DN interaction from meson exchange

A model of the DN interaction is presented which is developed in close analogy to the meson-exchange KbarN potential of the Juelich group utilizing SU(4) symmetry constraints. The main ingredients of the interaction are provided by vector meson (rho, omega) exchange and higher-order box diagrams involving D*N, D\Delta, and D*\Delta intermediate states. The coupling of DN to the pi-Lambda_c and pi-Sigma_c channels is taken into account. The interaction model generates the Lambda_c(2595) resonance dynamically as a DN quasi-bound state. Results for DN total and differential cross sections are presented and compared with predictions of an interaction model that is based on the leading-order Weinberg-Tomozawa term. Some features of the Lambda_c(2595) resonance are discussed and the role of the near-by pi-Sigma_c threshold is emphasized. Selected predictions of the orginal KbarN model are reported too. Specifically, it is pointed out that the model generates two poles in the partial wave corresponding to the Lambda(1405) resonance.Comment: 14 pages, 8 figure

Impact of previous tobacco use with or without cannabis on first psychotic experiences in patients with first-episode psychosis

Objective: There is high prevalence of cigarette smoking in individuals with first-episode psychosis (FEP) prior to psychosis onset. The purpose of the study was to determine the impact of previous tobacco use with or without cannabis on first psychotic experiences in FEP and the impact of this use on age of onset of symptoms, including prodromes. Methods: Retrospective analyses from the naturalistic, longitudinal, multicentre, “Phenotype-Genotype and Environmental Interaction. Application of a Predictive Model in First Psychotic Episodes (PEPs)” Study. The authors analysed sociodemographic/clinical data of 284 FEP patients and 231 matched healthy controls, and evaluated first psychotic experiences of patients using the Symptom Onset in Schizophrenia Inventory. Results: FEP patients had significantly higher prevalence of tobacco, cannabis, and cocaine use than controls. The FEP group with tobacco use only prior to onset (N = 56) had more sleep disturbances (42.9% vs 18.8%, P = 0.003) and lower prevalence of negative symptoms, specifically social withdrawal (33.9% vs 58%, P = 0.007) than FEP with no substance use (N = 70), as well as lower prevalence of ideas of reference (80.4% vs 92.4%, P = 0.015), perceptual abnormalities (46.4% vs 67.4%, P = 0.006), hallucinations (55.4% vs 71.5%, P = 0.029), and disorganised thinking (41.1% vs 61.1%, P = 0.010) than FEP group with previous tobacco and cannabis use (N = 144). FEP patients with cannabis and tobacco use had lower age at first prodromal or psychotic symptom (mean = 23.73 years [SD = 5.09]) versus those with tobacco use only (mean = 26.21 [SD = 4.80]) (P = 0.011). Conclusions: The use of tobacco alone was not related to earlier age of onset of a first psychotic experience, but the clinical profile of FEP patients is different depending on previous tobacco use with or without cannabis. © 2021 The Author

A longitudinal study of gene expression in first-episode schizophrenia; exploring relapse mechanisms by co-expression analysis in peripheral blood

Little is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse. © 2021, The Author(s)

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: differences between males and females

BackgroundDeficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset.Materials and methodsThe initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up.ResultsFEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = −0.307, p = 0.012) were significantly associated with functioning.ConclusionOur data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended

Three-dimensional full automated software in the evaluation of the left ventricle function: from theory to clinical practice

Left ventricular systolic function evaluation is an essential part of all transthoracic echocardiographic (TTE) studies. 3D echocardiography (3DE) is superior to 2D and is recommended as the method of choice. However, since it is time consuming and requires training, it is rarely performed. Different automatic analysis software tries to overcome these limitations but they need to be accurate and reproducible before they can be used clinically. The aim of this study was to test the accuracy and reproducibility of new 3D automatic quantitative software in everyday clinical practice. 69 patients referred to our Echo Lab for a clinically indicated echocardiographic examination were included. All patients underwent a full TTE with 3D image acquisition. Left ventricular volumes and ejection fraction (LVEF) were obtained using Heart Model software, and compared with conventional 3D volumetric data. Automated analysis was performed using three different sliders setting, with or without regional editing if necessary. 20 patients underwent a cardiac magnetic resonance (CMR) study the same day of the echo and automated measurements were also compared with a CMR reference. Intra- and inter-technique comparisons including linear regression with Pearson correlation coefficients and Bland–Altman analyses were calculated. Mean age of the patients was 59 years, with 49.3% male. The automated 3DE model demonstrated excellent correlation with the conventional 3DE measurements of LVEF, using three different sliders settings (r = 0.906; r = 0.898 and r = 0.940). Correlations with CMR values were very good as well (r = 0.888; r = 0.869; r = 0.913). Similarly, no significant differences were noted between the values of EDV and ESV, measured with the automated model or CMR, with excellent correlation (EDV: r = 0.892, r = 0.842, 0.910; ESV: r = 0.925, r = 0.860, r = 0.907). Finally, volumes calculated with the automated software were significantly greater than those obtained manually, but they showed a very good correlation (EDV: r = 0.875, r = 0.856, r = 0.891; ESV: r = 0.929, r = 0.879, r = 949). 3D automatic software for LV quantification is feasible and shows excellent correlations with both CMR and 3D echocardiography, considered the gold standard. No clinically relevant differences were noted when applying different border settings. This technique holds promise to facilitate the integration of 3D TTE into clinical practice

Prognostic implications of cardiac magnetic resonance feature tracking derived multidirectional strain in patients with chronic aortic regurgitation

Objective: Speckle-tracking echocardiography (STE) deformation parameters detect latent LV dysfunction in chronic aortic regurgitation (AR) and are associated with outcomes. The aim of the study was to evaluate cardiac magnetic resonance (CMR) feature tracking (FT) deformation parameters in asymptomatic patients with AR and implications in outcomes. Methods: Fifty-five patients with AR and 54 controls were included. Conventional functional CMR parameters, aortic regurgitant volume, and fraction were assessed. CMR-FT analysis was performed with a dedicated software. Clinical data was obtained from hospital records. A combined endpoint included all-cause mortality, cardiovascular mortality, aortic valve surgery, or cardiovascular hospital admission due to heart failure. Results: Left ventricular (LV) mechanics is impaired in patients with significant AR. Significant differences were noted in global longitudinal strain (GLS) between controls and AR patients (− 19.1 ± 2.9% vs − 16.5 ± 3.2%, p < 0.001) and among AR severity groups (− 18.3 ± 3.1% vs − 16.2 ± 1.6% vs − 15 ± 3.5%; p = 0.02 for AR grades I–II, III, and IV). In univariate and multivariate analyses, circumferential strain (GCS) and global radial strain (GRS) but not GLS were associated with and increased risk of the end point with a HR of 1.26 (p = 0.016, 1.04–1.52) per 1% worsening for GCS and 0.90 (p = 0.012, 0.83–0.98) per 1% worsening for GRS. Conclusions: CMR-FT myocardial deformation parameters are impaired in patients with AR not meeting surgical criteria. GLS decreases early in the course of the disease and is a marker of AR severity while GCS and GRS worsen later but predict a bad prognosis, mainly the need of aortic valve surgery. Key Points: • CMR feature tracking LV mechanic parameters may be reduced in significant chronic AR with normal EF. • LV mechanics, mainly global longitudinal strain, worsens as AR severity increases. • LV mechanics, specially global radial and circumferential strain, is associated with a worse prognosis in AR patients

Mid-term outcome of severe tricuspid regurgitation: Are there any differences according to mechanism and severity?

Aims: Patients with significant tricuspid regurgitation (TR) addressed according the new classification in torrential TR may have different prognosis compared with just severe TR patients. We sought to determine distribution and mechanism of consecutive severe TR patients, in accordance with aetiology and severity by applying the new proposed classification scheme and their long-term outcomes. Methods and results: Between January and December 2013, 249 patients with significant TR referred to the cardiac imaging unit (mean age 79.9 ± 10.2 years; 29.8% female) were included. Patients were divided according to aetiology in six groups, and TR severity was reclassified into severe, massive, and torrential TR. The follow-up period was of 313 ± 103 days. When considering cardiovascular mortality, patients in the massive/torrential group showed the highest number of events (P < 0.007). Patients with TR due to pulmonary diseases had the worst prognosis according to different aetiology. Noteworthy, the best predictors for the combined endpoint [cardiovascular mortality and readmission admission for heart failure (HF)] were TR severity according to the new classification [hazard ratio (HR) 2.48, 95% confidence interval (CI) 1.25-4.93] and clinical scores such as New York Heart Association classification and congestive status (HR 1.78, 95% CI 1.28-2.49; HR 2.08, 95% CI 1.06-4.06, respectively). Conclusion: Patients with massive/torrential TR and patients with comorbidities, especially pulmonary disease, were identified as populations at higher risk of death and readmission for HF. New classification scheme and clinical assessment may establish who may benefit the most of intensive therapeutic treatments and intervention on the tricuspid valve

Genetic Variants of ABCC10, a Novel Tenofovir Transporter, Are Associated With Kidney Tubular Dysfunction

Background. Tenofovir (TFV) causes kidney tubular dysfunction (KTD) in some patients, but the mechanism is poorly understood. Genetic variants in TFV transporters are implicated; we explored whether ABCC10 transports TFV and whether ABCC10 single-nucleotide polymorphisms (SNPs) are associated with KTD