Effect of upper airway fat on tongue dilation during inspiration in awake people with obstructive sleep apnea

Study Objectives: To investigate the effect of upper airway fat composition on tongue inspiratory movement and obstructive sleep apnea (OSA). Methods: Participants without or with untreated OSA underwent a 3T magnetic resonance imaging (MRI) scan. Anatomical measurements were obtained from T2-weighted images. Mid-sagittal inspiratory tongue movements were imaged using tagged MRI during wakefulness. Tissue volumes and percentages of fat were quantified using an mDIXON scan. Results: Forty predominantly overweight participants with OSA were compared to 10 predominantly normal weight controls. After adjusting for age, BMI, and gender, the percentage of fat in the tongue was not different between groups (analysis of covariance [ANCOVA], p = 0.45), but apnoeic patients had a greater tongue volume (ANCOVA, p = 0.025). After adjusting for age, BMI, and gender, higher OSA severity was associated with larger whole tongue volume (r = 0.51, p < 0.001), and greater dilatory motion of the anterior horizontal tongue compartment (r = -0.33, p = 0.023), but not with upper airway fat percentage. Higher tongue fat percentage was associated with higher BMI and older age (Spearman r = 0.43, p = 0.002, and r =0.44, p = 0.001, respectively), but not with inspiratory tongue movements. Greater inspiratory tongue movement was associated with larger tongue volume (e.g. horizontal posterior compartment, r = -0.44, p = 0.002) and smaller nasopharyngeal airway (e.g. oblique compartment, r = 0.29, p = 0.040). Conclusions: Larger tongue volume and a smaller nasopharynx are associated with increased inspiratory tongue dilation during wakefulness in people with and without OSA. This compensatory response was not influenced by higher tongue fat content. Whether this is also true in more obese patient populations requires further investigation

The relationship between mandibular advancement, tongue movement, and treatment outcome in obstructive sleep apnea

Study Objectives: To characterize how mandibular advancement enlarges the upper airway via posterior tongue advancement in people with obstructive sleep apnea (OSA) and whether this is associated with mandibular advancement splint (MAS) treatment outcome. Methods: One-hundred and one untreated people with OSA underwent a 3T magnetic resonance (MRI) scan. Dynamic mid-sagittal posterior tongue and mandible movements during passive jaw advancement were measured with tagged MRI. Upper airway cross-sectional areas were measured with the mandible in a neutral position and advanced to 70% of maximum advancement. Treatment outcome was determined after a minimum of 9 weeks of therapy. Results: Seventy-one participants completed the study: 33 were responders (AHI50% AHI reduction), 11 were partial responders (>50% AHI reduction but AHI>10 events/hr), and 27 nonresponders (AHI reduction 4 mm). In comparison, a model using only baseline AHI correctly classified 50.0% of patients (5-fold cross-validated 52.5%, n = 40). Conclusions: Tongue advancement and upper airway enlargement with mandibular advancement in conjunction with baseline AHI improve treatment response categorization to a satisfactory level (69.2%, 5-fold cross-validated 62.5%)

Microarray analysis of expression of cell death-associated genes in rat spinal cord cells exposed to cyclic tensile stresses in vitro

<p>Abstract</p> <p>Background</p> <p>The application of mechanical insults to the spinal cord results in profound cellular and molecular changes, including the induction of neuronal cell death and altered gene expression profiles. Previous studies have described alterations in gene expression following spinal cord injury, but the specificity of this response to mechanical stimuli is difficult to investigate in vivo. Therefore, we have investigated the effect of cyclic tensile stresses on cultured spinal cord cells from E15 Sprague-Dawley rats, using the FX3000^®Flexercell Strain Unit. We examined cell morphology and viability over a 72 hour time course. Microarray analysis of gene expression was performed using the Affymetrix GeneChip System^®, where categorization of identified genes was performed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) systems. Changes in expression of 12 genes were validated with quantitative real-time reverse transcription polymerase chain reaction (RT-PCR).</p> <p>Results</p> <p>The application of cyclic tensile stress reduced the viability of cultured spinal cord cells significantly in a dose- and time-dependent manner. Increasing either the strain or the strain rate independently was associated with significant decreases in spinal cord cell survival. There was no clear evidence of additive effects of strain level with strain rate. GO analysis identified 44 candidate genes which were significantly related to "apoptosis" and 17 genes related to "response to stimulus". KEGG analysis identified changes in the expression levels of 12 genes of the mitogen-activated protein kinase (MAPK) signaling pathway, which were confirmed to be upregulated by RT-PCR analysis.</p> <p>Conclusions</p> <p>We have demonstrated that spinal cord cells undergo cell death in response to cyclic tensile stresses, which were dose- and time-dependent. In addition, we have identified the up regulation of various genes, in particular of the MAPK pathway, which may be involved in this cellular response. These data may prove useful, as the accurate knowledge of neuronal gene expression in response to cyclic tensile stress will help in the development of molecular-based therapies for spinal cord injury.</p

Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases

The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance

Case Study: Imaging of Apnea Termination in a Patient with Obstructive Sleep Apnea during Natural Sleep

A 55-year-old woman who presented to the sleep clinic with severe sleep apnea (OSA) (apnea-hypopnea index [AHI] 62) and excessive somnolence (Epworth Sleepiness Scale score 18/24), was imaged with MRI using the Spatial Modulation of Magnetization tagging sequence awake and asleep to visualize upper airway tissue movement. Awake quiet breathing resulted in minimal movement of upper airway tissues. Asleep sequences taken during airway opening post-apnea demonstrated neck extension, mandibular advancement, and widespread tongue deformation accompanying contraction of genioglossus. At the end of the asleep image sequence, the nasopharyngeal airway had a cross-sectional area larger than during quiet breathing awake and there was antero-lateral movement in the lateral walls. In conclusion, the airway responds to apnea by widespread contraction of the genioglossus, followed by mandibular advancement and neck extension. All these maneuvers stabilize and open the airway

Sources of child restraint information utilized by parents in NSW

Abstract Suboptimal child restraint practices are widespread and parental knowledge about child restraint use influences child restraint practices. In this analysis we examine parent-reported sources of child restraint information and their influence on observed child restraint practices. Data collected during a crosssectional study of restraint use among 503 NSW children aged 0-12 years was used in this analysis. Few children were unrestrained (&lt;1%) but the prevalence of suboptimal restraint use was high (38% moderately or seriously incorrect, 52% inappropriate). Approximately one in five parents reported having obtained information about child restraints within the 6 months prior to observation. The primary information sources were the RTA (27%), health providers, e.g. child health clinics and ante-natal programs, (11%) and the media (17%). There were significant associations between information source and appropriateness of restraint, but no association with correctness of restraint use. Parents of the youngest children were more likely to get information from health providers and parents of older children more likely to use other sources. Of the 302 child restraint users, one third had parents who reported using a restraint fitting station. These children were significantly more likely to be appropriately restrained. However there was no association between fitting station use and correctness of restraint use. This information is useful for the development of targeted optimal restraint campaigns, and suggests a need for a broader review of how and what messages are being delivered by different information providers

Models of the pulsatile hydrodynamics of cerebrospinal fluid flow in the normal and abnormal intracranial system

Images obtained from magnetic resonance imaging have helped to ascertain that both the cerebrospinal fluid (CSF) and brain move in a pulsatile manner within the cranium. However, these images are not able to reveal any quantitative information on the physiological forces that are associated with pulsatile motion. Understanding both the pressure and velocity flow field of CSF in the ventricles is important to help understand the mechanics of hydrocephalus. Four separate fluid structure interaction models of the ventricular system in the sagittal plane were created for this purpose. The first model was of a normal brain. The second and third models were pathological brain models with aqueductal stenosis at various locations along the fluid pathway. The fourth model was of a hydrocephalic brain. Results revealed the hydrodynamics of CSF pulsatile flow in the ventricles of these models. Most importantly, it has also revealed the different changes in CSF pulsatile hydrodynamics caused by the various locations of fluid flow obstructions.7 page(s

Differences in Child Restraint Related Attitudes and Behaviours Amongst Non English Speaking Background (NESB) and English Speaking Background (ESB) Families

Differences in child restraint related attitudes and behaviours amongst non English speaking background (NESB) and English speaking background (ESB) families. Burton, D. M., Bilston, L.E., Brown, J. Abstract The aim of this study is to identify differences in restraint related attitudes and knowledge amongst NESB and ESB families using data collected through a state wide telephone survey sample. Information was obtained on age, size, restraint practices, parental knowledge of child occupant safety and attitudes using a structured interview. The results suggest that NESB families have significantly less knowledge about appropriate restraint use, and are more confident in their knowledge than those from ESB families. They are more likely to perceive their child as being unhappy or uncomfortable in their restraint and more likely to negotiate restraint choice with their children. Financial costs appear to be more important to this group. There was also a difference in perception of crash risk amongst NESB and ESB families. This study demonstrates interventions to increase appropriate restraint use may need to be culturally tailored to effectively reach NESB families

Inwardly rectifying potassium channel 4.1 expression in post-traumatic syringomyelia

Post-traumatic syringomyelia (PTS) is a serious neurological disorder characterized by fluid filled cavities that develop in the spinal cord. PTS is thought to be caused by an imbalance between fluid inflow and outflow in the spinal cord, but the underlying mechanisms are unknown. The ion channel Kir4.1 plays an important role in the uptake of K⁺ ions from the extracellular space and release of K⁺ ions into the microvasculature, generating an osmotic gradient that drives water movement. Changes in Kir4.1 expression may contribute to disturbances in K⁺ homeostasis and subsequently fluid imbalance. Here we investigated whether changes in Kir4.1 protein expression occur in PTS. Western blotting and immunohistochemistry were used to evaluate Kir4.1 and glial fibrillary acidic protein (GFAP) expression in a rodent model of PTS at 3 days, 1, 6 or 12 weeks post-surgery. In Western blotting experiments, Kir4.1 expression increased 1 week post-surgery at the level of the cavity. Immunohistochemical analysis examined changes in the spinal parenchyma directly in contact with the syrinx cavity. In these experiments, there was a significant decrease in Kir4.1 expression in PTS animals compared to controls at 3 days and 6 weeks post-surgery, while an up-regulation of GFAP in PTS animals was observed at 1 and 12 weeks. This suggests that while overall Kir4.1 expression is unchanged at these time-points, there are many astrocytes surrounding the syrinx cavity that are not expressing Kir4.1. The results demonstrate a disturbance in the removal of K⁺ ions in tissue surrounding a post-traumatic syrinx cavity. It is possible this contributes to water accumulation in the injured spinal cord leading to syrinx formation or exacerbation of the underlying pathology.13 page(s