Pseudorabies Virus Prevalence in Lung Samples of Hunted Wild Boars in Northwestern Greece.

Aujeszky's Disease, caused by the pseudorabies virus (PRV), is an acute, often fatal disease affecting mainly pigs and incidentally other animals. While eradicated in several countries, PRV persists in wild boar populations, posing a risk to domestic pigs. This study investigates PRV prevalence in wild boars in the region of Epirus, located in the northwest of Greece.

Biological characterization of AB-343, a novel and potent SARS-CoV-2 M inhibitor with pan-coronavirus activity.

Since the SARS-CoV-2 outbreak, there have been ongoing efforts to identify antiviral molecules with broad coronavirus activity to combat COVID-19. SARS-CoV-2's main protease (M) is responsible for processing the viral polypeptide into non-structural proteins essential for replication. Here, we present the biological characterization of AB-343, a covalent small-molecule inhibitor of SARS-CoV-2 M with potent activity in both cell-based (EC = 0.

Structure-Activity Relationships and Discovery of ()-5-(-Butyl)-11-(difluoromethoxy)-9-methoxy-2-oxo-1,2,5,6-tetrahydropyrido[2',1':2,3]imidazo[4,5-]quinoline-3-carboxylic Acid (AB-161), a Novel Orally Available and Liver-Centric HBV RNA Destabilizer.

Lowering hepatitis B surface antigen (HBsAg) levels from covalently closed circular DNA (cccDNA) and the integrated genome could reduce the persistence of hepatitis B virus (HBV) infection. Since HBV replication occurs in the liver and to ameliorate the peripheral neuropathy observed with a first-generation tricyclic 4-pyridone PAPD5/7 inhibitor () having high systemic exposure, we focused on increasing the hepatocyte concentration and reducing plasma levels. Optimization of a novel series of PAPD5/7 inhibitors that decrease HBsAg levels led to the tetracyclic 2-pyridone , which was similarly potent to and but showed dramatically higher rodent liver-to-plasma ratios.

A DNA base-specific sequence interposed between CRX and NRL contributes to RHODOPSIN expression.

Gene expression emerges from DNA sequences through the interaction of transcription factors (TFs) with DNA cis-regulatory sequences. In eukaryotes, TFs bind to transcription factor binding sites (TFBSs) with differential affinities, enabling cell-specific gene expression. In this view, DNA enables TF binding along a continuum ranging from low to high affinity depending on its sequence composition; however, it is not known whether evolution has entailed a further level of entanglement between DNA-protein interaction.

Rational Design of Macrocyclic Noncovalent Inhibitors of SARS-CoV-2 M from a DNA-Encoded Chemical Library Screening Hit That Demonstrate Potent Inhibition against Pan-Coronavirus Homologues and Nirmatrelvir-Resistant Variants.

The recent global COVID-19 pandemic has highlighted treatments for coronavirus infection as an unmet medical need. The main protease (M) has been an important target for the development of SARS-CoV-2 direct-acting antivirals. Nirmatrelvir as a covalent M inhibitor was the first such approved therapy.

Preclinical and clinical antiviral characterization of AB-836, a potent capsid assembly modulator against hepatitis B virus.

HBV capsid assembly modulators (CAMs) target the core protein and inhibit pregenomic RNA encapsidation and viral replication. HBV CAMs also interfere with cccDNA formation during de novo infection, which in turn suppresses transcription and production of HBV antigens. In this report, we describe the antiviral activities of AB-836, a potent and highly selective HBV CAM.

Control of Hepatitis B Virus with Imdusiran, a Small Interfering RNA Therapeutic.

Chronic hepatitis B is a global health concern with a high risk of end-stage liver disease. Current standard-of-care agents have low cure rates, and new therapies are needed. Small interfering RNAs (siRNAs) that target viral RNAs fulfill a gap not addressed by standard-of-care agents and may contribute to a functional cure.

Conformationally Constrained Isoquinolinones as Orally Efficacious Hepatitis B Capsid Assembly Modulators.

Isoquinolinone-based HBV capsid assembly modulators that bind at the dimer:dimer interface of HBV core protein have been shown to suppress viral replication in chronic hepatitis B patients. Analysis of their binding mode by protein X-ray crystallography has identified a region of the small molecule where the application of a constraint can lock the preferred binding conformation and has allowed for further optimization of this class of compounds. Key analogues demonstrated single digit nM EC values in reducing HBV DNA in a HepDE19 cellular assay in addition to favorable ADME and pharmacokinetic properties, leading to a high degree of oral efficacy in a relevant hydrodynamic injection mouse model of HBV infection, with effecting a 3 log decline in serum HBV DNA levels at a once daily dose of 1 mg/kg.

Prevalence of Neospora caninum and associated risk factors in semi-intensive female water buffaloes reared in Greece, using an ELISA kit on milk samples.

Neospora caninum is an apicomplexan (family: Sarcocystidae) protozoan parasite with a global distribution. In the N. caninum life cycle, dogs and other related canids are the definitive hosts, while other animals such as water buffaloes (Bubalus bubalis) constitute the intermediate host for this parasite.

Rational Design, Synthesis, and Structure-Activity Relationship of a Novel Isoquinolinone-Based Series of HBV Capsid Assembly Modulators Leading to the Identification of Clinical Candidate AB-836.

Inhibition of Hepatitis B Virus (HBV) replication by small molecules that modulate capsid assembly and the encapsidation of pgRNA and viral polymerase by HBV core protein is a clinically validated approach toward the development of new antivirals. Through definition of a minimal pharmacophore, a series of isoquinolinone-based capsid assembly modulators (CAMs) was identified. Structural biology analysis revealed that lead molecules possess a unique binding mode, exploiting electrostatic interactions with accessible phenylalanine and tyrosine residues.

Innovative treatments for obesity and NAFLD: A bibliometric study on antioxidants, herbs, phytochemicals, and natural compounds.

The increasing scientific interest in antioxidants and naturally derived compounds as potential remedies for obesity and non-alcoholic fatty liver disease (NAFLD) has led to extensive research. The objective of this bibliometric analysis is to present an updated perspective on the topic of antioxidants, herbs, phytochemicals, and natural compounds, in the control of obesity and NAFLD, to identify new areas for future research. Publications from the years 2012-2022 were retrieved using the Scopus database.

First detection of Cupriavidus gilardii in a bovine neonatal diarrhea outbreak.

Background: Cupriavidus gilardii is an aerobic, gram-negative, motile, glucose-nonfermenting bacillus, first described in 1999. Typically, it exhibits low pathogenicity in humans, causing opportunistic infections primarily in individuals with compromised immune systems. This bacterium has been also found in various environmental sources such as plants and contaminated soils.

Discovery of -Linked Nucleoside Analogues with Antiviral Activity against SARS-CoV-2.

The recent COVID-19 pandemic underscored the limitations of currently available direct-acting antiviral treatments against acute respiratory RNA-viral infections and stimulated major research initiatives targeting anticoronavirus agents. Two novel nsp5 protease (MPro) inhibitors have been approved, nirmatrelvir and ensitrelvir, along with two existing nucleos(t)ide analogues repurposed as nsp12 polymerase inhibitors, remdesivir and molnupiravir, but a need still exists for therapies with improved potency and systemic exposure with oral dosing, better metabolic stability, and reduced resistance and toxicity risks. Herein, we summarize our research toward identifying nsp12 inhibitors that led to nucleoside analogues and , which showed favorable pan-coronavirus activity in cell-infection screens, were metabolized to active triphosphate nucleotides in cell-incubation studies, and demonstrated target (nsp12) engagement in biochemical assays.

Preclinical Antiviral and Safety Profiling of the HBV RNA Destabilizer AB-161.

HBV RNA destabilizers are a class of small-molecule compounds that target the noncanonical poly(A) RNA polymerases PAPD5 and PAPD7, resulting in HBV RNA degradation and the suppression of viral proteins including the hepatitis B surface antigen (HBsAg). AB-161 is a next-generation HBV RNA destabilizer with potent antiviral activity, inhibiting HBsAg expressed from cccDNA and integrated HBV DNA in HBV cell-based models. AB-161 exhibits broad HBV genotype coverage, maintains activity against variants resistant to nucleoside analogs, and shows additive effects on HBV replication when combined with other classes of HBV inhibitors.

White Paper: American Gastroenterological Association Position Statement: The Future of IBD Care in the United States-Removing Barriers and Embracing Opportunities.

Despite incredible growth in systems of care and rapidly expanding therapeutic options for people with inflammatory bowel disease, there are significant barriers that prevent patients from benefiting from these advances. These barriers include restrictions in the form of prior authorization, step therapy, and prescription drug coverage. Furthermore, inadequate use of multidisciplinary care and inflammatory bowel disease specialists limits patient access to high-quality care, particularly for medically vulnerable populations.

Exploring public interest in gut microbiome dysbiosis, NAFLD, and probiotics using Google Trends.

Scientific interest related to the role of gut microbiome dysbiosis in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has now been established and is constantly growing. Therefore, balancing dysbiosis, through probiotics, would be a potential therapy. In addition to scientific interest, on the other hand, it is important to evaluate the interest in these topics among the population.

Structure-Activity Relationships and Discovery of ()-6-Isopropyl-2-methoxy-3-(3-methoxypropoxy)-10-oxo-5,10-dihydro-6-pyrido[1,2-][1,7]naphthyridine-9-carboxylic Acid (AB-452), a Novel Orally Available HBV RNA Destabilizer.

Approved therapies for hepatitis B virus (HBV) treatment include nucleos(t)ides and interferon alpha (IFN-α) which effectively suppress viral replication, but they rarely lead to cure. Expression of viral proteins, especially surface antigen of the hepatitis B virus (HBsAg) from covalently closed circular DNA (cccDNA) and the integrated genome, is believed to contribute to the persistence of HBV. This work focuses on therapies that target the expression of HBV proteins, in particular HBsAg, which differs from current treatments.

Indication of West Nile Virus (WNV) Lineage 2 Overwintering among Wild Birds in the Regions of Peloponnese and Western Greece.

West Nile virus (WNV), a zoonotic mosquito-borne virus, has recently caused human outbreaks in Europe, including Greece. Its transmission cycle in nature includes wild birds as amplifying hosts and ornithophilic mosquito vectors. The aim of this study was to assess WNV circulation among wild birds from two regions of Greece, Peloponnese and Western Greece, during 2022.

The surgical treatment of Morgagni hernias in adults: a systematic review for the standardization of laparoscopic surgical repair.

A Morgagni hernia is a congenital diaphragmatic hernia that is rarely diagnosed in adults, and the technique for its repair has not yet been standardized. This review will give an overview of the different laparoscopic methods reported by other authors, highlighting the key points indicating a good repair to help standardize the technique. A systematic review of the available articles on PubMed was conducted according to PRISMA 2020 by two authors independently in May 2022.

Design, synthesis, and structure-activity relationship of a bicyclic HBV capsid assembly modulator chemotype leading to the identification of clinical candidate AB-506.

Disruption of the HBV capsid assembly process through small-molecule interaction with HBV core protein is a validated target for the suppression of hepatitis B viral replication and the development of new antivirals. Through combination of key structural features associated with two distinct series of capsid assembly modulators, a novel aminochroman-based chemotype was identified. Optimization of anti-HBV potency through generation of SAR in addition to further core modifications provided a series of related functionalized aminoindanes.

Efficacy of the Hepcon system in reducing hemorrhagic and thrombotic complications in antiphospholipid syndrome patients undergoing cardiac surgery.

Introduction: Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration.

Intraoperative push enteroscopy for treatment of occult small bowel bleed due to hemorrhagic bleed and tumor: a report of two cases.

Small bowel bleeds, while uncommon, are often challenging with regard to diagnosis and therapeutic intervention. This is primarily due to their occult nature, the location offending lesions and limitations of current technology used to assess them. This review highlights two patients who presented with signs and symptoms of a small bowel bleed, where initial diagnostic workups were inconclusive, and intraoperative enteroscopy served a diagnostic and therapeutic role.

[A model of continuity of care for not residents through medical-nursing teleconsultation in a Hub & Spoke network].

Unlabelled: . A model of continuity of care for not residents through medical-nursing teleconsultation in a Hub & Spoke network.

Introduction: The Seasonal Continuity of Care (CAS) is a service of the Bergamo Health Protection Agency that provides medical and healthcare services, guaranteeing outpatient or home care to Italian and foreign tourists and seasonal workers during the months of July and August.

Gut Microbiome in the Progression of NAFLD, NASH and Cirrhosis, and Its Connection with Biotics: A Bibliometric Study Using Dimensions Scientific Research Database.

There is growing evidence that gut microbiota dysbiosis is linked to the etiopathogenesis of nonalcoholic fatty liver disease (NAFLD), from the initial stage of disease until the progressive stage of nonalcoholic steatohepatitis (NASH) and the final stage of cirrhosis. Conversely, probiotics, prebiotics, and synbiotics have shown promise in restoring dysbiosis and lowering clinical indicators of disease in a number of both preclinical and clinical studies. Additionally, postbiotics and parabiotics have recently garnered some attention.

Awake laparoscopic cholecystectomy: A case report and review of literature.

Background: Laparoscopic cholecystectomy (LC) is one of the most widely practiced surgical procedures in abdominal surgery. Patients undergo LC during general anaesthesia; however, in recent years, several studies have suggested the ability to perform LC in patients who are awake. We report a case of awake LC and a literature review.