Doubly resonant semilinear elliptic problems via nonsmooth critical point theory

AbstractWe consider the existence of weak solutions for classical doubly resonant semilinear elliptic problems. We show how the main technical assumptions can be used to define appropriate metrics on the underlying function space, so that extensions of the results already known in the literature can be obtained using only basic facts from critical point theory for continuous functionals on complete metric spaces

Characterization of ovarian follicle reserve depletion in Ames dwarf mice.

Publicado: Proceedings of the 29th Annual Meeting of the Brazilian Embryo Technology Society (SBTE); Gramado, RS, Brazil, August 20th to 23rd, 2015, and 31st Meeting of the European Embryo Transfer Association (AETE); Ghent, Belgium, September 11th and 12th, 2015. Abstracts

POS0702 PREGNANCY IN SLE PATIENTS TREATED WITH BELIMUMAB: EXPERIENCE FROM 3 ITALIAN CENTERS

Background:Belimumab (BEL) is a monoclonal antibody approved for SLE treatment but few data are available about its use before or during pregnancy.Objectives:Our study aims to describe pregnancies in SLE patients who have discontinued BEL before conception, at positive pregnancy test or during pregnancy.Methods:Data from prospectively-followed pregnancies (2014-2020) in SLE patients treated with BEL in 3 Italian centers where retrospectively collected, focusing on maternal disease activity, obstetric and neonatal outcome. Continuous data are expressed as median [min-max].Results:Thirteen SLE pregnancies were analyzed (median age at conception 32 [24-41] years; 77% spontaneous, 69% primigravidae). All patients had positive ANA and anti-dsDNA antibodies; 4 had anti-Ro antibodies (31%); 4 had anti-phospholipid antibodies (aPL; 1 single, 2 double and 1 triple positivity). Seven patients (54%) had a history of lupus nephritis (LN); 2 patients (15%) had a concomitant diagnosis of antiphospholipid syndrome (1 thrombotic-APS and 1 thrombotic+obstetric-APS).Ten (77%) pregnancies were planned and the use of BEL with regard to pregnancy was agreed with the patient during preconception counseling. At preconception visit, 8 patients were in remission while 5 had active disease (median SLEDAI 3 [0-8]).BEL (11 intravenous, 2 subcutaneous) was stopped in 2 cases before conception, in 7 at positive pregnancy test and in 4 during pregnancy (2 at 11th week, 1 at 22nd, 1 at 24th); median duration of treatment at discontinuation was 29 [4-68] months. Other treatments during pregnancy were: oral prednisone in 12 cases (92%); intravenous methylprednisolone in 1 (8%); hydroxychloroquine in 10 (77%); chloroquine in 1 (8%); azathioprine in 5 (39%); calcineurin inhibitors in 5 (39%); low-dose acetylsalicylic acid in 10 (77%); low molecular weight heparin in 9 (69%).Three flares occurred during the 3rd trimester in patients who stopped BEL at positive pregnancy test.Live-births occurred in 92% of the pregnancies. A patient with thrombotic+obstetric-APS and LN, underwent assisted reproductive technology (embryo donation) and developed eclampsia (25thweek), an urgent cesarean section was performed and the newborn died after 3 days. One pre-eclampsia occurred in a patient with history of LN, double aPL positivity and active disease. One miscarriage at 11th week occurred; no early miscarriages (10thweek)1/2 (50%)0/70/4Perinatal death0/20/71/4* (25%)IUGR: IntraUterine Growth Restriction; PROM: Premature Rupture of Membrane; pPROM: pretermPROM; *in the same patient (history of thrombotic and obstetric-APS and lupus nephritis) who underwent Assisted Reproductive Technologies (embryo donation).No malformations were recorded. Two newborns were transferred to the Intensive Care Unit (1 for milk protein intolerance and 1 for desaturation).Eight newborns received vaccinations according to national schedule (missing data for 3). Five newborns were breastfed, 1 received formula milk and 5 mixed-feeding. BEL was resumed in 7/13 patients after pregnancy (in 4 cases for flare), after a median period of 5 [4-22] months.Conclusion:While more data are needed, this small series suggests that BEL might be a therapeutic option for SLE patients during pregnancy planning, similarly to other biological drugs used in chronic forms of arthritis.Disclosure of Interests:None declare

Species-specific consequences of an E40K missense mutation in superoxide dismutase 1 (SOD1)

A glutamic acid to lysine (E40K) residue substitution in superoxide dismutase 1 (SOD1) is associated with canine degenerative myelopathy: the only naturally occurring large animal model of amyotrophic lateral sclerosis (ALS). The E40 residue is highly conserved across mammals, except the horse, which naturally carries the (dog mutant) K40 residue. Here we hypothesized that in vitro expression of mutant dog SOD1 would recapitulate features of human ALS (ie, SOD1 protein aggregation, reduced cell viability, perturbations in mitochondrial morphology and membrane potential, reduced ATP production, and increased superoxide ion levels); further, we hypothesized that an equivalent equine SOD1 variant would share similar perturbations in vitro, thereby explain horses’ susceptibility to certain neurodegenerative diseases. As in human ALS, expression of mutant dog SOD1 was associated with statistically significant increased aggregate formation, raised superoxide levels (ROS), and altered mitochondrial morphology (increased branching (form factor)), when compared to wild‐type dog SOD1‐expressing cells. Similar deficits were not detected in cells expressing the equivalent horse SOD1 variant. Our data helps explain the ALS‐associated cellular phenotype of dogs expressing the mutant SOD1 protein and reveals that species‐specific sequence conservation does not necessarily predict pathogenicity. The work improves understanding of the etiopathogenesis of canine degenerative myelopathy

Practice pattern for the use of intravenous iloprost for the treatment of peripheral vasculopathy in systemic sclerosis: A case–control study from the Italian national multicenter “SPRING” (Systemic Sclerosis Progression InvestiGation) Registry

Background: Intravenous iloprost has been widely used for the treatment of systemic sclerosis peripheral vasculopathy. No agreement has been found on the regimen and the dosage of intravenous iloprost in different scleroderma subset conditions. This study aimed to evaluate the modalities of intravenous iloprost administration within a large cohort of systemic sclerosis patients from the SPRING Registry and to identify any associated clinical-demographic, instrumental or therapeutic data.Patients and Methods: Data of systemic sclerosis patients treated with intravenous iloprost for at least 1 year (case group) were retrospectively analyzed, including different timing and duration of intravenous iloprost session, and compared with those of untreated patients (control group).Results: Out of 1895 analyzed patients, 937 (49%) received intravenous iloprost treatment, while 958 (51%) were assigned to the control group. Among cases, about 70% were treated every 4 weeks, 24% with an interval of more than 4 weeks, and only 6% of less than 4 weeks. Most patients receiving the treatment every 4 weeks, or less, underwent infusion cycle for 1 day only, while if it was scheduled with an interval of more than 4 weeks, a total number of 5 consecutive days of infusions was the preferred regimen. The comparison between the two groups revealed that patients treated with intravenous iloprost had a higher frequency of DUs (p < 0.001), pitting scars (p < 0.001), diffuse cutaneous involvement (p < 0.001), interstitial lung disease (p < 0.002), as well as higher rates of anti-topoisomerase I, "late" scleroderma pattern at nailfold videocapillaroscopy. These findings were confirmed by multivariate analysis.Conclusion: Our data provide a picture on the Italian use of intravenous iloprost among systemic sclerosis patients and showed that it was usually employed in patients with a more aggressive spectrum of the disease. The disparity of intravenous iloprost treatment strategies in the different centers suggests the need of a rational therapeutical approach based on the clinical characteristics of different patients' subsets

Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study—Joint and Skin (BeRLiSS-JS)

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. Results. DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). Conclusions. Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up

A kaleidoscope of photosynthetic antenna proteins and their emerging roles

The latest fundamental knowledge obtained on the light-harvesting mechanisms of the antenna proteins can be bridged to biotechnical optimization of photosynthesis.Photosynthetic light-harvesting antennae are pigment-binding proteins that perform one of the most fundamental tasks on Earth, capturing light and transferring energy that enables life in our biosphere. Adaptation to different light environments led to the evolution of an astonishing diversity of light-harvesting systems. At the same time, several strategies have been developed to optimize the light energy input into photosynthetic membranes in response to fluctuating conditions. The basic feature of these prompt responses is the dynamic nature of antenna complexes, whose function readily adapts to the light available. High-resolution microscopy and spectroscopic studies on membrane dynamics demonstrate the crosstalk between antennae and other thylakoid membrane components. With the increased understanding of light-harvesting mechanisms and their regulation, efforts are focusing on the development of sustainable processes for effective conversion of sunlight into functional bio-products. The major challenge in this approach lies in the application of fundamental discoveries in light-harvesting systems for the improvement of plant or algal photosynthesis. Here, we underline some of the latest fundamental discoveries on the molecular mechanisms and regulation of light harvesting that can potentially be exploited for the optimization of photosynthesis