Synthesis of a di-O-acylated deoxynojirimycin (DNJ) derivative and evaluation of its antibacterial and antibiofilm activity against Staphylococcus aureus and Stenotrophomonas maltophilia.

Herein we report the synthesis of a novel di-O-acylated DNJ derivative, conceived to study whether iminosugar derivatization with a lipophilic acyl moiety could positively affect its antibacterial properties. The well-known PS-TPP/I/ImH activating system was used to readily install the acyl chains on the iminosugar, leading to the desired compound in high yield. Biological assays revealed that a di-O-lauroyl DNJ derivative enhanced the antibacterial effect of gentamicin and amikacin against S.

Nanostructural Modulation of G-Quadruplex DNA in Neurodegeneration: Orotate Interaction Revealed Through Experimental and Computational Approaches.

The natural compound orotic acid and its anionic form, orotate, play a pivotal role in various biological processes, serving as essential intermediates in pyrimidine de novo synthesis, with demonstrated connections to dietary, supplement, and neurodrug applications. A novel perspective on biomolecular aggregation at the nanoscale, particularly pertinent to neurodegeneration, challenges the established paradigm positing that peptide (amyloid beta) and protein (tau) aggregation mainly govern the molecular events underlying prevalent neuropathologies. Emerging biological evidence indicates a notable role for G-quadruplex (G4) DNA aggregation in neurodegenerative processes affecting neuronal cells, particularly in the presence of extended (GC) repeats in nuclear DNA sequences.

Structural commonalities determined by physicochemical principles in the complex polymorphism of the amyloid state of proteins.

Advances in solid-state nuclear magnetic resonance (ssNMR) spectroscopy and cryogenic electron microscopy (cryoEM) have revealed the polymorphic nature of the amyloid state of proteins. Given the association of amyloid with protein misfolding disorders, it is important to understand the principles underlying this polymorphism. To address this problem, we combined computational tools to predict the specific regions of the sequence forming the β-spine of amyloid fibrils with the availability of 30, 83 and 24 amyloid structures deposited in the Protein Data Bank (PDB) and Amyloid Atlas (AAt) for the amyloid β (Aβ) peptide, α-synuclein (αS), and the 4R isoforms of tau, associated with Alzheimer's disease, Parkinson's disease, and various tauopathies, respectively.

Mild-Temperature Catalyzed Hydrosilylation for Simplified Carbohydrate Functionalization of Porous Silicon Nanoparticles.

Porous silicon is one of the most explored nanostructured materials in various biomedical applications owing to its remarkable properties. However, its inherent chemical instability mandates a robust surface modification procedure, and proper surface bioengineering is essential to ensure its effectiveness in the biomedical field. In this study, we introduce a one-pot functionalization strategy that simultaneously stabilizes porous silicon nanoparticles and decorates their surface with carbohydrates through hydrosilylation chemistry, combining mild temperatures and a Lewis acid catalyst.

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.

Differences between MINOCA and type 2 myocardial infarction: An ITALIAN observational study.

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) and type 2 myocardial infarction (MI), both presenting as non-ST-elevation MI (NSTEMI), are often grouped together due to overlapping symptoms. The aim of our study is to compare their characteristics and prognosis to distinguish between them.

Methods: Among 7815 patients with NSTEMI who underwent coronary angiography between 2005 and 2022 we identified 538 patients with diagnosis of MINOCA (n = 301; 3,9 %) and type 2 MI (n = 237; 3 %).

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.

Advancing Patient Safety: The Future of Artificial Intelligence in Mitigating Healthcare-Associated Infections: A Systematic Review.

Background: Healthcare-associated infections are infections that patients acquire during hospitalization or while receiving healthcare in other facilities. They represent the most frequent negative outcome in healthcare, can be entirely prevented, and pose a burden in terms of financial and human costs. With the development of new AI and ML algorithms, hospitals could develop new and automated surveillance and prevention models for HAIs, leading to improved patient safety.

Molecular Sex Differences and Clinical Gender Efficacy in Opioid Use Disorders: From Pain Management to Addiction.

Opioids have been utilized for both medical and recreational purposes since their discovery. Primarily recognized for their analgesic properties, they are also associated with the development of tolerance and dependence, contributing to a significant public health concern worldwide. Sex differences in opioid use disorder reveal that while men historically exhibit higher rates of abuse, women may develop dependence more quickly and are more susceptible to the addictive nature of opioids.

Comparative Toxicological Analyses of Traditional Matrices and Blow Fly Larvae in Four Cases of Highly Decomposed Human Cadavers.

In forensic investigation, determining the time and cause of death becomes challenging, especially in cases where the remains are found in advanced decomposition, rendering traditional toxicological samples unavailable or unreliable. Entomotoxicology, an emerging methodology within forensic science, leverages insect specimens collected from cadavers as alternative toxicological samples. Several laboratory and field research studies have highlighted the efficacy in detecting various drugs, toxins, and elements absorbed by insects feeding on cadaveric tissues, even at low concentrations.

Unraveling the relationship among insulin resistance, IGF-1, and amyloid-beta 1-40: Is the definition of type 3 diabetes applicable in the cardiovascular field?

The concept of "type 3 diabetes" has emerged to define alterations in glucose metabolism that predispose individuals to the development of Alzheimer's disease (AD). Novel evidence suggests that changes in the insulin/insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis, which are characteristic of Diabetes Mellitus, are one of the major factors contributing to excessive amyloid-beta (Aβ) production and neurodegenerative processes in AD. Moreover, molecular findings suggest that insulin resistance and dysregulated IGF-1 signaling promote atherosclerosis via endothelial dysfunction and a pro-inflammatory state.

Leveraging Machine Learning-Guided Molecular Simulations Coupled with Experimental Data to Decipher Membrane Binding Mechanisms of Aminosterols.

Understanding the molecular mechanisms of the interactions between specific compounds and cellular membranes is essential for numerous biotechnological applications, including targeted drug delivery, elucidation of the drug mechanism of action, pathogen identification, and novel antibiotic development. However, estimation of the free energy landscape associated with solute binding to realistic biological systems is still a challenging task. In this work, we leverage the Time-lagged Independent Component Analysis (TICA) in combination with neural networks (NN) through the Deep-TICA approach for determining the free energy associated with the membrane insertion processes of two natural aminosterol compounds, trodusquemine (TRO), and squalamine (SQ).

Simultaneous multi-targeted forensic toxicological screening in biological matrices by MRM-IDA-EPI mode.

The toxicologist ascertains drug assumptions in case of paediatric intoxications and death for overdose. The analytical approach consists of initially screening and consequently confirming drug positivity. We developed a toxicological screening method and validated its use comparing the results with a LC-MS/MS analysis.

South Tyrol Healthcare Company: A Look at a Peculiar Model of Claims Management in Italy and Analysis of Its Last 11 Years.

Background: Alternative Disputes Resolution (ADR) systems are becoming increasingly important tools in recent years for the management and resolution of health responsibility cases, but their dissemination and efficiency are still poorly described. The purpose of this paper is to present an ADR system in the autonomous province of Bolzano: the Conciliation Commission.

Methods: systematic collection of all claims of the South Tyrol Sanitary Service that were dealt with in the Conciliation Commission from 1 January 2012 to 31 December 2022.

Mucocele of the appendix: case report of a rare disease with changing diagnostic-therapeutic behavior.

Mucinous appendicular neoplasms are a rare and heterogeneous group of tumors, whose treatment may vary based on histologic features and extent. We present a case of low-grade appendiceal mucinous neoplasm mimicking an acute appendicitis scenario. The patient underwent appendectomy along with resection of the caecal fundus.

Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO), predicts future major adverse cardiovascular events after myocardial infarction.

Objective: Trimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome.

Methods And Results: Blood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge.

Higher-order G-quadruplex structures and porphyrin ligands: Towards a non-ambiguous relationship.

Herein, we evaluated the interaction of the tetracationic porphyrin HTCPPSpm4 with three distinct DNA G-quadruplex (G4) models, i.e., the tetramolecular G4 d(TGGGGT) (Q), the 5'-5' stacked G4-dimer [d(CGGAGGT)] (Q), and a mixture of 5'-5' stacked G-wires [d(5'-CGGT-3'-3'-GGC-5')] (Q).

Cardiac SARS-CoV-2 Infection, Involvement of Cytokines in Postmortem Immunohistochemical Study.

In the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, significant attention was given to pulmonary manifestations. However, cardiac involvement is increasingly recognized as a critical factor influencing the prognosis, leading to myocardial damage, heart failure, acute coronary syndromes, potentially lethal arrhythmic events, and sudden cardiac death. Despite these findings, there is a lack of studies detailing the necroscopic, macroscopic, and microscopic cardiac changes associated with SARS-CoV-2.

Ethnicity and sudden cardiac death in athletes: insights from a large United Kingdom registry.

Aims: The relationship between ethnicity and causes of sudden cardiac death (SCD) in athletes is poorly understood.

Objectives: To investigate aetiology of SCD among different ethnicities in a large cohort of athletes.

Methods And Results: Between 1994 and November 2022, 7880 cases of SCD were consecutively referred from all over the United Kingdom to our national cardiac pathology centre; 848 (11%) were athletes.

Applicability of a Chemiluminescence Immunoassay to Screen Postmortem Bile Specimens and Its Agreement with Confirmation Analysis.

Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis.

Persistence of vitamin D deficiency among Italian patients with acute myocardial infarction.

Background And Aims: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic.

Methods And Results: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022).