Epidemiology and Resistance Profiles of Bacteria Isolated from Blood Samples in Septic Patients at Emergency Department Admission: A 6-year Single Center Retrospective Analysis from Northern Italy.

Objectives: This study aimed to investigate the microbiological and clinical heterogeneity of community-onset bloodstream infections (BSIs) and identify features to support targeted empirical antibiotic therapy in the Emergency Department (ED).

Methods: Clinical and microbiological data from 992 BSI cases (1,135 isolates) diagnosed within 24 hours of ED admission at IRCCS Humanitas Research Hospital, Milan, Italy (January 2015-June 2022), were analyzed. Drug resistance was interpreted using EUCAST-2023.

Distinct chromosomal mutation associated with cefiderocol resistance in : a combined bioinformatics and mass spectrometry approach to unveil and validate the -acquired chemoresistance.

is a significant public health concern due to the emergence of antibiotic-resistant strains. Cefiderocol (FDC), a novel siderophore cephalosporin, has shown promise as a last-line treatment for multidrug-resistant Gram-negative bacteria. However, the emergence of -acquired FDC-resistant strains highlights the need for advanced tools to identify resistance-associated genomic mutations and address the challenges of FDC susceptibility testing.

Melatonin modulates the Notch1 signaling pathway and Sirt3 in the hippocampus of hypoxic-ischemic neonatal rats.

The Notch1 signaling pathway plays a crucial role in the development of the central nervous system, governing pivotal functional activities in the brain, such as neurogenesis. Sirt3 is instrumental in managing mitochondrial homeostasis and is essential to cell survival. Dysregulation of these signaling pathways is implicated in the pathogenesis of a wide range of diseases, including neurodegenerative disorders such as stroke.

Dendritic cell vaccines as cancer treatment: focus on 13 years of manufacturing and quality control experience in advanced therapy medicinal products.

Background Aims: Dendritic cells (DCs) are professional antigen-presenting cells of the mammalian immune system. Ex vivo differentiated DCs represent a unique Advanced Therapy Medicinal Product (ATMP), used in several clinical trials as personalized cancer immunotherapy. The therapy's reliability depends on its capacity to produce high-quality mature DCs (mDCs) in compliance with Good Manufacturing Practices.

In vitro CAR-T cell killing: validation of the potency assay.

For advanced therapy medicinal products, the development and validation of potency assays are required, in accordance with international guidelines, to characterise the product and obtain reliable and consistent data. Our purpose was to validate the killing assay for the evaluation of autologous anti-CD19 chimeric antigen receptor (CAR) T potency. We used CD4 + and CD8 + lymphocytes or anti-CD19 CAR-T cells as effector cells and REH (CD19 +) or MOLM-13 (CD19 -) cell lines as target cells.

Microbial composition associated with biliary stents in patients undergoing pancreatic resection for cancer.

Malignant bile duct obstruction is typically treated by biliary stenting, which however increases the risk of bacterial infections. Here, we analyzed the microbial content of the biliary stents from 56 patients finding widespread microbial colonization. Seventeen of 36 prevalent stent species are common oral microbiome members, associate with disease conditions when present in the gut, and include dozens of biofilm- and antimicrobial resistance-related genes.

Melatonin Modulates Cell Cycle Dynamics and Promotes Hippocampal Cell Proliferation After Ischemic Injury in Neonatal Rats.

Promoting neural cell proliferation may represent an important strategy for enhancing brain repair after developmental brain injury. The present study aimed to assess the effects of melatonin on cell proliferation after an ischemic injury in the developing hippocampus, focusing on cell cycle dynamics. After in vivo neonatal hypoxia-ischemia (HI), hippocampal cell cycle dynamics were assessed by flow cytometry, together with histological evaluation of dentate gyrus cellularity and proliferation.

Aula Verde (tree room) as a link between art and science to raise public awareness of nature-based solutions.

Nature-based solutions inherently require a multifaceted perspective that encompasses diverse fields. The aim of this project is to develop more effective nature-based solutions, climate action and environmental awareness by breaking down boundaries between disciplines and fostering a co-creative process. Concepts of ecology and urban forestry were combined with the research on political ecology, environmental humanities, land art, regenerative art, performing art, participatory art, and more-than-human art.

Increase in invasive group A streptococcal infections in Milan, Italy: a genomic and clinical characterization.

Background: Group A Streptococcus (GAS) causes multiple clinical manifestations, including invasive (iGAS) or even life-threatening (severe-iGAS) infections. After the drop in cases during COVID-19 pandemic, in 2022 a sharp increase of GAS was reported globally.

Methods: GAS strains collected in 09/2022-03/2023 in two university hospitals in Milan, Italy were retrospectively analyzed.

Hypoxic ischemic brain injury: animal models reveal new mechanisms of melatonin-mediated neuroprotection.

Oxidative stress (OS) and inflammation play a key role in the development of hypoxic-ischemic (H-I) induced brain damage. Following H-I, rapid neuronal death occurs during the acute phase of inflammation, and activation of the oxidant-antioxidant system contributes to the brain damage by activated microglia. So far, in an animal model of perinatal H-I, it was showed that neuroprostanes are present in all brain damaged areas, including the cerebral cortex, hippocampus and striatum.

MSIpixel: a fully automated pipeline for compound annotation and quantitation in mass spectrometry imaging experiments.

Mass spectrometry imaging (MSI) is commonly used to map the spatial distribution of small molecules within complex biological matrices. One of the major challenges in imaging MS-based spatial metabolomics is molecular identification and metabolite annotation, to address this limitation, annotation is often complemented with parallel bulk LC-MS2-based metabolomics to confirm and validate identifications. Here we applied MSI method, utilizing data-dependent acquisition, to visualize and identify unknown molecules in a single instrument run.

Biomimetic superabsorbent hydrogel acts as a gut protective dynamic exoskeleton improving metabolic parameters and expanding A. muciniphila.

The rising prevalence of obesity and metabolic disorders worldwide highlights the urgent need to find new long-term and clinically meaningful weight-loss therapies. Here, we evaluate the therapeutic potential and the mechanism of action of a biomimetic cellulose-based oral superabsorbent hydrogel (OSH). Treatment with OSH exerts effects on intestinal tissue and gut microbiota composition, functioning like a protective dynamic exoskeleton.

MiR-126 and miR-146a as Melatonin-Responsive Biomarkers for Neonatal Brain Ischemia.

Despite advances in obstetric and neonatal care, challenges remain in early identification of neonates with encephalopathy due to hypoxia-ischemia who are undergoing therapeutic hypothermia. Therefore, there is a deep search for biomarkers that can identify brain injury. The aims of this study were to investigate the serum and brain expressions of two potential biomarkers, miR-126/miR-146a, in a preclinical model of hypoxia-ischemia (HI)-induced brain injury, and to explore their modulation during melatonin treatment.

The gut-brain vascular axis in neuroinflammation.

The multifaceted microbiota characterizing our gut plays a crucial role in maintaining immune, metabolic and tissue homeostasis of the intestine as well as of distal organs, including the central nervous system. Microbial dysbiosis is reported in several inflammatory intestinal diseases characterized by the impairment of the gut epithelial and vascular barriers, defined as leaky gut, and it is reported as a potential danger condition associated with the development of metabolic, inflammatory and neurodegenerative diseases. Recently, we pointed out the strict connection between the gut and the brain via a novel vascular axis.

Melatonin in Newborn Infants Undergoing Surgery: A Pilot Study on Its Effects on Postoperative Oxidative Stress.

Surgery is frequently associated with excessive oxidative stress. Melatonin acts as an antioxidant and transient melatonin deficiency has been described in neonatal surgical patients. This randomized, blinded, prospective pilot study tested the hypothesis that oral melatonin supplementation in newborn infants undergoing surgery is effective in reducing perioperative oxidative stress.

The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic-Ischemic Brain Injury.

The endocannabinoid (EC) system is a complex cell-signaling system that participates in a vast number of biological processes since the prenatal period, including the development of the nervous system, brain plasticity, and circuit repair. This neuromodulatory system is also involved in the response to endogenous and environmental insults, being of special relevance in the prevention and/or treatment of vascular disorders, such as stroke and neuroprotection after neonatal brain injury. Perinatal hypoxia-ischemia leading to neonatal encephalopathy is a devastating condition with no therapeutic approach apart from moderate hypothermia, which is effective only in some cases.

Melatonin, tunneling nanotubes, mesenchymal cells, and tissue regeneration.

Mesenchymal stem cells are multipotent stem cells that reside in many human tissues and organs. Mesenchymal stem cells are widely used in experimental and clinical regenerative medicine due to their capability to transdifferentiate into various lineages. However, when transplanted, they lose part of their multipotency and immunomodulatory properties, and most of them die after injection into the damaged tissue.

Stability Program in Dendritic Cell Vaccines: A "Real-World" Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center.

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute.

Unveiling the gut-brain axis: structural and functional analogies between the gut and the choroid plexus vascular and immune barriers.

The vasculature plays an essential role in the development and maintenance of blood-tissue interface homeostasis. Knowledge on the morphological and functional nature of the blood vessels in every single tissue is, however, very poor, but it is becoming clear that each organ is characterized by the presence of endothelial barriers with different properties fundamental for the maintenance of tissue resident immune homeostasis and for the recruitment of blood-trafficking immune cells. The tissue specificity of the vascular unit is dependent on the presence of differentiated endothelial cells that form continues, fenestrated, or sinusoidal vessels with different grades of permeability and different immune receptors, according to how that particular tissue needs to be protected.

Human-rat integrated microRNAs profiling identified a new neonatal cerebral hypoxic-ischemic pathway melatonin-sensitive.

Neonatal encephalopathy (NE) is a pathological condition affecting long-term neurodevelopmental outcomes. Hypothermia is the only therapeutic option, but does not always improve outcomes; hence, researchers continue to hunt for pharmaceutical compounds. Melatonin treatment has benefitted neonates with hypoxic-ischemic (HI) brain injury.