Metabolomic approach to profile functional and metabolic changes in heart failure

Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction

Tobacco Smoking Is a Strong Predictor of Failure of Conservative Treatment in Hinchey IIa and IIb Acute Diverticulitis-A Retrospective Single-Center Cohort Study

Background and Objectives: Therapeutic management of patients with complicated acute diverticulitis remains debatable. The primary objective of this study is to identify predictive factors for the failure of conservative treatment of Hinchey IIa and IIb diverticular abscesses. Materials and Methods: This is a retrospective cohort study that included patients hospitalized from 1 January 2014 to 31 December 2022 at the Emergency Surgery Department of the Cagliari University Hospital (Italy), diagnosed with acute diverticulitis complicated by Hinchey grade IIa and IIb abscesses. The collected variables included the patient's baseline characteristics, clinical variables on hospital admission, abscess characteristics at the contrast-enhanced CT scan, clinical outcomes of the conservative therapy, and follow-up results. Univariable and multivariable logistic regression models were used to identify prognostic factors of conservative treatment failure and success. Results: Two hundred and fifty-two patients diagnosed with acute diverticulitis were identified from the database search, and once the selection criteria were applied, 71 patients were considered eligible. Conservative treatment failed in 25 cases (35.2%). Univariable analysis showed that tobacco smoking was the most significant predictor of failure of conservative treatment (p = 0.007, OR 7.33, 95%CI 1.55; 34.70). Age (p = 0.056, MD 6.96, 95%CI -0.18; 0.99), alcohol drinking (p = 0.071, OR 4.770, 95%CI 0.79; 28.70), platelets level (p = 0.087, MD -32.11, 95%CI -0.93; 0.06), Hinchey stage IIa/IIb (p = 0.081, OR 0.376, 95%CI 0.12; 1.11), the presence of retroperitoneal air bubbles (p = 0.025, OR 13.300, 95%CI 1.61; 291.0), and the presence of extraluminal free air at a distance (p = 0.043, OR 4.480, 95%CI 1.96; 20.91) were the other variables possibly associated with the risk of failure. In the multivariable logistic regression analysis, only tobacco smoking was confirmed to be an independent predictor of conservative treatment failure (p = 0.006; adjusted OR 32.693; 95%CI 2.69; 397.27). Conclusion: The role of tobacco smoking as a predictor of failure of conservative therapy of diverticular abscess scenarios highlights the importance of prevention and the necessity to reduce exposure to modifiable risk factors

Arabidopsis Topless-related 1 mitigates physiological damage and growth penalties of induced immunity

Transcriptional corepressors of the Topless (TPL) family regulate plant hormone and immunity signaling. The lack of a genome-wide profile of their chromatin associations limits understanding of the TPL family roles in transcriptional regulation. Chromatin immunoprecipitation with sequencing (ChIP-Seq) was performed on Arabidopsis thaliana lines expressing GFP-tagged Topless-related 1 (TPR1-GFP) with and without constitutive immunity via Enhanced Disease Susceptibility 1 (EDS1). RNA-Seq profiling of the TPR1-GFP lines and pathogen-infected tpl/tpr mutants, combined with measuring immunity, growth, and physiological parameters was employed to investigate TPL/TPR roles in immunity and defense homeostasis. TPR1 was enriched at promoter regions of c. 1400 genes and c. 10% of the detected binding required EDS1 immunity signaling. In a tpr1 tpl tpr4 (t3) mutant, resistance to bacteria was slightly compromised, and defense-related transcriptional reprogramming was weakly reduced or enhanced, respectively, at early (< 1 h) and late 24 h stages of bacterial infection. The t3 plants challenged with bacteria or pathogen-associated molecular pattern nlp24 displayed photosystem II dysfunctions. Also, t3 plants were hypersensitive to phytocytokine pep1 at the level of root growth inhibition. Transgenic expression of TPR1 rescued these t3 physiological defects. We propose that TPR1 and TPL family proteins function in Arabidopsis to reduce detrimental effects associated with activated transcriptional immunity

Autophagy-related protein LC3 and Beclin-1 in the first trimester of pregnancy

Autophagy is a degradation process that acts in response to environmental stressors. Recently, autophagy has been detected in normal term, preeclamptic and intrauterine growth-restricted placentas. The object of this work was to investigate the presence of autophagy in first trimester voluntary interruption of pregnancy placental villi by the expression of autophagy-related proteins, light chain 3 (LC3), and Beclin-1. In first trimester placental villi laser scanning confocal microscopy (LSCM) analysis revealed LC3 and Beclin-1 immunoreactivity prevalently located in villous cytotrophoblasts. Using LSCM, LC3, and Beclin-1 were localized to the cytoplasm of the trophoblast layer in human full-term placentas. Beclin-1 expression and LC3 activation were confirmed by western blotting. These data emphasize that autophagy activation is different among cytotrophoblasts and syncytiotrophoblasts depending on the gestational age and thus we speculate that autophagy might play a prosurvival role throughout human pregnancy

Improving Social and Personal Rhythm Dysregulation in Young and Old Adults with Bipolar Disorder: Post-Hoc Analysis of a Feasibility Randomized Controlled Trial Using Virtual Reality-Based Intervention

Introduction: Rehabilitative interventions employing technology play a crucial role in bipolar disorder (BD) treatment. The study aims to appraise the virtual reality (VR)-based cognitive remediation (CR) and the interpersonal rhythm approaches to treatment outcomes of BD across different age groups. Methods: Post-hoc analysis of a 12-week randomizedcontrolled cross-over feasibility trial involving people with mood disorders (BD, DSM-IV) aged 18–75 years old: thirty-nine exposed to the experimental VR-based CR vs 25 waiting list controls. People with BD relapse, epilepsy or severe eye diseases (due to the potential VR risks exposure) were excluded. Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) was used to measure the outcome. Results: Cases and controls did not statistically significantly differ in age and sex distributions. Personal rhythm scores improved over the study follow-up in the experimental vs the control group (APC = 8.7%; F = 111.9; p &lt; 0.0001), both in young (18–45 years) (APC = 5.5%; F = 70.46; p &lt; 0.0001) and, to a lesser extent, older (&gt;46 years) adults (APC = 10.5%; F = 12.110; p = 0.002). Conclusions: This study observed improved synchronization of personal and social rhythms in individuals with BD after a virtual reality cognitive remediation intervention, particularly in social activity, daily activities, and chronotype, with greater benefits in the younger population

A Recovery-Oriented Program for People with Bipolar Disorder through Virtual Reality-Based Cognitive Remediation: Results of a Feasibility Randomized Clinical Trial

Background: Cognitive impairment is a frequent consequence of bipolar disorder (BD) that is difficult to prevent and treat. In addition, the quality of the preliminary evidence on the treatment of BD through Cognitive Remediation (CR) with traditional methods is poor. This study aims to evaluate the feasibility of a CR intervention with fully immersive Virtual Reality (VR) as an additional treatment for BD and offers preliminary data on its efficacy. Methods: Feasibility randomized controlled cross-over clinical study, with experimental condition lasting three months, crossed between two groups. Experimental condition: CR fully immersive VR recovery-oriented program plus conventional care; Control condition: conventional care. The control group began the experimental condition after a three months period of conventional care (waiting list). After the randomization of 50 people with BD diagnosis, the final sample consists of 39 participants in the experimental condition and 25 in the control condition because of dropouts. Results: Acceptability and tolerability of the intervention were good. Compared to the waitlist group, the experimental group reported a significant improvement regarding cognitive functions (memory: p = 0.003; attention: p = 0.002, verbal fluency: p = 0.010, executive function: p = 0.003), depressive symptoms (p = 0.030), emotional awareness (p = 0.007) and biological rhythms (p = 0.029). Conclusions: The results are preliminary and cannot be considered exhaustive due to the small sample size. However, the evidence of efficacy, together with the good acceptability of the intervention, is of interest. These results suggest the need to conduct studies with larger samples that can confirm this data. Trial registration: ClinicalTrialsgov NCT05070065, registered in September 202

Arabidopsis Topless-related 1 mitigates physiological damage and growth penalties of induced immunity

Transcriptional corepressors of the Topless (TPL) family regulate plant hormone and immunity signaling. The lack of a genome-wide profile of their chromatin associations limits understanding of the TPL family roles in transcriptional regulation. Chromatin immunoprecipitation with sequencing (ChIP-Seq) was performed on Arabidopsis thaliana lines expressing GFP-tagged Topless-related 1 (TPR1-GFP) with and without constitutive immunity via Enhanced Disease Susceptibility 1 (EDS1). RNA-Seq profiling of the TPR1-GFP lines and pathogen-infected tpl/tpr mutants, combined with measuring immunity, growth, and physiological parameters was employed to investigate TPL/TPR roles in immunity and defense homeostasis. TPR1 was enriched at promoter regions of c. 1400 genes and c. 10% of the detected binding required EDS1 immunity signaling. In a tpr1 tpl tpr4 (t3) mutant, resistance to bacteria was slightly compromised, and defense-related transcriptional reprogramming was weakly reduced or enhanced, respectively, at early (< 1 h) and late 24 h stages of bacterial infection. The t3 plants challenged with bacteria or pathogen-associated molecular pattern nlp24 displayed photosystem II dysfunctions. Also, t3 plants were hypersensitive to phytocytokine pep1 at the level of root growth inhibition. Transgenic expression of TPR1 rescued these t3 physiological defects. We propose that TPR1 and TPL family proteins function in Arabidopsis to reduce detrimental effects associated with activated transcriptional immunity

Variation in plant Toll/Interleukin-1 receptor domain protein dependence on ENHANCED DISEASE SUSCEPTIBILITY 1

Toll/Interleukin-1 receptor (TIR) domains are integral to immune systems across all kingdoms. In plants, TIRs are present in nucleotide-binding leucine-rich repeat (NLR) immune receptors, NLR-like, and TIR-only proteins. Although TIR-NLR and TIR signaling in plants require the ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) protein family, TIRs persist in species that have no EDS1 members. To assess whether particular TIR groups evolved with EDS1, we searched for TIR-EDS1 co-occurrence patterns. Using a large-scale phylogenetic analysis of TIR domains from 39 algal and land plant species, we identified 4 TIR families that are shared by several plant orders. One group occurred in TIR-NLRs of eudicots and another in TIR-NLRs across eudicots and magnoliids. Two further groups were more widespread. A conserved TIR-only group co-occurred with EDS1 and members of this group elicit EDS1-dependent cell death. In contrast, a maize (Zea mays) representative of TIR proteins with tetratricopeptide repeats was also present in species without EDS1 and induced EDS1-independent cell death. Our data provide a phylogeny-based plant TIR classification and identify TIRs that appear to have evolved with and are dependent on EDS1, while others have EDS1-independent activity

Wiskott-Aldrich syndrome protein-mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells

Mutations in Wiskott-Aldrich syndrome (WAS) protein (WASp), a regulator of actin dynamics in hematopoietic cells, cause WAS, an X-linked primary immunodeficiency characterized by recurrent infections and a marked predisposition to develop autoimmune disorders. The mechanisms that link actin alterations to the autoimmune phenotype are still poorly understood. We show that chronic activation of plasmacytoid dendritic cells (pDCs) and elevated type-I interferon (IFN) levels play a role in WAS autoimmunity. WAS patients display increased expression of type-I IFN genes and their inducible targets, alteration in pD

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe