A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.

The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes.

Absolute depth-resolved optic axis measurement with catheter-based polarization sensitive optical coherence tomography.

Imaging depth-resolved birefringence and optic axis orientation with polarization sensitive optical coherence tomography (PS-OCT) unveils details of tissue structure and organization that can be of high pathophysiologic, mechanistic, and diagnostic value. For catheter-based PS-OCT, the dynamic rotation of the fiber optic probe, in addition to the polarization effects of the system components, complicates the reliable and robust reconstruction of the sample's optic axis orientation. Addressing this issue, we present a new method for the reconstruction of absolute depth-resolved optic axis orientation in catheter-based PS-OCT by using the intrinsic retardance of the protecting catheter sheath as a stable guide star signal.

A chemigenetic indicator based on a synthetic chelator and a green fluorescent protein for imaging of intracellular sodium ions.

A chemigenetic indicator with an affinity suitable for imaging of intracellular sodium ions (Na) in mammalian cells was developed. The indicator, based on a chimera of green fluorescent protein (GFP) and HaloTag labeled with a synthetic crown ether chelator, was produced by a combination of rational design and directed evolution. In mammalian cells the indicator exhibited an approximately 100% increase in excitation ratio when the cells were treated with 20 mM Na and an ionophore.

Music Perception in Older Adults With Hearing Loss: Protective Effect of Musical Experience.

Objectives: The goal of this project was to investigate the impact of musical experience, hearing loss, and age on music perception in older adults. The authors hypothesized that older adults with a varying degree of musical experience would perform better at music perception tasks than their counterparts without musical experience while controlling for age and hearing loss.

Design: This study used a descriptive correlational cross-sectional design.

High-Performance Chemigenetic Potassium Ion Indicator.

Potassium ion (K) is the most abundant metal ion in cells and plays an indispensable role in practically all biological systems. Although there have been reports of both synthetic and genetically encoded fluorescent K indicators, there remains a need for an indicator that is genetically targetable, has high specificity for K versus Na, and has a high fluorescent response in the red to far-red wavelength range. Here, we introduce a series of chemigenetic K indicators, designated as the HaloKbp1 series, based on the bacterial K-binding protein (Kbp) inserted into HaloTag7 self-labeled with environmentally sensitive rhodamine derivatives.

Cortical norepinephrine-astrocyte signaling critically mediates learned behavior.

Updating behavior based on feedback from the environment is a crucial means by which organisms learn and develop optimal behavioral strategies. Norepinephrine (NE) release from the locus coeruleus (LC) has been shown to mediate learned behaviors such that in a task with graded stimulus uncertainty and performance, a high level of NE released after an unexpected outcome causes improvement in subsequent behavior. Yet, how the transient activity of LC-NE neurons, lasting tens of milliseconds, influences behavior several seconds later, is unclear.

Delphi consensus recommendations for the management of chronic insomnia in Canada.

Objective: The lack of current Canadian practice guidelines for the management of insomnia poses a challenge for healthcare providers (HCP) in selecting the appropriate treatment options. This study aimed to establish expert consensus recommendations for the management of chronic insomnia in Canada.

Composition Of The Committee: Sixteen multidisciplinary experts in sleep medicine and insomnia across Canada developed consensus recommendations based on their knowledge of the literature and their practical experience.

Attention, working memory, and inhibitory control in aging: Comparing amateur singers, instrumentalists, and active controls.

Despite the ubiquity of musical activities, little is known about the specificity of their association with executive functions. In this cross-sectional study, we examined this relationship as a function of age. Our main hypotheses were that executive functions would decline in older age, that this relationship would be reduced in singers and instrumentalists compared to nonmusician active controls, and that the amount of musical experience would be more strongly associated with executive functions compared to the specific type of activity.

Predictability of sleep in insomnia: sleep patterns of patients from a sleep psychology clinic.

The present study aims at identifying sleep patterns in insomnia in a clinical sample using three strategies to define poor nights. Sleep diaries and self-reported questionnaires were collected from 77 clinical patients with insomnia. The conditional probabilities of observing a poor night after 1, 2, or 3 consecutive poor nights were computed according to three strategies with same criteria for sleep onset latency, wake after sleep onset, and sleep efficiency, but varying criterion for total sleep time.

Effect of a prescription digital therapeutic for chronic insomnia on post-treatment insomnia severity, depression, and anxiety symptoms: results from the real-world DREAM study.

Introduction: Chronic insomnia is a substantial public health burden that often presents with co-occurring depression and anxiety. Randomized clinical trials and preliminary real-world evidence have shown that digitally delivered cognitive-behavioral therapy for insomnia (dCBT-I) is associated with improvements in insomnia, but real-world evidence is needed to determine the true impact of digital CBT-I. This pragmatic study aimed to evaluate the benefits of treating chronic insomnia with a tailored prescription digital therapeutic in a real-world population.

Characterizing the heterogeneity of disruptions in the resolution of trauma among women exposed to childhood maltreatment.

The previously observed heterogeneity in developmental and intergenerational trajectories of childhood trauma may root from interindividual differences in the way trauma-exposed individuals have resolved these experiences. The current study explored whether distinctive patterns of impaired mentalization in relation to trauma could be identified in a sample of 825 pregnant women who experienced childhood maltreatment and whether these heterogeneous patterns were marked by significant differences in internalized and externalized problems during pregnancy, intimate partner violence, personality dysfunctions, and antenatal attachment. A latent profile analysis applied to the seven subscales of the unraveled interindividual variability in mentalizing impairments among pregnant women exposed to childhood maltreatment by identifying five distinctive types of psychological responses to trauma, each being associated in cross-sectional analyses with a specific set of symptoms and dysfunctions.

Using the DRS-8 to measure unresolved/disorganized attachment: Associations with states of mind on the adult attachment interview, psychopathology, and offspring social-emotional development.

Background: Unresolved/disorganized (U/d) attachment states of mind are associated with poor outcomes across numerous domains of functioning. However, the validity of existing self-report instruments measuring this construct remains questionable.

Objectives: The aim of the current study was to validate the DRS-8, an alternative version of the Disorganized Response Scale (DRS), by assessing its construct validity, internal consistency, and criterion validity with the U/d attachment scales on the Adult Attachment Interview (AAI).

An hetero-modal deep learning framework for medical image synthesis applied to contrast and non-contrast MRI.

Some pathologies such as cancer and dementia require multiple imaging modalities to fully diagnose and assess the extent of the disease. Magnetic resonance imaging offers this kind of polyvalence, but examinations take time and can require contrast agent injection. The flexible synthesis of these imaging sequences based on the available ones for a given patient could help reduce scan times or circumvent the need for contrast agent injection.

Chronic Social Defeat Stress Induces Pathway-Specific Adaptations at Lateral Habenula Neuronal Outputs.

The lateral habenula (LHb) has emerged as a pivotal brain region implicated in depression, displaying hyperactivity in human and animal models of depression. While the role of LHb efferents in depressive disorders has been acknowledged, the specific synaptic alterations remain elusive. Here, employing optogenetics, retrograde tracing, and ex vivo whole-cell patch-clamp techniques, we investigated synaptic transmission in male mice subjected to chronic social defeat stress (CSDS) at three major LHb neuronal outputs: the dorsal raphe nucleus (DRN), the ventral tegmental area (VTA), and the rostromedial tegmental nucleus (RMTg).

A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice.

Astrocytes control brain activity via both metabolic processes and gliotransmission, but the physiological links between these functions are scantly known. Here we show that endogenous activation of astrocyte type-1 cannabinoid (CB1) receptors determines a shift of glycolysis towards the lactate-dependent production of D-serine, thereby gating synaptic and cognitive functions in male mice. Mutant mice lacking the CB1 receptor gene in astrocytes (GFAP-CB1-KO) are impaired in novel object recognition (NOR) memory.

Influence of Sensory Monitoring on Speech Breathing Planning Processes: An Exploratory Study in Aging Speakers Reporting Dyspnea.

Purpose: Previous studies have suggested that inspirations during speech pauses are influenced by the length of adjacent utterances, owing to respiratory motor planning and physiological recovery processes. The goal of this study was to examine how attention to respiratory sensations may influence these processes in aging speakers with dyspnea, by measuring the effect of sensory monitoring on the relationship between utterance length and the occurrence of inspirations, as well as on functional voice and respiratory measures.

Method: Seventeen adults aged 50 years and older with complaints of voicing-related dyspnea completed a repeated-measures protocol consisting of a 2-week baseline phase and a 4-week sensory monitoring phase.