Sleep loss increases the experience of pain. However, the brain mechanisms underlying altered pain processing following sleep deprivation are unknown. Moreover, it remains unclear whether ...ecologically modest night-to-night changes in sleep, within an individual, confer consequential day-to-day changes in experienced pain. Here, we demonstrate that acute sleep deprivation amplifies pain reactivity within human (male and female) primary somatosensory cortex yet blunts pain reactivity in higher-order valuation and decision-making regions of the striatum and insula cortex. Consistent with this altered neural signature, we further show that sleep deprivation expands the temperature range for classifying a stimulus as painful, specifically through a lowering of pain thresholds. Moreover, the degree of amplified reactivity within somatosensory cortex following sleep deprivation significantly predicts this expansion of experienced pain across individuals. Finally, outside of the laboratory setting, we similarly show that even modest nightly changes in sleep quality (increases and decreases) within an individual determine consequential day-to-day changes in experienced pain (decreases and increases, respectively). Together, these data provide a novel framework underlying the impact of sleep loss on pain and, furthermore, establish that the association between sleep and pain is expressed in a night-to-day, bidirectional relationship within a sample of the general population. More broadly, our findings highlight sleep as a novel therapeutic target for pain management within and outside the clinic, including circumstances where sleep is frequently short yet pain is abundant (e.g., the hospital setting).
Are you experiencing pain? Did you have a bad night of sleep? This study provides underlying brain and behavioral mechanisms explaining this common co-occurrence. We show that sleep deprivation enhances pain responsivity within the primary sensing regions of the brain's cortex yet blunts activity in other regions that modulate pain processing, the striatum and insula. We further establish that even subtle night-to-night changes in sleep in a sample of the general population predict consequential day-to-day changes in pain (bidirectionally). Considering the societal rise in chronic pain conditions in lock-step with the decline in sleep time through the industrial world, our data support the hypothesis that these two trends may not simply be co-occurring but are significantly interrelated.
The sleep-deprived human brain Krause, Adam J; Simon, Eti Ben; Mander, Bryce A ...
Nature reviews. Neuroscience,
07/2017, Letnik:
18, Številka:
7
Journal Article
Recenzirano
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How does a lack of sleep affect our brains? In contrast to the benefits of sleep, frameworks exploring the impact of sleep loss are relatively lacking. Importantly, the effects of sleep deprivation ...(SD) do not simply reflect the absence of sleep and the benefits attributed to it; rather, they reflect the consequences of several additional factors, including extended wakefulness. With a focus on neuroimaging studies, we review the consequences of SD on attention and working memory, positive and negative emotion, and hippocampal learning. We explore how this evidence informs our mechanistic understanding of the known changes in cognition and emotion associated with SD, and the insights it provides regarding clinical conditions associated with sleep disruption.
The mRNA N6-methyladenosine (m6A) modification has emerged as an essential regulator of normal and malignant hematopoiesis. Inactivation of the m6A mRNA reader YTHDF2, which recognizes m6A-modified ...transcripts to promote m6A-mRNA degradation, results in hematopoietic stem cell (HSC) expansion and compromises acute myeloid leukemia. Here we investigate the long-term impact of YTHDF2 deletion on HSC maintenance and multilineage hematopoiesis. We demonstrate that Ythdf2-deficient HSCs from young mice fail upon serial transplantation, display increased abundance of multiple m6A-modified inflammation-related transcripts, and chronically activate proinflammatory pathways. Consistent with the detrimental consequences of chronic activation of inflammatory pathways in HSCs, hematopoiesis-specific Ythdf2 deficiency results in a progressive myeloid bias, loss of lymphoid potential, HSC expansion, and failure of aged Ythdf2-deficient HSCs to reconstitute multilineage hematopoiesis. Experimentally induced inflammation increases YTHDF2 expression, and YTHDF2 is required to protect HSCs from this insult. Thus, our study positions YTHDF2 as a repressor of inflammatory pathways in HSCs and highlights the significance of m6A in long-term HSC maintenance.
Poor sleep is associated with hypertension, a major risk factor for cardiovascular disease. However, the mechanism(s) through which sleep loss affects cardiovascular health remains largely unknown, ...including the brain and body systems that regulate vascular function.
Sixty-six healthy adults participated in a repeated-measures, crossover, experimental study involving assessments of cardiovascular function and brain connectivity after a night of sleep and a night of sleep deprivation.
First, sleep deprivation significantly increased blood pressure-both systolic and diastolic. Interestingly, this change was independent of any increase in heart rate, inferring a vasculature-specific rather than direct cardiac pathway. Second, sleep loss compromised functional brain connectivity within the vascular control network, specifically the insula, anterior cingulate, amygdala, and ventral and medial prefrontal cortices. Third, sleep loss-related changes in brain connectivity and vascular tone were not independent, but significantly interdependent, with changes within the vascular control brain network predicting the sleep-loss shift toward hypertension.
These findings establish an embodied framework in which sleep loss confers increased risk of cardiovascular disease through an impact upon central brain control of vascular tone, rather than a direct impact on accelerated heart rate itself.
It has long been thought that links between affect and sleep are bidirectional. However, few studies have directly assessed the relationships between: (1) pre-sleep affect and sleep ...electroencephalogram (EEG) activity; and (2) sleep EEG activity and post-sleep affect. This study aims to systematically explore the correlations between pre-/post-sleep affect and EEG activity during sleep. In a community sample of adults (n = 51), we measured participants' positive and negative affect in the evening before sleep and in the next morning after sleep. Participants slept at their residence for 1 night of EEG recording. Using Fourier transforms, the EEG power at each channel was estimated during rapid eye movement sleep and non-rapid eye movement sleep for the full range of sleep EEG frequencies. We first present heatmaps of the raw correlations between pre-/post-sleep affect and EEG power during rapid eye movement and non-rapid eye movement sleep. We then thresholded the raw correlations with a medium effect size |r| ≥ 0.3. Using a cluster-based permutation test, we identified a significant cluster indicating a negative correlation between pre-sleep positive affect and EEG power in the alpha frequency range during rapid eye movement sleep. This result suggests that more positive affect during the daytime may be associated with less fragmented rapid eye movement sleep that night. Overall, our exploratory results lay the foundation for confirmatory research on the relationship between daytime affect and sleep EEG activity.
There is evidence for e-Health interventions for full-blown depression. Little is known regarding commonly untreated subthreshold depression in primary care. This randomized controlled multi-centre ...trial assessed reach and two-year-effects of a proactive e-Health intervention (ActiLife) for patients with subthreshold depression.
Primary care and hospital patients were screened for subthreshold depression. Over 6 months, ActiLife participants received three individualized feedback letters and weekly messages promoting self-help strategies against depression, e.g., dealing with unhelpful thoughts or behavioural activation. The primary outcome depressive symptom severity (Patient Health Questionnaire;PHQ-8) and secondary outcomes were assessed 6, 12 and 24 months.
Of those invited, n = 618(49.2 %) agreed to participate. Of them, 456 completed the baseline interview and were randomized to ActiLife (n = 227) or assessment only (n = 226). Generalised estimation equation analyses adjusting for site, setting and baseline depression revealed that depressive symptom severity declined over time, with no significant group differences at 6 (mean difference = 0.47 points; d = 0.12) and 24 months (mean difference = −0.05 points; d = −0.01). Potential adverse effects were observed at 12 months, with higher depressive symptom severity for ActiLife than control participants (mean difference = 1.33 points; d = 0.35). No significant differences in rates of reliable deterioration or reliable improvement of depressive symptoms were observed. ActiLife increased applied self-help strategies at 6 (mean difference = 0.32; d = 0.27) and 24 months (mean difference = 0.22; d = 0.19), but not at 12 months (mean difference = 0.18; d = 0.15).
Self-report measures and lack of information on patients' mental health treatment.
ActiLife yielded satisfactory reach and increased the use of self-help strategies. Data were inconclusive in terms of depressive symptom changes.
•Active recruitment in primary care reaches many individuals with depression.•Individuals with a broad range of symptom severity could be involved in ActiLife.•ActiLife fostered self-help strategies in individuals with depressive symptoms.•There was no support for positive effects on depression symptom reduction.
Azeotropic distillation is typically required to achieve fluorine‐18 radiolabeling during the production of positron emission tomography (PET) imaging agents. However, this time‐consuming process ...also limits fluorine‐18 incorporation, due to radioactive decay of the isotope and its adsorption to the drying vessel. In addressing these limitations, the fluorine‐18 radiolabeling of one model rhenium(I) complex is reported here, which is significantly improved under conditions that do not require azeotropic drying. This work could open a route towards the investigation of a simplified metal‐mediated late‐stage radiofluorination method, which would expand upon the accessibility of new PET and PET‐optical probes.
18 and I like it: A novel fluorine‐18 radiolabeling method has been found to circumvent the need for preliminary azeotropic distillation. The method involves complexation to a rhenium(I) center, and is of particular importance in the expanded scope of positron emission tomography (PET) imaging agent design. Results were verified through the monitoring of multiple reaction conditions by employing microfluidic technologies in flow.
The ancient Mediterranean port city of Ashkelon, identified as "Philistine" during the Iron Age, underwent a marked cultural change between the Late Bronze and the early Iron Age. It has been long ...debated whether this change was driven by a substantial movement of people, possibly linked to a larger migration of the so-called "Sea Peoples." Here, we report genome-wide data of 10 Bronze and Iron Age individuals from Ashkelon. We find that the early Iron Age population was genetically distinct due to a European-related admixture. This genetic signal is no longer detectible in the later Iron Age population. Our results support that a migration event occurred during the Bronze to Iron Age transition in Ashkelon but did not leave a long-lasting genetic signature.
Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is ...poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.
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