Introduction
In Italy, lockdown due to COVID-19 health emergency started on March 10 and partially ended on May 3rd, 2020. There was a significant increase of psychological distress and symptoms of ...mental illness, and worsening of quality of sleep in the general population.
Methods
Participants completed an anonymous web-based survey that include questionnaires about sleep and anxiety and depression symptoms. Our sample included 400 subjects: 307 students (mean age 22.84 ± 2.68) and 93 university administration staff workers (mean age 37.02 ± 12.46).
Results
we found an increase in Bed Time hour, Sleep Latency, and Wake-Up time between before and during COVID-19 emergency and a worsening of sleep quality and of insomnia symptoms. In particular, during the lockdown, the impact of the delay in Bed Time and in Wake-Up was more pronounced in students. In workers, we observed a prevalence of maintenance insomnia before COVID-19 of 24% that significantly increase during COVID-19 reaching 40%, while workers with difficulties in sleep initiation were only 15% that increased to 42%. In our sample, 27.8% showed depressive symptoms, while 34.3% showed anxious symptoms, in particular in students.
Conclusion
The impact of lockdown was greater in students than in workers, and in females than in males. Concerning the psycho-emotional aspects, about one-third of our sample showed depressive or anxious symptoms. The results of our study may provide support for the implementation of some interventions for well-being in pandemic condition.
Metabolic changes within the cell and its niche affect cell fate and are involved in many diseases and disorders including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) ...is the etiological agent of Kaposi's sarcoma (KS). KSHV latently infected cells express only a subset of viral genes, mainly located within the latency-associated region, among them 12 microRNAs. Notably, these miRNAs are responsible for inducing the Warburg effect in infected cells. Here we identify a novel mechanism enabling KSHV to manipulate the metabolic nature of the tumour microenvironment. We demonstrate that KSHV infected cells specifically transfer the virus-encoded microRNAs to surrounding cells via exosomes. This flow of genetic information results in a metabolic shift toward aerobic glycolysis in the surrounding non-infected cells. Importantly, this exosome-mediated metabolic reprogramming of neighbouring cells supports the growth of infected cells, thereby contributing to viral fitness. Finally, our data show that this miRNA transfer-based regulation of cell metabolism is a general mechanism used by other herpesviruses, such as EBV, as well as for the transfer of non-viral onco-miRs. This exosome-based crosstalk provides viruses with a mechanism for non-infectious transfer of genetic material without production of new viral particles, which might expose them to the immune system. We suggest that viruses and cancer cells use this mechanism to shape a specific metabolic niche that will contribute to their fitness.
Obstructive sleep apnea (OSA) is commonly associated with neurocognitive impairments that have not been consistently related to specific brain structure abnormalities. Knowledge of the brain ...structures involved in OSA and the corresponding functional implications could provide clues to the pathogenesis of cognitive impairment and its reversibility in this disorder.
To investigate the cognitive deficits and the corresponding brain morphology changes in OSA, and the modifications after treatment, using combined neuropsychologic testing and voxel-based morphometry.
A total of 17 patients treatment-naive to sleep apnea and 15 age-matched healthy control subjects underwent a sleep study, cognitive tests, and magnetic resonance imaging. After 3 months of treatment, cognitive and imaging data were collected to assess therapy efficacy.
Neuropsychologic results in pretreatment OSA showed impairments in most cognitive areas, and in mood and sleepiness. These impairments were associated with focal reductions of gray-matter volume in the left hippocampus (entorhinal cortex), left posterior parietal cortex, and right superior frontal gyrus. After treatment, we observed significant improvements involving memory, attention, and executive-functioning that paralleled gray-matter volume increases in hippocampal and frontal structures.
The cognitive and structural deficits in OSA may be secondary to sleep deprivation and repetitive nocturnal intermittent hypoxemia. These negative effects may be recovered by consistent and thorough treatment. Our findings highlight the importance of early diagnosis and successful treatment of this disorder.
Whether adjuvant therapy with aromatase inhibitors (AIs) causes sleep disturbances or not in postmenopausal women with early breast cancer (EBC) is still a controversial issue.
Between March 2014 and ...November 2017, validated questionnaires for assessing insomnia, anxiety, depression, quality of life (QoL) and restless legs syndrome (RLS) were administered to 160 EBC patients at baseline and after 3, 6, 12, and 24 months of AI therapy.
AI therapy significantly decreased the patients’ QoL, but did not influence insomnia, anxiety or depression. However, it significantly increased the frequency and severity of RLS. Patients with RLS at baseline (19%) or who developed RLS during AI therapy (26.3%) reported statistically lower quality of sleep, higher anxiety and depression, and worse QoL compared to patients who never reported RLS (54.7%).
Although AI therapy does not affect sleep quality, it may increase RLS frequency. The presence of RLS could identify a group of EBC patients who may benefit from psychological support.
•Aromatase inhibitors (AIs) are the main adjuvant treatment in hormone receptor-positive early breast cancer (EBC) in postmenopausal patients.•Sleep disturbances are common in cancer patients and the role of AIs is not clearly defined.•AI therapy did not worsen sleep disturbances, anxiety, and depression, but increases frequency and severity of restless legs syndrome (RLS).•EBC patients with RLS are more fragile and suffer from higher levels of .•Insomnia, anxiety, depression, and worse overall quality of life.
Viruses manipulate host cells to enhance their replication, and the identification of cellular factors targeted by viruses has led to key insights into both viral pathogenesis and cell biology. In ...this study, we develop an HIV reporter virus (HIV-AFMACS) displaying a streptavidin-binding affinity tag at the surface of infected cells, allowing facile one-step selection with streptavidin-conjugated magnetic beads. We use this system to obtain pure populations of HIV-infected primary human CD4+ T cells for detailed proteomic analysis, and quantitate approximately 9000 proteins across multiple donors on a dynamic background of T cell activation. Amongst 650 HIV-dependent changes (q < 0.05), we describe novel Vif-dependent targets FMR1 and DPH7, and 192 proteins not identified and/or regulated in T cell lines, such as ARID5A and PTPN22. We therefore provide a high-coverage functional proteomic atlas of HIV infection, and a mechanistic account of host factors subverted by the virus in its natural target cell.
The seminal description of the cellular restriction factor APOBEC3G and its antagonism by HIV-1 Vif has underpinned two decades of research on the host-virus interaction. We recently reported that ...HIV-1 Vif is also able to degrade the PPP2R5 family of regulatory subunits of key cellular phosphatase PP2A (PPP2R5A-E; Greenwood et al., 2016; Naamati et al., 2019). We now identify amino acid polymorphisms at positions 31 and 128 of HIV-1 Vif which selectively regulate the degradation of PPP2R5 family proteins. These residues covary across HIV-1 viruses in vivo, favouring depletion of PPP2R5A-E. Through analysis of point mutants and naturally occurring Vif variants, we further show that degradation of PPP2R5 family subunits is both necessary and sufficient for Vif-dependent G2/M cell cycle arrest. Antagonism of PP2A by HIV-1 Vif is therefore independent of APOBEC3 family proteins, and regulates cell cycle progression in HIV-infected cells.
Most patients with idiopathic REM sleep behavior disorder (iRBD) present peculiar repetitive leg jerks during sleep in their clinical spectrum, called periodic leg movements (PLMS). The clinical ...differentiation of iRBD patients with and without PLMS is challenging, without polysomnographic confirmation. The aim of this study is to develop a new Machine Learning (ML) approach to distinguish between iRBD phenotypes. Heart rate variability (HRV) data were acquired from forty-two consecutive iRBD patients (23 with PLMS and 19 without PLMS). All participants underwent video-polysomnography to confirm the clinical diagnosis. ML models based on Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), and eXtreme Gradient Boosting (XGBoost) were trained on HRV data, and classification performances were assessed using Leave-One-Out cross-validation. No significant clinical differences emerged between the two groups. The RF model showed the best performance in differentiating between iRBD phenotypes with excellent accuracy (86%), sensitivity (96%), and specificity (74%); SVM and XGBoost had good accuracy (81% and 78%, respectively), sensitivity (83% for both), and specificity (79% and 72%, respectively). In contrast, LR had low performances (accuracy 71%). Our results demonstrate that ML algorithms accurately differentiate iRBD patients from those without PLMS, encouraging the use of Artificial Intelligence to support the diagnosis of clinically indistinguishable iRBD phenotypes.
To search for discriminating biomarkers, 30 patients with idiopathic rapid‐eye‐movements sleep behavior disorder (iRBD) were compared with 17 patients with RBD within narcolepsy type 1. Both groups ...underwent extensive examinations, including skin biopsy searching for phosphorylated α‐synuclein deposits and whole‐night video‐polysomnography. Skin biopsy was positive for phosphorylated α‐synuclein deposits in 86.7% of iRBD patients and in none of narcoleptic patients. The analysis of video‐polysomnographic motor events showed differences in their occurrence throughout the night in the two groups. iRBD and RBD due to narcolepsy do have different clinical and pathological findings, confirming a different pathophysiology.
Abstract
Shelterin, the telomeric protein complex, plays a crucial role in telomere homeostasis. In fission yeast, telomerase is recruited to chromosome ends by the shelterin component Tpz1 and its ...binding partner Ccq1, where telomerase binds to the 3′ overhang to add telomeric repeats. Recruitment is initiated by the interaction of Ccq1 with the telomerase subunit Est1. However, how telomerase is released following elongation remains to be established. Here, we show that Ccq1 also has a role in the suppression of telomere elongation, when coupled with the Clr4 histone H3 methyl-transferase complex and the Clr3 histone deacetylase and nucleosome remodelling complex, SHREC. We have dissected the functions of Ccq1 by establishing a Ccq1-Est1 fusion system, which bypasses the telomerase recruitment step. We demonstrate that Ccq1 forms two distinct complexes for positive and negative telomerase regulation, with Est1 and Clr3 respectively. The negative form of Ccq1 promotes dissociation of Ccq1-telomerase from Tpz1, thereby restricting local telomerase activity. The Clr4 complex also has a negative regulation activity with Ccq1, independently of SHREC. Thus, we propose a model in which Ccq1-Est1 recruits telomerase to mediate telomere extension, whilst elongated telomeric DNA recruits Ccq1 with the chromatin-remodelling complexes, which in turn releases telomerase from the telomere.
Obstructive sleep apnea (OSA) is characterized by the frequent presence of neuro-cognitive impairment. Recent studies associate cognitive dysfunction with altered resting-state brain connectivity ...between key nodes of the executive and default-mode networks, two anti-correlated functional networks whose strength of activation increases or decreases with cognitive activity, respectively. To date no study has investigated a relationship between cognitive impairment in OSA and brain connectivity during an active working-memory challenge. We thus investigated the effect of OSA on working-memory performance and underlying brain connectivity.
OSA patients and matched healthy controls underwent functional magnetic resonance imaging (fMRI) scanning while performing a 2-back working-memory task. Standard fMRI analyses highlighted the brain regions activated at increasing levels of working-memory load, which were used as seeds in connectivity analyses. The latter were based on a multiregional Psycho-Physiological-Interaction (PPI) approach, to unveil group differences in effective connectivity underlying working-memory performance.
Compared with controls, in OSA patients normal working-memory performance reflected in: a) reduced interhemispheric effective connectivity between the frontal “executive” nodes of the working-memory network, and b) increased right-hemispheric connectivity among regions mediating the “salience-based” switch from the default resting-state mode to the effortful cognitive activity associated with the executive network. The strength of such connections was correlated, at increasing task-demands, with executive (Stroop test) and memory (Digit Span test) performance in neuro-cognitive evaluations.
The analysis of effective connectivity changes during a working-memory challenge provides a complementary window, compared with resting-state studies, on the mechanisms supporting preserved performance despite functional and structural brain modifications in OSA.
•Sleep apnea (OSA) is frequently characterized by neuro-cognitive impairment.•We addressed brain connectivity underlying working-memory (WM) in OSA.•Normal WM reflected in reduced interhemispheric connectivity in the executive network.•Normal WM reflected in increased connectivity between salience and default networks.•Brain connectivity highlights compensatory mechanisms supporting performance in OSA.
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