Rational design and synthesis of novel N-benzylindole-based epalrestat analogs as selective aldose reductase inhibitors: An unexpected discovery of a new glucose-lowering agent (AK-4) acting as a mitochondrial uncoupler.

Diabetes mellitus is one of the most frequent metabolic diseases associated with hyperglycemia. Although antidiabetic drugs reduce hyperglycemia, diabetic patients suffer from abnormal fluctuations in blood glucose levels leading to the onset of long-term complications. Aldose reductase inhibitors are considered a promising strategy for regulating the occurrence of diabetic-specific comorbidities.

Dosimetry of microbeam radiotherapy by flexible hydrogenated amorphous silicon detectors.

Detectors that can provide accurate dosimetry for microbeam radiation therapy (MRT) must possess intrinsic radiation hardness, a high dynamic range, and a micron-scale spatial resolution. In this work we characterize hydrogenated amorphous silicon detectors for MRT dosimetry, presenting a novel combination of flexible, ultra-thin and radiation-hard features.Two detectors are explored: an n-type/intrinsic/p-type planar diode (NIP) and an NIP with an additional charge selective layer (NIP + CSC).

A chemical modification of a peroxisome proliferator-activated receptor pan agonist produced a shift to a new dual alpha/gamma partial agonist endowed with mitochondrial pyruvate carrier inhibition and antidiabetic properties.

New analogs of the PPAR pan agonist AL29-26 encompassed ligand (S)-7 showing potent activation of PPARα and -γ subtypes as a partial agonist. In vitro experiments and docking studies in the presence of PPAR antagonists were performed to help interpretation of biological data and investigate the main interactions at the binding sites. Further in vitro experiments showed that (S)-7 induced anti-steatotic effects and enhancement of the glucose uptake.

Quantitative EEG and prognosis for recovery in post-stroke patients: The effect of lesion laterality.

Objective: There is emerging confidence that quantitative EEG (qEEG) has the potential to inform clinical decision-making and guide individualized rehabilitation after stroke, but consensus on the best EEG biomarkers is needed for translation to clinical practice. This study investigates the spatial qEEG spectral and symmetry distribution in patients with a left/right hemispheric stroke, to evaluate their side-specific prognostic power in post-acute rehabilitation outcome.

Methods: Resting-state 19-channel EEG recordings were collected with clinical information on admission to intensive inpatient rehabilitation (within 30 days post stroke), and six months post stroke.

EVOO Polyphenols Exert Anti-Inflammatory Effects on the Microglia Cell through TREM2 Signaling Pathway.

In Alzheimer's disease (AD), microglia, brain resident immune cells, become chronically inflammatory and neurotoxic. In recent years, neuroinflammation has attracted particular interest in the scientific community. The genetic variants of molecules associated with ''microgliopathies'', including the triggering receptor expressed in myeloid cells-2 (TREM2), result in increased risk of developing AD and cognitive decline.

Simultaneous Determination by Selective Esterification of Trimellitic, Phthalic, and Maleic Anhydrides in the Presence of Respective Acids.

Trimellitic, phthalic, and maleic anhydrides are important building blocks to produce polymers and additives, such as plasticizers. In humans, the exposure to these compounds can cause several health issues. In European Union and USA, their presence in substances and mixtures is restricted by CLP Regulation (no.

Do changes in SSEP amplitude over time predict the outcome of comatose survivors of cardiac arrest?

Aim: To assess if the amplitude of the N20 wave (N20Amp) of somatosensory evoked potentials (SSEPs) changes between 12-24 h and 72 h from the return of spontaneous circulation (ROSC) after cardiac arrest and if an N20Amp decrease predicts poor neurological outcome (CPC 3-5) at six months.

Setting: Retrospective analysis of the ProNeCA multicentre prognostication study dataset. (NCT03849911).

Performance of 3D diamond detectors in small field dosimetry: The impact of pixel size.

Purpose: Small photon beams used in radiotherapy techniques have inherent characteristics of charge particle disequilibrium and high-dose gradient making accurate dosimetry for such fields very challenging. By means of a 3D manufacturing technique, it is possible to create arrays of pixels with a very small sensitive volume for radiotherapy dosimetry. We investigate the impact of 3D pixels size on absorbed dose sensitivity, linearity of response with dose rate, reproducibility and beam profile measurements.

AIRO Breast Cancer Group .

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.

Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis.

GM1 gangliosidosis is a rare lysosomal disease caused by the deficiency of the enzyme β-galactosidase (β-Gal; ; E.C. 3.

The "End Life" of the Grape Pomace Waste Become the New Beginning: The Development of a Virtuous Cycle for the Green Synthesis of Gold Nanoparticles and Removal of Emerging Contaminants from Water.

During the last decades, the demand for processes developed according to the Circular Economy Principles has increased, searching for an alternative life for wastes. For this purpose, a one-pot green approach is exploited during this work to synthesize gold nanoparticles (AuNPs) by using grape pomace waste from . A raw aqueous extract of grape seeds, skin, and stems is used for AuNPs synthesis.

Magnetron Sputtered CsPbCl Perovskite Detectors as Real-Time Dosimeters for Clinical Radiotherapy.

The aim of this study is to investigate the feasibility of manufacturing thin real-time relative dosimeters for clinical radiotherapy (RT) with potential applications for transmission monitoring in vivo dosimetry and pre-treatment dose verifications. Thin (≈1μm) layers of a high sensitivity, wide bandgap semiconductor, the inorganic perovskite CsPbCl, have been grown for the first time by magnetron sputtering on plastic substrates equipped with electrode arrays. Prototype devices have been tested in real-time configuration to evaluate the dose delivered by a 6MV photon beam from a linear accelerator.

A chemoinformatics search for peroxisome proliferator-activated receptors ligands revealed a new pan-agonist able to reduce lipid accumulation and improve insulin sensitivity.

The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in the regulation of the metabolic homeostasis and therefore represent valuable therapeutic targets for the treatment of metabolic diseases. The development of more balanced drugs interacting with PPARs, devoid of the side-effects showed by the currently marketed PPARγ full agonists, is considered the major challenge for the pharmaceutical companies. Here we present a chemoinformatics search approach for new ligands that let us identify a novel PPAR pan-agonist with a very attractive activity profile being able to reduce lipid accumulation and improve insulin sensitivity.

Smart Magnetic Nanocarriers for Multi-Stimuli On-Demand Drug Delivery.

In this study, we report the realization of drug-loaded smart magnetic nanocarriers constituted by superparamagnetic iron oxide nanoparticles encapsulated in a dual pH- and temperature-responsive poly (N-vinylcaprolactam-co-acrylic acid) copolymer to achieve highly controlled drug release and localized magnetic hyperthermia. The magnetic core was constituted by flower-like magnetite nanoparticles with a size of 16.4 nm prepared by the polyol approach, with good saturation magnetization and a high specific absorption rate.

Activated fibroblasts enhance cancer cell migration by microvesicles-mediated transfer of Galectin-1.

Cancer-associated fibroblasts (CAFs) are one of the main components of the stromal compartment in the tumor microenvironment (TME) and the crosstalk between CAFs and cancer cells is essential for tumor progression and aggressiveness. Cancer cells mediate an activation process, converting normal fibroblasts into CAFs, that are characterized by modified expression of many proteins and increased production and release of microvesicles (MVs), extracellular vesicles generated by outwards budding from the cell membrane. Recent evidence underlined that the uptake of CAF-derived MVs changes the overall protein content of tumor cells.

Immunotherapy and radiotherapy in melanoma: a multidisciplinary comprehensive review.

Melanoma is an extremely aggressive tumor and is considered to be an extremely immunogenic tumor because compared to other cancers it usually presents a well-expressed lymphoid infiltration. The aim of this paper is to perform a multidisciplinary comprehensive review of the evidence available about the combination of radiotherapy and immunotherapy for melanoma. Radiation, in fact, can increase tumor antigens visibility and promote priming of T cells but can also exert immunosuppressive action on tumor microenvironment.

SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study.

Aim: To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome.

Setting: Multicentre study in 13 Italian intensive care units.

Methods: The N20amp in microvolts (μV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology.

Large-Area SiPM Pixels (LASiPs): A cost-effective solution towards compact large SPECT cameras.

Single Photon Emission Computed Tomography (SPECT) scanners based on photomultiplier tubes (PMTs) are still largely employed in the clinical environment. A standard camera for full-body SPECT employs ~50-100 PMTs of 4-8 cm diameter and is shielded by a thick layer of lead, becoming a heavy and bulky system that can weight a few hundred kilograms. The volume, weight and cost of a camera can be significantly reduced if the PMTs are replaced by silicon photomultipliers (SiPMs).

Into Clinical Practice: Diagnosis and Therapy of Retroperitoneal Fibrosis.

Purpose Of The Review: We aim to review the most relevant diagnostic features and treatment options of retroperitoneal fibrosis, in order to provide a useful guide for clinical practice.

Recent Findings: The recent literature highlights the role of imaging studies such as computed tomography, magnetic resonance imaging and positron emission tomography as useful tools for the diagnosis of retroperitoneal fibrosis, with retroperitoneal biopsy being reserved to atypical cases. The treatment approach is mainly conservative and is based on the use of medical therapies plus urological interventions.

Is there inter-observer variation in the interpretation of SSEPs in comatose cardiac arrest survivors? Further considerations following the Italian multicenter ProNeCa study.

Background: Bilateral absence of N20 peak in median nerve Somatosensory Evoked Potentials (SSEPs) is considered the most valid predictor of poor outcome in comatose survivors after cardiopulmonary resuscitation. We investigated the consistency in interpreting SSEP recordings in a multicentre study.

Methods: 44 SSEP recordings randomly extracted from 600 recordings of 392 patients included in the "Prognostication of Neurological outcome after Cardiac Arrest (ProNeCa) study" were blindly read by three expert neurophysiologists.

Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells.

Acriflavine (ACF) is an antiseptic with anticancer properties, blocking the growth of solid and haematopoietic tumour cells. Moreover, this compound has been also shown to overcome the resistance of cancer cells to chemotherapeutic agents. ACF has been shown to target hypoxia-inducible factors (HIFs) activity, which are key effectors of hypoxia-mediated chemoresistance.