A CD Study of a Structure-Based Selection of -Heterocyclic Bis-Carbene Gold(I) Complexes as Potential Ligands of the G-Quadruplex-Forming Human Telomeric hTel23 Sequence.

Herein, we report the structure-based selection via molecular docking of four -heterocyclic bis-carbene gold(I) complexes, whose potential as ligands for the hTel23 G-quadruplex structure has been investigated using circular dichroism (CD) spectroscopy, CD melting, and polyacrylamide gel electrophoresis (PAGE). The complex containing a bis(1,2,3,4,6,7,8,9-octahydro-11-11-pyridazino[1,2-a]indazol-11-yl) scaffold induces a transition from the hybrid (3 + 1) topology to a prevalent parallel G-quadruplex conformation, whereas the complex featuring a bis(2-(2-acetamidoethyl)-3-imidazo[1,5-a]pyridin-3(2)-yl) moiety disrupted the original G-quadruplex structure. These results deserve particular attention in light of the recent findings on the pathological involvements of G-quadruplexes in neurodegenerative diseases.

Novel Approaches for the Early Detection of Glaucoma Using Artificial Intelligence.

Background: If left untreated, glaucoma-the second most common cause of blindness worldwide-causes irreversible visual loss due to a gradual neurodegeneration of the retinal ganglion cells. Conventional techniques for identifying glaucoma, like optical coherence tomography (OCT) and visual field exams, are frequently laborious and dependent on subjective interpretation. Through the fast and accurate analysis of massive amounts of imaging data, artificial intelligence (AI), in particular machine learning (ML) and deep learning (DL), has emerged as a promising method to improve the early detection and management of glaucoma.

Urinary Tract Infections in Kidney Transplant Patients: An Open Challenge-Update on Epidemiology, Risk Factors and Management.

Urinary tract infections are one of the main complications in kidney transplant patients, with a significant impact on graft function and survival. In fact, it is estimated that up to 74% of kidney transplant patients experience at least one episode of UTIs in the first year after transplantation, with an increased risk of graft loss and an increased risk of mortality. Several risk factors have been identified, such as female gender, old age, diabetes mellitus, immunosuppression, pre-transplant UTIs, urinary tract abnormalities, and prolonged dialysis.

How Does Physical Activity Modulate Hormone Responses?

Physical activity highly impacts the neuroendocrine system and hormonal secretion. Numerous variables, both those related to the individual, including genetics, age, sex, biological rhythms, nutritional status, level of training, intake of drugs or supplements, and previous or current pathologies, and those related to the physical activity in terms of type, intensity, and duration of exercise, or environmental conditions can shape the hormonal response to physical exercise. The aim of this review is to provide an overview of the effects of physical exercise on hormonal levels in the human body, focusing on changes in concentrations of hormones such as cortisol, testosterone, and insulin in response to different types and intensities of physical activity.

Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic de-repression of the double homeobox 4 (DUX4) gene, leading to asymmetric muscle weakness and atrophy that begins in the facial and scapular muscles and progresses to the lower limbs. This incurable condition can severely impair muscle function, ultimately resulting in a loss of ambulation. A thorough analysis of molecular factors associated with the varying degrees of muscle impairment in FSHD is still lacking.

Oceanic Breakthroughs: Marine-Derived Innovations in Vaccination, Therapy, and Immune Health.

The vast, untapped potential of the world's oceans is revealing groundbreaking advancements in human health and vaccination. Microalgae such as spp. and are emerging as resources for recombinant vaccine development with specific and heterologous genetic tools used to boost production of functional recombinant antigens in and spp.

Post COVID-19 vaccination coverage recovery model.

Vaccination is a crucial tool for the primary prevention of infectious diseases. Thanks to the widespread of vaccinations it has been possible to eradicate very serious diseases. Unfortunately, vaccination coverage in Italy has been decreasing starting from 2015, getting worse during COVID-19.

Long-term oritavancin therapy for shoulder prosthetic joint infection: A case guided by therapeutic drug monitoring (TDM).

Oritavancin is a novel long-acting lipoglycopeptide with in vitro activity against methicillin-resistant (MR) Gram-positive pathogens and a good bactericidal activity even in presence of biofilm forming bacteria. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, as for prosthetic joint infections (PJI), which, in more than half of cases, are caused by MR Gram positive organisms. W reported a case of a man in his eighties with a late shoulder PJI caused by methicillin resistant (MRSE) with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy.

Pursuing Polypharmacology: Benzothiopyranoindoles as G-Quadruplex Stabilizers and Topoisomerase I Inhibitors for Effective Anticancer Strategies.

Here, we explored the benzothiopyranoindole scaffold to develop antiproliferative agents with a polypharmacological profile targeting both G-quadruplex (G4)-structures and Topoisomerase (Topo) I enzyme. In a preliminary optimization phase, compound was selected from an in-house collection as a suitable lead for the rational development of a small library of analogs (-). When assayed in NIH's NCI-60 Human Cancer Cell Line In Vitro Screen Program, compound and its demethylated analogue showed significant antiproliferative/cytotoxic activity.

A Reappraisal on cortical myoclonus and brief Remarks on myoclonus of different Origins.

Myoclonus has multiple clinical manifestations and heterogeneous generators and etiologies, encompassing a spectrum of disorders and even physiological events. This paper, developed from a teaching course conducted by the Neurophysiology Commission of the Italian League against Epilepsy, aims to delineate the main types of myoclonus, identify potential underlying neurological disorders, outline diagnostic procedures, elucidate pathophysiological mechanisms, and discuss appropriate treatments. Neurophysiological techniques play a crucial role in accurately classifying myoclonic phenomena, by means of simple methods such as EEG plus polymyography (EEG + Polymyography), evoked potentials, examination of long-loop reflexes, and often more complex protocols to study intra-cortical inhibition-facilitation In clinical practice, EEG + Polymyography often represents the first step to identify myoclonus, acquire signals for off-line studies and plan the diagnostic work-up.

Rare Primitive Lung Adenocarcinoma in Larynx: A Case Report.

Laryngeal metastasis from a primitive distant cancer is a rare finding in clinical practice. In this paper is presented the case of a 63-year-old patient treated for lung adenocarcinoma metastasis in the supraglottic larynx. A review of literature suggests how the treatment of this kind of case is not unique.

The Non-invasive Assessment of the Pulmonary Circulation-Right Ventricular Functional Unit: Diagnostic and Prognostic Implications.

The pulmonary circulation and the right ventricle play a pivotal role in the global hemodynamics of human beings, so much so that their close interaction is encapsulated in the concept of a "morpho-functional unit". In this review we aim to pinpoint the strengths and weaknesses of various noninvasive established techniques. The goal is to detect early morphologic and/or functional changes in the pulmonary circulation and right ventricular unit, which is crucial for tailoring treatments and prognostic assessments.

Normal Hemodynamic Response to Exercise.

Exercise pulmonary hypertension has been invasively defined as mean pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min. Recent advances suggest the sustainable role of exercise Doppler echocardiography for the study of the right heart and pulmonary circulation unit (RH-PCU). Herein, the authors review the invasive versus non-invasive monitoring of the RH-PCU response to exercise in healthy subjects.

Engineering an oncolytic adenoviral platform for precise delivery of antisense peptide nucleic acid to modulate PD-L1 overexpression in cancer cells.

Cancer immunotherapy is focused on stimulating the immune system against cancer cells by exploiting immune checkpoint mechanisms. PD-1/PD-L1 is one of the most known immune checkpoints due to the widespread upregulation of the Programmed Death Ligand 1 (PD-L1) transmembrane protein in cancer tissues. Accordingly, taking advantage of the ability of oncolytic adenoviruses (OAd) to specifically infect and kill tumor cells over healthy ones, here, we developed a targeted delivery platform based on OAd to selectively deliver in cancer cells an antisense peptide nucleic acid (PNA) targeting the PD-L1 mRNA.

Who and how to screen for endogenous hypercortisolism in patients with mood disorders.

A strict association exists between mood disorders and endogenous hypercortisolism, namely Cushing's syndrome (CS). Indeed, CS is characterized by a wide range of mood disorders, such as major depression, generalized anxiety, panic disorders, bipolar disorders up to psychosis, with major depression being the most frequent, with a prevalence of 50-80%, and potentially representing the clinical onset of disease. Despite this observation, the exact prevalence of hypercortisolism in patients with mood disorders is unknown and who/how to screen for endogenous hypercortisolism among patients with mood disorders is still unclear.

Imaging in sensorineural and conductive hearing loss-an educational review.

Hearing loss is the most common sensory impairment globally and can affect all ages. It can be classified into two categories, conductive and sensorineural, though both conditions may coexist. Various causes may be responsible for hearing loss including congenital, infectious, inflammatory and neoplastic.

Mitochondrial Dysfunction in Parkinson's Disease: A Contribution to Cognitive Impairment?

Among the non-motor symptoms associated with Parkinson's disease (PD), cognitive impairment is one of the most common and disabling. It can occur either early or late during the disease, and it is heterogeneous in terms of its clinical manifestations, such as Subjective Cognitive Dysfunction (SCD), Mild Cognitive Impairment (MCI), and Parkinson's Disease Dementia (PDD). The aim of the present review is to delve deeper into the molecular mechanisms underlying cognitive decline in PD.