Publications by authors named "F Alessio"

281 Publications

Sex Differences in Lung Imaging and SARS-CoV-2 Antibody Responses in a COVID-19 Golden Syrian Hamster Model.

mBio 2021 Jul 13:e0097421. Epub 2021 Jul 13.

W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

In the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more severe outcomes are reported in males than in females, including hospitalizations and deaths. Animal models can provide an opportunity to mechanistically interrogate causes of sex differences in the pathogenesis of SARS-CoV-2. Adult male and female golden Syrian hamsters (8 to 10 weeks of age) were inoculated intranasally with 10 50% tissue culture infective dose (TCID) of SARS-CoV-2/USA-WA1/2020 and euthanized at several time points during the acute (i.e., virus actively replicating) and recovery (i.e., after the infectious virus has been cleared) phases of infection. There was no mortality, but infected male hamsters experienced greater morbidity, losing a greater percentage of body mass, developed more extensive pneumonia as noted on chest computed tomography, and recovered more slowly than females. Treatment of male hamsters with estradiol did not alter pulmonary damage. Virus titers in respiratory tissues, including nasal turbinates, trachea, and lungs, and pulmonary cytokine concentrations, including interferon-β (IFN-β) and tumor necrosis factor-α (TNF-α), were comparable between the sexes. However, during the recovery phase of infection, females mounted 2-fold greater IgM, IgG, and IgA responses against the receptor-binding domain of the spike protein (S-RBD) in both plasma and respiratory tissues. Female hamsters also had significantly greater IgG antibodies against whole-inactivated SARS-CoV-2 and mutant S-RBDs as well as virus-neutralizing antibodies in plasma. The development of an animal model to study COVID-19 sex differences will allow for a greater mechanistic understanding of the SARS-CoV-2-associated sex differences seen in the human population. Men experience more severe outcomes from coronavirus disease 2019 (COVID-19) than women. Golden Syrian hamsters were used to explore sex differences in the pathogenesis of a human isolate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After inoculation, male hamsters experienced greater sickness, developed more severe lung pathology, and recovered more slowly than females. Sex differences in disease could not be reversed by estradiol treatment in males and were not explained by either virus replication kinetics or the concentrations of inflammatory cytokines in the lungs. During the recovery period, antiviral antibody responses in the respiratory tract and plasma, including to newly emerging SARS-CoV-2 variants, were greater in female than in male hamsters. Greater lung pathology during the acute phase combined with lower antiviral antibody responses during the recovery phase of infection in males than in females illustrate the utility of golden Syrian hamsters as a model to explore sex differences in the pathogenesis of SARS-CoV-2 and vaccine-induced immunity and protection.
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http://dx.doi.org/10.1128/mBio.00974-21DOI Listing
July 2021

Economic Stress at Work: Its Impact over Absenteeism and Innovation.

Int J Environ Res Public Health 2021 05 15;18(10). Epub 2021 May 15.

Department of Experimental and Clinical Medicine, University of Florence, Largo Piero Palagi 1, 50139 Florence, Italy.

Economic stress has been recognized as a major threat to the well-being and performance of workers, especially during times of global economic crisis. An interesting and relatively unexplored research topic concerns the associations between economic stress and employee job outcomes such as innovative behaviors, indispensable for business survival. The aim of the present study was to investigate the relationship between economic stress, absenteeism and innovation. We considered both a direct and a mediation hypothesis and hypothesized that economic stress can have a negative influence on innovation directly and indirectly through increased absenteeism. A cross-sectional study was performed during 2018 and 2019 in an Italian food factory. A sample of 578 employees completed the Stress Questionnaire, the Janssen's nine-item scale and a single-item regarding absenteeism. All relationships are supported by empirical data. As expected, the results indicated that economic stress is negatively related to innovation and positively related to absenteeism, which, in turn, plays a mediating role in the relationship between economic stress and innovative behavior. Herewith, those employees with higher levels of economic stress show higher levels of absenteeism contributing at the same time to a decrease in innovative behaviors. These findings show the importance of economic stress in understanding individual work outcomes and highlight the need to promote adequate intervention programs.
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http://dx.doi.org/10.3390/ijerph18105265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156033PMC
May 2021

Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort.

Chest 2021 May 21. Epub 2021 May 21.

Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD.

Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV progression in current smokers.

Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV decline among individuals with COPD or baseline emphysema?

Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <-950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated.

Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV % predicted, 0.83; 95% CI, -0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema.

Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline.

Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.05.007DOI Listing
May 2021

Angular Analysis of the B^{+}→K^{*+}μ^{+}μ^{-} Decay.

Phys Rev Lett 2021 Apr;126(16):161802

Laboratoire Leprince-ringuet (llr), Palaiseau, France.

We present an angular analysis of the B^{+}→K^{*+}(→K_{S}^{0}π^{+})μ^{+}μ^{-} decay using 9  fb^{-1} of pp collision data collected with the LHCb experiment. For the first time, the full set of CP-averaged angular observables is measured in intervals of the dimuon invariant mass squared. Local deviations from standard model predictions are observed, similar to those in previous LHCb analyses of the isospin-partner B^{0}→K^{*0}μ^{+}μ^{-} decay. The global tension is dependent on which effective couplings are considered and on the choice of theory nuisance parameters.
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http://dx.doi.org/10.1103/PhysRevLett.126.161802DOI Listing
April 2021

Imaging infections in patients using pathogen-specific positron emission tomography.

Sci Transl Med 2021 04;13(589)

Center for Infection and Inflammation Imaging Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

represent the largest group of bacterial pathogens in humans and are responsible for severe, deep-seated infections, often resulting in sepsis or death. They are also a prominent cause of multidrug-resistant (MDR) infections, and some species are recognized as biothreat pathogens. Tools for noninvasive, whole-body analysis that can localize a pathogen with specificity are needed, but no such technology currently exists. We previously demonstrated that positron emission tomography (PET) with 2-deoxy-2-[F]fluoro-d-sorbitol (F-FDS) can selectively detect infections in murine models. Here, we demonstrate that uptake of F-FDS by bacteria occurs via a metabolically conserved sorbitol-specific pathway with rapid in vitro F-FDS uptake noted in clinical strains, including MDR isolates. Whole-body F-FDS PET/computerized tomography (CT) in 26 prospectively enrolled patients with either microbiologically confirmed infection or other pathologies demonstrated that F-FDS PET/CT was safe, could rapidly detect and localize infections due to drug-susceptible or MDR strains, and differentiated them from sterile inflammation or cancerous lesions. Repeat imaging in the same patients monitored antibiotic efficacy with decreases in PET signal correlating with clinical improvement. To facilitate the use of F-FDS, we developed a self-contained, solid-phase cartridge to rapidly (<10 min) formulate ready-to-use F-FDS from commercially available 2-deoxy-2-[F]fluoro-d-glucose (F-FDG) at room temperature. In a hamster model, F-FDS PET/CT also differentiated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia from secondary pneumonia-a leading cause of complications in hospitalized patients with COVID-19. These data support F-FDS as an innovative and readily available, pathogen-specific PET technology with clinical applications.
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http://dx.doi.org/10.1126/scitranslmed.abe9805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120649PMC
April 2021