Hypoxemia during rapid eye movement sleep mediates memory impairment in older adults at risk for dementia via CA1 hippocampal volume loss.

BACKGROUND AND PURPOSE: Obstructive sleep apnea is associated with increased dementia risk. Nocturnal hypoxemia, which can be more severe during rapid eye movement (REM) sleep, may be a key mechanism. This study examines how REM hypoxemia affects memory and explores whether hippocampal vulnerability to hypoxemia mediates this effect in older adults at risk for dementia. METHODS: Older adults aged ≥50 years (N = 338) with subjective or mild cognitive impairment (i.e., objective impairment) underwent neuropsychological, mood, and medical assessment, magnetic resonance imaging scanning (n = 135), and overnight polysomnography. Verbal learning and memory were assessed with the Rey Auditory Verbal Learning Test. REM sleep hypoxemia was measured using the Oxygen Desaturation Index-3% (REM-ODI). Hippocampal subfield (CA1, CA3, subiculum, and dentate gyrus) volumes were derived from T1 and high-resolution hippocampus T2 scans. We determined whether the relationship between REM-ODI and learning and memory was mediated by hippocampal subfield volume. Analyses were repeated in non-REM sleep to determine whether the effects were REM-specific. RESULTS: Although there was not a direct effect of REM-ODI on verbal learning (p > 0.05) or memory (p > 0.05), mediation analyses showed a significant indirect effect of high REM-ODI on poorer verbal learning (ß = -0.09, 95% confidence interval [CI] = -0.238 to -0.005) and memory (ß = -0.100, 95% CI = -0.255 to -0.005), which was mediated by CA1 volume. These associations were absent in non-REM sleep (p > 0.05). CONCLUSIONS: Hypoxemia during REM sleep may impair memory in people at risk for dementia by reducing CA1 hippocampal volume. Research is needed to explore whether interventions targeting REM sleep hypoxemia are protective against memory decline.

A Novel In Silico Method for Molecular Mimicry Detection Finds a Formin with the Potential to Manipulate the Maize Cell Cytoskeleton.

Molecular mimicry is one of the evolutionary strategies that parasites use to manipulate the host metabolism and perform an effective infection. This phenomenon has been observed in several animal and plant pathosystems. Despite the relevance of this mechanism in pathogenesis, little is known about it in fungus-plant interactions. For that reason, we performed an in silico method to select plausible mimicry candidates for the Ustilago maydis-maize interaction. Our methodology used a tripartite sequence comparison between the parasite, the host, and nonparasitic organisms' genomes. Furthermore, we used RNA sequencing information to identify gene coexpression, and we determined subcellular localization to detect potential cases of colocalization in the imitator-imitated pairs. With these approximations, we found a putative extracellular formin in U. maydis with the potential to rearrange the host cell cytoskeleton. In parallel, we detected at least two maize genes involved in the cytoskeleton rearrangement differentially expressed under U. maydis infection; thus, this find increases the expectation for the potential mimicry role of the fungal protein. The use of several sources of data led us to develop a strict and replicable in silico methodology to detect molecular mimicry in pathosystems with enough information available. Furthermore, this is the first time that a genomewide search has been performed to detect molecular mimicry in a U. maydis-maize system. Additionally, to allow the reproducibility of this experiment and the use of this pipeline, we created a Web server called Molecular Mimicry Finder.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

[Use of NSAIDs in traumatology]. / Du bon usage des AINS en traumatologie.

In traumatology, non-steroidal anti-inflammatory drugs (NSAIDs) are widely used, due to their efficacy in controlling pain and safety profile. Nonetheless, experimental and retrospective studies about the use of NSAIDs in traumatology raise the question about a possible negative influence on bone remodeling through inhibition of prostaglandin synthesis. The results from these studies must be interpreted with caution, as bone repair can be influenced by several parameters. When used in the case of sprains or tendinitis, unwanted side effects of NSAIDs seem to be limited; on the other hand, benefits in terms of antalgic effect are less clear. We have conducted a review of the literature aimed to suggest practical solutions for the use of NSAIDs in traumatology.

Different heart rate variability profile during sleep in mid-later life adults with remitted early-onset versus late-onset depression.

BACKGROUND: In mid-later life adults, early-onset and late-onset (i.e., onset ≥50 years) depression appear to be underpinned by different pathophysiology yet have not been examined in relation to autonomic function. Sleep provides an opportunity to examine the autonomic nervous system as the physiology changes across the night. Hence, we aimed to explore if autonomic profile is altered in mid-later life adults with remitted early-onset, late-onset and no history of lifetime depression. METHODS: Participants aged 50-90 years (n = 188) from a specialised clinic underwent a comprehensive clinical assessment and completed an overnight polysomnography study. General Linear Models were used to examine the heart rate variability differences among the three groups for four distinct sleep stages and the wake after sleep onset. All analyses controlled for potential confounders - age, sex, current depressive symptoms and antidepressant usage. RESULTS: For the wake after sleep onset, mid-later life adults with remitted early-onset depression had reduced standard deviation of Normal to Normal intervals (SDNN; p = .014, d = -0.64) and Shannon Entropy (p = .004, d = -0.46,) than those with no history of lifetime depression. Further, the late-onset group showed a reduction in high-frequency heart rate variability (HFn.u.) during non-rapid eye movement sleep stage 2 (N2; p = .005, d = -0.53) and non-rapid eye movement sleep stage 3 (N3; p = .009, d = -0.55) when compared to those with no lifetime history. LIMITATIONS: Causality between heart rate variability and depression cannot be derived in this cross-sectional study. Longitudinal studies are needed to examine the effects remitted depressive episodes on autonomic function. CONCLUSION: The findings suggest differential autonomic profile for remitted early-onset and late-onset mid-later life adults during sleep stages and wake periods. The differences could potentially serve as peripheral biomarkers in conjunction with more disease-specific markers of depression to improve diagnosis and prognosis.

Thalamic abnormalities in older adults with remitted early-onset depression using structural magnetic resonance imaging.

BACKGROUND: The thalamus is a key diencephalic structure involved in major depressive disorder (MDD). Studies have consistently revealed abnormalities in thalamic volumes in older adults with late-onset depression (LOD), however abnormalities in older adults with early-onset depression (EOD) have not yet been well-studied. METHODS: Fifty-nine euthymic participants with a history of EOD and fifty-nine matched comparison participants without a lifetime history of depression underwent neuroimaging, medical and neuropsychological assessments. Thalamic volumes were compared between groups. To investigate the previously-proposed right hemispheric (RH) dominance theory of MDD, we explored the bilateral, right and left hemispheric (LH) thalamic volumes. Multiple regression analyses were used to evaluate between-group and within-group effects. Correlational analyses examined associations between group and cognitive performance. RESULTS: Relative to the comparison group, those with EOD had significantly larger bilateral, LH and RH thalamic volumes. Those with EOD, those who were younger, and those who had fewer years of education demonstrated larger bilateral and LH thalamic volumes. For RH thalamic volumes, those with EOD and those who were younger demonstrated larger RH thalamic volumes. EOD within-group models were also run to assess associations between relevant depression variables. The results showed that only age was significant for bilateral and RH thalamic volumes. For the LH thalamic volumes, the model was not significant. No significant correlations were found between cognitive performance and EOD groups. CONCLUSION: Older adults with a history of EOD showed significantly larger bilateral, RH and LH thalamic volumes. Further research is needed to delineate potential underlying mechanisms of this change.

Does endogenous cholecystokinin modulate alcohol intake?

Alcohol use disorder or alcoholism is characterized by uncontrollable alcohol use and intoxication, as well as a heightened state of anxiety after alcohol withdrawal. Ethanol-associated stimuli also drive the urge to drink by means of classical conditioning. Alcoholism has been considered a dopamine (DA) dysregulation syndrome that involves the activity of the central amygdala circuitry of anxiety. Cholecystokinin (CCK) is the most abundant neuropeptide in the mammal brain, where it activates two receptors, CCK1 and CCK2. Genetic evidence relates CCK1 receptors to alcoholism in humans. CCK2 activity has been associated with the onset of human anxiety. CCK modulates DA release in the nucleus accumbens (NAc) and it is expressed in the γ-aminobutyric acid (GABA)-expressing basket interneurons in the cerebral cortex. CCK interacts with serotonin (5-HT) neurotransmission through 5-HT3 receptors to regulate mesocorticolimbic pathways and with GABA to attenuate anxiety in the amygdala. Finally, CCK stimulates the release of orexins and oxytocin in the hypothalamus, two relevant hypothalamic neuropeptides involved in signaling satiety for ethanol and well-being respectively. Given the "dimmer-switch" function of endogenous CCK in the neurotransmission by 5-HT, DA, GABA, and glutamate in normal and pathological behaviors (Ballaz and Bourin, 2020), we hypothesize that CCK adjusts functioning of the reward and anxiety circuitries altered by ethanol. This review gathers data supporting this hypothesis, and suggests mechanisms underlying a role for endogenous CCK in alcoholism.