Hyphenation of 2D NMR With Hydrogenative PHIP.

Parahydrogen induced polarisation (PHIP) is often used to enhance the sensitivity of NMR, with the purpose of extending the applicability of the technique. Nuclear spin hyperpolarisation obtained via PHIP is generally localised on the protons derived from the addition of para-enriched hydrogen to an unsaturated substrate. This limitation has been previously addressed by pulse schemes that can spread this hyperpolarised magnetisation through the entire network of J-coupled protons in the product molecule.

The sex prevalence of lower limb varicose vein networks.

Objective: To determine the sex prevalence of lower limb varicose networks fed by reflux of the great saphenous vein (GSV), anterior accessory saphenous vein (AASV), and small saphenous vein singularly or in combination.

Methods: We scanned by the means of the same color Doppler ultrasound protocol 3000 lower limbs in 1500 consecutive patients, affected by symptomatic chronic venous insufficiency from 2013 to 2023. Limbs with normal venous function, incomplete scans, or that were affected by post-thrombotic syndrome, pelvic reflux, isolated perforator reflux, venous malformation, phlebolymphedema and Clinical, Etiological, Anatomical, Pathophysiological clinical class C5 and C6 were excluded from the final analysis.

Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model.

Objective: To characterize aspects of triiodothyronine (T3) induced chondrocyte terminal maturation within the molecular osteoarthritis pathophysiology using the previously established T3 human ex vivo osteochondral explant model.

Designs: RNA-sequencing was performed on explant cartilage obtained from OA patients (n = 8), that was cultured ex vivo with or without T3 (10 ng/ml), and main findings were validated using RT-qPCR in an independent sample set (n = 22). Enrichment analysis was used for functional clustering and comparisons with available OA patient RNA-sequencing and GWAS datasets were used to establish relevance for OA pathophysiology by linking to OA patient genomic profiles.

Is schedule IV suvorexant an appropriate reference drug of abuse to use in preclinical abuse liability testing in the rat?

The abuse potential of novel CNS-active drug candidates with low specificity for known receptors involved in abuse might be complex to test preclinically relative to an appropriate reference drug of abuse. Suvorexant, a Schedule IV dual orexin receptor antagonist was investigated for its potential use as a reference drug in Drug Discrimination Learning (DDL) studies. Firstly, toxicokinetic properties of suvorexant were determined in male and female rats after single oral doses of 160 and 325 mg/kg in MC and PEG400.

Abuse potential assessment of the dual orexin receptor antagonist daridorexant in rats.

Background: Drugs that act on the central nervous system (CNS) and have sedative effects can lead to abuse in humans. New CNS-active drugs often require evaluation of their abuse potential in dedicated animal models before marketing approval. Daridorexant is a new dual orexin receptor antagonist (DORA) with sleep-promoting properties in animals and humans.

Failure of the dual orexin receptor antagonist suvorexant to engender drug discrimination in rats.

For abuse potential assessment, U.S. Food and Drug Administration (FDA) requests that new, brain-penetrating drugs are ideally compared with approved drugs that share the mechanism of action and are judged to have abuse liability by the Drug Enforcement Agency.

Keratose Self-Cross-Linked Wound Dressing for Iron Sequestration in Chronic Wounds.

Chronic wound diseases affect a large part of the world population, and therefore, novel treatments are becoming fundamental. People with chronic wounds show high iron and protease levels due to genetic disorders or other comorbidities. Since it was demonstrated that iron plays an important role in chronic wounds, being responsible for oxidative processes (ROS generation), while metalloproteinases prevent wound healing by literally "eating" the growing skin, it is crucial to design an appropriate wound dressing.

International Union of Angiology consensus document on vascular compression syndromes.

Vascular compression syndromes (VCS) are rare diseases, but they may cause significant symptoms interfering with the quality of life (QoL) of patients who are often in their younger age. Given their infrequent occurrence, multiform clinical and anatomical presentation, and absence of dedicated guidelines from scientific societies, further knowledge of these conditions is required to investigate and treat them using modern imaging and surgical (open or endovascular) techniques. This consensus document will focus on known VCS, affecting the arterial and venous system.

Improving door-to-reperfusion time in acute ischemic stroke during the COVID-19 pandemic: experience from a public comprehensive stroke center in Brazil.

Background: The global COVID-19 pandemic has had a devastating effect on global health, resulting in a strain on healthcare services worldwide. The faster a patient with acute ischemic stroke (AIS) receives reperfusion treatment, the greater the odds of a good functional outcome. To maintain the time-dependent processes in acute stroke care, strategies to reorganize infrastructure and optimize human and medical resources were needed.

Randomized controlled trial on occupational graduated compression clinical and cost-effectiveness.

Background: Subjects exposed to occupational standing are at risk of developing chronic venous disease. Graduated compression stockings (GCS) counteract venous hypertension. Aim of the present investigation was to assess GCS clinical and cost effectiveness in prolonged standing up workers.

Cerebral Outflow Discrepancies in Recurrent Benign Paroxysmal Positional Vertigo: Focus on Ultrasonographic Examination.

This prospective pilot study aimed to evaluate whether cerebral inflow and outflow abnormalities assessed by ultrasonographic examination could be associated with recurrent benign paroxysmal positional vertigo (BPPV). Twenty-four patients with recurrent BPPV, affected by at least two episodes, and diagnosed according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria, evaluated at our University Hospital, between 1 February 2020 and 30 November 2021, have been included. At the ultrasonographic examination, 22 of 24 patients (92%) reported one or more alterations of the extracranial venous circulation, among those considered for the diagnosis of chronic cerebrospinal venous insufficiency (CCSVI), although none of the studied patients were found to have alterations in the arterial circulation.

Validation of a new model of selective antegrade cerebral perfusion with circulatory arrest in rats.

Background: Selective antegrade cerebral perfusion (SACP) is adopted as an alternative to deep hypothermic circulatory arrest (DHCA) during aortic arch surgery. However, there is still no preclinical evidence to support the use of SACP associated with moderate hypothermia (28-30°C) instead of DHCA (18-20°C). The present study aims to develop a reliable and reproducible preclinical model of cardiopulmonary bypass (CPB) with SACP applicable for assessing the best temperature management.

NMR Discrimination of d- and l-α-Amino Acids at Submicromolar Concentration via Parahydrogen-Induced Hyperpolarization.

Differentiation of enantiomers represents an important research area for pharmaceutical, chemical, and food industries. However, enantiomer separation is a laborious task that demands complex analytical techniques, specialized equipment, and expert personnel. In this respect, discrimination and quantification of d- and l-α-amino acids is no exception, generally requiring extensive sample manipulation, including isolation, functionalization, and chiral separation.

High-throughput 3D microvessel-on-a-chip model to study defective angiogenesis in systemic sclerosis.

In early systemic sclerosis (Scleroderma, SSc), the vasculature is impaired. Although the exact etiology of endothelial cell damage in SSc remains unclear, it is hypothesized that endothelial to mesenchymal transition (EndoMT) plays a key role. To perform physiologically relevant angiogenic studies, we set out to develop an angiogenesis-on-a-chip platform that is suitable for assessing disease parameters that are relevant to SSc and other vasculopathies.

Analysis of Complex Mixtures by Chemosensing NMR Using -Hydrogen-Induced Hyperpolarization.

Nuclear magnetic resonance (NMR) is a powerful technique for chemical analysis. The use of NMR to investigate dilute analytes in complex systems is, however, hampered by its relatively low sensitivity. An additional obstacle is represented by the NMR signal overlap.

Hydrophobic Derivatives of Sulfated Hyaluronic Acid as Drug Delivery Systems for Multi-Target Intra-Articular Treatment of Post-Traumatic Osteoarthritis.

During osteoarthritis (OA) development, chondrocytes progressively decompensate, upregulating proteolytic enzymes and reducing the key growth factors involved in promoting chondrocyte anabolism. A combined therapeutic approach is needed to address this multifactorial pathology, which affects the whole joint. Based on the literature, three promising targets for OA treatment have been selected: MMP3 (matrix metallopeptidase 3), TRPV4 (transient receptor potential cation channel subfamily V member 4) and mTOR (mammalian target of rapamycin).

Development of mAb-based polyglutamine-dependent and polyglutamine length-independent huntingtin quantification assays with cross-site validation.

Huntington's disease (HD) is caused by an expansion of the CAG trinucleotide repeat domain in the huntingtin gene that results in expression of a mutant huntingtin protein (mHTT) containing an expanded polyglutamine tract in the amino terminus. A number of therapeutic approaches that aim to reduce mHTT expression either locally in the CNS or systemically are in clinical development. We have previously described sensitive and selective assays that measure human HTT proteins either in a polyglutamine-independent (detecting both mutant expanded and non-expanded proteins) or in a polyglutamine length-dependent manner (detecting the disease-causing polyglutamine repeats) on the electrochemiluminescence Meso Scale Discovery detection platform.

Nitric Oxide in Selective Cerebral Perfusion Could Enhance Neuroprotection During Aortic Arch Surgery.

Background: Hypothermic circulatory arrest (HCA) in aortic arch surgery has a significant risk of neurological injury despite the newest protective techniques and strategies. Nitric oxide (NO) could exert a protective role, reduce infarct area and increase cerebral perfusion. This study aims to investigate the possible neuroprotective effects of NO administered in the oxygenator of selective antegrade cerebral perfusion (SCP) during HCA.

Efficacy of Pulsatile Flow Perfusion in Adult Cardiac Surgery: Hemodynamic Energy and Vascular Reactivity.

The role of pulsatile (PP) versus non-pulsatile (NP) flow during a cardiopulmonary bypass (CPB) is still debated. This study's aim was to analyze hemodynamic effects, endothelial reactivity and erythrocytes response during a CPB with PP or NP. Fifty-two patients undergoing an aortic valve replacement were prospectively randomized for surgery with either PP or NP flow.

Physical fitness changes induced by thermal aquatic standardized exercise in chronic venous disease patients.

Background: Lack of physical activity represents a risk factor for both cardiovascular and chronic venous diseases (CVD), nevertheless a specific exercise protocol for CVD patient is still missing. This investigation was aimed to assess the impact of a standardized exercise protocol in a thermal water environment on physical fitness and quality-of-life (QoL) in CVD patients.

Methods: Sixteen (16) CVD patients performed 5 standardized exercise sessions in a thermal water pool.

Parahydrogen Hyperpolarization Allows Direct NMR Detection of α-Amino Acids in Complex (Bio)mixtures.

The scope of non-hydrogenative parahydrogen hyperpolarization (nhPHIP) techniques has been expanding over the last years, with the continuous addition of important classes of substrates. For example, pyruvate can now be hyperpolarized using the Signal Amplification By Reversible Exchange (SABRE) technique, offering a fast, efficient and low-cost PHIP alternative to Dynamic Nuclear Polarization for metabolic imaging studies. Still, important biomolecules such as amino acids have so far resisted PHIP, unless properly functionalized.

An approach to fast 2D nuclear magnetic resonance at low concentration based on p-H -induced polarization and nonuniform sampling.

Recent developments in para-hydrogen-induced polarization (PHIP) methods allow the nuclear magnetic resonance (NMR) detection of specific classes of compounds, down to sub-micromolar concentration in solution. However, when dealing with complex mixtures, signal resolution requires the acquisition of 2D PHIP-NMR spectra, which often results in long experimental times. This strongly limits the applicability of these 2D PHIP-NMR techniques in areas in which high-throughput analysis is required.