An in vivo humanized model to study homing and sequestration of Plasmodium falciparum transmission stages in the bone marrow

IntroductionRecent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of P. falciparum malaria by providing a “niche” for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized in vivo models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.MethodsWe report a novel experimental system based on the infusion of immature P. falciparum gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.ResultsWe demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.DiscussionOur model represents a powerful tool to study BM function and the interplay essential for parasite transmission in P. falciparum malaria and can be extended to study other infections in which the human BM plays a role

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Villa Guicciardini Corsi Salviati. Arte e storia

International audienc

Zero-Knowledge Sets With Short Proofs

International audienceZero knowledge sets (ZKS), introduced by Micali, Rabin, and Kilian in 2003, allow a prover to commit to a secret set S in a way such that it can later prove, non interactively, statements of the form x ∈ S (or x ∉ S), without revealing any further information (on top of what explicitly revealed by the inclusion/exclusion statements above) on S, not even its size. Later, Chase abstracted away the Micali, Rabin, and Kilian's construction by introducing an elegant new variant of commitments that they called (trapdoor) mercurial commitments. Using this primitive, it was shown how to construct zero knowledge sets from a variety of assumptions (both general and number theoretic). This paper introduces the notion of trapdoor q -mercurial commitments (ssr qTMCs), a notion of mercurial commitment that allows the sender to commit to an ordered sequence of exactly q messages, rather than to a single one. Following the previous work, it is shown how to construct ZKS from ssr qTMCs and collision resistant hash functions. Then, it is presented an efficient realization of ssr qTMCs that is secure under the so called Strong Diffie Hellman (SDH) assumption, a number theoretic conjecture recently introduced by Boneh and Boyen. Using such scheme as basic building block, it is obtained a construction of ZKS that allows for proofs that are much shorter with respect to the best previously known implementations. In particular, for an appropriate choice of the parameters, our proofs are up to 33% shorter for the case of proofs of membership, and up to 73% shorter for the case of proofs of nonmembership. Experimental tests confirm practical time performances

Effects of low-carbohydrate diet therapy in overweight subjects with autoimmune thyroiditis: possible synergism with ChREBP

The thyroid is one of the metabolism regulating glands. Its function is to determine the amount of calories that the body has to burn to maintain normal weight. Thyroiditides are inflammatory processes that mainly result in autoimmune diseases. We have conducted the present study in order to have a clear picture of both autoimmune status and the control of body weight. We have evaluated the amount of either thyroid hormones, or antithyroid, or anti-microsomal, or anti-peroxidase antibodies (Abs) in patients with high amounts of Abs. In a diet devoid of carbohydrates (bread, pasta, fruit, and rice), free from goitrogenic food, and based on body mass index, the distribution of body mass and intracellular and extracellular water conducted for 3 weeks gives the following results: patients treated as above showed a significant reduction of antithyroid (-40%, P<0.013), anti-microsomal (-57%, P<0.003), and anti-peroxidase (-44%, P<0,029) Abs. Untreated patients had a significant increase in antithyroid (+9%, P<0.017) and anti-microsomal (+30%, P<0.028) Abs. Even the level of anti-peroxidase Abs increased without reaching statistical significance (+16%, P>0064). With regard to the body parameters measured in patients who followed this diet, reduction in body weight (-5%, P<0.000) and body mass index (-4%, P<0.000) were observed. Since 83% of patients with high levels of autoantibodies are breath test positive to lactase with a lactase deficit higher than 50%, this fact led us to hypothesize a correlation with carbohydrate-responsive element-binding protein and therefore a possible role of carbohydrate metabolism in the development and maintenance of autoimmune thyroiditis associated with body weight increase and slower basic metabolism

Secukinumab Drug Survival in Psoriasis and Psoriatic Arthritis Patients: A 24-Month Real-Life Study

none8noSecukinumab effectiveness has been demonstrated in both psoriasis (PsO) and psoriatic arthritis (PsA). However, it is unknown whether patients with arthritis may carry a risk factor for withdrawal.Ortolan, Augusta; Lorenzin, Mariagrazia; Leo, Giovanni; Pampaloni, Francesca; Messina, Francesco; Doria, Andrea; Piaserico, Stefano; Ramonda, RobertaOrtolan, Augusta; Lorenzin, Mariagrazia; Leo, Giovanni; Pampaloni, Francesca; Messina, Francesco; Doria, Andrea; Piaserico, Stefano; Ramonda, Robert

Secukinumab Drug Survival in Psoriasis and Psoriatic Arthritis Patients: A 24-Month Real-Life Study

Background: Secukinumab effectiveness has been demonstrated in both psoriasis (PsO) and psoriatic arthritis (PsA). However, it is unknown whether patients with arthritis may carry a risk factor for withdrawal. Objective: To identify predictors of secukinumab survival, including the presence of arthritis, in PsO and PsA. Methods: Consecutive PsO and PsA patients initiating secukinumab were enrolled and followed up every 6 months, up to 24 months or discontinuation. Medical history, disease activity indices and body mass index (BMI) were collected. Kaplan-Meier curves and log-rank test were used to analyze differences in drug survival according to sex, BMI, biological therapy line in the whole population (psoriatic disease), and separately for PsO/PsA. A multivariable Cox regression model was built to assess whether presence of arthritis (main independent variable) may influence drug survival by having time to secukinumab discontinuation as outcome. Results were expressed as hazard ratio and 95% confidence interval. Results: Sixty-two PsO and 90 PsA patients were enrolled. Retention rate at 12 and 24 months, respectively, was 85% and 61% for PsO and 68% and 57% for PsA. In the whole population, naïve patients had a higher chance of drug survival (log-rank = 4.06; p = 0.04); in PsA, obese patients had a significantly higher chance to discontinue secukinumab (log-rank = 5.25; p = 0.021). The multivariable Cox regression showed that arthritis was independently associated with a higher risk of secukinumab discontinuation (hazard ratio 2.43; 95% confidence interval 1.06-5.55, p = 0.035) after adjusting for age, sex, gender, BMI, therapy line and PsO severity at baseline. Conclusions: Our data confirmed a very good response to secukinumab in both PsO and PsA patients. However, presence of arthritis might affect drug survival

Polysomnographic Findings in Fragile X Syndrome Children with EEG Abnormalities

Fragile X syndrome (FXS) is a genetic syndrome with intellectual disability due to the loss of expression of the FMR1 gene located on chromosome X (Xq27.3). This mutation can suppress the fragile X mental retardation protein (FMRP) with an impact on synaptic functioning and neuronal plasticity. Among associated sign and symptoms of this genetic condition, sleep disturbances have been already described, but few polysomnographic reports in pediatric age have been reported. This multicenter case-control study is aimed at assessing the sleep macrostructure and at analyzing the presence of EEG abnormalities in a cohort of FXS children. We enrolled children with FXS and, as controls, children with typical development. All subjects underwent at least 1 overnight polysomnographic recording (PSG). All recorded data obtained from patients and controls were compared. In children with FXS, all PSG-recorded parameters resulted pathological values compared to those obtained from controls, and in FXS children only, we recorded interictal epileptiform discharges (IEDs), as diffuse or focal spikes and sharp waves, usually singles or in brief runs with intermittent or occasional incidence. A possible link between IEDs and alterations in the circadian sleep-wake cycle may suggest a common dysregulation of the balance between inhibitory and excitatory pathways in these patients. The alteration in sleep pattern in children with FXS may negatively impact the neuropsychological and behavioral functioning, adding increasing burn of the disease on the overall management of these patients. In this regard, treating physicians have to early detect sleep disturbances in their patients for tailored management, in order to prevent adjunctive comorbidities