Conjugation of Antibodies and siRNA Duplexes to Polymer Nanoparticles via Maleimide-Thiol Chemistry.

Polymeric nanoparticles (NPs) have shown great promise as highly modifiable platforms that can be applied across many different disease states. They are advantageous because they can encapsulate a range of hydrophobic and hydrophilic cargoes while having customizable surface properties. Depending on the desired biointerfacing capabilities, the surface of polymeric NPs can be modified with moieties, such as antibodies, peptides, nucleic acids, and more.

The complexity of addressing equity in COVID-19-related global health governance and population health research priorities in Canada: a multilevel qualitative study.

Background: Since COVID-19 emerged in 2020, the promotion of health equity, including in research, has further been challenged worldwide by both global health governance (GHG) processes and decisions, and national public health control measures. These global and national decisions have also led to the 'covidization' of health research agendas where resources have been massively channelled to address COVID-19, especially during the first years of the pandemic. This situation could potentially result in current and future population health research priorities not explicitly tackling equity as a central tenet.

Real-world adoption of left bundle branch area pacing: Insights from the Conduction-System pacing Italian Network Group (C-SING).

Background And Objective: Left bundle branch area pacing (LBBAP) is increasingly used for treating bradycardia and heart failure. However, real-world data are limited. The Conduction-System Pacing Italian Network Group (C-SING) collected prospective data on LBBAP procedures in a nationwide context.

Encapsulation of Leaf Polyphenols in Liposomes: A Study on Their Antimicrobial Activity to Turn a Byproduct into a Tool to Treat Bacterial Infection.

According to the innovative and sustainable perspective of the circular economy model, leaves, a solid byproduct generated every year in large amounts by the olive oil production chain, are considered a valuable source of bioactive compounds, such as polyphenols, with many potential applications. In particular, the following study aimed to valorize olive leaves in order to obtain products with potential antibacterial activity. In this study, olive leaf extracts, rich in polyphenols, were prepared by ultrasound-assisted extraction using green solvents, such as ethanol and water.

Identifying Patients with Heart Failure Eligible for Guideline-Directed Medical Therapy.

A majority of patients with heart failure (HF) do not receive adequate medical therapy as recommended by clinical guidelines. One major obstacle encountered by population health management (PHM) programs to improve medication usage is the substantial burden placed on clinical staff who must manually sift through electronic health records (EHRs) to ascertain patients' eligibility for the guidelines. As a potential solution, the study team developed a rule-based system (RBS) that automatically parses the EHR for identifying patients with HF who may be eligible for guideline-directed therapy.

Swallowing function in patients with spinal muscular atrophy before and after the introduction of new gene-based therapies: what has changed?

Objective: Individuals diagnosed with Spinal Muscular Atrophy (SMA), particularly those presenting with the most severe phenotypes, have long contended with significant swallowing dysfunction. The recent emergence of efficacious advanced therapy has fundamentally altered the landscape of SMA management. By encompassing both the pre and post gene-based therapy eras within our analysis, we endeavour to elucidate the potential impact of these novel therapeutic interventions on this function.

In vitro assessment of an intraoral scanner accuracy on abutments with horizontal preparation geometries and subgingival margins.

Objectives: This study evaluated the accuracy of the Medit i700 intraoral scanner (IOS) in capturing horizontal tooth preparations at different depths below the gingival margin and assessed its ability to detect surfaces beyond the finish line.

Methods: Using CAD software, two abutments of a standard maxillary first molar were designed with horizontal preparation and 0.8 mm chamfer at 1 mm and 2 mm depths below the gingival margin.

Facilitators and challenges in collaboration between public health units and faith-based organizations to promote COVID-19 vaccine confidence in Ontario.

Background: Equitable access to vaccination remains a concern, particularly among population groups made structurally vulnerable. These population groups reflect the diversity of communities that are confronted with structural barriers caused by systemic racism and oppression and result in them experiencing suffer disadvantage and discrimination based on citizenship, race, ethnicity, ancestry, religion, spiritual beliefs, and/or gender identity. In Canada, Ontario public health units (PHUs) engage with faith-based organizations (FBOs) to improve vaccine confidence among populations made structurally vulnerable.

An Intraoperative Ultrasound Evaluation of Axillary Lymph Nodes: Cassandra Predictive Models in Patients with Breast Cancer-A Multicentric Study.

Axillary lymph node (ALN) staging is crucial for the management of invasive breast cancer (BC). Although various radiological investigations are available, ultrasound (US) is the preferred tool for evaluating ALNs. Despite its immediacy, widespread use, and good predictive value, US is limited by intra- and inter-operator variability.

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.

Long-term outcomes following ultrathin vs thin-strut drug-eluting stents for percutaneous coronary intervention: an updated systematic review and meta-analysis of randomized control trials.

Objectives: Current thin-strut 2 generation drug eluting stents (DES) are considered as optimal standard of care for revascularization of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). Ultrathin (≤ 70 μm strut thickness) strut DES have recently been shown to reduce target lesion failure (TLF) compared to thin-strut DES. Therefore, in order to assess the validity of improved outcomes associated with ultrathin-strut DES, we conducted an updated meta-analysis that includes recently published follow-ups of previously conducted randomized controlled trials (RCTs).

Outcomes of Mechanical Thrombectomy in Patients With Acute Basilar Artery Occlusion With Mild to Moderate Symptoms.

Background And Objectives: The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) with basilar artery occlusion (BAO) and a baseline National Institute of Health Stroke Scale (NIHSS) score <10 is unclear because this subpopulation has been substantially excluded from large clinical trials. The aim of our study was to determine whether MT ± IV thrombolysis (IVT) improves functional outcomes compared with IVT alone in patients with BAO and a NIHSS score <10.

Methods: We emulated a hypothetical trial including adult patients with BAO, a baseline NIHSS score <10, and prestroke modified Rankin scale (mRS) scores 0-2, comparing MT (±IVT) with IVT alone.

Stroke thrombectomy in the elderly: A propensity score matched study on a nationwide real-world registry.

Introduction: Data on safety and efficacy of endovascular thrombectomy (EVT) for acute ischemic stroke in older patients are limited and controversial, and people aged 80 or older were under-represented in randomized trials. Our aim was to assess EVT effect for ischemic stroke patients aged ⩾80 at a nationwide level.

Patients And Methods: The cohort included stroke patients undergoing EVT from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS).

Symptom profile, case and symptom clustering, clinical and demographic characteristics of a multicentre cohort of 1297 patients evaluated for Long-COVID.

Background: Long-COVID symptoms remain incompletely defined due to a large heterogeneity in the populations studied, case definitions, and settings of care. The aim of this study was to assess, in patients accessing care for Long-COVID, the profile of symptoms reported, the possible clustering of symptoms and cases, the functional status compared to pre-infection, and the impact on working activity.

Methods: Multicentre cohort study with a collection of both retrospective and prospective data.

Filtering coupled Wright-Fisher diffusions.

Coupled Wright-Fisher diffusions have been recently introduced to model the temporal evolution of finitely-many allele frequencies at several loci. These are vectors of multidimensional diffusions whose dynamics are weakly coupled among loci through interaction coefficients, which make the reproductive rates for each allele depend on its frequencies at several loci. Here we consider the problem of filtering a coupled Wright-Fisher diffusion with parent-independent mutation, when this is seen as an unobserved signal in a hidden Markov model.

The Effects of a Stepped-Care Mental Health Program on Trauma Recidivism at a Level 1 Trauma Center.

Objectives: This study aimed to analyze the effects of a stepped-care mental health program (TRRP) on trauma recidivism at a single institution.

Designs: Retrospective review.

Setting: Single level 1 trauma center.

Identification of a New Promising BAG3 Modulator Featuring the Imidazopyridine Scaffold.

The antiapoptotic BAG3 protein plays a crucial role in cellular proteostasis and it is involved in several signalling pathways governing cell proliferation and survival. Owing to its multimodular structure, it possesses an extensive interactome including the molecular chaperone HSP70 and other specific cellular partners, which make it an eminent factor in several pathologies, particularly in cancer. Despite its potential as a therapeutic target, very few BAG3 modulators have been disclosed so far.

NMDA receptors regulate the firing rate set point of hippocampal circuits without altering single-cell dynamics.

Understanding how neuronal circuits stabilize their activity is a fundamental yet poorly understood aspect of neuroscience. Here, we show that hippocampal network properties, such as firing rate distribution and dimensionality, are actively regulated, despite perturbations and single-cell drift. Continuous inhibition of N-methyl-D-aspartate receptors (NMDARs) ex vivo lowers the excitation/inhibition ratio and network firing rates while preserving resilience to perturbations.

Toward On-Demand Polymorphic Transitions of Organic Crystals via Side Chain and Lattice Dynamics Engineering.

Controlling polymorphism, namely, the occurrence of multiple crystal forms for a given compound, is still an open technological challenge that needs to be addressed for the reliable manufacturing of crystalline functional materials. Here, we devised a series of 13 organic crystals engineered to embody molecular fragments undergoing specific nanoscale motion anticipated to drive cooperative order-disorder phase transitions. By combining polarized optical microscopy coupled with a heating/cooling stage, differential scanning calorimetry, X-ray diffraction, low-frequency Raman spectroscopy, and calculations (density functional theory and molecular dynamics), we proved the occurrence of cooperative transitions in all the crystalline systems, and we demonstrated how both the molecular structure and lattice dynamics play crucial roles in these peculiar solid-to-solid transformations.

Ultra-processed food consumption is associated with the acceleration of biological aging in the Moli-sani Study.

Background: Healthy diets have been inversely associated with biological aging. However, the nutritional content is only one aspect of the overall food health potential, and more recently, increasing attention has been paid to nonnutrient food characteristics, such as food processing.

Objectives: To examine the association of ultra-processed food (UPF) consumption with biological aging measured by circulating blood biomarkers.