Differentiating Vogt-Koyanagi-Harada syndrome from recurrent optic neuritis: a case report and review of the literature concerning Hispanic patients

Abstract Background First recognized at the beginning of twentieth century and named after three authors who independently described some affected patients, Vogt-Koyanagi-Harada syndrome is a rare multisystemic autoimmune disease targeting melanin-containing tissues of the eye, meninges, inner ear and skin. It predominantly affects Asian people, but also people with darker skin pigmentation such as Native Americans and Hispanics (Mestizos), whose ancestors moved from Asia across the Bering strait to North America and further down to Central and South America. Heterogenous presentation is observed, especially among different ethnic groups. Here we describe the case of an Hispanic South American patient presenting with multiple visual relapses and thus mimicking recurrent optic neuritis; we provide insights into the differential diagnosis and a brief review of the literature concerning the epidemiology of Vogt-Koyanagi-Harada syndrome in Hispanic patients compared with other ethnic groups. Case presentation A 34-year-old Ecuadorian woman presented over years with multiple relapses involving the visual system. She was investigated in both neurologic and ophthalmic clinical settings. Brain Magnetic Resonance Imaging, cerebrospinal fluid examination, Spectral Domain Optical Coherence Tomography and Fluorescein Angiography were performed. She was misdiagnosed first as an optic neuritis pointing to a demyelinating disorder, then as a posterior scleritis. Due to the protean manifestations of Vogt-Koyanagi-Harada syndrome and the incomplete clinical presentation at the beginning, the right diagnosis was made only at a later disease stage using retrospective criteria. Conclusions Hispanic patients often present without extraocular symptoms in early phases of the disease and they have globally lower rates of intertegumentary signs compared to Asian patients. The diagnosis of a multisystemic disease such as Vogt-Koyanagi-Harada syndrome is a challenge involving specialists operating in different medical fields; especially in urban multiethnic populations, rare etiologies of common symptoms have to be taken into account when performing a differential diagnosis

The interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow

The ontogeny of bone marrow and its stromal compartment, which is generated from skeletal stem/progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/parathyroid hormone–related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment

Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size

Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment. Osteoblasts that participate in the niche produce varying amounts of OPN in response to stimulation. Using studies that combine OPN-deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell number and function in a stem cell–nonautonomous manner. The OPN-null microenvironment was sufficient to increase the number of stem cells associated with increased stromal Jagged1 and Angiopoietin-1 expression and reduced primitive hematopoietic cell apoptosis. The activation of the stem cell microenvironment with parathyroid hormone induced a superphysiologic increase in stem cells in the absence of OPN. Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation

CSF β-amyloid and white matter damage: a new perspective on Alzheimer's disease

Objective: To assess the connection between amyloid pathology and white matter (WM) macro- and micro-structural damage in demented patients compared with controls. Methods: Eighty-five participants were recruited: 65 with newly diagnosed Alzheimer’s disease (AD), non-AD dementia or mild cognitive impairment (MCI), and 20 age- and sex-matched heatlhy controls. β-amyloid1-42 (Aβ) levels were determined in cerebrospinal fluid (CSF) samples from all patients and 5 controls. Among patients, 42 had pathological CSF Aβ levels (Aβ+), while 23 had normal CSF Aβ levels (Aβ-). All participants underwent neurological examination, neuropsychological testing and brain magnetic resonance imaging (MRI). We used T2-weighted scans to quantify white matter (WM) lesion loads (LL), and diffusion weighted images (DWI) to assess their microstructural substrate. Non-parametric statistical tests were used for between-group comparisons and multiple regression analyses. Results: We found an increased WM-LL in Aβ(+) compared to both, healthy controls (p=0.003) and Aβ(-) patients (p=0.02). Interestingly, CSF Aβ concentration was the best predictor patients’ WM-LL (r=-0.30, p<0.05) when using age as a covariate. Lesion apparent diffusion coefficient (ADC) value was higher in all patients than in controls (p=0.0001), and correlated with WM-LL (r=0.41, p=0.001). In Aβ(+), WM-LL correlated with WM microstructural damage in the left peritrigonal WM (p<0.0001). Conclusions: WM damage is crucial in Alzheimer’s disease (AD) pathogenesis. The correlation between CSF Aβ levels and WM-LL suggests a direct link between amyloid pathology and WM macro- and microstructural damage

Bone Marrow Osteoblast Damage by Chemotherapeutic Agents

Hematopoietic reconstitution, following bone marrow or stem cell transplantation, requires a microenvironment niche capable of supporting both immature progenitors and stem cells with the capacity to differentiate and expand. Osteoblasts comprise one important component of this niche. We determined that treatment of human primary osteoblasts (HOB) with melphalan or VP-16 resulted in increased phospho-Smad2, consistent with increased TGF-β1 activity. This increase was coincident with reduced HOB capacity to support immature B lineage cell chemotaxis and adherence. The supportive deficit was not limited to committed progenitor cells, as human embryonic stem cells (hESC) or human CD34+ bone marrow cells co-cultured with HOB pre-exposed to melphalan, VP-16 or rTGF-β1 had profiles distinct from the same populations co-cultured with untreated HOB. Functional support deficits were downstream of changes in HOB gene expression profiles following chemotherapy exposure. Melphalan and VP-16 induced damage of HOB suggests vulnerability of this critical niche to therapeutic agents frequently utilized in pre-transplant regimens and suggests that dose escalated chemotherapy may contribute to post-transplantation hematopoietic deficits by damaging structural components of this supportive niche

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia, North Italy, 21 to 28 February 2020

We describe clinical characteristics, treatments and outcomes of 44 Caucasian patients with coronavirus disease (COVID-19) at a single hospital in Pavia, Italy, from 21\u201328 February 2020, at the beginning of the outbreak in Europe. Seventeen patients developed severe disease, two died. After a median of 6 days, 14 patients were discharged from hospital. Predictors of lower odds of discharge were age&gt;65 years, antiviral treatment and for severe disease, lactate dehydrogenase &gt;300 mg/dL

Lack of SARS-CoV-2 RNA environmental contamination in a tertiary referral hospital for infectious diseases in Northern Italy

none140noNAnoneColaneri M.; Seminari E.; Piralla A.; Zuccaro V.; Di Filippo A.; Baldanti F.; Bruno R.; Mondelli M.U.; Brunetti E.; Di Matteo A.; Maiocchi L.; Pagnucco L.; Mariani B.; Ludovisi S.; Lissandrin R.; Parisi A.; Sacchi P.; Patruno S.F.A.; Michelone G.; Gulminetti R.; Zanaboni D.; Novati S.; Maserati R.; Orsolini P.; Vecchia M.; Sciarra M.; Asperges E.; Sambo M.; Biscarini S.; Lupi M.; Roda S.; Chiara Pieri T.; Gallazzi I.; Sachs M.; Valsecchi P.; Perlini S.; Alfano C.; Bonzano M.; Briganti F.; Crescenzi G.; Giulia Falchi A.; Guarnone R.; Guglielmana B.; Maggi E.; Martino I.; Pettenazza P.; Pioli di Marco S.; Quaglia F.; Sabena A.; Salinaro F.; Speciale F.; Zunino I.; De Lorenzo M.; Secco G.; Dimitry L.; Cappa G.; Maisak I.; Chiodi B.; Sciarrini M.; Barcella B.; Resta F.; Moroni L.; Vezzoni G.; Scattaglia L.; Boscolo E.; Zattera C.; Michele Fidel T.; Vincenzo C.; Vignaroli D.; Bazzini M.; Iotti G.; Mojoli F.; Belliato M.; Perotti L.; Mongodi S.; Tavazzi G.; Marseglia G.; Licari A.; Brambilla I.; Daniela B.; Antonella B.; Patrizia C.; Giulia C.; Giuditta C.; Marta C.; Rossana D.; Milena F.; Bianca M.; Roberta M.; Enza M.; Stefania P.; Maurizio P.; Elena P.; Antonio P.; Francesca R.; Antonella S.; Maurizio Z.; Guy A.; Laura B.; Ermanna C.; Giuliana C.; Luca D.; Gabriella F.; Gabriella G.; Alessia G.; Viviana L.; Claudia L.; Valentina M.; Simona P.; Marta P.; Alice B.; Giacomo C.; Irene C.; Alfonso C.; Di Martino R.; Di Napoli A.; Alessandro F.; Guglielmo F.; Loretta F.; Federica G.; Alessandra M.; Federica N.; Giacomo R.; Beatrice R.; Maria S.I.; Monica T.; Nepita Edoardo V.; Calvi M.; Tizzoni M.; Nicora C.; Triarico A.; Petronella V.; Marena C.; Muzzi A.; Lago P.; Comandatore F.; Bissignandi G.; Gaiarsa S.; Rettani M.; Bandi C.Colaneri, M.; Seminari, E.; Piralla, A.; Zuccaro, V.; Di Filippo, A.; Baldanti, F.; Bruno, R.; Mondelli, M. U.; Brunetti, E.; Di Matteo, A.; Maiocchi, L.; Pagnucco, L.; Mariani, B.; Ludovisi, S.; Lissandrin, R.; Parisi, A.; Sacchi, P.; Patruno, S. F. A.; Michelone, G.; Gulminetti, R.; Zanaboni, D.; Novati, S.; Maserati, R.; Orsolini, P.; Vecchia, M.; Sciarra, M.; Asperges, E.; Sambo, M.; Biscarini, S.; Lupi, M.; Roda, S.; Chiara Pieri, T.; Gallazzi, I.; Sachs, M.; Valsecchi, P.; Perlini, S.; Alfano, C.; Bonzano, M.; Briganti, F.; Crescenzi, G.; Giulia Falchi, A.; Guarnone, R.; Guglielmana, B.; Maggi, E.; Martino, I.; Pettenazza, P.; Pioli di Marco, S.; Quaglia, F.; Sabena, A.; Salinaro, F.; Speciale, F.; Zunino, I.; De Lorenzo, M.; Secco, G.; Dimitry, L.; Cappa, G.; Maisak, I.; Chiodi, B.; Sciarrini, M.; Barcella, B.; Resta, F.; Moroni, L.; Vezzoni, G.; Scattaglia, L.; Boscolo, E.; Zattera, C.; Michele Fidel, T.; Vincenzo, C.; Vignaroli, D.; Bazzini, M.; Iotti, G.; Mojoli, F.; Belliato, M.; Perotti, L.; Mongodi, S.; Tavazzi, G.; Marseglia, G.; Licari, A.; Brambilla, I.; Daniela, B.; Antonella, B.; Patrizia, C.; Giulia, C.; Giuditta, C.; Marta, C.; D'Alterio, Rossana; Milena, F.; Bianca, M.; Roberta, M.; Enza, M.; Stefania, P.; Maurizio, P.; Elena, P.; Antonio, P.; Francesca, R.; Antonella, S.; Maurizio, Z.; Guy, A.; Laura, B.; Ermanna, C.; Giuliana, C.; Luca, D.; Gabriella, F.; Gabriella, G.; Alessia, G.; Viviana, L.; Meisina, Claudia; Valentina, M.; Simona, P.; Marta, P.; Alice, B.; Giacomo, C.; Irene, C.; Alfonso, C.; Di Martino, R.; Di Napoli, A.; Alessandro, F.; Guglielmo, F.; Loretta, F.; Federica, G.; Albertini, Alessandra; Federica, N.; Giacomo, R.; Beatrice, R.; Maria, S. I.; Monica, T.; Nepita Edoardo, V.; Calvi, M.; Tizzoni, M.; Nicora, C.; Triarico, A.; Petronella, V.; Marena, C.; Muzzi, A.; Lago, P.; Comandatore, F.; Bissignandi, G.; Gaiarsa, S.; Rettani, M.; Bandi, C

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Measurement of the J/ψ pair production cross-section in pp collisions at s=13 \sqrt{s}=13 TeV

The production cross-section of J/ψ pairs is measured using a data sample of pp collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s}=13$ TeV, corresponding to an integrated luminosity of 279 ±11 pb$^{−1}$. The measurement is performed for J/ψ mesons with a transverse momentum of less than 10 GeV/c in the rapidity range 2.0 < y < 4.5. The production cross-section is measured to be 15.2 ± 1.0 ± 0.9 nb. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the J/ψ pair are measured and compared to theoretical predictions.The production cross-section of $J/\psi$ pairs is measured using a data sample of $pp$ collisions collected by the LHCb experiment at a centre-of-mass energy of $\sqrt{s} = 13 \,{\mathrm{TeV}}$, corresponding to an integrated luminosity of $279 \pm 11 \,{\mathrm{pb^{-1}}}$. The measurement is performed for $J/\psi$ mesons with a transverse momentum of less than $10 \,{\mathrm{GeV}}/c$ in the rapidity range $2.0<y<4.5$. The production cross-section is measured to be $15.2 \pm 1.0 \pm 0.9 \,{\mathrm{nb}}$. The first uncertainty is statistical, and the second is systematic. The differential cross-sections as functions of several kinematic variables of the $J/\psi$ pair are measured and compared to theoretical predictions