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The impact of SARS-CoV-2 infection in pregnancy remains underexplored. Here, the authors provide a comprehensive characterization of virus and immunological parameters in 31 SARS-CoV-2-infected pregnant women, finding evidence of vertical transmission in two of the mother-child pairs.

Interaction of strong laser fields with matter provides powerful tools to image transient dynamics with high spatiotemporal resolution. The authors investigate strong-field ionisation of laser-aligned molecules showing the effect of molecular alignment on the photoelectron dynamics and the resulting influence of the molecular frame in imaging experiments.

Abstract Background There are limited data regarding the impact of bioresorbable polymer drug eluting stent (BP-DES) compared to durable polymer drug eluting stent (DP-DES) in patients treated with percutaneous coronary intervention using ultrathin stents in left main or bifurcations. Methods In the RAIN registry (ClinicalTrials NCT03544294, june 2018 retrospectively registered) patients with a ULM or bifurcation stenosis treated with PCI using ultrathin stents (struts thinner than 81 μm) were enrolled. The primary endpoint was the rate of target lesion revascularization (TLR); major adverse cardiovascular events (MACE, a composite of all-cause death, myocardial infarction, TLR and stent thrombosis) and its components, along with target vessel revascularization (TVR) were the secondary ones. A propensity score with matching analysis to compare patients treated with BP-DES versus DP-DES was also assessed. Results From 3001 enrolled patients, after propensity score analysis 1400 patients (700 for each group) were selected. Among them, 352 had ULM disease and 1048 had non-LM bifurcations. At 16 months (12–22), rates of TLR (3.7% vs 2.9%, p = 0.22) and MACE were similar (12.3% vs. 11.6%, p = 0.74) as well as for the other endpoints. Sensitivity analysis of outcomes after a two-stents strategy, showed better outcome in term of MACE (20.4% vs 10%, p = 0.03) and TVR (12% vs 4.6%, p = 0.05) and a trend towards lower TLR in patients treated with BP-DES. Conclusion In patients with bifurcations or ULM treated with ultrathin stents BP-DES seems to perform similarly to DP-DES: the trends toward improved clinical outcomes in patients treated with the BP-DES might potentially be of value for speculating the stent choice in selected high-risk subgroups of patients at increased risk of ischemic events. Trial registration ClinicalTrials.gov Identifier: NCT03544294 . Retrospectively registered June 1, 2018.

IntroductionCardiovascular (CV) disease is the leading mortality cause among women, yet an alarming misrepresentation of women in CV studies and a low awareness of the impact of CV among women still persist to date. The Monzino Women Heart Center has been established as a clinical and research program dedicated to primary prevention of CV disease in women.MethodsPatients aged between 35 and 60 years and with no history of CV disease underwent a comprehensive evaluation including a cardiologic outpatient visit with electrocardiogram, individual CV risk calculation, first-level cardiovascular examinations and a psychological assessment.ResultsA total of 635 women, with a mean age of 52.2 ± 6.4 participated to the project on a voluntary basis during the period January 2017–August 2021. Included patients had a high level of education (40.4% with a graduate or postgraduate university degree), the majority of them, in a stable couple and with children, were actively working. More than half of the patients performed physical activity on a regular basis. Prevalence of traditional CV risk factors were family history (70.2%), hypertension (46%), hypercholesterolemia (22%) and diabetes (14%). Early or premature menopause was reported by 17.7% of the patients, gestational hypertension and diabetes by 4.96 and 1.7%, respectively. Symptoms of depression were reported by 27%; nearly 36% of the participants rated high score of state anxiety and 41% of trait anxiety. Nearly 69% of the participants showed moderate-to-high perceived stress. The mean value of perceived general self-efficacy was moderate (mean = 28.78, SD = 4.69).ConclusionA CV prevention program dedicated to women can help identifying a considerable number of patients with risk factors for whom early interventions can help reducing the risk of developing CV disease. Psychological assessment might unmask depression or anxiety disorders, which might have a potential long-terme detrimental effect on CV health.

IntroductionIn recent years, the new third-generation ultrathin bioresorbable-polymer sirolimus-eluting stent (BP-SES), characterized by some of the thinnest struts among commercially available devices (60–80 μm) and an amorphous silicon carbide coating, has been introduced for the treatment of coronary artery disease (CAD). The present study aimed to assess different clinical outcomes and safety of this drug-eluting stent in male and female patients in a real-world setting.MethodsThe present study is a retrospective analysis including all patients treated with BP-SES between January 2017 and December 2019 at a single high-volume center. Follow-up data, including stress test results and clinical setting, were collected during outpatient visits or by telephone contact. Patients symptomatic for angina or with a positive stress test were addressed to CT scan/coronary angiogram. The main study outcome was target lesion failure (TLF), defined as a composite of cardiovascular death, target vessel myocardial infarction, or target lesion revascularization.ResultsOverall, 66 (15.9%) female and 349 (84.1%) male patients were included; women were older (median age 70 vs. 66, P = 0.003) and with a lower body mass index (BMI) (25.0 vs. 26.1, P = 0.010) compared to men, with no other relevant differences in baseline characteristics. Indication for percutaneous coronary intervention (PCI) was acute coronary syndrome in 86 (20.7%) of the cases, with no significant differences between male and female patients. A total of 558 lesions were treated with BP-SES stents, 90 in women and 468 in men (1.36 vs. 1.34 lesions per patient, P = 0.83); cumulative stent length (33.6 vs. 38.4 mm, P = 0.078), and mean stent diameter (2.92 vs. 3.0 mm, P = 0.39) did not differ in women compared to men. Technical and clinical successes were achieved in all patients. Stent thrombosis (ST) occurred in 2 (0.5%) patients, both men. TLF occurred in 10 (2.9%) men and 2 (3.0%) women after a median follow-up of 402 days, without significant differences at log-rank analysis (2.34 events per 100 patient-years in men, 2.53 in women; P = 0.80).ConclusionUltrathin struts BP-SES showed to be a safe and effective option for the treatment of CAD in both women and men, with a very low ST rate and favorable long-term outcomes.

It is well established that pregnancy induces deep changes in the immune system. This is part of the physiological adaptation of the female organism to the pregnancy and the immunological tolerance toward the fetus. Indeed, over the three trimesters, the suppressive T regulatory lymphocytes are progressively more represented, while the expression of co-stimulatory molecules decreases overtime. Such adaptations relate to an increased risk of infections and progression to severe disease in pregnant women, potentially resulting in an altered generation of long-lived specific immunological memory of infection contracted during pregnancy. How potent is the immune response against SARS-CoV-2 in infected pregnant women and how long the specific SARS-CoV-2 immunity might last need to be urgently addressed, especially considering the current vaccinal campaign. To address these questions, we analyzed the long-term immunological response upon SARS-CoV-2 infection in pregnant women from delivery to a six-months follow-up. In particular, we investigated the specific antibody production, T cell memory subsets, and inflammation profile. Results show that 80% developed an anti-SARS-CoV-2-specific IgG response, comparable with the general population. While IgG were present only in 50% of the asymptomatic subjects, the antibody production was elicited by infection in all the mild-to-critical patients. The specific T-cell memory subsets rebalanced over-time, and the pro-inflammatory profile triggered by specific SARS-CoV-2 stimulation faded away. These results shed light on SARS-CoV-2-specific immunity in pregnant women; understanding the immunological dynamics of the immune system in response to SARS-CoV-2 is essential for defining proper obstetric management of pregnant women and fine tune gender-specific vaccinal plans.

BackgroundAortic stenosis (AS) is the most common valve disorder characterized by fibro-calcific remodeling of leaflets. Recent evidence indicated that there is a sex-related difference in AS development and progression. Fibrotic remodeling is peculiar in women’s aortic valves, while men’s leaflets are more calcified. Our study aimed to assess aortic valve fibrosis (AVF) in a severe AS cohort using non-invasive diagnostic tools and determine whether sex-specific pathological pathways and cell types are associated with severe AS.Materials and MethodsWe have included 28 men and 28 women matched for age with severe AS who underwent echocardiography and cardiac contrast-enhanced computed tomography (CT) before intervention. The calcium and fibrosis volumes were assessed and quantified using the ImageJ thresholding method, indexed calcium and fibrosis volume were calculated by dividing the volume by the aortic annular area. For a deeper understanding of molecular mechanisms characterizing AS disorder, differentially expressed genes and functional inferences between women and men’s aortic valves were carried out on a publicly available microarray-based gene expression dataset (GSE102249). Cell types enrichment analysis in stenotic aortic valve tissues was used to reconstruct the sex-specific cellular composition of stenotic aortic valves.ResultsIn agreement with the literature, our CT quantifications showed that women had significantly lower aortic valve calcium content compared to men, while fibrotic tissue composition was significantly higher in women than men. The expression profiles of human stenotic aortic valves confirm sex-dependent processes. Pro-fibrotic processes were prevalent in women, while pro-inflammatory ones, linked to the immune response system, were enhanced in men. Cell-type enrichment analysis showed that mesenchymal cells were over-represented in AS valves of women, whereas signatures for monocytes, macrophages, T and B cells were enriched men ones.ConclusionsOur data provide the basis that the fibro-calcific process of the aortic valve is sex-specific, both at gene expression and cell type level. The quantification of aortic valve fibrosis by CT could make it possible to perform population-based studies and non-invasive assessment of novel therapies to reduce or halt sex-related calcific aortic valve stenosis (CAVS) progression, acting in an optimal window of opportunity early in the course of the disease.

Conflicting results are available regarding the influence of ACEi/ARBs on the risk of COVID-19 infection, while less is known about their impact on the clinical outcome of patients with STEMI diagnosed with COVID-19. Our aim was to evaluate the impact of ACEi/ARBs therapy on in-hospital mortality and clinical outcomes of patients with STEMI during the COVID-19 pandemic. We retrospectively analyzed consecutive patients with STEMI hospitalized from February 20 to May 10, 2020 in four Hospitals in Lombardy. SARS-COV-2 diagnosis was performed by nasopharyngeal swab test. Procedural outcome, respiratory complications, and in-hospital mortality were reported. Univariate and multivariate analyses were performed by logistic regressions. Our population was represented by 182 patients with STEMI, 76.9% of which were males, and mean age was 67 ± 12.5. Hypertension was reported in 53.3%, and 29.1% was treated with ACEi/ARBs. COVID-19 diagnosis was confirmed in 17.1% of the patients. In-hospital mortality (13.2%) was significantly higher in patients with COVID-19 (31 vs. 10%, p = 0.003), even if ejection fraction [OR 0.93 (95% CI) 0.87–0.99; p = 0.03] and respiratory complications [OR 9.39 (95% CI) 1.91–45.9; p = 0.006] were the only two independent predictors. The incidence of COVID-19 infection was not influenced by ACEi/ARBs (16.5 in naïve vs. 18.8%) whose presence on admission did not correlate with respiratory complications or mortality both in the case of discontinuation and maintenance. In conclusion, in a high-risk population, such as that of patients with STEMI, the potential benefit of ACEi/ARB discontinuation in patients with COVID-19 is overcome by its detrimental effect. Intensive care, additional preventive respiratory investigations, regardless of swab test result, should be suggested for all patients admitted for STEMI during the pandemic.

Background: Patients with sepsis with a concomitant coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of patients with sepsis with a concomitant COVID-19, and we developed a risk score for the estimation of sepsis risk in COVID-19.Methods: We conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry, NCT04334291). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus.Results: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), hemoptysis, peripheral oxygen saturation (SpO2) 1.5 mg/dl. By assigning odds ratio (OR) weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1–11.8%); intermediate-risk group (24.8–53.8%); and high-risk-group (58.3–100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased BP, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to hemoptysis.Conclusions: The HOPE Sepsis Score including nine parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.

We describe the case of a 72-year-old man with severe, asymptomatic in-stent restenosis detected 4 years after index carotid artery stenting (CAS). The patient was deemed at low risk and scheduled for re-angioplasty with a drug-coated balloon as per institution protocol. What at first seemed a simple case suddenly turned into a series of cerebral and vascular complications that were successfully managed with a mix of peripheral, coronary, and imaging techniques.

Inadvertent perforation of the left internal mammary artery during a blind approach to the subclavian vein for pacemaker or central venous catheter insertion is an emergency that requires immediate treatment. Covered stent deployment is a quick and effective treatment, especially in patients with hemodynamic instability. The procedure may be safely performed by using the radial approach. (Level of Difficulty: Intermediate.)

Molecular movies provide crucial information of fundamental processes like energy and charge transfer, bond breaking etc. Here the authors show the time evolution of the rotational wave packet called the molecular movie of OCS molecules by Coulomb explosion imaging.

Gallium incorporation in silicate glasses gives rise to compounds in which the nucleation and growth of Ga-oxide nanostructures can be designer controlled so as to obtain a number of functional properties for photonic applications. However, despite planar geometry pertains to a large part of modern technology, no information is available yet on the scalability of Ga-oxide segregation mechanisms in oxide thin films. In fact, incorporated Ga-oxide nanostructures have only been obtained in bulk materials. Here we show that deposition of Ga-alkali-germanosilicate thin films by radiofrequency-plasma sputtering gives rise to Ga-oxide nanostructures incorporated in an amorphous matrix. X-ray diffraction, X-ray reflectivity, small-angle X-ray scattering, and atomic force microscopy data unveil the formation of lenticular nanoaggregates, only a few nm thick, even in as-deposited materials as a result of two-dimensional aggregation of spinel-like Ga2O3 nanoparticles. Importantly, the aggregate size distribution is controlled not only by the temperature but also by the film thickness when it is reduced from 102 nm to only a few nm. The results open the way to the design of oxide-in-oxide thin films with incorporated networks of nanostructures which can act as percolation paths for unconventional electric responses in neuromorphic functional systems.

Background: A strong association between aortic valve sclerosis (AVSc), the earliest manifestation of calcific aortic valve disease, and atherosclerosis exists. The aim of the study was to evaluate the predictive capabilities of AVSc on long-term all-cause mortality, in patients requiring carotid endarterectomy (CEA).Methods and Results: 806 consecutive CEA patients were enrolled. Preoperative echocardiography was used to assess AVSc. Computed tomography angiography was applied for plaque characterization. Kaplan-Meier curves, Cox linear regression, and area under the receiving operator characteristic (AUC) curve analyses were used to evaluate the predictive capability of AVSc. Overall, 348 of 541 patients had AVSc (64%). Age, diabetes, and estimated glomerular filtration rate (eGFR) were associated with AVSc. In the 5-year follow-up, AVSc group had a mortality rate of 16.7% while in no-AVSc group was 7.8%. Independent predictors of all-cause mortality were age, sex, eGFR, left ventricular ejection fraction, and AVSc. After adjustments, AVSc was associated with a significant increase in all-cause mortality risk (hazard ratio, HR = 1.9; 95%CI: 1.04–3.54; p = 0.038). We stratify our cohort based on carotid atheromatous plaque-type: soft, calcified, and mixed-fibrotic. In patients with mixed-fibrotic plaques, the mortality rate of AVSc patients was 15.5% compared to 2.4% in no-AVSc patients. In this group, AVSc was associated with an increased long-term all-cause mortality risk with an adjusted HR of 12.8 (95%CI: 1.71–96.35; p = 0.013), and the AUC, combing eGFR and AVSc was 0.77 (p < 0.001).Conclusions: Our findings indicate that AVSc together with eGFR may be used to improve long-term risk stratification of patients undergoing CEA surgery.

Background: Protozoa of the genus Leishmania are characterized by their capacity to target macrophages and Dendritic Cells (DCs). These microorganisms could thus be exploited for the delivery of antigens to immune cells. Leishmania tarentolae is regarded as a non-pathogenic species; it was previously used as a biofactory for protein production and has been considered as a candidate vaccine or as an antigen delivery platform. However, results on the type of immune polarization determined by L. tarentolae are still inconclusive. Methods: DCs were derived from human monocytes and exposed to live L. tarentolae, using both the non-engineered P10 strain, and the same strain engineered for expression of the spike protein from SARS-CoV-2. We then determined: (i) parasite internalization in the DCs; and (ii) the capacity of the assayed strains to activate DCs and the type of immune polarization. Results: Protozoan parasites from both strains were effectively engulfed by DCs, which displayed a full pattern of maturation, in terms of MHC class II and costimulatory molecule expression. In addition, after parasite infection, a limited release of Th1 cytokines was observed. Conclusions: Our results indicate that L. tarentolae could be used as a vehicle for antigen delivery to DCs and to induce the maturation of these cells. The limited cytokine release suggests L. tarentolae as a neutral vaccine vehicle that could be administered in association with appropriate immune-modulating molecules.

Il saggio indaga l'origine e il significato di una curiosa schedina in endecasillabi presente tra le carte leopardiane conservate alla Biblioteca Nazionale di Napoli, che gli editori moderni usano chiamare Esercizi di memoria e di cui si fornisce qui un'originale interpretazione. Leopardi era infatti solito redigere schedine in versi preparatorie, in particolare allo Zibaldone, e si può credere che esse venissero redatte quando l'autore non aveva agio o modo di dedicarsi alla stesura del diario con la stessa assiduità che gli era concessa a Recanati. Simili operazioni potrebbero in particolare collocarsi in quei periodi in cui Leopardi soggiornava fuori casa ed era soggetto a spostamenti: gli appunti servivano probabilmente a fissare gli estremi di pensieri da sviluppare, e la forma in versi forniva all'autore un’occupazione durante i viaggi in carrozza. Viene dunque proposta l'ipotesi che Leopardi abbia potuto scrivere almeno una parte del recto del primo foglietto durante il suo soggiorno a Roma del 1822-23, quando la stesura dello Zibaldone era praticamente interrotta, per fissare delle idee da sviluppare al suo ritorno. Il saggio mira infine a ricostruire le trame che collegano libri, fatti e persone nel "labirinto di associazioni" costruito da Leopardi al momento della scrittura.

Dysnatremia is associated with increased mortality in patients with community-acquired pneumonia. SARS-COV2 (Severe-acute-respiratory syndrome caused by Coronavirus-type 2) pneumonia can be fatal. The aim of this study was to ascertain whether admittance dysnatremia is associated with mortality, sepsis, or intensive therapy (IT) in patients hospitalized with SARS-COV2 pneumonia. This is a retrospective study of the HOPE-COVID-19 registry, with data collected from January 1th through April 31th, 2020. We selected all hospitalized adult patients with RT-PCR-confirmed SARS-COV2 pneumonia and a registered admission serum sodium level (SNa). Patients were classified as hyponatremic (SNa 145 mmol/L). Multivariable analyses were performed to elucidate independent relationships of admission hyponatremia and hypernatremia, with mortality, sepsis, or IT during hospitalization. Four thousand six hundred sixty-four patients were analyzed, median age 66 (52–77), 58% males. Death occurred in 988 (21.2%) patients, sepsis was diagnosed in 551 (12%) and IT in 838 (18.4%). Hyponatremia was present in 957/4,664 (20.5%) patients, and hypernatremia in 174/4,664 (3.7%). Both hyponatremia and hypernatremia were associated with mortality and sepsis. Only hyponatremia was associated with IT. In conclusion, hyponatremia and hypernatremia at admission are factors independently associated with mortality and sepsis in patients hospitalized with SARS-COV2 pneumonia.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04334291, NCT04334291.

In this work we present the case of SARS-CoV-2 infection in a 1.5-year-old boy affected by severe Wiskott-Aldrich Syndrome with previous history of autoinflammatory disease, occurring 5 months after treatment with gene therapy. Before SARS-CoV-2 infection, the patient had obtained engraftment of gene corrected cells, resulting in WASP expression restoration and early immune reconstitution. The patient produced specific immunoglobulins to SARS-CoV-2 at high titer with neutralizing capacity and experienced a mild course of infection, with limited inflammatory complications, despite pre-gene therapy clinical phenotype.

Summary: Seasonality of acute viral respiratory diseases is a well-known and yet not fully understood phenomenon. Several models have been proposed to explain the regularity of yearly recurring outbreaks and the phase differences observed at different latitudes on the Earth. Such models consider known internal causes, primarily the periodic emergence of new virus variants that evade the host immune response. Yet, this alone is generally unable to explain the regularity of recurrences and the observed phase differences.Here we show that seasonality of viral respiratory diseases, as well as its distribution with latitude on the Earth, can be fully explained by the virucidal properties of UV-B and UV-A solar photons through a daily, minute-scale, resonant forcing mechanism. Such an induced periodicity can last, virtually unperturbed, from tens to hundreds of cycles, and even in the presence of internal dynamics (host's loss of immunity) much slower than seasonal will, on a long period, generate seasonal oscillations.

Effective antiviral immune responses rely on the host’s genetic background and its interaction with the surrounding environment [...]

While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-specific antibodies, as well as the expression of factors involved in the anti-viral immune response were analyzed. Moreover, we set up an in vitro coinfection assay to study the mechanisms correlated to the coinfection process. Our results did not show any increased risk of severe COVID-19 in HIV-positive young individuals. In those subjects who contracted SARS-CoV-2 infection, an increase in IL-10 expression and production was observed. Furthermore, in the in vitro coinfection assay, we revealed a reduction in SARS-CoV-2 replication associated to an upregulation of IL-10. We speculate that IL-10 could play a crucial role in the course of SARS-CoV-2 infection in HIV-positive individuals. These results might help defining clinical management of HIV/SARS-CoV-2 co-infected young individuals, or putative indications for vaccination schedules in this population.

In this paper, we report X-ray absorption and core-level electron spectra of the nucleobase derivative 2-thiouracil at the sulfur L1- and L2,3-edges. We used soft X-rays from the free-electron laser FLASH2 for the excitation of isolated molecules and dispersed the outgoing electrons with a magnetic bottle spectrometer. We identified photoelectrons from the 2p core orbital, accompanied by an electron correlation satellite, as well as resonant and non-resonant Coster–Kronig and Auger–Meitner emission at the L1- and L2,3-edges, respectively. We used the electron yield to construct X-ray absorption spectra at the two edges. The experimental data obtained are put in the context of the literature currently available on sulfur core-level and 2-thiouracil spectroscopy.

Diffraction imaging studies of free individual nanoparticles have so far been restricted to XUV and X-ray free - electron laser facilities. Here the authors demonstrate the possibility of using table-top XUV laser sources to image prolate shapes of superfluid helium droplets.

Background: Haplotype-specific alternative splicing of the endoplasmic reticulum (ER) aminopeptidase type 2 (ERAP2) gene results in either full-length (FL, haplotype A) or alternatively spliced (AS, haplotype B) mRNA. HapA/HapA homozygous (HomoA) subjects show a reduced susceptibility to HIV-1 infection, probably secondary to the modulation of the antigen processing/presenting machinery. ERAP1 was recently shown to be secreted from the plasma membrane in response to activation; we investigated whether ERAP2 can be released as well and if the secreted form of this enzyme retains its antiviral function.Methods: Human monocyte derived macrophages (MDMs) were differentiated from peripheral blood mononuclear cells (PBMCs) isolated from 6 HomoA healthy controls and stimulated with IFNγ and LPS. ERAP2-FL secretion was evaluated by mass spectrometry. PBMCs (14 HomoA and 16 HomoB) and CD8-depleted PBMCs (CD8−PBMCs) (4 HomoA and 4 HomoB) were in vitro HIV-infected in the absence/presence of recombinant human ERAP2-FL (rhERAP2) protein; p24 viral antigen quantification was used to assess viral replication. IFNγ and CD69 mRNA expression, as well as the percentage of perforin-producing CD8+ T Lymphocytes, were analyzed 3 and 7-days post in vitro HIV-1-infection, respectively. The effect of rhERAP2 addition in cell cultures on T cell apoptosis, proliferation, activation, and maturation was evaluated as well on 24 h-stimulated PBMCs.Results: ERAP2 can be secreted from human MDMs in response to IFNγ/LPS stimulation. Notably, the addition of rhERAP2 to PBMC and CD8−PBMC cultures resulted in the reduction of viral replication, though these differences were statistically significant only in PBMCs (p < 0.05 in both HomoA and HomoB). This protective effect was associated with an increase in IFNγ and CD69 mRNA expression and in the percentage of perforin-expressing CD107+CD8+ cells. RhERAP2 addition also resulted in an increase in CD8+ activated lymphocyte (CD25+HLA−DRII+) and Effector Memory/Terminally differentiated CD8+ T cells ratio.Conclusions: This is the first report providing evidence for the release of ERAP2 in the secretome of immunocompetent cells. Data herein also indicate that exogenous ERAP2-FL exerts its protective function against HIV-1 infection, even in HomoB subjects who do not genetically produce it. Presumably, this defensive extracellular feature is only partially dependent on immune system modulation.

Nos mais recentes debates críticos acerca da filosofia de Platão, a doutrina da reminiscência tem suscitado um interesse comparativamente menor em relação aos outros temas tratados na obra do pensador ateniense. Grande parte dos estudiosos modernos tende a considerar a reminiscência um método de pesquisa, bem como a marginalizar a referência a dois mundos e o trânsito da alma entre eles. O que pretendo demonstrar neste artigo é que não só a teoria da reminiscência é a condição de possibilidade necessária das nossas operações cognitivas (e não um método de pesquisa), como também o é apenas e só em virtude da sua valência metafísica.

For Plato, the basic tool of philosophical knowledge is logos, not only in the general sense of "reason," but also in the specific sense of knowledge attained by means of "discourse", namely a reason that has a fundamentally linguistic character. This seems to imply that the logos is entirely transparent to itself; and consequently, as we can deduce from the analysis consecrated in the Theaetetus to the so called "theory of the dream", that the elements of which the logos is composed are fully intelligible and devoid of any opacity. However, this claim seems to fail in the Cratylus, where the attempt to show the intelligibility of the elements of language, i.e. letters and syllables, does not succeed. A possible solution to this problem lies in the fact that the elements of language, unlike the natural elements, exhaust their nature in the role they play within the language itself; and therefore the knowledge of this role, just as in the case of the pieces of chess, coincides with the knowledge of the element as a whole.

We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathological assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs’ GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-α. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.

We had access to both components of a couple who became infected with human immunodeficiency virus (HIV)-1 through sexual behavior during the early initial phase of infection and before initiation of therapy. We analyzed blood samples obtained at the time of diagnosis and after six months of combined antiretroviral therapy. Next-generation sequencing (NGS) and phylogenetic analyses were used to investigate the transmission and evolution of HIV-1 quasispecies. Phylogenetic analyses were conducted using Bayesian inference methods. Both partners were infected with an HIV-1 B subtype. No evidence of viral recombination was observed. The lowest intrapersonal genetic distances were observed at baseline, before initiation of therapy, and in particular in the V1V2 fragment (distances ranging from 0.102 to 0.148). One HIV-1 single variant was concluded to be dominant in all of the HIV-1 regions analyzed, although some minor variants could be observed. The same tree structure was observed both at baseline and after six months of therapy. These are the first extended phylogenetic analyses performed on both members of a therapy-naïve couple within a few weeks of infection, and in which the effect of antiretroviral therapy on viral evolution was analyzed. Understanding which HIV-1 variants are most likely to be transmitted would allow a better understanding of viral evolution, possibly playing a role in vaccine design and prevention strategies.

The aim of this study was to determine the prevalence of T helper 9 (Th9) lymphocytes in rheumatoid arthritis (RA) patients and to identify a possible association between the percentage of Th9 and the discontinuation of a biological treatment with an anti-tumor necrosis factor (TNF) (infliximab). We collected peripheral blood mononuclear cells (PBMCs) from 55 consecutive RA outpatients and 10 healthy controls. Among RA patients, 15 were not receiving any immunosuppressive drug, 20 were successfully treated with infliximab and 20 discontinued infliximab because of adverse events or inefficacy and were treated with other biological agents. PBMCs were cultured with/without infliximab 50 mg/L for 18 h, and the percentage of Th9 cells was assessed by means of flow cytometry. Th9 lymphocytes were identified as interferon gamma, interleukin (IL)4-, IL17-, IL9-secreting cluster of differentiation 4 (CD4)+ T cells. Cytometric analysis revealed no significant decrease in the percentage of Th9 cells after infliximab exposure in any of the groups, although it was lower in healthy controls than RA patients either before and after the infliximab stimulation assay. Th9 cells are IL-9-secreting T helper lymphocytes whose role in RA is still poorly known. IL-9 levels are increased in RA patients, in whom this cytokine plays a crucial role. Th9 cells are the major producers of IL-9, and their prevalence is higher in RA patients than in healthy subjects; however our experiment in vitro does not demonstrate an association between Th9 lymphocytes and the response to infliximab. Further studies are required to evaluate the real involvement of Th9 population in the immunogenicity of anti-TNF agents.

Bacterial cellulose nanocrystals (BCNCs) obtained by enzymatic hydrolysis have been loaded in pullulan biopolymer for use as nanoparticles in the generation of high-oxygen barrier coatings intended for food packaging applications. Bacterial cellulose (BC) produced by Komagataeibacter sucrofermentans was hydrolyzed by two different enzymatic treatments, i.e., using endo-1,4-β-glucanases (EGs) from Thermobifida halotolerans and cellulase from Trichoderma reesei. The hydrolytic activity was compared by means of turbidity experiments over a period of 145 h, whereas BCNCs in their final state were compared, in terms of size and morphology, by atomic force microscopy (AFM) and dynamic light scattering (DLS). Though both treatments led to particles of similar size, a greater amount of nano-sized particles (≈250 nm) were observed in the system that also included cellulase enzymes. Unexpectedly, transmission electron microscopy (TEM) revealed that cellulose nanoparticles were round-shaped and made of 4–5 short (150–180 nm) piled whiskers. Pullulan/BCNCs nanocomposite coatings allowed an increase in the overall oxygen barrier performance, of more than two and one orders of magnitude (≈0.7 mL·m−2·24 h−1), of pure polyethylene terephthalate (PET) (≈120 mL·m−2·24 h−1) as well as pullulan/coated PET (≈6 mL·m−2·24 h−1), with no significant difference between treatments (hydrolysis mediated by EGs or with the addition of cellulase). BCNCs obtained by enzymatic hydrolysis have the potential to generate high oxygen barrier coatings for the food packaging industry.