Revealing inconsistencies between Epworth scores and apnea-hypopnea index when evaluating obstructive sleep apnea severity: a clinical retrospective chart review

IntroductionA common practice in clinical settings is the use of the Epworth Sleepiness Scale (ESS) and apnea-hypopnea index (AHI) to demonstrate the severity of obstructive sleep apnea (OSA). However, several instances were noted where there were discrepancies in the reported severity between Epworth scores and AHI in our patient sample, prompting an investigation into whether OSA severity as demonstrated by AHI or predicted by ESS quantification of sleepiness is primarily responsible for inconsistencies.MethodsDiscrepancies were examined between Epworth scores and AHI by categorizing patients into two categories of inconsistency: individuals with either ESS < 10 and AHI ≥ 15 events/h or ESS ≥ 10 and AHI < 15 events/h. The potential influence of sex on these categories was addressed by assessing whether a significant difference was present between mean Epworth scores and AHI values for men and women in the sample. We investigated BMI both by itself as its own respective variable and with respect to the sex of the individuals, along with a consideration into the role of anxiety. Furthermore, we tested anxiety with respect to sex.ResultsIn the first category of inconsistency the average ESS of 5.27 ± 0.33 suggests a normal level of daytime sleepiness. However, this contrasts with the average AHI of 32.26 ± 1.82 events/h which is indicative of severe OSA. In the second category the average ESS of 14.29 ± 0.47 suggests severe daytime sleepiness, contradicting the average AHI of 9.16 ± 0.44 events/h which only indicates mild OSA. Sex, BMI (both as a variable by itself and with respect to sex), and anxiety (both as a variable by itself and with respect to sex) contributed to observed inconsistencies.ConclusionThe findings of our study substantiate our hypothesis that Epworth scores should be de-emphasized in the assessment of OSA and a greater importance should be placed on measures like AHI. While Epworth scores offer insights into patients’ daytime sleepiness levels and the perceived severity of their OSA, the inconsistencies highlighted in our results when compared to AHI-based OSA severity underscore their potential inaccuracy. Caution is advised when utilizing Epworth scores for evaluating OSA severity in clinical settings

Molecular dissection of the photoreceptor ribbon synapse: physical interaction of Bassoon and RIBEYE is essential for the assembly of the ribbon complex

The ribbon complex of retinal photoreceptor synapses represents a specialization of the cytomatrix at the active zone (CAZ) present at conventional synapses. In mice deficient for the CAZ protein Bassoon, ribbons are not anchored to the presynaptic membrane but float freely in the cytoplasm. Exploiting this phenotype, we dissected the molecular structure of the photoreceptor ribbon complex. Identifiable CAZ proteins segregate into two compartments at the ribbon: a ribbon-associated compartment including Piccolo, RIBEYE, CtBP1/BARS, RIM1, and the motor protein KIF3A, and an active zone compartment including RIM2, Munc13-1, a Ca2+ channel α1 subunit, and ERC2/CAST1. A direct interaction between the ribbon-specific protein RIBEYE and Bassoon seems to link the two compartments and is responsible for the physical integrity of the photoreceptor ribbon complex. Finally, we found the RIBEYE homologue CtBP1 at ribbon and conventional synapses, suggesting a novel role for the CtBP/BARS family in the molecular assembly and function of central nervous system synapses

A new model for molecule exchange in the brain microvascular system: consequences of capillary occlusions in Alzheimer's disease

The brain microvascular system is a key actor in Alzheimer’s disease (AD) development. Indeed, a significant decrease of cerebral blood flow is the earliest biomarker of AD. In vivo TPLSM of cortical vasculature in APP/PS1 mice suggests the mechanism underlying the blood flow reduction is capillary occlusions. Leucocytes adhere to inflamed vessel walls and limit the flow. The impact of capillary occlusions on blood flow has been quantified numerically in large (>10000 vessels) anatomical networks in humans and mice. The regional blood flow has been found to depend linearly with no threshold effect on the fraction of capillary occlusions, so that a small fraction of stalls (2-4%) yields a significant decrease in blood flow (5-12%). Such flow decrease has a strong impact on nutrient delivery and waste clearance. That is why we devised a new model to study the effect of capillary stalling on molecule transport. The geometry of anatomical networks is too complex to use classic numerical approaches like finite elements. Instead, our model, inspired by pore-network approaches, reduces computational costs while capturing most of the underlying physics. To derive this model, we apply upscaling methods to the 3D transport equations within each vessel to obtain 1D average equations along the axis. Contrary to previous models, this new formulation describes accurately radial concentration gradients, capturing effects like longitudinal dispersion. We further use a Green’s function formulation to calculate the concentration fields inside the tissue where diffusion and reaction occur. The coupling between vessels and tissues is modelled using a membrane condition representing the blood brain barrier. This new molecule transport model is coupled with our previously validated blood flow model to examine the effects of capillary stalling on molecular exchange in transient and stationary regimes in anatomical networks. In particular, in stationnary regimes, we demonstrate an increase of the extraction coefficient with the proportion of stalled capillaries, which does not compensate for the associated blood flow reduction

Neutrophil adhesion in brain capillaries reduces cortical blood flow and impairs memory function in Alzheimer’s disease mouse models.

Cerebral blood flow (CBF) reductions in Alzheimer’s disease patients and related mouse models have been recognized for decades, but the underlying mechanisms and resulting consequences for Alzheimer’s disease pathogenesis remain poorly understood. In APP/PS1 and 5xFAD mice we found that an increased number of cortical capillaries had stalled blood flow as compared to in wild-type animals, largely due to neutrophils that had adhered in capillary segments and blocked blood flow. Administration of antibodies against the neutrophil marker Ly6G reduced the number of stalled capillaries, leading to both an immediate increase in CBF and rapidly improved performance in spatial and working memory tasks. This study identified a previously uncharacterized cellular mechanism that explains the majority of the CBF reduction seen in two mouse models of Alzheimer’s disease and demonstrated that improving CBF rapidly enhanced short-term memory function. Restoring cerebral perfusion by preventing neutrophil adhesion may provide a strategy for improving cognition in Alzheimer’s disease patients

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Sensorimotor stroke alters hippocampo-thalamic network activity

Many stroke survivors experience persisting episodic memory disturbances. Since hippocampal and para-hippocampal areas are usually spared from the infarcted area, alterations of memory processing networks remote from the ischemic brain region might be responsible for the observed clinical symptoms. To pinpoint changes in activity of hippocampal connections and their role in post-stroke cognitive impairment, we induced ischemic stroke by occlusion of the middle cerebral artery (MCAO) in adult rats and analyzed the functional and structural consequences using activity-dependent manganese (Mn2+) enhanced MRI (MEMRI) along with behavioral and histopathological analysis. MCAO caused stroke lesions of variable extent along with sensorimotor and cognitive deficits. Direct hippocampal injury occurred in some rats, but was no prerequisite for cognitive impairment. In healthy rats, injection of Mn2+ into the entorhinal cortex resulted in distribution of the tracer within the hippocampal subfields into the lateral septal nuclei. In MCAO rats, Mn2+ accumulated in the ipsilateral thalamus. Histopathological analysis revealed secondary thalamic degeneration 28 days after stroke. Our findings provide in vivo evidence that remote sensorimotor stroke modifies the activity of hippocampal-thalamic networks. In addition to potentially reversible alterations in signaling of these connections, structural damage of the thalamus likely reinforces dysfunction of hippocampal-thalamic circuitries