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Background and Objective: Metabolic syndrome (MetS) is a clinical condition associated with higher rates of overall and cardiovascular mortality. There is scarce evidence regarding the impact of MetS on surgical and functional outcomes for patients undergoing partial nephrectomy (PN) for clinically localized small renal masses (SRMs)., Methods: We analyzed data from a prospectively maintained institutional database for 690 patients with cT1a renal cancer undergoing PN between 2000 and 2023 at a tertiary referral center. MetS was defined according to international guidelines. Cumulative incidence curves were used to estimate the 5-yr risk of stage IIIB-V chronic kidney disease (CKD) stage and other-cause mortality (OCM). Multivariable regression models were used to analyze the impact of MetS on the risk of complications, acute kidney injury (AKI), stage IIIB-V CKD, and OCM., Key Findings and Limitations: Overall, 10% of the PN cohort had MetS. The MetS group was older (median age 70 yr, interquartile range [IQR] 65-74 vs 61 yr, IQR 50-69; p  < 0.001) and had worse preoperative kidney function (median estimated glomerular filtration rate 65 [IQR 62-81] vs 88 [IQR 69-98] ml/min/1.73 m 2 ; p  < 0.001) than the group without MetS. The MetS group had higher incidence of complications (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.05-3.08; p  = 0.03) and postoperative AKI (OR 3.17, 95% CI 1.54-6.41; p  = 0.001). The 5-yr risk of stage IIIB-V CKD (45% vs 7.2%; hazard ratio [HR] 2.34, 95% CI 1.27-4.30; p  = 0.006) and OCM (14% vs 3.5%; HR 3.00, 95% CI 1.06-8.55; p  = 0.039) were also higher in the MetS group. The main limitations are the extended accrual time and unmeasured confounders that could potentially affect outcomes., Conclusions and Clinical Implications: Patients with MetS had worse postoperative, functional, and survival outcomes after SRM surgery in comparison to patients without MetS. Multidisciplinary care could help in reducing the preoperative metabolic burden in these patients. Further research should explore if alternative approaches (eg, surveillance or focal therapy) could minimize postoperative comorbidities and protect long-term renal function in this population., Patient Summary: Patients with a condition called metabolic syndrome who have part of their kidney removed for small kidney tumors are at higher risk of complications and long-term kidney issues. Patient care from a multidisciplinary team could help in reducing the metabolic burden before surgery. Further research is needed to explore if less invasive treatment options could reduce these risks., (© 2024 The Author(s).)

Background: Social media (SM) use constitutes a large portion of midadolescents' daily lives as a way of peer interaction. A significant percentage of adolescents experience intense or problematic social media use (PSMU), an etiologically complex behavior potentially associated with psychological distress. To date, studies longitudinally testing for risk or protective factors of PSMU, and collecting qualitative data are still scarce among midadolescents. Self-help interventions specifically targeting PSMU in this population and involving midadolescents in co-creation are needed., Objective: The 2-year SMART multicenter project aims to (1) advance knowledge on PSMU; (2) co-design an unguided self-help app for promoting awareness and functional SM use; and (3) test feasibility and provide preliminary findings on its effectiveness to further improve and adapt the app., Methods: The SMART project is organized in 3 phases: phase 1 will focus on knowledge advancement on PSMU and its risk and protective factors using a longitudinal design; phase 2 will explore adolescents perspectives using qualitative approach and will co-design an unguided self-help app for reducing PSMU, which will be evaluated and adapted in phase 3. Around 1500 midadolescents (aged 14-18 years) will be recruited in northern, central, and southern Italy to investigate the potential intra- and interpersonal psychological risk and protective factors for PSMU and define specific PSMU profiles and test for its association with psychological distress. Subjective (self-report) PSMU's psychosocial risk or protective factors will be assessed at 3 different time points and Ecological Momentary Assessment (EMA) will be used. Moreover, focus groups will be performed in a subsample of midadolescents to collect the adolescents' unique point of view on PSMU and experiences with SM. Those previous results will inform the self-help app, which will be co-designed through working groups with adolescents. Subsequently, the SMART app will be deployed and adapted, after testing its feasibility and potential effectiveness in a pilot study., Results: The project is funded by the Italian Ministry of University and Research as part of a national grant (PRIN, "Progetti di Rilevante Interesse Nazionale"). The research team received an official notice of research funding approval in July 2023 (Project Code 2022LC4FT7). The project was preregistered on Open Science Framework, while the ethics approval was obtained in November 2023. We started the enrollments in December 2023, with the final follow-up data to be collected within May 2025., Conclusions: The innovative aspects of the SMART project will deepen the conceptualization of PSMU and of its biopsychosocial antecedents among midadolescents, with relevant scientific, technological, and socioeconomic impacts. The advancement of knowledge and the developed self-help app for PSMU will timely respond to midadolescents' increased loneliness and psychological burden due to COVID-19 pandemic and humanitarian crisis., Trial Registration: OSF Registries; https://osf.io/2ucnk/., International Registered Report Identifier (irrid): DERR1-10.2196/58739., (©Valeria Donisi, Laura Salerno, Elisa Delvecchio, Agostino Brugnera. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.09.2024.)

Colon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertaken so far, including the use of drug cocktails and polypharmacology. Heme oxygenase-1 (HO-1) is an emerging molecular target in the treatment of various cancers. We recently demonstrated that a combination of HO-1 inhibitors with 5-FU and the corresponding hybrids SI1/17, SI1/20, and SI1/22, possessed anticancer activity against prostate and lung cancer cells. In this work, we evaluated these hybrids in a model of colon cancer and found that SI1/22 and the respective combo have greater potency than 5-FU. Particularly, compounds inhibit HO-1 activity in cell lysates, increase ROS and the expression of HO-1, SOD, and Nrf2. Moreover, we observed a decrease of pro-caspase and an increase in cleaved PARP-1 and p62, suggesting apoptotic and autophagic cell death and potential application of these drugs as anticancer agents.

Background: A compromised cardiac autonomic function has been found in subjects with insulin resistance related disorders such as obesity, impaired glucose tolerance (IGT) and type 2 diabetes and confers an increased risk of adverse cardiovascular outcomes. Growing evidence indicate that 1 h plasma glucose levels (1hPG) during an oral glucose tolerance test (OGTT) ≥ 155 mg/dl identify amongst subjects with normal glucose tolerance (NGT) a new category of prediabetes (NGT 1 h-high), harboring an increased risk of cardiovascular organ damage. In this study we explored the relationship between 1 h post-load hyperglycemia and cardiac autonomic dysfunction., Methods: Presence of cardiac autonomic neuropathy (CAN) defined by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV), assessed by 24-h electrocardiography were evaluated in 88 non-diabetic subjects subdivided on the basis of OGTT data in: NGT with 1 h PG < 155 mg/dl (NGT 1 h-low), NGT 1 h-high and IGT., Results: As compared to subjects with NGT 1 h-low, those with NGT 1 h-high and IGT were more likely to have CARTs defined CAN and reduced values of the 24 h time domain HVR parameters including standard deviation of all normal heart cycles (SDNN), standard deviation of the average RR interval for each 5 min segment (SDANN), square root of the differences between adjacent RR intervals (RMSSD), percentage of beats with a consecutive RR interval difference > 50 ms (PNN50) and Triangular index. Univariate analyses showed that 1hPG, but not fasting and 2hPG, was inversely associated with all the explored HVR parameters and positively with CARTs determined presence of CAN. In multivariate regression analysis models including several confounders we found that 1hPG was an independent contributor of HRV and presence of CAN., Conclusion: Subjects with 1hPG ≥ 155 mg/dl have an impaired cardiac autonomic function., (© 2024. The Author(s).)

Sudden cardiac death (SCD) prevention in cardiomyopathies such as hypertrophic (HCM), dilated (DCM), non-dilated left ventricular (NDLCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) remains a crucial but complex clinical challenge, especially among younger populations. Accurate risk stratification is hampered by the variability in phenotypic expression and genetic heterogeneity inherent in these conditions. This article explores the multifaceted strategies for preventing SCD across a spectrum of cardiomyopathies and emphasizes the integration of clinical evaluations, genetic insights, and advanced imaging techniques such as cardiac magnetic resonance (CMR) in assessing SCD risks. Advanced imaging, particularly CMR, not only enhances our understanding of myocardial architecture but also serves as a cornerstone for identifying at-risk patients. The integration of new research findings with current practices is essential for advancing patient care and improving survival rates among those at the highest risk of SCD. This review calls for ongoing research to refine risk stratification models and enhance the predictive accuracy of both clinical and imaging techniques in the management of cardiomyopathies.

Herein, we describe the design, synthesis, and in vitro biological evaluation of HO-1 inducers endowed with cytotoxic effects mediated by ferroptosis activation. Using the natural HO-1 inducer caffeic acid phenethyl ester (CAPE) as a chemical scaffold, new derivatives were synthesized by performing modifications in the cathecol moiety and in the phenethyl ester aromatic ring. Biological assays aimed at evaluating an imbalanced activity of ferroptosis key players identified that 2-(1 H -indol-3-yl)ethyl cinnamate (compound 24 ) possesses improved anticancer activity toward the MDA-MB 231 triple negative breast cancer cell line when compared to CAPE. Increased ROS and LOOH levels, reduced GSH levels, imbalanced mitochondrial activity, and restored cell viability after ferrostatin-1 treatment suggested a ferroptotic mechanism of action, which did not involve GPX4 inhibition. Compound 24 represents an intriguing hit compound useful for the identification of novel ferroptosis inducers., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

The eco-morphodynamic activity of large tropical rivers interacts with riparian vegetation causing implications for the carbon cycle within inland waters. Through a multi-temporal analysis of satellite data spanning the years 2000-2019, we analyzed rivers exceeding 200 m in width across the tropical regions, revealing a Carbon Pump mechanism driving an annual mobilization of 12.45 million tons of organic carbon. The study identifies fluvial eco-morphological signatures as proxies for carbon mobilization, emphasizing the link between river migration and carbon dynamics. To enhance accessibility, our results are encapsulated in a visually compelling WebGIS application, offering a comprehensive understanding of the eco-geomorphological influences on the global carbon cycle within large tropical rivers. Our findings are instrumental in determining the carbon intensity of future hydropower dams, thereby contributing to informed decision-making in the realm of sustainable energy infrastructure. This study elucidates the intricate relationships that govern the nexus of tropical river dynamics, riparian ecosystems, and the global carbon cycle., (© 2024. The Author(s).)

Objective: An individual's attachment style may impact how they interact with their therapy group. This study examined the moderating role of a group member's attachment on the dynamic relationships between that group member's (actor) and other group members' (partner) therapeutic alliances and symptom outcomes. Method: This is a secondary analysis of data from a trial testing the outcome of emotionally-focused group therapy for binge-eating disorder. The sample consisted of 2,360 sessions nested within 118 group members who attended a 20-session treatment. Patients recorded binge eating episodes (BEE), their body weight and an alliance measure session-by-session., Results: Dynamic structural equation modelling showed decreases in BEE and weight over the therapy. When attachment style was not included in the model, higher-than-average partner's alliance scores in the previous session were related to decreases in BEE in the current session. Attachment style moderated these actor and partner effects. For patients with preoccupied attachments, higher-than-average actor alliance in the previous session was related to subsequent decreases in BEE. For patients with dismissing or disorganized attachments, higher partner alliance in the previous session was related to subsequent decreases in BEE., Conclusion: Group members' attachment characteristics can play a role in the development of alliance-outcome patterns in group therapy.

Background: Understanding the incidence, causes, and trends of sudden cardiac death (SCD) among young competitive athletes is critical to inform preventive policies., Methods: This study included National Collegiate Athletic Association athlete deaths during a 20-year time frame (July 1, 2002, through June 30, 2022). Athlete deaths were identified through 4 separate independent databases and search strategies (National Collegiate Athletic Association resolutions list, Parent Heart Watch database and media reports, National Center for Catastrophic Sports Injury Research database, and insurance claims). Autopsy reports and medical history were reviewed by an expert panel to adjudicate causes of SCD., Results: A total of 143 SCD cases in National Collegiate Athletic Association athletes were identified from 1102 total deaths. The National Collegiate Athletic Association resolutions list identified 117 of 143 (82%), the Parent Heart Watch database or media reports identified 89 of 143 (62%), the National Center for Catastrophic Sports Injury Research database identified 63 of 143 (44%), and insurance claims identified 27 of 143 (19%) SCD cases. The overall incidence of SCD was 1:63 682 athlete-years (95% CI, 1:54 065-1:75 010). Incidence was higher in male athletes than in female athletes (1:43 348 [95% CI, 1:36 228-1:51 867] versus 1:164 504 [95% CI, 1:110 552-1:244 787] athlete-years, respectively) and Black athletes compared with White athletes (1:26 704 [1:20 417-1:34 925] versus 1:74 581 [1:60 247-1:92 326] athlete-years, respectively). The highest incidence of SCD was among Division I male basketball players (1:8188 [White, 1:5848; Black, 1:7696 athlete-years]). The incidence rate for SCD decreased over the study period (5-year incidence rate ratio, 0.71 [95% CI, 0.61-0.82]), whereas the rate of noncardiovascular deaths remained stable (5-year incidence rate ratio, 0.98 [95% CI, 0.94-1.04]). Autopsy-negative sudden unexplained death (19.5%) was the most common postmortem examination finding, followed by idiopathic left ventricular hypertrophy or possible cardiomyopathy (16.9%) and hypertrophic cardiomyopathy (12.7%), in cases with enough information for adjudication (118 of 143). Eight cases of death were attributable to myocarditis over the study period (1 case from January 1, 2020, through June 30, 2022), with none attributed to COVID-19 infection. SCD events were exertional in 50% of cases. Exertional SCD was more common among those with coronary artery anomalies (100%) and arrhythmogenic cardiomyopathy (83%)., Conclusions: The incidence of SCD in college athletes has decreased. Male sex, Black race, and basketball are associated with a higher incidence of SCD., Competing Interests: Disclosures Dr Ackerman is a consultant for Abbott, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, Thryv Therapeutics, and UpToDate. Dr Ackerman and Mayo Clinic are involved in an equity/royalty relationship with AliveCor, Anumana, ARMGO Pharma, and Pfizer. None of these entities was involved in this study. Dr Baggish has received funding from the National Institute of Health/National Heart, Lung, and Blood Institute, the National Football Players Association, the American Heart Association, and the American Medical Society for Sports Medicine to study cardiovascular outcomes among elite athletes and receives compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, and US Rowing. Dr Drezner has received funding from the American Medical Society for Sports Medicine, the American Heart Association, and the National Center for Catastrophic Sports Injury Research. Dr Harmon has received funding from the American Medical Society for Sports Medicine, Football Research, Inc, the Pac-12, and the American Heart Association. Dr Kucera is supported by funds from the National Center for Catastrophic Sports Injury Research.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with unknown etiology. To date, the identification of new diagnostic, prognostic and progression biomarkers of IPF turns out to be necessary. MicroRNA (miRNA) are small non-coding RNAs which negatively regulate gene expression at the post-transcriptional level in several biological and pathological processes. An aberrant regulation of gene expression by miRNA is often associated with various diseases, including IPF. As result, miRNAs have emerged as potential biomarkers with relevance to pulmonary fibrosis. Several reports suggested that miRNAs are secreted as microvesicles or exosome, and hance they are stable and can be readily detected in the circulation. In the contest of miRNAs as circulating biomarkers, different studies show their role in various types of interstitial lung diseases and suggest that these small molecules could be used as prognostic markers of the disease. Exosomes are small, lipid-bound vesicles able to carry various elements of the naïve cells such as proteins, lipids, mRNAs and miRNA to facilitate cell communication under normal and diseases condition. Exosomal miRNAs (exo-miRNA) have been studied in relation to many diseases. However, there is little or no knowledge regarding exo-miRNA in bronchoalveolar lavage (BAL) in IPF. Our study's aim is to evaluate the changes in the expression of two exo-miRNAs in BAL, respectively miR-21 and miR-92a, through highlighting the differences between IPF, progressive pulmonary fibrosis (PPF) and not-progressive pulmonary fibrosis (nPPF)., Methods: Exosomes were characterized by Western Blot and Multiplex Surface Marker Analysis. Exosomal miRNA expression was performed by qRT-PCR. ANOVA or Kruskal-Wallis test, based on data normality, was used to compare the differential expression between groups., Results: MiR-21 expression was significantly higher in the nPPF group than in both IPF and PPF. A result that could point above a possible role of miR-21, as a biomarker in the differential diagnosis between PPF and nPPF. MiR-92a, indeed, was down regulated in PPF compared to IPF and down regulated in PPF compared to nPPF., Conclusions: This study demonstrated the putative role of both miR-21 and miR-92a as possible biomarkers of pulmonary fibrosis progression. Moreover, the role of exo-miRNAs is examined as a possible future direction that could lead to new therapeutic strategies for the treatment of progressive and non-progressive pulmonary fibrosis., (© 2023. The Author(s).)

Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses.

Chronic pain caused by persistent inflammation is current in multiple diseases and has a strong negative impact on society. It is commonly associated with several mental illnesses, which can exert a negative influence on pain perception, and needs to be eradicated. Nevertheless, actual therapies are not sufficiently safe and effective. Recent reports demonstrate that the induction of heme oxygenase-1 (HO-1) enzyme produces analgesic effects in animals with osteoarthritis pain and reverses the grip strength loss caused by sciatic nerve crush. In this research, we evaluated the potential use of three new HO-1 inducers, 1m, 1a, and 1b, as well as dimethyl fumarate (DMF), for treating persistent inflammatory pain induced by the subplantar injection of complete Freud's adjuvant and the functional deficits and emotional sickness associated. The modulator role of these treatments on the inflammatory and antioxidant pathways were also assessed. Our findings revealed that repeated treatment, for four days, with 1m, 1a, 1b, or DMF inhibited inflammatory pain, reversed grip strength deficits, and reversed the linked anxious- and depressive-like behaviors, with 1m being the most effective. These treatments also suppressed the up-regulation of the inflammasome NLRP3 and activated the expression of the Nrf2 transcription factor and the HO-1 and superoxide dismutase 1 enzymes in the paw and/or amygdala, thus revealing the anti-inflammatory and antioxidant capacity of these compounds during inflammatory pain. Results suggest the use of 1m, 1a, 1b, and DMF, particularly 1m, as promising therapies for inflammatory pain and the accompanying functional disabilities and emotional diseases.

Objective: A growing body of evidence suggests that online gaming increased during the COVID-19 outbreak. This systematic review aims to summarize extant literature that reported on problematic gaming among both adolescents and adults during the pandemic and to identify available research on the bidirectional association between problematic gaming and mental health outcomes., Method: A systematic search was carried out through PubMed, Web of Knowledge and AGRIS, Embase, Medline, PsychINFO (from January 2020 to January 2023), using keywords related to problematic gaming and mental health outcomes. Both cross-sectional and longitudinal empirical studies which used validated measures of problematic gaming and mental health outcomes during the COVID-19 pandemic were included., Results: Twenty-five empirical articles were eligible for the current review, comprising 28,978 participants. The majority of the selected studies had cross-sectional designs. Overall, most eligible studies showed significant association between problematic gaming and negative mental health outcomes during the pandemic. Correlations were mostly found between problematic gaming, depression and anxiety., Conclusions: Future research focusing on the relationship between problematic gaming and mental health outcomes should go beyond the considerable weaknesses due to methodological limitations of cross-sectional design, sampling and measures., Competing Interests: Competing interests: None., (© 2023 Giovanni Fioriti Editore s.r.l.)

Previous research suggested that during the COVID-19 pandemic, mental distress did not affect all people equally. This longitudinal study aims to examine joint trajectories of depressive, anxiety, and stress symptoms in a sample of Italian adults during the pandemic, and to identify psychosocial predictors of distress states. We analyzed four-wave panel data from 3,931 adults who had received assessments of depressive, anxiety and stress symptoms between April 2020 and May 2021. Trajectories of individual psychological distress were identified by Latent Class Growth Analysis (LCGA) with parallel processes, and multinomial regression models were conducted to identify baseline predictors. Parallel process LCGA identified three joint trajectory classes for depression, anxiety and stress symptoms. Most individuals (54%) showed a resilient trajectory. However, two subgroups showed vulnerable joint trajectories for depression, anxiety and stress. Expressive suppression, intolerance to uncertainty, and fear of COVID-19 were risk characteristics associated with vulnerable trajectories for mental health distress. Moreover, vulnerability to mental health distress was higher in females, younger age groups and those unemployed during the first lockdown. Findings support the fact that group heterogeneity could be detected in the trajectories of mental health distress during the pandemic and it may help to identify subgroups at risk of worsening states., Competing Interests: Declaration of Competing Interest None of the authors report any conflicts of interest with this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The aims of the present study are: (1) to determine classes of adolescents with homogeneous patterns of smartphone or social media use; and (2) to examine the level of distress across the empirically derived profiles. Three hundred and forty adolescents (M age = 15.61, SD = 1.19; 38.2% females) participated in a cross-sectional survey. Participants provided objective trace data on time spent on smartphones and applications, as well as self-reported social media addiction, social media use intensity, online social comparison, emotion dysregulation, and psychological distress. Latent class analysis (LCA) with total smartphone use categorized participants into three classes. Participants in Class 3 (19%) showed a more impaired functioning profile, with a tendency towards social media addiction and greater levels of distress. LCAs with the amount of time devoted to specific applications are more heterogeneous, and results showed that heavy use of social media apps was not consistently connected to the most impaired psychosocial profiles. Although the amount of mobile screen time can be a characteristic of problematic users, the link between social media usage and an adolescent's psychological characteristics is mixed. More research is needed to explore the interplay between mobile screen time and social media usage among adolescents.

Background: Three-dimensional cell culture systems hold great promise for bridging the gap between in vitro cell-based model systems and small animal models to study tissue biology and disease. Among 3D cell culture systems, stem-cell-derived spheroids have attracted significant interest as a strategy to better mimic in vivo conditions. Cardiac stem cell/progenitor (CSC)-derived spheroids (CSs) provide a relevant platform for cardiac regeneration., Methods: We compared three different cell culture scaffold-free systems, (i) ultra-low attachment plates, (ii) hanging drops (both requiring a 2D/3D switch), and (iii) agarose micro-molds (entirely 3D), for CSC-derived CS formation and their cardiomyocyte commitment in vitro., Results: The switch from a 2D to a 3D culture microenvironment per se guides cell plasticity and myogenic differentiation within CS and is necessary for robust cardiomyocyte differentiation. On the contrary, 2D monolayer CSC cultures show a significant reduced cardiomyocyte differentiation potential compared to 3D CS culture. Forced aggregation into spheroids using hanging drop improves CS myogenic differentiation when compared to ultra-low attachment plates. Performing CS formation and myogenic differentiation exclusively in 3D culture using agarose micro-molds maximizes the cardiomyocyte yield., Conclusions: A 3D culture system instructs CS myogenic differentiation, thus representing a valid model that can be used to study adult cardiac regenerative biology.

There is an increasing interest in understanding the connection between the immune and cardiovascular systems, which are highly integrated and communicate through finely regulated cross-talking mechanisms. Recent evidence has demonstrated that the immune system does indeed have a key role in the response to cardiac injury and in cardiac regeneration. Among the immune cells, macrophages appear to have a prominent role in this context, with different subtypes described so far that each have a specific influence on cardiac remodeling and repair. Similarly, there are significant differences in how the innate and adaptive immune systems affect the response to cardiac damage. Understanding all these mechanisms may have relevant clinical implications. Several studies have already demonstrated that stem cell-based therapies support myocardial repair. However, the exact role that cardiac macrophages and their modulation may have in this setting is still unclear. The current need to decipher the dual role of immunity in boosting both heart injury and repair is due, at least for a significant part, to unresolved questions related to the complexity of cardiac macrophage phenotypes. The aim of this review is to provide an overview on the role of the immune system, and of macrophages in particular, in the response to cardiac injury and to outline, through the modulation of the immune response, potential novel therapeutic strategies for cardiac regeneration.

Although the concept of Fear of Missing Out (FoMO) is permeated with individual fears about the lack of social connection, the relationship between FoMO and feelings of loneliness has been the subject of limited research. The aim of this study was to examine bidirectional associations between FoMO and loneliness via a three-wave, random intercept, cross-lagged panel model. Drawing on a survey with 494 adult participants across three waves (45.3 percent participated in Time 2 and 38.7 percent participated at Time 3) during the COVID-19 pandemic, we found that participants with higher FoMO also reported heightened levels of loneliness across the three waves, at a between-person level. Furthermore, loneliness had significant negative cross-lagged associations with subsequent FoMO, at within-person level. The cross-lagged paths between FoMO and subsequent loneliness were not significant. Participants who usually spend more daily time using social media reported higher levels of FoMO. The findings of the study contribute to clarifying the temporal relationship between FoMO and loneliness, by suggesting that FoMO may not represent a risk factor for heightened feelings of loneliness, but it can be triggered by feelings of social isolation and lack of relationships.

In this work, we extend the concept of 5-fluorouracil/heme oxygenase 1 (5-FU/HO-1) inhibitor hybrid as an effective strategy for enhancing 5-FU-based anticancer therapies. For this purpose, we designed and synthesized new mutual prodrugs, named SI 1/20 and SI 1/22, in which the two active parent drugs (i. e., 5-FU and an imidazole-based HO-1 inhibitor) were connected through an easily cleavable succinic linker. Experimental hydrolysis rate, and in silico ADMET predictions were indicative of good drug-likeness and pharmacokinetic properties. Novel hybrids significantly reduced the viability of prostate DU145 cancer cells compared to the parent compounds 5-FU and HO-1 inhibitor administered alone or in combination. Interestingly, both compounds showed statistically significant lower toxicity, than 5-FU at the same dose, against non-tumorigenic human benign prostatic hyperplasia (BPH-1) cell line. Moreover, the newly synthesized mutual prodrugs inhibited the HO-1 activity both in a cell-free model and in vitro, as well as downregulated the HO-1 expression and increased the reactive oxygen species (ROS) levels., (© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

The eco-morphodynamic activity of large tropical rivers in South and Central America is analyzed to quantify the carbon flux from riparian vegetation to inland waters. We carried out a multi-temporal analysis of satellite data for all the largest rivers in the Neotropics (i.e, width > 200 m) in the period 2000-2019, at 30 m spatial resolution. We developed a quantification of a highly efficient Carbon Pump mechanism. River morphodynamics is shown to drive carbon export from the riparian zone and to promote net primary production by an integrated process through floodplain rejuvenation and colonization. This pumping mechanism alone is shown to account for 8.9 million tons/year of carbon mobilization in these tropical rivers. We identify signatures of the fluvial eco-morphological activity that provide proxies for the carbon mobilization capability associated with river activity. We discuss river migration-carbon mobilization nexus and effects on the carbon intensity of planned hydroelectric dams in the Neotropics. We recommend that future carbon-oriented water policies on these rivers include a similar analysis., (© 2023. The Author(s).)

Introduction: A complex and bidirectional relationship between eating and psychological symptoms in individuals with obesity has been proposed. This study aims to identify the specific processes playing a role in this association, using a data-driven approach., Methods: Two hundred ninety-four adults with obesity, including 106 (36 %) with binge-eating disorder, were consecutively admitted to a specialized public center. They completed self-report questionnaires to assess emotion regulation, interpersonal problems, self-esteem, binge-eating symptoms, and expectancies regarding eating behaviors. To assess the interplay among eating and psychological variables, a network analysis was used. The bridge function analysis was also performed to identify the bridge nodes among three communities (eating symptoms, interpersonal and emotional problems)., Results: The network was stable. Limited access to emotion regulation strategies, eating helps manage negative affect, and non-assertiveness were the nodes with the highest strength centrality. Lack of emotional clarity, non-assertiveness, socially inhibition, and binge-eating were the nodes with the highest bridge strength., Limitations: The main limitation of the study is the cross-sectional nature of the findings which prevents to infer causality regarding the association between symptoms in the network., Discussion: An interplay between eating symptoms and affective and interpersonal factors characterizes individuals with obesity. Across the variety of psychological problems associated with obesity, the present study suggests specific psychological variables and their connections that could be addressed to improve treatment outcome., Competing Interests: Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

Objective: The aim of this study was to examine the processes involved in a guided self-help (GSH) pre-treatment intervention (RecoveryMANTRA) for patients with anorexia nervosa (AN), by measuring the levels of patient/mentor Language Style Matching (LSM). RecoveryMANTRA was supported by student mentors or peer mentors (recovered individuals) over six weekly chat-based sessions. We examined whether LSM during RecoveryMANTRA predicted patients'working alliance with the clinic therapist, motivation, eating disorder (ED) and general psychopathology. A further aim was to examine differences in LSM between student mentors and peer mentors., Method: 87 AN adults received RecoveryMANTRA plus treatment as usual. The LSM algorithm was used to calculate verbal attunement between patient and mentor. Participants were assessed at baseline and at the end of the intervention., Results: Both early (1 st session) and late (6 th session) LSM predicted higher working alliance with the clinic therapist. Moreover, late LSM predicted lower EDs symptoms at the end of the RecoveryMANTRA intervention. Patient/peer mentor dyads showed higher late verbal attunement than patient/student mentor dyads., Conclusions: These findings suggests that in the early phase of treatment relational aspects can impact on engagement with treatment. Verbal attunement in a GSH for AN is associated with working alliance and better clinical outcome., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Objective: This paper used network analysis to test the associations between eating disorder-related psychopathology and carers' responses to anorexia nervosa symptoms in adolescents. Additionally, the prognostic value of central and bridge network nodes was explored., Method: This is a secondary analysis of a three-armed randomised-controlled-trial of adolescents with anorexia nervosa (n = 149) and their primary carer (n = 149) who were allocated to either treatment as usual (TAU), or one of two versions of a carer skills intervention (ECHO) added to TAU. A network analysis was run in the full sample. The prognostic role of central and bridge nodes was tested through multiple regression analyses., Results: Carers' depression and emotional over-involvement, as well as patients' depression showed the highest strength centrality. Patients' depression and carers' accommodation exhibited the highest bridge expected influence. Across the full sample, and in the ECHO group, carers' accommodation predicted patients' higher body mass index (BMI), while patients' depression predicted worse psychosocial functioning at 1-year follow-up. In the ECHO group, higher carers' depression also predicted lower BMI., Conclusions: Carers' accommodation and depression in both carers and patients were involved in the maintenance of psychopathology in adolescents with anorexia nervosa. Depression in both patients and carers is a potential treatment target for family interventions., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

The social isolation and the subsequent, increased use of Social Networking Sites due to the COVID-19 pandemic have had an impact on subjective well-being around the world. The present longitudinal study examined whether changes in psychological distress and well-being during the Italian second wave of the pandemic differ among people with different levels of Problematic Facebook Use (PFU). A total of 493 participants (M age  = 24.55 ± 7.25; 80.3% females) completed measures of passive use of Facebook, social comparison orientation on Facebook, fear of missing out, psychological distress (depressive symptoms and fear of COVID-19 pandemic) and well-being across three waves. Latent class analysis (LCA) categorized participants into three groups with different PFU levels: healthy users, moderate PFU users, and high PFU users. Hierarchical linear modeling (HLM) showed that the between-person level (class membership) accounted for most of the variability in psychological distress and well-being. No significant changes were found in psychological distress and well-being over time, but the High PFU users showed greater levels of psychological distress and lower levels of well-being at each time point. The findings of this study suggest that the relationship between PFU, psychological distress and well-being may reflect trait-like time-invariant differences between individuals rather than state-like changes., (© 2022. The Author(s).)

Gambling Disorder (GD) is a condition constituting a public health concern, with a burden of harm which is much greater than that of drug addiction. Patients with GD are generally reluctant to pharmacologic treatment and seem to prefer nonpharmacological interventions. Therefore, this proof-of-concept study aimed to investigate the feasibility of continuous Theta Burst Stimulation (cTBS) on the pre-SMA in six patients (5 males, 1 female), aged 30-64 years, with a DSM-5 diagnosis of Gambling Disorder and no comorbid mood disorders. Participants received over 10 sessions of Continuous TBS (cTBS) over pre-SMA bilaterally and have been evaluated using rating scales, including the PG-YBOCS and the CGI, before treatment (T0), at day 10 of treatment (T1) and at day 30 after treatment (T2); cTBS intervention was safe and without side effects. Since the design of our study does not allow us to draw conclusions on the effectiveness of the intervention with respect to the improvement of the functioning of the subject with GD, a more in-depth study, including a sham condition, neurocognitive measures of disinhibition and decision making, and collecting follow-up data on the sustained effect of TBS over a longer period is ongoing., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)