostomy in patients with (YLRI) and without (NLRI) lower respiratory infections. Methods: We prospectively collected 127 tracheal aspirates across four consecutive meteorological seasons (quarters) from 40 patients, of whom 20 developed LRIs and 20 remained healthy. All aspirates were collected when patients had no LRI. We generated 16S rRNA-based microbial profiles (~250 bp) in a MiSeq platform and analyzed them using Mothur and the SILVAv123 database. Differences in microbial diversity and taxon normalized (via negative binomial distribution) abundances were assessed using linear mixed effects models and multivariate analysis of variance. Results and discussion Alpha-diversity (ACE, Fisher and phylogenetic diversity) and beta-diversity (Bray-Curtis, Jaccard and Unifrac distances) indices varied significantly (P<0.05) between NLRI and YLRI microbiotas from tracheostomised patients. Additionally, Haemophilus was significantly (P = 0.009) more abundant in YLRI patients than in NLRI patients, while Acinetobacter, Corynebacterium and Pseudomonas (P<0.05) showed the inverse relationship. We did not detect significant differences in diversity and bacterial abundance among seasons. This result disagrees with previous evidence suggesting seasonal variation in airway microbiotas. Further study is needed to address the interaction between microbes and LRI during times of health and disease

In Vivo Assessment of Bone Graft/Endplate Contact Pressure in a Caprine Interbody Pseudarthrosis Model: A Preliminary Biomechanical Characterization of the Fusion Process for the Development of a Microelectromechanical Systems (MEMS) Biosensor.

BackgroundIn this preliminary study we used a goat model to quantify pressure at an interbody bone graft interface. Although the study was designed to assess fusion status, the concept behind the technology could lead to early detection of implant failure and potential hazardous complications related to motion-preservation devices. The purpose of this study was to investigate the feasibility of in vivo pressure monitoring as a strategy to determine fusion status.MethodsTelemetric pressure transducers were implanted, and pressure at the bone graft interfaces of cervical interbody fusion autografts placed into living goats (Groups A and B) was evaluated. Group A constituted the 4-month survival group and Group B the 6-month survival group. One goat served as the study control (Group C) and was not implanted with a pressure transducer. An additional six cadaveric goat cervical spines (Group D) were obtained from a local slaughterhouse and implanted with bone grafts and ventral plates and used for in vitro biomechanical comparison to the specimens from Groups A and B.ResultsAll goats demonstrated an increase in interface pressure within the first 10 days postoperatively, with the largest relative change in pressure occurring between the sixth and ninth days. The goats from Groups A and B had a 200% to 400% increase in relative pressure.ConclusionsAlthough this was a pilot study to assess pressure as an indicator for a fusion or pseudarthrosis, the preliminary data suggest that early bone healing is detectable by an increase in pressure. Thus, pressure may serve as an indicator of fusion status by detecting altered biomechanical parameters

In Vivo Assessment of Bone Graft/Endplate Contact Pressure in a Caprine Interbody Pseudarthrosis Model: A Preliminary Biomechanical Characterization of the Fusion Process for the Development of a Microelectromechanical Systems (MEMS) Biosensor.

BackgroundIn this preliminary study we used a goat model to quantify pressure at an interbody bone graft interface. Although the study was designed to assess fusion status, the concept behind the technology could lead to early detection of implant failure and potential hazardous complications related to motion-preservation devices. The purpose of this study was to investigate the feasibility of in vivo pressure monitoring as a strategy to determine fusion status.MethodsTelemetric pressure transducers were implanted, and pressure at the bone graft interfaces of cervical interbody fusion autografts placed into living goats (Groups A and B) was evaluated. Group A constituted the 4-month survival group and Group B the 6-month survival group. One goat served as the study control (Group C) and was not implanted with a pressure transducer. An additional six cadaveric goat cervical spines (Group D) were obtained from a local slaughterhouse and implanted with bone grafts and ventral plates and used for in vitro biomechanical comparison to the specimens from Groups A and B.ResultsAll goats demonstrated an increase in interface pressure within the first 10 days postoperatively, with the largest relative change in pressure occurring between the sixth and ninth days. The goats from Groups A and B had a 200% to 400% increase in relative pressure.ConclusionsAlthough this was a pilot study to assess pressure as an indicator for a fusion or pseudarthrosis, the preliminary data suggest that early bone healing is detectable by an increase in pressure. Thus, pressure may serve as an indicator of fusion status by detecting altered biomechanical parameters

Alluvial plots of mean relative proportions of most abundant (≥3%) phyla and genera in microbiomes from patients with (YLRI) and without (NLRI) lower respiratory infections (LRI) across meteorological seasons.

<p>Alluvial plots of mean relative proportions of most abundant (≥3%) phyla and genera in microbiomes from patients with (YLRI) and without (NLRI) lower respiratory infections (LRI) across meteorological seasons.</p

Box plots of phylogenetic alpha-diversity of microbiotas from patients with (YLRI) and without (NLRI) lower respiratory infections (LRI) (A) and of microbiotas from YLRI and NLRI patients across meteorological seasons (B).

<p>Box plots of phylogenetic alpha-diversity of microbiotas from patients with (YLRI) and without (NLRI) lower respiratory infections (LRI) (A) and of microbiotas from YLRI and NLRI patients across meteorological seasons (B).</p

Clinical characteristics of the studied cohort.

<p>NLRI = patients with no lower respiratory infections. YLRI = patients with lower respiratory infections.</p

Mean alpha-diversity indices and mean relative proportions of dominant phyla and genera (>3%) in decreasing order of abundance for ALL samples (NLRI+YLRI), patients with no lower respiratory infections (NLRI) and patients with lower respiratory infections (YLRI).

<p>Linear mixed-effects (LME) models results are shown for alpha-diversity indices and taxa proportions, while permutational multivariate analysis of variance (adonis) results are shown for beta-diversity indices. Significance of LME models analyses was estimated using ANOVA type II or III with Satterthwaite approximation. For each test we report the relevant F statistic (<i>F</i>), degrees of freedom (<i>DF</i>) and significance (<i>P(>F)</i>). Significant associations are indicated in bold.</p

Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model

Item does not contain fulltextThe beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in the form of electrical evoked potentials, but also to cortico-thalamo-cortical network activity (spike-wave discharges, SWD and afterdischarges), white matter changes representing extra cortico-thalamic functions and depressive-like behavior were investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal months 2-3 or 4-5), or ethosuximide for 4 months (2-5) in their drinking water, while control rats drank plain water. EEG measurements were made during treatment, and 6 days and 2 months post treatment. Behavioral test were also done 6 days post treatment. DTI was performed ex vivo post treatment. SWD were suppressed during treatment, and 6 days and 2 months post treatment in the 4 month treated group, as well as the duration of AD elicited by cortical electrical stimulation 6 days post treatment Increased fractional anisotropy in corpus callosum and internal capsula on DTI was found, an increased P8 evoked potential amplitude and a decreased immobility in the forced swim test. Shorter treatments with ETX had no large effects on any parameter. Chronic ETX has widespread effects not only within but also outside the circuitry in which SWD are initiated and generated, including preventing epileptogenesis and reducing depressive-like symptoms. The treatment of patients before symptom onset might prevent many of the adverse consequences of chronic epilepsy.13 p