Thiol-Reactive or Redox-Active: Revising a Repurposing Screen Led to a New Invalidation Pipeline and Identified a True Noncovalent Inhibitor Against Papain-like Protease from SARS-CoV-2.

The SARS-CoV-2 papain-like protease PLpro has multiple roles in the viral replication cycle, related to both its polypeptide cleavage function and its ability to antagonize the host immune response. Targeting the PLpro function is recognized as a promising mechanism to modulate viral replication, while supporting host immune responses. However, the development of PLpro-specific inhibitors remains challenging.

Retrospective matched case-control comparison of Totally Robotic Sleeve Gastrectomy (RSG) during the learning curve with Laparoscopic Sleeve Gastrectomy (LSG): why is operative time different?

Robotic approach is slowly rising in metabolic surgery, and laparoscopy is still considered the gold standard for Sleeve Gastrectomy. Aim of our study was to assess and compare outcomes of RSG through a matched comparison with LSG. Retrospective search of prospectively maintained database of our surgical department was carried out find all consecutive patients who underwent RSG from April 2023 to August 2024.

Altered Intracerebellar Functional Connectivity in Friedreich's Ataxia: A Graph-Theory Functional MRI Study.

Historically, Friedreich's Ataxia (FRDA) has been linked to a relatively preserved cerebellar cortex. Recent advances in neuroimaging have revealed altered cerebello-cerebral functional connectivity (FC), but the extent of intra-cerebellar FC changes and their impact on cognition remains unclear. This study investigates intra-cerebellar FC alterations and their cognitive implications in FRDA.

Nutritional Strategies for Battling Obesity-Linked Liver Disease: the Role of Medical Nutritional Therapy in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Management.

Purpose Of Review: This narrative review explores the role of Medical Nutritional Therapy (MNT) in managing Metabolic-Associated Steatotic Liver Disease (MASLD), previously known as nonalcoholic fatty liver disease. It aims to examine the effectiveness of specific nutritional strategies in preventing and treating this obesity-linked liver disease.

Recent Findings: Emerging evidence underscores the benefits of the Mediterranean diet, low-carbohydrate diets, and intermittent fasting in reducing liver fat, improving insulin sensitivity, and mitigating inflammation.

Echocardiography in the Ventilated Patient: What the Clinician Has to Know.

Heart and lung sharing the same anatomical space are influenced by each other. Spontaneous breathing induces dynamic changes in intrathoracic pressure, impacting cardiac function, particularly the right ventricle. In intensive care units (ICU), mechanical ventilation (MV) and therefore positive end-expiratory pressure (PEEP) are often applied, and this inevitably influences cardiac function.

Cys44 of SARS-CoV-2 3CL affects its catalytic activity.

SARS-CoV-2 encodes a 3C-like protease (3CL) that is essential for viral replication. This cysteine protease cleaves viral polyproteins to release functional nonstructural proteins, making it a prime target for antiviral drug development. We investigated the inhibitory effects of halicin, a known c-Jun N-terminal kinase inhibitor, on 3CL.

Pemphigus and Bullous Pemphigoid Following COVID-19 Vaccination: A Systematic Review.

The COVID-19 pandemic has encouraged the rapid development and licensing of vaccines against SARS-CoV-2. Currently, numerous vaccines are available on a global scale and are based on different mechanisms of action, including mRNA technology, viral vectors, inactive viruses, and subunit particles. Mass vaccination conducted worldwide has highlighted the potential development of side effects, including ones with skin involvement.

The Role of Therapeutic Endoscopic Ultrasound in Management of Malignant Double Obstruction (Biliary and Gastric Outlet): A Comprehensive Review with Clinical Scenarios.

Endoscopic ultrasound (EUS)-guided interventions have revolutionized the management of malignant biliary obstruction (MBO) and gastric outlet obstruction (GOO), providing minimally invasive alternatives with improved outcomes. These procedures have significantly reduced the need for high-risk surgical interventions or percutaneous alternatives and have provided effective palliative care for patients with advanced gastrointestinal and bilio-pancreatic malignancies. EUS-guided biliary drainage (EUS-BD) techniques, including hepaticogastrostomy (EUS-HGS), choledochoduodenostomy (EUS-CDS), and antegrade stenting (EUS-AS), offer high technical and clinical success rates, with a good safety profile particularly when Endoscopic Retrograde Cholangiopancreatography (ERCP) is not feasible.

Stoma Acceptance Mediates Body Image Distress and Mental Health-Related Quality of Life: A Single-Center Study on Radical Cystectomy Patients with Ureterostomy.

Muscle-invasive bladder cancer and subsequent radical cystectomy with ureterocutaneostomy significantly impact patients' body image and quality of life, potentially increasing the risk of adverse mental health outcomes. Acceptance may represent a psychosocial resource to buffer the effects of body image impairment on health, thereby supporting stoma adjustment and preserving quality of life. This study aimed to investigate the mediating role of stoma acceptance in the relationship between body image distress and mental health.

Myopia in Children: Epidemiology, Genetics, and Emerging Therapies for Treatment and Prevention.

Refractive errors, particularly myopia, are among the most prevalent visual impairments globally, with rising incidence in children and adolescents. This review explores the epidemiology and risk factors associated with the development of refractive errors, focusing on the environmental and lifestyle factors contributing to the current surge in myopia. We provide an overview of key genetic factors and molecular pathways driving the pathogenesis of myopia and other refractive errors, emphasizing the complex interplay between genetic predisposition and environmental triggers.

Advancing Glaucoma Treatment During Pregnancy and Breastfeeding: Contemporary Management Strategies and Prospective Therapeutic Developments.

The management of glaucoma in pregnancy and breastfeeding requires a careful evaluation of treatment choices to guarantee the well-being of both the mother and the developing fetus. This review explores the intricacies of controlling glaucoma in pregnant and breastfeeding women, including a comprehensive overview of existing glaucoma treatment methods, clinical guidelines, and future therapeutic approaches. The efficacy and safety profiles of traditional treatment approaches, such as topical and systemic medicines and surgical treatments, are evaluated specifically about their use during pregnancy and breastfeeding.

Impact of Nursing Interventions via Telephone and Email on the Quality of Life of Patients with Inflammatory Bowel Disease: Preliminary Results of a Comparative Observational Study.

Background: Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, is a heterogeneous chronic condition characterized by periods of relapse and remission. Ulcerative colitis involves inflammation of the colon and rectum mucosa, while Crohn's disease causes deeper, transmural inflammation affecting all four gut layers from the mouth to the anus and can lead to complications such as fistulation. IBD significantly impacts patients' physical and psychological well-being, thus reducing their quality of life (QoL).

Chemical Profile and Promising Applications of L. Flowers.

Although edible flowers have been historically principally used due to their visual appeal and smell, the world is discovering their value as innovative and natural sources of bioactive compounds. L. (CpL), a plant from the Cucurbitaceae family, is widely cultivated for its edible fruits and flowers, which are rich in polyphenols and carotenoids-compounds known for their potent antioxidant and anti-inflammatory properties.

Long-Term Efficacy and Safety of Nutritional and Pharmacological Strategies for Obesity.

Purpose Of Review: This review examines the long-term efficacy and safety of various nutritional and pharmacological strategies for managing obesity. The focus is on the Mediterranean diet (MedDiet), very low-energy ketogenic therapy (VLEKT), and pharmacological interventions such as naltrexone/bupropion and liraglutide. Given the chronic nature of obesity, understanding the sustainability and impact of these treatments over time is critical.

Design, Synthesis, and Anticancer Activity of Drug-like Iron Chelators/G-Quadruplex Binders as Synergic Dual Targeting Agents.

Iron homeostasis is strictly related to numerous physiological pathways including cell cycle progression and cell growth. The newest anticancer strategies focus on either depleting the cells with a suitable chelator or increasing their loading by administering iron complexes to induce ferroptosis. Iron depletion inhibits cell proliferation, while iron overload induces the damage of guanine nucleobases in G-quadruplex structures via ROS generation, leading to genome instability.

The density histograms-derived computerized integrated index (CII) predicts mortality in idiopathic pulmonary fibrosis.

Quantitative assessment of the extent of radiological alterations in interstitial lung diseases is a promising field of application that goes beyond the limitations of qualitative scoring. Analysis of density histograms, i.e.

Retrospective Study on Short-Term Reverse Cardiac Remodeling in Obese Patients Undergoing Sleeve Gastrectomy.

Severe obesity is closely associated with an increased risk of comorbidities and alterations in cardiac structure and function. The primary objective of this study was to investigate cardiovascular (CV) risk factors and ventricular remodeling in individuals from an obese population eligible for bariatric surgery. The secondary objective was to evaluate changes in anthropometric, clinical laboratory, and echocardiographic measurements 12 weeks after surgery compared to baseline values.

Development and Characterization of Biocompatible Cellulose-Tetraphenylethylene Hydrazone Self-Assembling Nanomicelles with Acidity-Triggered Release of Doxorubicin for Cancer Therapy.

The development of anticancer diagnostic and therapeutic strategies is of crucial importance to improve efficacy and therapeutic specificity. Here, we describe the synthesis and characterization of fluorescent self-assembling nanomicelles (NMs) based on a biocompatible polysaccharide (cellulose, CE) functionalized with a tetraphenyl ethylene derivative (TPEHy) and loaded with Doxorubicin (DOX) with aggregation-induced emission (AIE) properties and pH-dependent drug release. We obtained CE-TPEHy-NMs with an average diameter of 60 ± 17 nm for unloaded NMs and 86 ± 25 nm for NMs loaded with DOX, respectively.

Report of the Italian Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome in the Target Therapy Era.

Background: Activated Phosphoinositide 3-Kinase (PI3K) δ Syndrome (APDS), an inborn error of immunity due to upregulation of the PI3K pathway, leads to recurrent infections and immune dysregulation (lymphoproliferation and autoimmunity).

Methods: Clinical and genetic data of 28 APDS patients from 25 unrelated families were collected from fifteen Italian centers.

Results: Patients were genetically confirmed with APDS-1 (n = 20) or APDS-2 (n = 8), with pathogenic mutations in the PIK3CD or PIK3R1 genes.

Behavioural, cognitive, and neurophysiological effects of a synbiotic supplementation enriched with pigmented corn extract or cornstarch in drug-naïve children with attention-deficit hyperactivity disorder: a randomised, double-blind, comparison-controlled clinical trial.

Background & Aims: Considerable interest has been recently given to the potential role of the gut-brain axis (GBA) -a two-way communication network between the gut microbiota and the central nervous system- in the pathogenesis of attention-deficit hyperactivity disorder (ADHD), suggesting the potential usefulness of probiotic and synbiotic supplementations. In light of the limited available evidence, synbiotic efficacy in ADHD children not taking medications should be clarified. This study aimed to investigate the efficacy of a synbiotic dietary supplementation on fatty acids levels as well as on microbiota composition, behaviour, cognition, and brain function in children with ADHD.

Sex-specific differences in echocardiographic parameters of risk stratification in pulmonary arterial hypertension.

Background: In healthy subjects, sex-differences in right heart function have already been detected for various echocardiographic parameters.

Research Question: The objective of the study was to investigate sex-differences in echocardiographic ESC/ERS risk stratification parameters and their impact on survival estimation in patients with pulmonary arterial hypertension (PAH).

Study Design And Methods: In this retrospective, cross-sectional study with a mean follow-up time of 3.

New Concepts in Circumareolar Mastopexy: The "Star Interlocking Suture"-A Case Series.

The circumareolar approach is one of the most popular and versatile in breast surgeries. Nevertheless, this approach usually implies a closure under tension which could lead to areolar distortion, scar widening and hypertrophic scarring. To prevent these complications, different surgical adjustments to this technique have been proposed, such as the Hammond's "Interlocking Gore-Tex suture.

Addressing brain metabolic connectivity in treatment-resistant schizophrenia: a novel graph theory-driven application of F-FDG-PET with antipsychotic dose correction.

Few studies using Positron Emission Tomography with F-fluorodeoxyglucose (F-FDG-PET) have examined the neurobiological basis of antipsychotic resistance in schizophrenia, primarily focusing on metabolic activity, with none investigating connectivity patterns. Here, we aimed to explore differential patterns of glucose metabolism between patients and controls (CTRL) through a graph theory-based approach and network comparison tests. PET scans with F-FDG were obtained by 70 subjects, 26 with treatment-resistant schizophrenia (TRS), 28 patients responsive to antipsychotics (nTRS), and 16 CTRL.

Clinical trial eligibility in PSP: Population representativeness and potential criteria adjustment based on PSP-NET findings.

Background: Progressive Supranuclear Palsy (PSP) is a rare, heterogeneous neurodegenerative disease for which no treatment is currently available. In the context of clinical trials, the representativeness of the included patients is crucial for the generalizability of the results. Herein, we present results from a multicenter perspective study to identify the most restrictive criteria for patient selection and to assess the representativeness of eligible patients.

Leveraging deep learning for identification and segmentation of "CAF-1/p60-positive" nuclei in oral squamous cell carcinoma tissue samples.

In the current study, we introduced a unique method for identifying and segmenting oral squamous cell carcinoma (OSCC) nuclei, concentrating on those predicted to have significant CAF-1/p60 protein expression. Our suggested model uses the StarDist architecture, a deep-learning framework designed for biomedical image segmentation tasks. The training dataset comprises painstakingly annotated masks created from tissue sections previously stained with hematoxylin and eosin (H&E) and then restained with immunohistochemistry (IHC) for p60 protein.