Discovery of CHF-6523, an Inhaled Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease.

The design of inhaled selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors for the treatment of inflammatory lung diseases was pursued. Knowledge-based design of a novel isocoumarin scaffold that was able to adopt a topology ensured the desired PI3Kδ selectivity. Achievement of low nanomolar cellular potencies through hinge binder group optimization, reduction of intrinsic permeability through head group optimization to extend lung retention, and screening of crystalline forms suitable for administration as dry powders culminated in the identification of compound .

Disseminated Echovirus 11 infection in a newborn in the Province of Bolzano, Italy.

Purpose: Recently, cases of serious illness in newborns infected with Echovirus 11 have been reported in Europe, including Italy. Here, we report the case of a newborn diagnosed with disseminated Echovirus 11 infection, which occurred in October 2023 in the Province of Bolzano, Italy.

Methods: A molecular screening, by Real-Time RT-PCR, was employed to analyse the cerebrospinal fluid, blood and stool samples, and nasal swabs.

Detection of Echovirus 11 lineage 1 in wastewater samples in Sicily.

We report the presence of Echovirus 11 (E11) in wastewater in Sicily (Southern Italy), since August 2022. Overall, the 5.4 % of sewage samples (7/130) collected in 2022 were positives for E11 and then the percentage of E11-positive sewage samples reached the value of 27.

Inborn errors of type I interferon immunity in patients with symptomatic acute hepatitis E.

Background And Aims: The clinical spectrum of human infection by HEV ranges from asymptomatic to severe acute hepatitis. Furthermore, HEV can cause diverse neurological manifestations, especially Parsonage-Turner syndrome. Here, we used a large-scale human genomic approach to search for genetic determinants of severe clinical presentations of HEV infection.

Fetal Screening in RH1 Negative Pregnant Women: Experience in Switzerland.

RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus.

Neuropathies related to hepatitis E virus infection: A prospective, matched case-control study.

Background: Acute hepatitis E virus (HEV) infection has recently emerged as a potential trigger for acute dysimmune neuropathies, but prospective controlled studies are lacking.

Aims: To compare the frequency of concomitant acute HEV infection in patients with neuralgic amyotrophy (NA), Guillain-Barré syndrome (GBS), and Bell's palsy with a matched control population.

Methods: Swiss multicenter, prospective, observational, matched case-control study over 3 years (September 2019-October 2022).

Seven Years of Culture Collection of : Antimicrobial Resistance and Molecular Epidemiology.

The emergence of isolates displaying resistance to antimicrobials, in particular to ceftriaxone monotherapy or ceftriaxone plus azithromycin, represents a global public health concern. This study aimed to analyze the trend of antimicrobial resistance in a 7-year isolate collection retrospective analysis in Italy. Molecular typing on a subsample of gonococci was also included.

Exploiting multivalency and cooperativity of gold nanoparticles for binding phosphatidylinositol (3,4,5)-trisphosphate at sub-nanomolar concentrations.

Cationic, monolayer-protected gold nanoparticles provide a multivalent charged surface and a hydrophobic monolayer that synergistically contribute to the binding of phosphatidylinositol (3,4,5)-trisphosphate, a relevant biomarker. The observed dissociation constant is in the picomolar region, providing the possibility of using these gold nanoparticles for the selective extraction of this molecule from biological fluids.

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell-depleting agents.

Administration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell-depleting agents that impair humoral immunity. However, little is known on the impact of anti-CD20 pre-exposition on the kinetics of SARS-CoV-2-specific antibodies. Here, we evaluated the relationship between anti-spike immunoglobulin G (IgG) kinetics and the clinical status or intra-host viral evolution after plasma therapy in 36 eligible hospitalized COVID-19 patients, pre-exposed or not to B-cell-depleting treatments.

Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy.

Intestinal barrier derangement allows intestinal bacteria and their products to translocate to the systemic circulation. Pseudomonas aeruginosa (PA) superimposed infection in critically ill patients increases gut permeability and leads to gut-driven sepsis. PA infections are challenging due to multi-drug resistance (MDR), biofilms, and/or antibiotic tolerance.

Terpinen-4-ol, the Main Bioactive Component of Tea Tree Oil, as an Innovative Antimicrobial Agent against .

(), responsible for a severe pneumonia called Legionnaires' disease, represents an important health burden in Europe. Prevention and control of contamination in warm water systems is still a great challenge often due to the failure in disinfection procedures. The aim of this study was to evaluate the in vitro activity of Terpinen-4-ol (T-4-ol) as potential agent for control, in comparison with the essential oil of (tea tree) (TTO.

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Ureidopropanamides as Formyl Peptide Receptor 2 (FPR2) Agonists to Target the Resolution of Inflammation in Central Nervous System Disorders.

Formyl peptide receptor 2 (FPR2) agonists can boost the resolution of inflammation and can offer alternative approaches for the treatment of pathologies with underlying chronic neuroinflammation, including neurodegenerative disorders. Starting from the FPR2 agonist previously identified in our laboratory and through fine-tuning of FPR2 potency and metabolic stability, we have identified a new series of ureidopropanamide derivatives endowed with a balanced combination of such properties. Computational studies provided insights into the key interactions of the new compounds for FPR2 activation.

Retrospective Analysis of Six Years of Acute Flaccid Paralysis Surveillance and Polio Vaccine Coverage Reported by Italy, Serbia, Bosnia and Herzegovina, Montenegro, Bulgaria, Kosovo, Albania, North Macedonia, Malta, and Greece.

Here we analyzed six years of acute flaccid paralysis (AFP) surveillance, from 2015 to 2020, of 10 countries linked to the WHO Regional Reference Laboratory, at the Istituto Superiore di Sanità, Italy. The analysis also comprises the polio vaccine coverage available (2015-2019) and enterovirus (EV) identification and typing data. Centralized Information System for Infectious Diseases and Laboratory Data Management System databases were used to obtain data on AFP indicators and laboratory performance and countries' vaccine coverage from 2015 to 2019.

Survey of diagnostic and typing capacity for enterovirus infection in Italy and identification of two echovirus 30 outbreaks.

Background: Enterovirus infections can cause a variety of illnesses, ranging from asymptomatic infections to severe illness and death.

Aim: To support polio eradication activities, in February 2019, the WHO Regional Reference Laboratory for polio in Italy, at the National Institute of Public Health (Istituto Superiore di Sanità), promoted an investigation on non-polio enterovirus laboratory capacity, with the support of the Italian Ministry of Health. The aim was to collect data on the assays used routinely for diagnostic purposes and to characterize enterovirus outbreaks strains by sequence analysis of the Viral Protein 1 region.

Control of Raw Pork Liver Sausage Production Can Reduce the Prevalence of HEV Infection.

After an acute hepatitis E (HEV) outbreak in Southern Switzerland, in January 2017 the local public health authorities started an active program of food chain control and public education. In this retrospective study, we analysed all laboratory-confirmed acute cases of HEV infection diagnosed between 2014 and 2020. In the period before the public health intervention, the number of cases increased steadily from 2014 (4 of 40 tests, 10%) reaching a peak in the last quarter of 2016 (42 of 285 tests, 14.

Haplotype structure defines effects of common DPYD variants c.85T > C (rs1801265) and c.496A > G (rs2297595) on dihydropyrimidine dehydrogenase activity: Implication for 5-fluorouracil toxicity.

Aims: The aim of this study was to identify risk variants and haplotypes that impair dihydropyrimidine dehydrogenase (DPD) activity and are, therefore, candidate risk variants for severe toxicity to 5-fluorouracil (5-FU) chemotherapy.

Methods: Plasma dihydrouracil/uracil (UH /U) ratios were measured as a population marker for DPD activity in a total of 1382 subjects from 4 independent studies. Genotype and haplotype correlations with UH /U ratios were assessed.

How donor selection criteria can be evaluated with limited scientific evidence: lessons learned from the TRANSPOSE project.

Background And Objective: Donor selection criteria (DSC) are a vital link in the chain of supply of Substances of Human Origin (SoHO) but are also subject to controversy and differences of opinion. Traditionally, DSC have been based on application of the precautionary principle.

Materials And Methods: From 2017 to 2020, TRANSPOSE (TRANSfusion and transplantation PrOtection and SElection of donors), a European research project, aimed to identify discrepancies between current DSC by proposing a standardized risk assessment method for all SoHO (solid organs excluded) and all levels of evidence.

Putting the spotlight on donation-related risks and donor safety - are we succeeding in protecting donors?

Background And Objective: The European consortium project TRANSPOSE (TRANSfusion and transplantation: PrOtection and SElection of donors) aimed to assess and evaluate the risks to donors of Substances of Human Origin (SoHO), and to identify gaps between current donor vigilance systems and perceived risks.

Materials And Methods: National and local data from participating organizations on serious and non-serious adverse reactions in donors were collected from 2014 to 2017. Following this, a survey was performed among participants to identify risks not included in the data sets.

The effects of intravenous iron supplementation on fatigue and general health in non-anemic blood donors with iron deficiency: a randomized placebo-controlled superiority trial.

We investigated whether intravenous iron supplementation improves fatigue and general health in non-anemic repeat adult blood donors with iron deficiency (ferritin ≤ 50 µg/L). Of 1,487 potentially eligible participants, 203 were randomly assigned to a single intravenous dose of 800 mg iron-carboxymaltose and 202 to placebo; 393 participants completed the trial. At 6 to 8 weeks after intervention, self-rated mean fatigue scores (numeric rating scale from 1-10, primary outcome) were 3.

Hospital discharges-based search of acute flaccid paralysis cases 2007-2016 in Italy and comparison with the National Surveillance System for monitoring the risk of polio reintroduction.

Background: Acute flaccid paralysis (AFP) surveillance has been adopted globally as a key strategy for monitoring the progress of the polio eradication initiative. Hereby, to evaluate the completeness of the ascertainment of AFP cases in Italy, a hospital-discharges based search was carried out.

Methods: AFP cases occurring between 2007 and 2016 among children under 15 years of age were searched in the Italian Hospital Discharge Records (HDR) database using specific ICD-9-CM diagnostic codes.