Aldosterone Synthase Inhibitors for Cardiorenal Protection: Ready for Prime Time?

Background: Aldosterone is the principal mineralocorticoid hormone and the final effector of the renin-angiotensin-aldosterone system. This hormone is primarily synthesized by the CYP11B2 enzyme and produced by the adrenal zona glomerulosa. Through genomic and non-genomic effects, it plays an important role in cardiovascular and renal disease.

Elucidation on the In Vivo Activity of the Bivalent Opioid Peptide MACE2 against Several Types of Chronic Pain.

Biphalin is a bivalent μ/δ opioid receptor agonist showing a promising therapeutic profile with reduced side effects, but as a peptide is limited by poor metabolic stability and blood-brain barrier penetration. To improve these features, we developed the ligand and showed initial in vivo efficacy. To further explore the druggability of this ligand, in this report, we tested metabolic stability in human plasma, receptor engagement by 3 different routes of administration using the tail-flick test, and efficacy in 2 different pathological and chronic pain models.

Impact of remote social interaction during the COVID-19 pandemic on the cognitive and psychological status of older adults with and without cognitive impairment: A randomized controlled study.

Background: Social isolation and loneliness have both been associated with psychological health and cognitive decline in older adults. This study investigated the impact of social interaction through remote communication technologies during the COVID-19 pandemic on the cognitive and psychological status of older adults with and without cognitive impairment.

Methods: Participants were recruited from Boston (USA) and Chieti (Italy).

The interplay among environmental sensitivity, job stressors, and leadership styles on employee well-being.

Investigating the role of individual differences in Environmental Sensitivity for well-being and stress at work is an emerging area of research with significant potential for practical implications in organizational management and human resources. Recent studies have begun to explore how individuals with high sensory-processing sensitivity (SPS) may be more vulnerable to work-related stress than their less sensitive peers, but may also derive greater benefits from positive job resources when available. The present study aims to investigate the role of leadership style in the complex interplay between individual differences in sensitivity, stress at work, and general well-being.

Investigating the impact of the regularization parameter on EEG resting-state source reconstruction and functional connectivity using real and simulated data.

Accurate EEG source localization is crucial for mapping resting-state network dynamics and it plays a key role in estimating source-level functional connectivity. However, EEG source estimation techniques encounter numerous methodological challenges, with a key one being the selection of the regularization parameter in minimum norm estimation. This choice is particularly intricate because the optimal amount of regularization for EEG source estimation may not align with the requirements of EEG connectivity analysis, highlighting a nuanced trade-off.

Carbon Monoxide Release from Aryl-Propargyl Dicobalt(0)Hexacarbonyl Derivatives: A Computational and Experimental Study.

In the present study, we focus on dinuclear cobalt-based CO-RMs with the aim of elucidating their CO release mechanism, as well as to understand how structural changes targeted to modify the electronic properties of these compounds can modulate CO delivery. To this end, we specifically synthesized a set of phenyl-propargyl-based CO-RMs bearing -NO, -H, and -OCH as para-substituents (R) with varying mesomeric influence (M) and different heteroatoms (X = NH, O, or S) linking the propargyl tail and the aromatic ring. The effects of R and X in modulating CO release were assessed by using several experimental and computational techniques to obtain a coherent picture and to shed light on the stability and release properties of Co-based CO-RMs.

Design, synthesis, and evaluation of novel thiadiazole derivatives as potent VEGFR-2 inhibitors: a comprehensive and study.

Objective: This study aims to investigate the potential of designed 2,3-dihydro-1,3,4-thiadiazole derivatives as anti-proliferative agents targeting VEGFR-2, utilizing a multidimensional approach combining and analyses.

Methods: The synthesized derivatives were evaluated for their inhibitory effects on MCF-7 and HepG2 cancer cell lines. Additionally, VEGFR-2 inhibition was assessed.

Beliefs on the ability to regulate negative emotions mediates the effects of competitive anger on task-focused self-efficacy in taekwondo athletes.

Self-efficacy (SE) refers to an individual's belief in their own ability to successfully execute specific tasks and produce desired outcomes. The focused SE on specific sports tasks has been shown to impact athletic performance by interacting with other self-evaluation processes, like self-efficacy beliefs in emotion-related regulation and effective emotion regulation. This study aims at investigating the mediating effect of SE in regulating negative affect in the relationship between anger and taekwondo task-focused SE.

A novel life for antitumor combretastatins: Recent developments of hybrids, prodrugs, combination therapies, and antibody-drug conjugates.

Since their discovery from natural sources, the potent cytotoxic effects of combretastatins were widely studied for the application in antitumor therapy. However, major pharmacokinetic issues as low water solubility and chemical instability of the double bond configuration prevented their use in therapy. A lot of efforts have been directed towards the search of novel strategies, allowing a safer use of combretastatins as anticancer agents.

Metoprolol disrupts inflammatory response of human cardiomyocytes via β-arrestin2 biased agonism and NF-κB signaling modulation.

Aims: Recent evidence supports non-class cardioprotective effects of metoprolol against neutrophil-mediated ischemia-reperfusion injury during exacerbated inflammation. Whether metoprolol exerts direct anti-inflammatory effect on cardiomyocytes is unknown. Accordingly, we aimed to investigate the direct anti-inflammatory effects of metoprolol in a cellular model of human induced pluripotent stem cell-derived cardiomyocytes (hiCMs) and to explore the role of β-arrestin2 (β-ARR2) biased agonism signaling pathway.

The cognitive architecture of verbal humor in schizophrenia.

Previous literature showed that people with schizophrenia have difficulties in humor comprehension and might differ from controls in the appreciation of humor, i.e., in perceived funniness.

Validation of clinical risk assessment scores for venous thromboembolism in patients with cancer: a population-based cohort study.

Background: Guidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE).

Objectives: We aimed to validate a new cancer-associated thrombosis (CAT) risk score in a population-based healthcare setting.

Methods: We used healthcare registry data and electronic medical records from the Central Denmark Region to calculate the new CAT risk score and the guideline-recommended Khorana score in patients with a first-time cancer diagnosis who initiated systemic cancer therapy.

Impact of Implant Surface and Smoking on Peri-Implant Human Bone: What we Learned from The Last 20 Years?

The present review summarizes the findings from human histological studies conducted over the past 20 years at the University of Guarulhos, Brazil, examining the impact of various implant surface topographies and smoking on peri-implant bone response. Seven different implant surfaces were evaluated in 90 partially or completely edentulous individuals using a total of 123 micro-implants. Histometric parameters, including bone-implant contact (BIC%), bone area within the threads (BA%), and bone density (BD), were assessed after an 8-week healing period.

Molecular Characterization of Enterococcus faecium Clinical Isolates Harbouring erm (T) from an Italian Hospital.

The presence of erm(T) gene conferring resistance to macrolides, lincosamides and streptogramin B (MLS), was screened in 296 enterococci collected from clinical samples in a central Italy hospital and seven Enterococcus faecium isolates resulted positive to erm(T) by PCR. All isolates were resistant to erythromycin, tetracycline, ciprofloxacin and ampicillin but susceptible to vancomycin and chloramphenicol. Whole Genome Sequencing analysis revealed that in five E.

Familial Mediterranean fever in children from central-southern Italy: a multicentric retrospective cohort study.

Introduction: Although familial Mediterranean fever (FMF) is a relevant disease in countries surrounding the Mediterranean Sea, there are still few reports from Italy.

Methods: We retrospectively evaluated patients with FMF diagnosed according to the EuroFever/PRINTO classification criteria in three pediatric rheumatology referral centers in central-southern Italy. Logistic regression analysis assessed the associations between age at disease onset and symptoms.

Choroidal and Choriocapillaris Changes after Photodynamic Therapy and Subthreshold Micropulse Laser Treatment for Central Serous Chorioretinopathy.

: The aim of the present study is to analyze choroidal and choriocapillaris structural and functional changes in eyes affected by Central serous chorioretinopathy after Photodynamic Therapy (PDT) and Subthreshold Micropulse laser (SML) treatment. : Forty-two eyes of forty-two patients were analyzed in this observational study. Twenty-four patients underwent SML treatment, whereas eighteen patients were treated with PDT.

Club Drugs and Psychiatric Outcomes: A Descriptive Case Series from Spain.

Background: illegal drugs significantly contribute to global health issues, with health complications often occurring not only in regular users with Substance Use Disorders (SUDs) but also in first-time and occasional users.

Methods: this study examines five clinical cases from a public hospital in Ibiza, Spain, where patients presented with acute psychiatric symptoms due to recreational drug use.

Results: Contrary to previous studies on SUDs, our patients typically had higher education levels and stable employment.