The non-coding RNA landscape of plasma cell dyscrasias

Despite substantial advancements have been done in the understanding of the pathogenesis of plasma cell (PC) disorders, these malignancies remain hard-to-treat. The discovery and subsequent characterization of non-coding transcripts, which include several members with diverse length and mode of action, has unraveled novel mechanisms of gene expression regulation often malfunctioning in cancer. Increasing evidence indicates that such non-coding molecules also feature in the pathobiology of PC dyscrasias, where they are endowed with strong therapeutic and/or prognostic potential. In this review, we aim to summarize the most relevant findings on the biological and clinical features of the non-coding RNA landscape of malignant PCs, with major focus on multiple myeloma. The most relevant classes of non-coding RNAs will be examined, along with the mechanisms accounting for their dysregulation and the recent strategies used for their targeting in PC dyscrasias. It is hoped these insights may lead to clinical applications of non-coding RNA molecules as biomarkers or therapeutic targets/agents in the near future

Evaluation of the management of Hr-HPV+/PapTest- women. Results at 1-year recall

With cervical cancer screening the choice of 1-year as a period of follow-up in positive high-risk HPV women without cytological lesions is still under discussion. We evaluated the management of these women and the role of HPV genotyping test. We did a cervical cancer screening study of women aged 35-64 with primary high-risk HPV test. Women positive for high-risk HPV with negative cytology were followed-up after 1 year. In this study we selected women with high-risk HPV+/PapTest- resulted high-risk HPV+ at recall and performed the PapTest and HPV genotyping test. The detection rate of squamous high grade (CIN2+) relative to the total screened cohort was 2.1‰, and it was 0.2‰ at the 1-year recall. The colposcopy performed in women referred at the 1-year recall accounted for 48.8% of the total (baseline + 1-year recall), and 84.3% of these women had no cytological lesions. The most frequent hr-HPV genotype detected was HPV16 and 66.7% of co-infections were due to HPV16 and HPV18. 54.5% of women presented a persistent infection at 1-year recall with the same HPV subtype, 50% of persistent infections was due to HPV16 and 16.7% of these were determined to be CIN2+ histological lesions. Our data show that it may be useful to extend the period of follow-up for women hr-HPV+/PapTest- so as to reduce the number of unnecessary colposcopies due to the transitory infections and that the genotyping test could help to identify the persistent infections in which HPV16 is involved

Management of women aged 25-34 with diagnosis of ASCUS in the screening center of Latina.

In cervical cancer screening program of Latina (Italy) the hr-HPV as primary test is performed only on women aged 35-64 while women aged 25-34 are invited to perform PapTest. The aim of this study was to evaluate the impact of the application of the PapTest in women aged 25-34 and to evaluate the management of ASCUS. Women aged 25-34 were invited to perform PapTest according to the Italian guidelines; women with diagnosis of LSIL+ were referred to colposcopy while women with diagnosis of ASCUS were referred to hr-HPV test and only women resulted positive were referred to colposcopy. The 4.0% of women resulted positive to PapTest and the referral rate to colposcopy was 3.5%. The PPV value for CIN2+ at colposcopy was 7.2% and the Detection Rate (DR) for CIN2+ was 2.40‰. The ASCUS category was diagnosed in 41.8% of women resulted positive to PapTest and between them the 70.6% resulted positive to the hr-HPV test. The referral rate to colposcopy of women resulted positive to hr-HPV test was 1.1%. The PPV for CIN2+ at colposcopy and the DR of CIN2+ was 8.4% and 0.96‰ respectively. Between women with diagnosis of ASCUS, only 6 women showed a CIN2+ lesion (4 CIN2 and 2 CIN3). The present study showed that this algorithm, applied to women aged 25-34, obtained a good performance in term of test specificity (98%) and confirm that the application of hr-HPV test in the management of ASCUS leads to a decreased of inappropriate colposcopy due to transitory infection in young women

Sex and gender differences in clinical and functional indices in subjects with schizophrenia and healthy controls: Data from the baseline and 4-year follow-up studies of the Italian Network for Research on Psychoses

Gender differences in clinical and psychosocial aspects of schizophrenia have been widely reported. Findings have not always been consistent, and some of them need further research. In a large sample of community dwelling persons with schizophrenia, we investigated gender differences in clinical, cognitive and functional indices, as well as their changes over a 4-year follow-up and their impact on real-life functioning. Gender differences in personal resources, cognitive and functional indices were explored also in a sample of healthy controls. Men with respect to women had an earlier age of illness onset, a worse premorbid adjustment in the academic domain, more severe avolition, expressive deficit and positive symptoms, lower prevalence of comorbidity for affective disorders, less frequent use of two coping strategies ('religion' and 'use of emotional support') and more frequent positive history of substance and alcohol abuse. In addition, men were more impaired in verbal learning, while women in reasoning/problem solving. Some patterns of gender differences observed in healthy controls were not confirmed in patients. Men's disadvantages in the clinical picture did not translate into a worse outcome. This finding may be related to the complex interplay of several factors acting as predictors or mediators of outcome

Does social cognition change? Evidence after 4 years from the Italian Network for Research on Psychoses

BackgroundDeficits in social cognition (SC) are significantly related to community functioning in schizophrenia (SZ). Few studies investigated longitudinal changes in SC and its impact on recovery. In the present study, we aimed: (a) to estimate the magnitude and clinical significance of SC change in outpatients with stable SZ who were assessed at baseline and after 4 years, (b) to identify predictors of reliable and clinically significant change (RCSC), and (c) to determine whether changes in SC over 4 years predicted patient recovery at follow-up. MethodsThe reliable change index was used to estimate the proportion of true change in SC, not attributable to measurement error. Stepwise multiple logistic regression models were used to identify the predictors of RCSC in a SC domain (The Awareness of Social Inference Test [TASIT]) and the effect of change in TASIT on recovery at follow-up. ResultsIn 548 participants, statistically significant improvements were found for the simple and paradoxical sarcasm of TASIT scale, and for the total score of section 2. The reliable change index was 9.8. A cut-off of 45 identified patients showing clinically significant change. Reliable change was achieved by 12.6% and RCSC by 8% of participants. Lower baseline TASIT sect. 2 score predicted reliable improvement on TASIT sect. 2. Improvement in TASIT sect. 2 scores predicted functional recovery, with a 10-point change predicting 40% increase in the probability of recovery. ConclusionsThe RCSC index provides a conservative way to assess the improvement in the ability to grasp sarcasm in SZ, and is associated with recovery

Autistic symptoms in unaffected first-degree relatives of people with schizophrenia: results from the Italian Network for Research on Psychoses multicenter study

Background. Autistic symptoms represent a frequent feature in schizophrenia spectrum disorders (SSD). However, the prevalence and the cognitive and functional correlates of autistic symptoms in unaffected first-degree relatives of people with SSD remain to be assessed.Methods. A total of 342 unaffected first-degree relatives related to 247 outpatients with schizophrenia were recruited as part of the multicenter study of the Italian Network for Research on Psychoses (NIRP). Autistic features were measured with the PANSS Autism Severity Scale. Three groups of participants, defined on the presence and severity of autistic symptoms, were compared on a wide array of cognitive and functional measures.Results. Of the total sample, 44.9% presented autistic symptoms; 22.8% showed moderate levels of autistic symptoms, which can be observed in the majority of people with SSD. Participants with higher levels of autistic symptoms showed worse performance on Working Memory (p = 0.014) and Social Cognition (p = 0.025) domains and in the Global Cognition composite score (p = 0.008), as well as worse on functional capacity (p = 0.001), global psychosocial functioning (p < 0.001), real-world interpersonal relationships (p < 0.001), participation in community activities (p = 0.017), and work skills (p = 0.006).Conclusions. A high prevalence of autistic symptoms was observed in first-degree relatives of people with SSD. Autistic symptoms severity showed a negative correlation with cognitive performance and functional outcomes also in this population and may represent a diagnostic and treatment target of considerable scientific and clinical interest in both patients and their first-degree relatives

The influence of autistic symptoms on social and non-social cognition and on real-life functioning in people with schizophrenia: Evidence from the Italian Network for Research on Psychoses multicenter study

BACKGROUND: Autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs), although conceptualized as separate entities, may share some clinical and neurobiological features. ASD symptoms may have a relevant role in determining a more severe clinical presentation of schizophrenic disorder but their relationships with cognitive aspects and functional outcomes of the disease remain to be addressed in large samples of individuals. AIMS: To investigate the clinical, cognitive, and functional correlates of ASD symptoms in a large sample of people diagnosed with schizophrenia. METHODS: The severity of ASD symptoms was measured with the PANSS Autism Severity Scale (PAUSS) in 921 individuals recruited for the Italian Network for Research on Psychoses multicenter study. Based on the PAUSS scores, three groups of subjects were compared on a wide array of cognitive and functional measures. RESULTS: Subjects with more severe ASD symptoms showed a poorer performance in the processing speed (p\ua0=\ua00.010), attention (p\ua0=\ua00.011), verbal memory (p\ua0=\ua00.035), and social cognition (p\ua0=\ua00.001) domains, and an overall lower global cognitive composite score (p\ua0=\ua00.010). Subjects with more severe ASD symptoms also showed poorer functional capacity (p\ua0=\ua00.004), real-world interpersonal relationships (p\ua0<\ua00.001), and participation in community-living activities (p\ua0<\ua00.001). CONCLUSIONS: These findings strengthen the notion that ASD symptoms may have a relevant impact on different aspects of the disease, crucial to the life of people with schizophrenia. Prominent ASD symptoms may characterize a specific subpopulation of individuals with SSD

Accuracy of self-assessment of real-life functioning in schizophrenia

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n=618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program