The transcription factor Snail is a master regulator of cellular identity and epithelial-to-mesenchymal transition (EMT) directly repressing a broad repertoire of epithelial genes. How chromatin ...modifiers instrumental to its activity are recruited to Snail-specific binding sites is unclear. Here we report that the long non-coding RNA (lncRNA) HOTAIR (for HOX Transcript Antisense Intergenic RNA) mediates a physical interaction between Snail and enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of the polycomb-repressive complex 2 and the main writer of chromatin-repressive marks. The Snail-repressive activity, here monitored on genes with a pivotal function in epithelial and hepatic morphogenesis, differentiation and cell-type identity, depends on the formation of a tripartite Snail/HOTAIR/EZH2 complex. These results demonstrate an lncRNA-mediated mechanism by which a transcriptional factor conveys a general chromatin modifier to specific genes, thereby allowing the execution of hepatocyte transdifferentiation; moreover, they highlight HOTAIR as a crucial player in the Snail-mediated EMT.
Although depression and mood-related disorders are common in persons with cancer, these conditions remain frequently overlooked in clinical practice. Negative consequences of depressive disorder ...spectrum have been reported (e.g. suicidal ideation, increase physical complications and somatic symptoms, negative influence on prognosis), indicating the need for routine screening, assessment and management.
A search of the major databases (Medline, Embase, PsycLIT, PsycINFO, and the Cochrane Library) was conducted on the reviews and meta-analyses available in order to summarize relevant data concerning depressive disorders spectrum in terms of prevalence, risk factors, and screening and assessment among patients with cancer across the trajectory of the disease.
The data show a prevalence of depression and depressive disorders between 5% and 60% according to the different diagnostic criteria, the tools used in the studies (e.g. semi-structured psychiatric interview and psychometric questionnaires), as well as the stage and type of cancer. Furthermore, despite the significant health care resources devoted to cancer care and the importance of addressing depressive symptoms, assessment and management of depressive spectrum disorders in cancer patients remains suboptimal.
Routine screening and adequate assessment of depressive spectrum disorders is necessary in patients with cancer in order to effectively manage the multifaceted and complex consequences on cancer care.
The shear modulus G of the sputum obtained by expectoration from cystic fibrosis patients is fundamental to determine the mesh size of the polymeric network pervading the sputum, a parameter related ...to lung functionality. The Akaike criterion revealed that in 55.2% of the examined samples, the best approach (among those considered) to determine G relied on the mechanical spectrum fitting by the generalised Maxwell model with relaxation times scaled by a factor 10. Thus, this approach was adopted to evaluate the mesh size distribution combining G knowledge with the determination of the average magnetic relaxation time (T.sub.2m) of sputum. As G and T.sub.2m determination can be negatively affected by sputum contamination by saliva, whose presence increases T.sub.2m and depresses G, we developed a proper "decontamination" procedure to obtain more reliable T.sub.2m and G estimations (necessary in 21% of the samples). This procedure allowed to strengthen the T.sub.2m correlation with lung functionality evaluated by FEV.sub.1 (normalised air volume emitted in the first second during a spirometry test). Keywords: rheology, low field NMR, cystic fibrosis, shear modulus, mesh size, saliva contamination
IntroductionBpolar disorder (BD) is a severe and chronic psychiatric disorder it is the sixth leading cause of disability among all illnesses worldwide. With regard to causes of premature mortality, ...patients with BD are at very high risk of suicide. Whereas risk factors for suicidal behaviors are multiple and complex, hopelessness appears to be a major independent risk factor for suicidality in BD. Compelling evidence has also demonstrated that BD is frequently associated with circadian rhythms alteration, contributing to its vulnerability, pathogenesis, and manifestations. in particular in the desynchronization of sleep and social life, has been associated with the severity of BD. Indeed hopelessness has never been studid in relation to circadian rhythms in BDObjectivesTo examine the role of chronobiological rhythm alterations in suicidal ideation and behaviors and its relation with hopelessness.MethodsOne hundred twenty-seven patients (77 females, mean age of 47.4 ± 12.5 years) with a major depressive episode and bipolar disorder (BD) type I or II (according to Structured Clinical Interview for DSM-5 assessment) were recruited in 2019 and assessed for depressive and manic symptoms (Beck Depression Inventory-II, Young Mania Rating Scale) and with the Biological Rhythms Interview of Assessment in Neuropsychiatry, Beck Hopelessness Scale, and Scale for Suicide Ideation. Univariate regression and mediation analyses were performed.ResultsForty-one patients (32.3%) showed clinically significant suicidal ideation and were more frequently affected by BD type I (P = .029) with mixed features (P = .022). Compared to nonsuicidal individuals, they had significantly more depressive symptoms (P = .019), higher emotional component of hopelessness (P = .037), and higher dysrhythmicity of sleep (P = .009), activities (P = .048), and social life (P = .019). Passive and active suicidal ideation and suicidal plans were best predicted by dysrhythmicity of sleep and social life. Dysrhythmicity of sleep and social life mediated the direct effect of depressive symptoms on passive and active suicidal ideation and also of active ideation on suicidal plans. The emotional component of hopelessness was related to dysrhythmicity of social life and mediated its effect on suicidal plans (P = .010).ConclusionsChronobiological alterations directly contributed to passive and active suicidal ideation and to suicidal preparation, with a key role of circadian rhythm alteration of sleep, activities, and social life. Chronobiological alterations also impacted the emotional component of hopelessness, hence indirectly contributing to suicidal ideations and plans. These findings call for the systematic screening of these dysrhythmicity dimensions when considering suicidal risk in individuals with BD.Disclosure of InterestNone Declared
IntroductionRecent theories hypothesized that chonobiological dis-rhythmicity might contribute to Bipolar disorders (BD) by dysregulating most of the systems involved in mood, stress and emotion ...regulation. In particular, the key role of sleep in regulating stress system and emotions has been hypothesized. Among other important factors contributing to BD the stress vulnerability/resilience dimension may play a key role. In particular low resilience has been associated with a dysregulation in emotions and stress response possibly involved in psychopathological process of BDsObjectivesThe study aimed to investigate the possible impact of resilience and emotion dysregulation on the clinical manifestations of bipolar disorders (BDs) focusing on the possible role of circadian rhythm alterations.MethodsA sample of 197 inpatients suffering from BD of type I (BDI) or II (BDII) were assessed during a major depressive episode using the Structural Clinical Interview for DSM-5 (SCID-5), the Beck Depression Inventory-II (BDI-II), the Young Mania Rating Scale (YMRS), Resilience Scale for Adults (RSA), Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), Difficulties in Emotion Regulation Scale (DERS) and the Scale for Suicide Ideation (SSI). Participants with or without circadian rhythm disturbances as measured with Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), were compared; regression and mediation analyses were computed.ResultsParticipants with circadian rhythms disturbances showed a greater severity of depressive symptoms, of suicidal risk, lower resilience and more disturbances in emotion regulation including impulsivity and regulatory strategies. The logistic regression revealed that circadian rhythm disturbances was related to depressive symptoms (O.R. 4.0), suicidal risk (OR 2.51), emotion dysregulation (OR 2.28) and low resilience (OR 2.72). At the mediation analyses, circadian rhythm alterations showed an indirect effect on depressive symptoms by impairing resilience (Z= 3.17, p=0.0014)/ emotional regulation (Z= 4.36, p<0.001) and on suicidal risk by affecting resilience (Z= 2.00, p=0.045) and favoring impulsivity (Z= 2.14, p=0.032).ConclusionsThe present findings may show that circadian rhythm alterations might play a key role in BD manifestations, as being correlated with more severe clinical presentations of depressive symptoms, suicidal risk, impaired resilience and emotional dysregulation. Addressing circadian rhythm alterations might potentially promote resilience and emotion regulation hence improving mood symptoms and suicidal risk in BDs.Disclosure of InterestNone Declared
The use of psychotropic drugs, namely those with an antidepressant profile (ADs), is a mandatory part of an integrated treatment of psychiatric disorders among cancer patients. We aimed to synthetize ...the most relevant data emerging from published studies to provide tips about the use of ADs in oncology.
A search was made of the major databases over the last 30 years (Embase/Medline, PsycLIT, PsycINFO, the Cochrane Library), including narrative reviews, systematic reviews and meta-analyses summarizing the results from observational studies and randomized clinical trials assessing effectiveness, safety profile, interactions, contraindications and use of ADs in oncology with regard to both psychiatric (depressive spectrum, stress-related, anxiety disorders) and cancer-related symptoms (e.g. pain, hot flashes and fatigue).
The weight of evidence supports the ef cacy of ADs for more severe major depression in individuals with cancer and as an adjuvant treatment in cancer-related symptoms, although the methodological limitations of reported randomized controlled trials do not permit definite conclusions. Data also indicate that there should be caution in the use of ADs in cancer patients in terms of their safety profile and potential clinically significant interactions with other prescribed medications. Practical recommendations that have been made for the use of ADs in cancer patients, in the context of a multimodal approach to depression treatment, have been summarized here.
ADs are a relatively safe and effective treatment for more severe major depression in cancer patients. However, more research is urgently needed regarding the efficacy of ADs in different cancer types and cancer settings, their interactions with anticancer agents and their additive benefit when integrated with psychosocial interventions.
Objectives Disclosing information on diagnosis, prognosis and treatment is a delicate process in oncology, although awareness levels have over time increased in people with cancer. However, ...individual characteristics should be considered when communicating difficult information. We conducted a multicentric study to explore the moderating role of coping styles on the relationship between information about cancer, quality of life and psychological distress. Methods In the period between October 2015 and February 2016, 288 patients with a diagnosis of a solid tumor were recruited from seven Italian oncology units. All participants were administered the Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC), the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), and the EORTC QLQ 25-item information module (INFO25). We explored the moderating effect of coping style with quality of life (QoL) and distress (DT) as dependent variables and information on cancer treatment as independent variable. Results Low levels of anxious preoccupation significantly moderated the relationship between information on treatment and QoL (R2 6%, p < 0.001), while low and medium levels of hopelessness significantly moderated the relationship between information on treatment and DT (R2 = 14%, p = 0.033). Adaptive coping strategies, such as fighting spirit and fatalism, and borderline strategies such as avoidance, did not play a role in this relationship. Conclusion Taking into account and evaluating coping mechanisms in cancer care is a priority when disclosing information on treatments, in order to tailor communication style to individual features.
Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers ...distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.
Abstract Subject-specific finite element models have been used to predict stress-state and fracture risk in individual patients. While many studies analysed quasi-axial loading configurations, only ...few works simulated sideways load configurations, such as those arising in a fall. The majority among these latter directly predicted bone strength, without assessing elastic strain prediction accuracy. The aim of the present work was to evaluate if a subject-specific finite element modelling technique from CT data that accurately predicted strains in quasi-axial loading configurations is suitable to accurately predict strains also when applying low magnitude loads in sideways configurations. To this aim, a combined numerical–experimental study was performed to compare finite element predicted strains with strain-gauge measurements from three cadaver proximal femurs instrumented with sixteen strain rosettes and tested non-destructively under twelve loading configurations, spanning a wide cone (0–30° for both adduction and internal rotation angles) of sideways fall scenarios. The results of the present study evidenced a satisfactory agreement between experimentally measured and predicted strains ( R2 greater than 0.9, RMSE% lower than 10%) and displacements. The achieved strain prediction accuracy is comparable to those obtained in state of the art studies in quasi-axial loading configurations. Still, the presence of the highest strain prediction errors (around 30%) in the lateral neck aspect would deserve attention in future studies targeting bone failure.
PDF
