A Case of Ketron-Goodman Disease

Pagetoid reticulosis (PR) is a rare form of cutaneous T-cell lymphoma [Mod Pathol 2000;13:502–510]. Two variants of the disease are described: the localized type Woringer-Kolopp disease (WKD) and the disseminated type Ketron-Goodman disease (KGD). KGD may have disseminated lesions, high rate of recurrence and a guarded prognosis [Mod Pathol 2000;13:502–510]. In patients with KGD, therefore, long-term observation is necessary. Disappearance of cutaneous lesions does not mean resolution of the disease [J Am Acad Dermatol 2002;47:183–186]. Herein we report the case of an 84-year-old man with erythematous patches of the trunk and the upper and lower extremities in whom the diagnosis of KGD was made. We describe this case for the rarity of this pathology and for the good response to therapy (IFN)

Wells Syndrome with Multiorgan Involvement Mimicking Hypereosinophilic Syndrome

Eosinophil-associated diseases represent a spectrum of heterogeneous disorders, where blood and cutaneous eosinophilia is the most important feature and eosinophils are the principal cause of cutaneous lesions. These diseases show some similarities in the clinical features but also many distinctive characteristics [Saurat et al., Dermatologia e malattie sessualmente trasmesse, Milano, Masson, 2000]. Wells syndrome is one of these disorders and is an uncommon recurrent inflammatory dermatosis, rarely associated to signs and symptoms of multiple organ involvement [Arch Dermatol 2006;142:1157–1161]. Hypereosinophilic syndrome, in contrast, constitutes a group of idiopathic disorders characterized by blood eosinophilia for at least 6 months, associated with single or multiple organ system dysfunction [Arch Dermatol 2006;142:1157–1161]. Clinically atypical Wells syndrome with multiorgan involvement is reported here. A correct diagnosis is difficult in this case, but clinical and histopathological features are compatible with this diagnosis. The reported condition likely represents a borderline hypereosinophilic disease, in which clinical features of both hypereosinophilic syndrome and Wells syndrome are present

A sigma model field theoretic realization of Hitchin's generalized complex geometry

We present a sigma model field theoretic realization of Hitchin's generalized complex geometry, which recently has been shown to be relevant in compactifications of superstring theory with fluxes. Hitchin sigma model is closely related to the well known Poisson sigma model, of which it has the same field content. The construction shows a remarkable correspondence between the (twisted) integrability conditions of generalized almost complex structures and the restrictions on target space geometry implied by the Batalin--Vilkovisky classical master equation. Further, the (twisted) classical Batalin--Vilkovisky cohomology is related non trivially to a generalized Dolbeault cohomology.Comment: 28 pages, Plain TeX, no figures, requires AMS font files AMSSYM.DEF and amssym.tex. Typos in eq. 6.19 and some spelling correcte

Emergent Gravity from Noncommutative Spacetime

We showed before that self-dual electromagnetism in noncommutative (NC) spacetime is equivalent to self-dual Einstein gravity. This result implies a striking picture about gravity: Gravity can emerge from electromagnetism in NC spacetime. Gravity is then a collective phenomenon emerging from gauge fields living in fuzzy spacetime. We elucidate in some detail why electromagnetism in NC spacetime should be a theory of gravity. In particular, we show that NC electromagnetism is realized through the Darboux theorem as a diffeomorphism symmetry G which is spontaneously broken to symplectomorphism H due to a background symplectic two-form $B_{\mu\nu}=(1/\theta)_{\mu\nu}$, giving rise to NC spacetime. This leads to a natural speculation that the emergent gravity from NC electromagnetism corresponds to a nonlinear realization G/H of the diffeomorphism group, more generally its NC deformation. We also find some evidences that the emergent gravity contains the structure of generalized complex geometry and NC gravity. To illuminate the emergent gravity, we illustrate how self-dual NC electromagnetism nicely fits with the twistor space describing curved self-dual spacetime. We also discuss derivative corrections of Seiberg-Witten map which give rise to higher order gravity.Comment: 50 pages; Cosmetic revision and updated reference

Plasma Cytokine Atlas Reveals the Importance of TH2 Polarization and Interferons in Predicting COVID-19 Severity and Survival

Although it is now widely accepted that host inflammatory response contributes to COVID-19 immunopathogenesis, the pathways and mechanisms driving disease severity and clinical outcome remain poorly understood. In the effort to identify key soluble mediators that characterize life-threatening COVID-19, we quantified 62 cytokines, chemokines and other factors involved in inflammation and immunity in plasma samples, collected at hospital admission, from 80 hospitalized patients with severe COVID-19 disease who were stratified on the basis of clinical outcome (mechanical ventilation or death by day 28). Our data confirm that age, as well as neutrophilia, lymphocytopenia, procalcitonin, D-dimer and lactate dehydrogenase are strongly associated with the risk of fatal COVID-19. In addition, we found that cytokines related to TH2 regulations (IL-4, IL-13, IL-33), cell metabolism (lep, lep-R) and interferons (IFNα, IFNβ, IFNγ) were also predictive of life-threatening COVID-19

Plasma Cytokine Atlas Reveals the Importance of TH2 Polarization and Interferons in Predicting COVID-19 Severity and Survival

Although it is now widely accepted that host inflammatory response contributes to COVID-19 immunopathogenesis, the pathways and mechanisms driving disease severity and clinical outcome remain poorly understood. In the effort to identify key soluble mediators that characterize life-threatening COVID-19, we quantified 62 cytokines, chemokines and other factors involved in inflammation and immunity in plasma samples, collected at hospital admission, from 80 hospitalized patients with severe COVID-19 disease who were stratified on the basis of clinical outcome (mechanical ventilation or death by day 28). Our data confirm that age, as well as neutrophilia, lymphocytopenia, procalcitonin, D-dimer and lactate dehydrogenase are strongly associated with the risk of fatal COVID-19. In addition, we found that cytokines related to TH2 regulations (IL-4, IL-13, IL-33), cell metabolism (lep, lep-R) and interferons (IFNα, IFNβ, IFNγ) were also predictive of life-threatening COVID-19

A human iPSC line capable of differentiating into functional macrophages expressing ZsGreen: a tool for the study and in vivo tracking of therapeutic cells

We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity. The high level of ZsGreen expression had no effect on the ability of macrophages to be activated to an M(LPS + IFNγ), M(IL10) or M(IL4) phenotype nor on their plasticity, assessed by their ability to switch from one phenotype to another. Thus, targeting of the AAVS1 locus in iPSCs allows for the production of fully functional, fluorescently tagged human macrophages that can be used for in vivo tracking in disease models. The strategy also provides a platform for the introduction of factors that are predicted to modulate and/or stabilize macrophage function. This article is part of the theme issue ‘Designer human tissue: coming to a lab near you’

Patients Recovering from Severe COVID-19 Develop a Polyfunctional Antigen-Specific CD4+ T Cell Response

Specific T cells are crucial to control SARS-CoV-2 infection, avoid reinfection and confer protection after vaccination. We have studied patients with severe or moderate COVID-19 pneumonia, compared to patients who recovered from a severe or moderate infection that had occurred about 4 months before the analyses. In all these subjects, we assessed the polyfunctionality of virus-specific CD4+ and CD8+ T cells by quantifying cytokine production after in vitro stimulation with different SARS-CoV-2 peptide pools covering different proteins (M, N and S). In particular, we quantified the percentage of CD4+ and CD8+ T cells simultaneously producing interferon-γ, tumor necrosis factor, interleukin (IL)-2, IL-17, granzyme B, and expressing CD107a. Recovered patients who experienced a severe disease display high proportions of antigen-specific CD4+ T cells producing Th1 and Th17 cytokines and are characterized by polyfunctional SARS-CoV-2-specific CD4+ T cells. A similar profile was found in patients experiencing a moderate form of COVID-19 pneumonia. No main differences in polyfunctionality were observed among the CD8+ T cell compartments, even if the proportion of responding cells was higher during the infection. The identification of those functional cell subsets that might influence protection can thus help in better understanding the complexity of immune response to SARS-CoV-2

Supersymmetric AdS_5 solutions of M-theory

We analyse the most general supersymmetric solutions of D=11 supergravity consisting of a warped product of five-dimensional anti-de-Sitter space with a six-dimensional Riemannian space M_6, with four-form flux on M_6. We show that M_6 is partly specified by a one-parameter family of four-dimensional Kahler metrics. We find a large family of new explicit regular solutions where M_6 is a compact, complex manifold which is topologically a two-sphere bundle over a four-dimensional base, where the latter is either (i) Kahler-Einstein with positive curvature, or (ii) a product of two constant-curvature Riemann surfaces. After dimensional reduction and T-duality, some solutions in the second class are related to a new family of Sasaki-Einstein spaces which includes T^{1,1}/Z_2. Our general analysis also covers warped products of five-dimensional Minkowski space with a six-dimensional Riemannian space.Comment: 40 pages. v2: minor changes, eqs. (2.22) and (D.12) correcte

Generalized Kaehler Potentials from Supergravity

We consider supersymmetric N=2 solutions with non-vanishing NS three-form. Building on worldsheet results, we reduce the problem to a single generalized Monge-Ampere equation on the generalized Kaehler potential K recently interpreted geometrically by Lindstrom, Rocek, Von Unge and Zabzine. One input in the procedure is a holomorphic function w that can be thought of as the effective superpotential for a D3 brane probe. The procedure is hence likely to be useful for finding gravity duals to field theories with non-vanishing abelian superpotential, such as Leigh-Strassler theories. We indeed show that a purely NS precursor of the Lunin-Maldacena dual to the beta-deformed N=4 super-Yang-Mills falls in our class.Comment: "38 pages. v3: improved exposition and minor mistakes corrected in sec. 4