Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Genetic and environmental bases of the interplay between magical ideation and personality

Sub-threshold psychotic symptoms are quite commonly present in general population. Among these, Magical Ideation (MI) has been proved to be a valid predictor of psychosis. However, the genetic and environmental influences on the interplay between MI and personality have not fully been explored. A total of 534 adult twins from the population-based Italian Twin Register were assessed for MI using the MI Scale (MIS) and for personality with the temperament and character inventory (TCI). A Multivariate Cholesky model was applied with Mx statistical program. The best-fitting model showed that additive genetic and unshared environmental factors explain approximately the same proportion of variance in MI, whereas a less strong genetic influence on personality traits emerged. Relevant correlations between MI and specific personality traits (novelty seeking, cooperativeness, self-directedness, self-transcendence) were found, suggesting shared influences for MI and these traits. Both genetic and environmental factors explained these correlations, with genetic factors playing a predominant role. Moderate-to-substantial genetic effects on MI and personality were found. Shared genetic and environmental effects underlie the phenotypic correlation between MI (psychosis-proneness) and personality traits, i.e. self-directedness (negative association) and self-transcendence (positive association), potentially representing predictive markers of psychosis liability related to schizotypy and personality

Investigation Of Shared Genetic Effects For Psychotic And Obsessive Symptoms In Young Adult Twins

Genetic and environmental architecture of psychotic and obsessive symptoms are not completely elucidated. This study estimated for these symptoms (i) the genetic and environmental components, (ii) the withinindividual association, and (iii) the extent to which this association originates from common genetic and environmental factors. Young adult twins (N=701) from the population-based Italian Twin Register were assessed for psychotic and obsessive\u2013compulsive symptoms by using the Symptom Check List (SCL-90). Multivariate Cholesky models were fitted by the Mx statistical program. No previous study used this design to examine the same dimensions. The best-fitting model included additive genetic and nonshared environmental components, each accounting for about half of total variance in the symptoms. Genetic influences on the different symptoms overlapped considerably (rg=0.81 to 0.99). Phenotypic correlations of psychotic symptoms and of psychotic with obsessive symptoms were high (r=0.61 to 0.76), with 53% to 69% explained by shared genetic effects. This study shows substantial genetic influence on psychotic and obsessive symptoms, and indicates that their co-occurrence may be due to genetic factors to a greater extent than to environmental effects. These results encourage the search for genetic and environmental factors underlying the covariance between different psychotic traits as well as between psychotic and obsessive traits

Screening for distress in cancer patients: a multicenter, nationwide study in Italy

BACKGROUND: Routine screening for distress is internationally recommended as a necessary standard for good cancer care, given its high prevalence and negative consequences on quality of life. The objective of the current study was to contribute to the Italian validation of the Distress Thermometer (DT) to determine whether the single item DT compared favorably with referent criterion measures. METHODS: In total, 1108 outpatients with cancer were recruited from 38 representative oncology centers in Italy. Each participant completed the DT and a list of 34 possible cancer-related problems (the Problem List), the Hospital Anxiety and Depression Scale (HADS), the 18-item Brief Symptom Inventory (BSI-18), and a short visual analog scale to determine the understandability of the tools. RESULTS: Receiver operating characteristic analysis revealed that DT cutoff scores 4 and 5 had optimal sensitivity and specificity relative to both HADS and BSI-18 cutoff scores for general caseness and more severe psychological distress, respectively. Patients with DTscores 4 (cases) were more likely to be women; to have had psychological problems in the past; to report more stressful events in the last year; and to currently have more family, emotional, and physical problems related to cancer or cancer treatment. Patients indicated that the DT was easier to fill out and to understand than the HADS, but not the BSI-18. CONCLUSIONS: The DT was identified as a simple and effective screening instrument for detecting distress in Italian cancer patients as a first step toward more properly referring those in need to psychosocial intervention

The DNA Translocase FANCM/MHF Promotes Replication Traverse of DNA Interstrand Crosslinks

The replicative machinery encounters many impediments, some of which can be overcome by lesion bypass or replication restart pathways, leaving repair for a later time. However, interstrand crosslinks (ICLs), which preclude DNA unwinding, are considered absolute blocks to replication. Current models suggest that fork collisions, either from one or both sides of an ICL, initiate repair processes required for resumption of replication. To test these proposals, we developed a single molecule technique for visualizing encounters of replication forks with ICLs, as they occur in living cells. Surprisingly, the most frequent patterns were consistent with replication traverse of an ICL, without lesion repair. The traverse frequency was strongly reduced by inactivation of the translocase and DNA binding activities of the FANCM/MHF complex. The results indicate that translocase-based mechanisms enable DNA synthesis to continue past ICLs, and that these lesions are not always absolute blocks to replication

Does Anxiety Increase Impulsivity in Patients with Bipolar Disorder or Major Depressive Disorder?

The objective of this study was to examine whether anxiety increases impulsivity among patients with bipolar disorder (BPD) and major depressive disorder (MDD). Subjects comprised 205 BPD (mean age \ub1 SD 36.6 \ub1 11.5 y; 29.3% males) and 105 with MDD (mean age \ub1 SD 38 \ub1 13.1 y; 29.5% males) diagnosed using the DSM-IV-SCID. Impulsivity was assessed with the Barratt Impulsivity Scale and anxiety with the Hamilton Anxiety Rating Scale. Comorbid anxiety disorders were present in 58.9% of the BPD and 29.1% of MDD. BPD were significantly more impulsive than MDD (p < 0.001), and both BPD and MDD subjects showed significantly higher impulsivity when anxiety was present either as a comorbidity (p = 0.010) or as a symptom (p = 0.011). Impulsivity rose more rapidly with increasing anxiety symptoms in MDD than in BPD. The presence of anxiety, either as a comorbid disorder or as current anxiety symptoms, is associated with higher impulsivity in subjects with either BPD or MDD

Mapping of a putative tumor suppressor locus to proximal 7p in Wilms tumors

Different findings suggest that alterations of chromosome 7 genes play a role in the development of Wilms tumors. To define the positions of these genes, we have accomplished a combined cytogenetic and molecular study on 11 sporadic Wilms tumors. In one case, where both chromosomes 7 were rearranged, the karyotypic picture was consistent with the presence of a tumor suppressor gene at 7p15. To test this hypothesis, a loss of heterozygosity analysis was performed using microsatellite markers. This revealed a common region of allele losses mapped to the proximal short arm of chromosome 7 and defined the position of the gene(s) involved in Wilms tumors within an interval of approximately 25 cM