Nitrogen dioxide pollution increases vulnerability to COVID-19 through altered immune function.

Previous ecological studies suggest the existence of possible interplays between the exposure to air pollutants and SARS-CoV-2 infection. Confirmations at individual level, however, are lacking. To explore the relationships between previous exposure to particulate matter < 10 µm (PM10) and nitrogen dioxide (NO2), the clinical outcome following hospital admittance, and lymphocyte subsets in COVID-19 patients with pneumonia. In 147 geocoded patients, we assessed the individual exposure to PM10 and NO2 in the 2 weeks before hospital admittance. We divided subjects according to the clinical outcome (i.e., discharge at home vs in-hospital death), and explored the lymphocyte-related immune function as an index possibly affecting individual vulnerability to the infection. As compared with discharged subjects, patients who underwent in-hospital death presented neutrophilia, lymphopenia, lower number of T CD45, CD3, CD4, CD16/56 + CD3 + , and B CD19 + cells, and higher previous exposure to NO2, but not PM10. Age and previous NO2 exposure were independent predictors for mortality. NO2 concentrations were also negatively related with the number of CD45, CD3, and CD4 cells. Previous NO2 exposure is a co-factor independently affecting the mortality risk in infected individuals, through negative immune effects. Lymphopenia and altered lymphocyte subsets might precede viral infection due to nonmodifiable (i.e., age) and external (i.e., air pollution) factors. Thus, decreasing the burden of air pollutants should be a valuable primary prevention measure to reduce individual susceptibility to SARS-CoV-2 infection and mortality.

Multiband Material with a Quasi-1D Band as a Robust High-Temperature Superconductor.

It is well known that superconductivity in quasi-one-dimensional (Q1D) materials is hindered by large fluctuations of the order parameter. They reduce the critical temperature and can even destroy the superconductivity altogether. Here it is demonstrated that the situation changes dramatically when a Q1D pair condensate is coupled to a higher-dimensional stable one, as in recently discovered multiband Q1D superconductors. The fluctuations are suppressed even by vanishingly small pair-exchange coupling between different band condensates and the superconductor is well described by the mean field theory. In this case the low dimensionality effects enhance the coherence of the system instead of suppressing it. As a result, the critical temperature of the multiband Q1D superconductor can increase by orders of magnitude when the system is tuned to the Lifshitz transition with the Fermi level close to the edge of the Q1D band.

From Klein to anti-Klein tunneling in graphene tuning the Rashba spin-orbit interaction or the bilayer coupling.

We calculate the transmission coefficient for a particle crossing a potential barrier in monolayer graphene with Rashba spin-orbit coupling and in bilayer graphene. We show that in both cases one can go from Klein tunneling regime, characterized by perfect normal transmission, to anti-Klein tunneling regime, with perfect normal reflection, by tuning the Rashba spin-orbit coupling for a monolayer or the interplane coupling for a bilayer graphene. We show that the intermediate regime is characterized by a non-monotonic behavior with oscillations and resonances in the normal transmission amplitude as a function of the coupling and of the potential parameters.

Dynamics and energy spectra of aperiodic discrete-time quantum walks.

We investigate the role of different aperiodic sequences in the dynamics of single quantum particles in discrete space and time. For this we consider three aperiodic sequences, namely, the Fibonacci, Thue-Morse, and Rudin-Shapiro sequences, as examples of tilings the diffraction spectra of which have pure point, singular continuous, and absolutely continuous support, respectively. Our interest is to understand how the order, intrinsically introduced by the deterministic rule used to generate the aperiodic sequences, is reflected in the dynamical properties of the quantum system. For this system we consider a single particle undergoing a discrete-time quantum walk (DTQW), where the aperiodic sequences are used to distribute the coin operations at different lattice positions (inhomogeneous DTQW) or by applying the same coin operation at all lattice sites at a given time but choosing different coin operation at each time step according to the chosen aperiodic sequence (time dependent DTQW). We study the energy spectra and the spreading of an initially localized wave packet for different cases, finding that in the case of Fibonacci and Thue-Morse tilings the system is superdiffusive, whereas in the Rudin-Shapiro case it is strongly subdiffusive. Trying to understand this behavior in terms of the energy spectra, we look at the survival amplitude as a function of time. By means of the echo we present strong evidence that, although the three orderings are very different as evidenced by their diffraction spectra, the energy spectra are all singular continuous except for the inhomogeneous DTQW with the Rudin-Shapiro sequence where it is discrete. This is in agreement with the observed strong localization both in real space and in the Hilbert space. Our paper is particularly interesting because quantum walks can be engineered in laboratories by means of ultracold gases or in optical waveguides, and therefore would be a perfect playground to study singular continuous energy spectra in a completely controlled quantum setup.

Magnetic confinement of massless Dirac fermions in graphene.

Because of Klein tunneling, electrostatic potentials are unable to confine Dirac electrons. We show that it is possible to confine massless Dirac fermions in a monolayer graphene sheet by inhomogeneous magnetic fields. This allows one to design mesoscopic structures in graphene by magnetic barriers, e.g., quantum dots or quantum point contacts.

Cutaneous response to irritants.

We evaluated the role of pre-existing dermatitis in the response to irritants by patch testing the skin of 40 healthy volunteers and the uninvolved skin of 480 subjects for 2 days. These latter were affected by active atopic dermatitis, psoriasis, eczema with positive and negative patch test reactions, urticaria and generalized pruritus. A first panel containing 15 micro L of aq. solutions of disodium laureth sulfosuccinate (NaLSS) 5% and 10%, potassium cocoate (KCC) 5%, potassium oleate (KOL) 5%, zinc coleth sulphate (ZnCS) 5%, sodium mireth sulphate (NaMS) 5%, sodium cocoamphoacetate (NaCCAA) 3% and 5%, was simultaneously applied to 1 site on the upper back. The results, scored by visual assessment, were compared to those observed when testing on the opposite side a second panel containing 15 micro L of aq. solutions of 3 well-known irritants, benzalkonium chloride (BAK) 1%, sodium lauryl sulphate (SLS) 1%, and dimethylsulphoxide (DMSO) 10%. Whilst the substances of the first panel and DMSO gave, on the whole, a scarce number of positive responses in all the tested groups, more evident differences in number, percent and mean intensity of the positive responses to BAK and SLS were found between the different groups. Although some of them seemed statistically significant, when the same values were evaluated by means of chi2 and Student t-test, they did not differ in a statistically significant way from the values found in healthy subjects. The results of this study seem to indicate that the substances of the first panel have a chemical structure that makes them quite safe in real-life conditions. In contrast, BAK and SLS have chemical properties that condition the number and intensity of the responses, making the role exerted by the pre-existing dermatosis quite marginal. In particular, there is no proof that the healthy skin of active atopic subjects is the most susceptible to the irritating effects of the tested substances.

Death of bystander cells by a novel pathway involving early mitochondrial damage in human immunodeficiency virus-related lymphadenopathy.

Destruction of immune cells in peripheral lymphoid tissues plays presumably a pivotal role in acquired immune deficiency syndrome pathogenesis. We found that cell suspensions obtained from lymph nodes of eight human immunodeficiency virus (HIV)-infected individuals contained variable proportions (2.1% to 18.3%, median 11.2%) of dead lymphocytes permeable to supravital dyes, represented by CD4+, CD8+, and B cells. The frequency of dead cells correlated directly (R = 0.847) with the amount of HIV provirus in the cell populations, and HIV provirus was enriched in the dead cell fractions. Similar proportions of dead cells were observed in cell suspensions from lymphadenopathic lymph nodes of HIV- donors, but not from small resting HIV- lymph nodes. Electron microscopic and flow cytometric analyses revealed that most dead cells from HIV+ lymph nodes lacked internucleosomal DNA fragmentation but displayed combined features of apoptosis and necrosis, eg, chromatin condensation and mitochondrial swelling. Cells with similar morphology were readily identified in lymph node tissue sections, and marked mitochondrial swelling could be occasionally observed in cells with otherwise normal morphology. Our findings have two major implications. One is that the in vivo cell death in HIV-infected lymph nodes occurs predominantly through a novel pathway, related to but distinct from classical apoptosis and characterised by early and severe mitochondrial damage. The second implication is that HIV-related lymphadenopathy is accompanied in vivo by massive destruction of uninfected lymph node cells. Comparable levels of cell death were observed in other inflammatory lymphadenopathies not related to HIV; however, the uniquely endless and generalized nature of HIV lymphadenopathy might render this "inflammatory" cell destruction a powerful pathogenetic mechanism, accounting for the progressive disruption and depletion of lymphoid tissues seen in HIV infection.

Comparison of the Vbeta repertoire in peripheral blood and in lymph nodes of HIV-infected subjects reveals skewed usage predominantly in CD8+ T cells.

Perturbations of the repertoire of variable-beta (Vbeta) regions of the T cell receptor have been observed in patients infected by HIV and have been attributed to stimulation by viral antigens or superantigens. We further sought for traces of HIV-induced perturbations by comparing Vbeta repertoire in peripheral blood and in lymphoid tissues of six infected patients. Vbeta expression was studied with a panel of 17 anti-Vbeta antibodies covering about 50% of the entire repertoire. We observed major divergences between lymph nodes and peripheral blood in the expression of several Vbeta segments, and these differences were significantly more frequent in CD8+ than in CD4+ T cells (P = 0.0097). Vbeta2 was perturbed in CD8 cells from all but one patient. One HIV-negative subject with localized reactive lymphadenopathy of unknown etiology had four perturbed Vbeta segments, including Vbeta2, in CD8+ cells, while another uninfected subject with an unreactive lymph node architecture had no perturbations. Our findings suggest that stimulation by HIV or by other antigens determines divergences in the Vbeta repertoire between lymphoid tissues and peripheral blood predominantly in CD8+ T cells.

Forcipomyia (Pterobosca) paludis (Macfie, 1936) (Diptera, Ceratopogonidae) on adult dragonflies (Odonata) in Sardinia, Italy.

Ceratopogonid midges, referred to Forcipomyia paludis, were recorded from five dragonfly species in Sardinia, Italy. All ceratopogonids were females and almost all were in the last phase of the gonotrophic cycle (gravid females). Although a parasitic association cannot be excluded, no evidence was obtained of the midge biting activity, neither by direct observation nor indirectly, by detecting the expected lesions on the host cuticle. The attachment to dragonflies of F. paludis (perhaps an autogenous species) might fit well with the hypothesis of a phoretic association which would favour the long range dispersal of the gravid females.

Activated and "memory" phenotype of circulating T lymphocytes in intrauterine life.

We examined the expression of T cell markers in the peripheral blood of five immunologically normal human fetuses at 18-20 weeks of gestational age. The distribution of T cells expressing CD1, CD3, CD4, CD8, CD56, and the alpha/beta and gamma/delta receptors for antigen was comparable to that of newborns and normal adults, except for the absence of gamma/delta cells expressing the delta TCS-1 epitope. The V beta repertoire, as evaluated by two-color flow cytometry using mAbs to specific V beta families, was also comparable to that of adult samples. A significant fraction (8.9 to 16.4%) of fetal CD3+ T cells expressed the alpha chain of IL-2R (CD25) in the absence of HLA-DR; this suggests that antigenic stimuli trigger, during intrauterine life, an unusual pathway of T cell activation. Consistent with this, 7 to 27% of fetal T cells were found to express the CD45R0 marker of "memory" cells.

Detection and characterization of apoptotic peripheral blood lymphocytes in human immunodeficiency virus infection and cancer chemotherapy by a novel flow immunocytometric method.

We have developed a quantitative and sensitive flow cytometric method for the detection of human apoptotic lymphocytes that, unlike previously described assays, allows their identification in mixed populations of peripheral blood leukocytes as well as their immunophenotyping. Apoptotic lymphocytes are identified on the basis of peculiar light scatter changes, reflecting their smaller size and their modified nucleus/cytoplasm organization, and of the decreased expression of surface CD45 molecules. Based on these criteria, apoptotic lymphocytes generated by exposure to ionizing radiation can be easily distinguished from viable cells and from necrotic lymphocytes generated by treatment with antibody and complement. Using this assay, we reappraised the phenomenon of the in vitro apoptosis of lymphocytes from patients with human immunodeficiency virus (HIV) infection. Lymphocytes from HIV patients, unlike those from normal HIV-negative subjects, undergo apoptosis upon simple in vitro culture. We found that the percentages of lymphocytes undergoing apoptosis were significantly higher in patients with low CD4 cell counts (< 400/microL) than in patients at earlier stages (> 400 CD4 cells/microL). However, phenotypic analysis disclosed that apoptotic lymphocytes generated in these cultures were mostly CD8+ T cells and CD19+ B cells. Thus, in contrast to what has been previously suggested, the phenomenon of in vitro lymphocyte apoptosis might not be pathogenetically related to the depletion of CD4+ T cells in acquired immunodeficiency syndrome. Nevertheless, it might represent an useful marker of disease progression. Our assay allows the analysis of unfractionated peripheral blood leukocytes and thus the identification of apoptotic lymphocytes circulating in vivo. Apoptotic lymphocytes could indeed be detected in the circulation of a patient with cancer shortly after high-dose cytotoxic chemotherapy. By contrast, no apoptotic lymphocytes could be detected in vivo in patients with early or advanced HIV infection.

Multicentre evaluation of the Bayer DAX system.

The analytical performance of the DAX, a high-throughput random access analyser, was studied according to ECCLS guidelines (ECCLS Document Vol. 3, No. 2, Beuth Verlag, Berlin, 1986) in a multicentre evaluation involving four laboratories. The trial took about 4 months. Determinations of 12 analytes produced more than 60,000 data. The imprecision study on 3 control sera for all analytes gave a within-run CV (median of 4 laboratories) which never exceeded 3% and was below 2% in 94% of the results. The median between-day CV was less than 3% in 92% of the results, with a highest value of 5.0%. No significant drift was detected during the 5-hour work period. No relevant sample- and cuvette-related carry-over was found. The manufacturer's claims concerning linearity were fulfilled or exceeded. The recovery of the assigned values for the control sera (median of 4 laboratories) ranged from 94 to 106%. In the method comparison on patients' samples, deviations were statistically significant in some cases, due to differences either in the methods used or in the calibration of the systems used for comparison; the regression lines, as inspected visually, and the coefficients of correlation were, however, generally acceptable. Imprecision and inaccuracy were within the acceptability limits as recommended by the Société Française de Biologie Clinique (SFBC) (Biochim. Clin. 12 (1988) 284-327) and the Deutsche Gesellschaft für Klinische Chemie (DGKC) (Dt. Arztebl. 85 (11) (1988) A697-A712). The limits of acceptance, proposed more recently by Fraser et al. (Eur. J. Clin. Chem. Clin. Biochem. 30 (1992) 311-317), were met in thirty-three of thirty-six cases. The alpha-amylase assay was significantly affected by bilirubin and haemolysis; interferences for the remaining analytes were predictable and well-known from the literature. The rate of sample throughput was found to be in agreement with that claimed by the manufacturer. The software did not present problems and was readily accepted by the operators. The practicability of the instrument was rated very good. Since the DAX is the primary chemistry analyzer in all four participating laboratories, the present experiments were necessarily intermixed with a large routine workload. Therefore, the system performance was assessed under definitely "usual" conditions. Because of its high productivity and reliability, the DAX is highly suitable for routine use in medium to large sized hospitals.

Reversible tubular dysfunction in alcohol abuse.

The discovery of an unexplained alkaline urine pH in a significant percentage of chronic alcoholic patients prompted us to evaluate some aspects of their tubular function. We studied 60 patients with a history of alcohol consumption of at least 160g daily for 10 years or more. Only patients without clinical and histopathological evidence of chronic liver disease were included in the study. The endogenous creatinine clearance was in the normal range in all patients. On the first day of hospitalisation 22 patients (36.6%) had a urine pH greater than 6.4 and a daily bicarbonate excretion ranging from 5.8 to 25.9mmol. The fractional urinary excretion of beta 2-microglobulin, sodium, potassium, chloride, calcium, phosphorus and uric acid were significantly increased compared with those of 38 alcoholic patients with urine pH less than 6.4 and those of 50 healthy controls. All these indices of tubular function improved during withdrawal, and after 30 days of abstinence their values did not differ from those of controls. This data provides evidence that in one-third of heavy drinkers alcohol abuse causes a complex tubular dysfunction which, at least in this stage of alcoholic disease, recovers with abstinence.