Bacteremic nosocomial pneumonia caused by Gram-negative bacilli: results from the nationwide ALARICO study in Italy.

Purpose: To describe the clinical characteristics and outcomes of patients with nosocomial pneumonia (NP) caused by carbapenem-resistant Gram-negative bacilli (CR-GNB) and to compare them to patients with NP caused by carbapenem-susceptible (CS)-GNB.

Methods: Prospective observational multicenter study including patients with bacteremic NP caused by GNB from the ALARICO Network (June 2018-January 2020). The primary outcome measure was 30-day mortality.

Investigating the influence of oral contraceptive pill use on multiple sclerosis risk using UK Biobank data.

Objective: To investigate the association between oral contraceptive (OC) pill use and the risk of developing multiple sclerosis (MS), attempting to address the limitations present in previous studies that produced conflicting results.

Design: A population-based cohort study using data from the UK Biobank.

Patients: The study included 181,058 women of white ethnicity born in England between 1937 and 1970, among which 1,131 had an MS diagnosis.

Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study.

Background: Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime.

Objective: We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort.

Methods: We used the UK Biobank data, considering the observation period from birth up to 31 December 2022.

Effectiveness of test-and-treat model with direct-acting antiviral for hepatitis C virus infection in migrants: a prospective interventional study in Italy.

Background: Migrants, mainly undocumented and low-income refugees, are at high risk of hepatitis C virus (HCV) infection, but are a difficult-to-reach and to-treat population. The aim of the study was to evaluate the effectiveness of a test and treat model with direct-acting antiviral for HCV infection in these migrants coming from low-income and living in southern Italy.

Methods: A prospective, multicenter, collaborative study based on a four-phase-program (educational counseling, screening, linkage-to-care and treatment) was designed in southern Italy; the study started in June 2018, was stopped in February 2020 because of the outbreak of SARS-CoV2 infection in Italy and was resumed in February 2021 until November 2021.

Genetic reversal of the globin switch concurrently modulates both fetal and sickle hemoglobin and reduces red cell sickling.

We previously reported initial clinical results of post-transcriptional gene silencing of BCL11A expression (NCT03282656) reversing the fetal to adult hemoglobin switch. A goal of this approach is to increase fetal hemoglobin (HbF) expression while coordinately reducing sickle hemoglobin (HbS) expression. The resulting combinatorial effect should prove effective in inhibiting HbS polymerization at lower physiologic oxygen values thereby mitigating disease complications.

Outcome of patients with carbapenem-resistant Acinetobacter baumannii infections treated with cefiderocol: A multicenter observational study.

Background: No clear evidence supports the use of cefiderocol as first line treatment in A. baumannii infections.

Methods: We conducted an observational retrospective/prospective multicenter study including all patients> 18 years with carbapenem-resistant A.

Characterization of hepatitis virus co-infections in a cohort of immigrants living in southern Italy.

To characterize viral hepatitis co-infections in a cohort of immigrants living in southern Italy. In a prospective multicenter study, all undocumented immigrants and low-income refugees consecutively evaluated for a clinical consultation at one of the five first-level clinical centers in southern Italy from January 2012 to February 2020 were enrolled. All subjects included in the study were screened for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) and anti-HIV; the HBsAg-positive were screened also for anti-delta.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

Background: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs).

Methods: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days.

Deep neural network automated segmentation of cellular structures in volume electron microscopy.

Volume electron microscopy is an important imaging modality in contemporary cell biology. Identification of intracellular structures is a laborious process limiting the effective use of this potentially powerful tool. We resolved this bottleneck with automated segmentation of intracellular substructures in electron microscopy (ASEM), a new pipeline to train a convolutional neural network to detect structures of a wide range in size and complexity.

Profile of Co-Infection Prevalence and Antibiotics Use among COVID-19 Patients.

Bacterial co-infection in COVID-19 patients significantly contributes to the worsening of the prognosis based on morbidity and mortality. Information on the co-infection profile in such patients could help to optimize treatment. The purpose of this study was to describe bacterial co-infections associated with microbiological, clinical, and laboratory data to reduce or avoid a secondary infection.

Hepatitis D virus infection in a large cohort of immigrants in southern Italy: a multicenter, prospective study.

Background: Since few data are available in the literature on the prevalence of anti-Delta-positive subjects in immigrant populations, the aim of the present study was to evaluate the demographic and virological characteristics of HDV infection in a large cohort of immigrants living in southern Italy.

Methods: Between January 2012 and February 2020 all immigrants attending one of the 5 first- level centers were enrolled and screened for HBsAg, the HBsAg-positive for anti-Delta and if positive, for HDV-RNA and HDV genotype.

Results: Of the 3521 immigrants observed in the study period, 3417 (97.

Early predictors of clinical deterioration in a cohort of outpatients with COVID-19 in southern Italy: A multicenter observational study.

Data regarding early predictors of clinical deterioration in patients with infection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still scarce. The aim of the study is to identify early symptoms or signs that may be associated with severe coronavirus disease 2019 (COVID-19). We conducted a multicentre prospective cohort study on a cohort of patients with COVID-19 in home isolation from March 2020 to April 2021.

SARS-CoV-2 requires acidic pH to infect cells.

Unlabelled: SARS-CoV-2 cell entry starts with membrane attachment and ends with spike-protein (S) catalyzed membrane fusion depending on two cleavage steps, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time 3D single virion tracking, we show fusion and genome penetration requires virion exposure to an acidic milieu of pH 6.

Beta-lactam monotherapy or combination therapy for bloodstream infections or pneumonia due to Pseudomonas aeruginosa: a meta-analysis.

Objectives: To compare the clinical and microbiological outcomes of patients treated with beta-lactam monotherapy or combination therapy for Pseudomonas aeruginosa infections.

Data Sources: MEDLINE, Google Scholar and the Cochrane Library.

Study Eligibility Criteria And Interventions: Experimental and observational studies published as full papers up to December 2020 that compared the efficacy of beta-lactams used as monotherapy or in combination with other active agents as empirical or targeted therapy for bloodstream infections or hospital-acquired pneumonia/ventilator-associated pneumonia due to P.

Inherited nuclear pore substructures template post-mitotic pore assembly.

Nuclear envelope assembly during late mitosis includes rapid formation of several thousand complete nuclear pore complexes (NPCs). This efficient use of NPC components (nucleoporins or "NUPs") is essential for ensuring immediate nucleocytoplasmic communication in each daughter cell. We show that octameric subassemblies of outer and inner nuclear pore rings remain intact in the mitotic endoplasmic reticulum (ER) after NPC disassembly during prophase.

Inappropriateness of Antibiotic Prescribing in Medical, Surgical and Intensive Care Units: Results of a Multicentre Observational Study.

The objectives of the present study were to provide a snapshot analysis of antibiotic appropriateness in two hospitals in Southern Italy in three specific areas, surgical, medical and intensive care, and to evaluate the risk factors associated with inappropriateness in antimicrobial prescriptions. We conducted a multicentre observational study in two hospitals in the Campania region. We collected data of all patients admitted on the day of evaluation to antibiotic therapy or prophylaxis through a case report form.

Standard versus high dose of rifampicin in the treatment of pulmonary tuberculosis: a systematic review and meta-analysis.

Objectives: A growing amount of evidence suggests that the rifampicin dosing currently recommended for tuberculosis treatment could be associated with inadequate exposure and unfavourable outcomes. We aimed to compare clinical and microbiological efficacy and safety outcomes of standard and higher rifampicin dosing.

Methods: Data sources were MEDLINE, Google Scholar and the Cochrane Library.

MetAP2 inhibition modifies hemoglobin S to delay polymerization and improves blood flow in sickle cell disease.

Sickle cell disease (SCD) is associated with hemolysis, vascular inflammation, and organ damage. Affected patients experience chronic painful vaso-occlusive events requiring hospitalization. Hypoxia-induced polymerization of sickle hemoglobin S (HbS) contributes to sickling of red blood cells (RBCs) and disease pathophysiology.

Directly Acting Antiviral-Based Treatment for HCV-Infected Persons Who Inject Drugs: A Multicenter Real-Life Study.

Background: We aimed to evaluate the factors associated with a virological response in a cohort of Hepatitis C virus (HCV)-infected people who inject drugs (PWID) treated with direct acting antivirals (DAAs).

Methods: We conducted a multicenter retrospective cohort study enrolling HCV-infected PWID treated with DAAs. The primary outcome evaluated was the sustained virological response (SVR12) rate.

Design and Validation of a Human Brain Endothelial Microvessel-on-a-Chip Open Microfluidic Model Enabling Advanced Optical Imaging.

We describe here the design and implementation of an microvascular open model system using human brain microvascular endothelial cells. The design has several advantages over other traditional closed microfluidic platforms: (1) it enables controlled unidirectional flow of media at physiological rates to support vascular function, (2) it allows for very small volumes which makes the device ideal for studies involving biotherapeutics, (3) it is amenable for multiple high resolution imaging modalities such as transmission electron microscopy (TEM), 3D live fluorescence imaging using traditional spinning disk confocal microscopy, and advanced lattice light sheet microscopy (LLSM). Importantly, we miniaturized the design, so it can fit within the physical constraints of LLSM, with the objective to study physiology in live cells at subcellular level.

Daptomycin-based aminoglycoside-sparing therapy for streptococcal endocarditis: a retrospective multicenter study.

Streptococci still represent common etiologic agents of infective endocarditis (IE). Although renal failure is frequently reported as an aminoglycoside-associated adverse event, last international guidelines recommend a beta-lactam/gentamicin combination therapy. We retrospectively evaluated the use of daptomycin-based aminoglycoside-sparing combination therapy for the treatment of streptococcal IE in seven referral hospitals in Italy.