Evaluative beliefs as mediators of the relationship between parental bonding and symptoms of paranoia and depression

This study was aimed to explore the distinct pathways that lead to depression and paranoia. We first examined the association of dysfunctional parenting experiences and negative self-evaluations in depression and paranoia. Furthermore, we also examined whether different self-evaluative beliefs could mediate the relationships between dysfunctional parenting experiences (i.e. parental overprotection or lack of care) and the development of depression and paranoia. A sample composed of 55 paranoid patients, 38 depressed patients and 44 healthy controls completed the Parental Bonding Instrument (PBI), the Evaluative Beliefs Scale (EBS) and some clinical scales. Our analyses revealed that lack of parental care and negative self–self evaluations were associated with depression symptoms. Analyses also revealed that parental overprotection and negative other–self evaluations were associated with paranoid symptoms. Furthermore, negative self–self and other–self evaluations fully mediated the relationship of parental overprotection and paranoia, whereas negative self–self evaluations partially mediated the relationship between lack of parental care and depression. These findings suggest that distinct patterns of parental practices may contribute to the development of different dysfunctional schemas which in turn may lead to either depression or paranoia.     

T2 hyperintensity along the cortico-spinal tract in cirrhosis relates to functional abnormalities

Magnetic resonance has shown T2 hyperintensity along the cortico-spinal tract in the brain of cirrhotic patients. This abnormality, which is reversible after liver transplantation, appears to correspond to mild edema. Because astrocytic edema present in hepatic encephalopathy may be responsible for neuronal dysfunction, we studied whether T2 hyperintensity along the cortico-spinal tract may relate to functional abnormalities. Twenty patients with cirrhosis underwent neuropsychologic tests, neurophysiologic study of the cortico-spinal tract with transcranial magnetic stimulation, and (1)H-magnetic resonance. The study was repeated 6 months after liver transplantation (n = 15) and was compared with a control group of healthy subjects (n = 11). Cirrhotic patients exhibited increased T2 signal and several functional abnormalities along the cortico-spinal tract (increased central motor conduction time, increased motor cortical threshold, and decreased motor-evoked potential amplitude). Functional abnormalities reversed after liver transplantation and were associated with normalization of T2 cortico-spinal hyperintensity and with improvement of minimal hepatic encephalopathy. In conclusion, T2 hyperintensity along the cortico-spinal tract in cirrhosis relates to functional abnormalities that are reversible after liver transplantation. These findings suggest that mild cerebral edema along the cortico-spinal pathway may cause neuronal dysfunction. These results support the participation of astrocytic edema in the pathogenesis of hepatic encephalopathy.     

Increased mitochondrial function downstream from KDM5A histone demethylase rescues differentiation in pRB-deficient cells

The retinoblastoma tumor suppressor protein pRb restricts cell growth through inhibition of cell cycle progression. Increasing evidence suggests that pRb also promotes differentiation, but the mechanisms are poorly understood, and the key question remains as to how differentiation in tumor cells can be enhanced in order to diminish their aggressive potential. Previously, we identified the histone demethylase KDM5A (lysine [K]-specific demethylase 5A), which demethylates histone H3 on Lys4 (H3K4), as a pRB-interacting protein counteracting pRB''s role in promoting differentiation. Here we show that loss of Kdm5a restores differentiation through increasing mitochondrial respiration. This metabolic effect is both necessary and sufficient to induce the expression of a network of cell type-specific signaling and structural genes. Importantly, the regulatory functions of pRB in the cell cycle and differentiation are distinct because although restoring differentiation requires intact mitochondrial function, it does not necessitate cell cycle exit. Cells lacking Rb1 exhibit defective mitochondria and decreased oxygen consumption. Kdm5a is a direct repressor of metabolic regulatory genes, thus explaining the compensatory role of Kdm5a deletion in restoring mitochondrial function and differentiation. Significantly, activation of mitochondrial function by the mitochondrial biogenesis regulator Pgc-1α (peroxisome proliferator-activated receptor γ-coactivator 1α; also called PPARGC1A) a coactivator of the Kdm5a target genes, is sufficient to override the differentiation block. Overexpression of Pgc-1α, like KDM5A deletion, inhibits cell growth in RB-negative human cancer cell lines. The rescue of differentiation by loss of KDM5A or by activation of mitochondrial biogenesis reveals the switch to oxidative phosphorylation as an essential step in restoring differentiation and a less aggressive cancer phenotype.     

POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.