Exploring hydrophilic 2,2-di(indol-3-yl)ethanamine derivatives against Leishmania infantum.

Herein we report the design and the synthesis of a library of new and more hydrophilic bisindole analogues based on our previously identified antileishmanial compound URB1483 that failed the preliminary in vivo test. The novel bisindoles were phenotypically screened for efficacy against Leishmania infantum promastigotes and simultaneously for toxicity on human macrophage-like THP-1 cells. Among the less toxic compounds, eight bisindoles showed IC50 below 10 μM.

It never rains but it pours: Austerity and mortality rate in peripheral areas.

This study examines the impact of austerity measures on mortality rates across Italian regions from 2003 to 2018. Since 2007, regions experiencing substantial healthcare financial deficits have been required to implement recovery plans (RPs). We use a recent difference-in-differences staggered matching estimator to assess the effects of this austerity policy on municipal-level monthly mortality rates.

Facebook reactions in the context of politics and social issues: a systematic literature review.

In February 2016, Facebook expanded the original "Like" button by introducing five additional "Reactions"-Love, Haha, Wow, Sad, and Angry-using modified versions of Unicode emojis. These reactions enable users to express more nuanced emotions towards posts. This literature review investigates scholarly research on user behavior in response to these reactions, with a focus on a broad spectrum of socioeconomic and psychological issues.

Periodontal Health and Its Relationship with Psychological Stress: A Cross-Sectional Study.

: Studies suggest that chronic psychological stress can lead to oral health deterioration, alter the immune response, and possibly contribute to increased inflammation, which can impact the physiological healing of periodontal tissues. This cross-sectional study seeks to assess and improve clinical understanding regarding the relationship between perceived stress, mindfulness, and periodontal health. : A total of 203 people were analyzed from December 2022 to June 2023.

Interaction between miR-142-3p and Val/Met Polymorphism Regulates Multiple Sclerosis Severity.

MiR-142-3p has recently emerged as key factor in tailoring personalized treatments for multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS) with heterogeneous pathophysiology and an unpredictable course. With its involvement in a detrimental regulatory axis with interleukin-1beta (IL1β), miR-142-3p orchestrates excitotoxic synaptic alterations that significantly impact both MS progression and therapeutic outcomes. In this study, we investigated for the first time the influence of individual genetic variability on the miR-142-3p excitotoxic effect in MS.

Boosting the Impact of EFMC Young Scientists Network Through the Creation of Working Groups.

The establishment of the Young Scientists Network (YSN) by the European Federation for Medicinal Chemistry (EFMC) served as a proactive response to the evolving landscape of the scientific community. The YSN aims to assist early-career medicinal chemists and chemical biologists by responding to emerging themes, such as the influence of social media, shifts in gender balance within the scientific population, and evolving educational opportunities. The YSN also ensures that the upcoming generation of scientists actively contributes to shape the EFMC's strategic direction while addressing their specific needs.

Easy one-pot synthesis of multifunctionalized indole-pyrrole hybrids as a new class of antileishmanial agents.

A chemoselective one-pot synthesis of pharmaceutically prospective indole-pyrrole hybrids by the formal [3 + 2] cycloaddition of 3-cyanoacetyl indoles (CAIs) with 1,2-diaza-1,3-dienes (DDs) has been developed. The new indole-pyrrole hybrids were phenotypically screened for efficacy against promastigotes. The most active compounds 3c, 3d, and 3j showed IC < 20 μM and moderate cytotoxicity, lower than miltefosine.

Physical activity, musculoskeletal disorders, burnout, and work engagement: a cross-sectional study on Italian white-collar employees.

Introduction: Both mental and physical health of office workers had a positive relationship with their work engagement, with the latter relationship being driven by the association of a healthy diet and physical activity (PA). This observational study aimed to investigate the associations between PA levels, musculoskeletal disorders (MSDs), burnout, and work engagement, in a sample of white-collar employees.

Methods: A total of 615 workers (age 42.

Extracellular vesicles secreted by cumulus cells contain microRNAs that are potential regulatory factors of mouse oocyte developmental competence.

The role of cumulus cells (CCs) in the acquisition of oocyte developmental competence is not yet fully understood. In a previous study, we matured cumulus-denuded fully-grown mouse oocytes to metaphase II (MII) on a feeder layer of CCs (FL-CCs) isolated from developmentally competent (FL-SN-CCs) or incompetent (FL-NSN-CCs) SN (surrounded nucleolus) or NSN (not surrounding nucleolus) oocytes, respectively. We observed that oocytes cultured on the former could develop into blastocysts, while those matured on the latter arrested at the 2-cell stage.

Pulling the lever in a hurry: the influence of impulsivity and sensitivity to reward on moral decision-making under time pressure.

Background: Making timely moral decisions can save a life. However, literature on how moral decisions are made under time pressure reports conflicting results. Moreover, it is unclear whether and how moral choices under time pressure may be influenced by personality traits like impulsivity and sensitivity to reward and punishment.

Adolescents' attitudes, habits, identity and social support in relation to physical activity after the COVID-19 pandemic.

This study focuses on adolescents' cognitive processes, behaviors and social support (SS) as they relate to physical activity (PA) before and after the pandemic. The aims of the study were: (1) to investigate the changes in adolescents' engagement in moderate and vigorous physical activity (MVPA), and examine the changes in PA-related attitudes and behaviors before and after the COVID-19 pandemic; (2) to analyze the correlations between the significant changes that were found, PA engagement, and SS. The survey targeted third-year middle school students of Italian nationality, attending male and female mixed classes, residents in urban, periphery and sub-urban areas, living in families with different incomes, and different habits of engaging in PA.

Assessing the potential of nematode metabarcoding for benthic monitoring of offshore oil platforms.

Environmental DNA metabarcoding is gaining momentum as a time and cost-effective tool for biomonitoring and environmental impact assessment. Yet, its use as a replacement for the conventional marine benthic monitoring based on morphological analysis of macrofauna is still challenging. Here we propose to study the meiofauna, which is much better represented in sediment DNA samples.

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF (Ru2) (tpy=2,2':6',2''-terpyridine).

Are incremental exercise relationships between rating of perceived exertion and oxygen uptake or heart rate reserve valid during steady-state exercises?

Background: Rating of perceived exertion (RPE) is considered a valid method for prescribing prolonged aerobic steady-state exercise (SSE) intensity due to its association with physiological indicators of exercise intensity, such as oxygen uptake (V̇O) or heart rate (HR). However, these associations between psychological and physiological indicators of exercise intensity were found during graded exercise tests (GXT) but are currently used to prescribe SSE intensity even though the transferability and validity of the relationships found during GXT to SSE were not investigated. The present study aims to verify whether (a) RPE-HR or RPE-V̇O relations found during GXTs are valid during SSEs, and (b) the duration and intensity of SSE affect these relations.

Attachment, Mentalization, Emotion Dysregulation, and Empathy in Eating Disorders: Comparing Anorexic and Bulimic Patients.

Eating disorders (EDs) represent a wide range of clinical symptoms related to food intake, body image, and weight issues, and include anorexia nervosa-restricting type (AN-R), anorexia nervosa-binge-purge type (AN-BP), and bulimia nervosa (BN). The aim was to investigate the characteristics of attachment, mentalization, emotion dysregulation, and empathy in a sample of 102 patients with EDs. A sample of 102 patients and therapists completed a series of measures for the assessment of ED pathology, mentalization, empathy, and emotion dysregulation.

Sports-Related Gastrointestinal Disorders: From the Microbiota to the Possible Role of Nutraceuticals, a Narrative Analysis.

Intense physical exercise can be related to a significant incidence of gastrointestinal symptoms, with a prevalence documented in the literature above 80%, especially for more intense forms such as running. This is in an initial phase due to the distancing of the flow of blood from the digestive system to the skeletal muscle and thermoregulatory systems, and secondarily to sympathetic nervous activation and hormonal response with alteration of intestinal motility, transit, and nutrient absorption capacity. The sum of these effects results in a localized inflammatory process with disruption of the intestinal microbiota and, in the long term, systemic inflammation.

Impact of a Discontinuous Training Program on Sedentary Behavior in Italian Type 2 Diabetes Older Patients: The Results of the TRIPL-A Randomized Controlled Trial.

: Physical activity is an important predictor of quality of life in older adults with type 2 diabetes (T2D). Unfortunately, most T2D adults adopt a sedentary lifestyle. The randomized, controlled TRIPL-A trial aims to verify the effect of a personalized, discontinuous exercise program on a sedentary lifestyle of T2D older adults.

Enantioselective organocatalytic strategies to access noncanonical α-amino acids.

Organocatalytic asymmetric synthesis has evolved over the years and continues to attract the interest of many researchers worldwide. Enantiopure noncanonical amino acids (ncAAs) are valuable building blocks in organic synthesis, medicinal chemistry, and chemical biology. They are employed in the elaboration of peptides and proteins with enhanced activities and/or improved properties compared to their natural counterparts, as chiral catalysts, in chiral ligand design, and as chiral building blocks for asymmetric syntheses of complex molecules, including natural products.

Chemical chaperones in metabolic fitness beyond protein folding.

Chemical chaperones are small molecules that improve protein folding, alleviating aberrant pathological phenotypes due to protein misfolding. Recent reports suggest that, in parallel with their role in relieving endoplasmic reticulum (ER) stress, chemical chaperones rescue mitochondrial function and insulin signaling. These effects may underlie their pharmacological action on metabolically demanding tissues.

Intelligent berberine-loaded erythrocytes attenuated inflammatory cytokine productions in macrophages.

Erythrocytes are impressive tools for drug delivery, especially to macrophages. Therefore, berberine was loaded into erythrocytes using both hypotonic pre-swelling and endocytosis methods to target macrophages. Physicochemical and kinetic parameters of the resulting carrier cells, such as drug loading/release kinetics, osmotic fragility, and hematological indices, were determined.

Replicative senescence and high glucose induce the accrual of self-derived cytosolic nucleic acids in human endothelial cells.

Recent literature shows that loss of replicative ability and acquisition of a proinflammatory secretory phenotype in senescent cells is coupled with the build-in of nucleic acids in the cytoplasm. Its implication in human age-related diseases is under scrutiny. In human endothelial cells (ECs), we assessed the accumulation of intracellular nucleic acids during in vitro replicative senescence and after exposure to high glucose concentrations, which mimic an in vivo condition of hyperglycemia.

CD99 Expression and Prognostic Impact in Glioblastoma: A Single-Center Cohort Study.

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms.

Exploring Negative Chemical Ionization of Per- and Polyfluoroalkyl Substances via a Liquid Electron Ionization LC-MS Interface.

Per- and polyfluoroalkyl substances (PFASs) are a class of aliphatic manufactured compounds comprising fluoro-chemicals with varied functional groups and stable carbon-fluorine bonds. They are defined as "forever chemicals" due to their persistent and bioaccumulative character. These substances have been detected in various environmental samples, including water, air, soil, and human blood, posing significant health hazards.

Transcriptional signatures in human macrophage-like cells infected by Leishmania infantum, Leishmania major and Leishmania tropica.

Background: In the Mediterranean basin, three Leishmania species have been identified: L. infantum, L. major and L.