Cytokine release syndrome in COVID-19 patients, a new scenario for an old concern. The fragile balance between infections and autoimmunity

On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk

Ash aggregation during the 11 February 2010 partial dome collapse of the Soufrière Hills Volcano, Montserrat

On 11 February 2010, Soufrière Hills Volcano, Montserrat, underwent a partial dome collapse (~ 50 × 106 m3) and a short-lived Vulcanian explosion towards the end. Three main pyroclastic units were identified N and NE of the volcano: dome-collapse pyroclastic density current (PDC) deposits, fountain-collapse PDC deposits formed by the Vulcanian explosion, and tephra-fallout deposits associated with elutriation from the dome-collapse and fountain-collapse PDCs (i.e. co-PDC fallout deposit). The fallout associated with the Vulcanian explosion was mostly dispersed E and SE by high altitude winds. All units N and NE of the volcano contain variable amounts and types of particle aggregates, although the co-PDC fallout deposit is associated with the largest abundance (i.e. up to 24 wt%). The size of aggregates found in the co-PDC fallout deposit increases with distance from the volcano and proximity to the sea, reaching a maximum diameter of 12 mm about 500 m from the coast. The internal grain size of all aggregates have nearly identical distributions (with Mdϕ ≈ 4–5), with particles in the size categories > 3 ϕ (i.e. < 250 μm) being distributed in similar proportions within the aggregates but in different proportions within distinct internal layers. In fact, most aggregates are characterized by a coarse grained central core occupying the main part of the aggregate, coated by a thin layer of finer ash (single-layer aggregates), while others have one or two additional layers accreted over the core (multiple-layer aggregates). Calculated aggregate porosity and settling velocity vary between 0.3 and 0.5 and 11–21 m s− 1, respectively. The aggregate size shows a clear correlation with both the core size and the size of the largest particles found in the core. The large abundance of aggregates in the co-PDC fallout deposits suggests that the buoyant plumes elutriated above PDCs represent an optimal environment for the formation (particle collision) and development (aggregate layering) of particle aggregates. However, specific conditions are required, including i) a large availability of water (in this case provided by the steam plumes associated with the entrance of PDCs into the ocean), ii) presence of plume regions with different grain-size features (i.e. both median size and sorting) that allows for the development of multiple layers, iii) strong turbulence that permits both particle collision and the transition of the aggregates through different plume regions, iv) presence of hot regions (e.g. PDCs) that promote aggregate preservation (in this case also facilitated by the presence of sea salt)

Mental disorders and work integration: a retrospective study in a northern italian town.

OBJECTIVES: THE PRESENT STUDY WAS CONDUCTED IN A VOCATIONAL INTEGRATION SERVICE OF A NORTHERN ITALIAN TOWN WITH TWO MAJOR AIMS: to assess vocational integration programs undertaken from 1(st) January 2004 to 1(st) January 2007; and to identify job tenure-associated predictors. METHODS: This is a retrospective study; we collected data such as gender, age, duration, type and outcome of the vocational integration program, and number of interventions performed by the vocational integration service. Self-report questionnaires were also used to assess the satisfaction of users, caregivers, practitioners, and of the company contacts involved in the study. RESULTS: The service has enrolled 84 users during the observation period. Out of these users, 64.3% of them still had their jobs after three years. Users, caregivers and company contacts expressed high levels of satisfaction for the support received by the vocational integration service. The company expressed less satisfaction for the collaboration received by the Departments of Mental Health (DMHs) that coached the users. The only variable associated to the outcome was the number of interventions that the users received before their placement on the job. CONCLUSIONS: Despite all the limits of this study, its results show that the chance of taking advantage of a supported job placement service has likely proven itself effective in helping people with mental disorders to obtain and maintain a competitive employment. Our results, however, also point to the necessity of implementing newer strategies meant to develop a greater integration among all services dealing with mentally ill people

Effects of PARP-1 Deficiency on Th1 and Th2 Cell Differentiation

T cell differentiation to effector Th cells such as Th1 and Th2 requires the integration of multiple synergic and antagonist signals. Poly(ADP-ribosy)lation is a posttranslational modification of proteins catalyzed by Poly(ADP-ribose) polymerases (PARPs). Recently, many reports showed that PARP-1, the prototypical member of the PARP family, plays a role in immune/inflammatory responses. Consistently, its enzymatic inhibition confers protection in several models of immune-mediated diseases, mainly through an inhibitory effect on NF-κB (and NFAT) activation. PARP-1 regulates cell functions in many types of immune cells, including dendritic cells, macrophages, and T and B lymphocytes. Our results show that PARP-1KO cells displayed a reduced ability to differentiate in Th2 cells. Under both nonskewing and Th2-polarizing conditions, naïve CD4 cells from PARP-1KO mice generated a reduced frequency of IL-4+ cells, produced less IL-5, and expressed GATA-3 at lower levels compared with cells from wild type mice. Conversely, PARP-1 deficiency did not substantially affect differentiation to Th1 cells. Indeed, the frequency of IFN-γ+ cells as well as IFN-γ production, in nonskewing and Th1-polarizing conditions, was not affected by PARP-1 gene ablation. These findings demonstrate that PARP-1 plays a relevant role in Th2 cell differentiation and it might be a target to be exploited for the modulation of Th2-dependent immune-mediated diseases

Delivery status of the ELI-NP gamma beam system

International audienceThe ELI-NP GBS is a high intensity and monochromatic gamma source under construction in Magurele (Romania). The design and construction of the Gamma Beam System complex as well as the integration of the technical plants and the commissioning of the overall facility, was awarded to the Eurogammas Consortium in March 2014. The delivery of the facility has been planned in for 4 stages and the first one was fulfilled in October 31st 2015. The engineering aspects related to the delivery stage 1 are presented

Beam manipulation for resonant plasma wakefield acceleration

Plasma-based acceleration has already proved the ability to reach ultra-high accelerating gradients. However the step towards the realization of a plasma-based accelerator still requires some e ff ort to guarantee high brightness beams, stability and reliability. A significant improvement in the efficiency of PWFA has been demonstrated so far accelerating a witness bunch in the wake of a higher charge driver bunch. The transformer ratio, therefore the energy transfer from the driver to the witness beam, can be increased by resonantly exciting the plasma with a properly pre-shaped drive electron beam. Theoretical and experimental studies of beam manipulation for resonant PWFA will be presented her

Synthetic analogue of the natural product piperlongumine as a potent inhibitor of breast cancer cell line migration

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORPiperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for disco283475484FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR2013/07600-32003/02176-72010/52327-52010/17329-72010/06741-42007/56140-4SEM INFORMAÇÃOSEM INFORMAÇÃOThis work was supported by the State of São Paulo Research Foundation (FAPESP, Fundação de Amparo à Pesquisa do Estado de São Paulo), grant No. 2013/07600-3; Biota-FAPESP, grant No. 2003/02176-7; SISBIOTA-CNPq-FAPESP, grant No. 2010/52327-5; Coordenação

Handgrip strength predicts persistent walking recovery after hip fracture surgery

Background In older people, hip fractures often lead to disability and death. We evaluated handgrip strength, an objective measure of physical function for bedridden patients, as a predictor of walking recovery in the year after fracture surgery. Methods This multicenter prospective cohort study included 504 patients, aged 70 years or more, who were admitted to the hospital for hip fracture surgery and were formerly able to walk independently. A multidimensional geriatric evaluation that included a physical examination, Short Portable Mental Status Questionnaire, Geriatric Depression Scale, Charlson Index, Basic Activities of Daily Living, and grip strength was administered at the time of admission. Follow-ups were performed every 3 months for 1 year after surgery to assess functional status and survival. The walking recovery probability was evaluated using multivariable logistic regression models. Results The mean age of the participants was 85.3 ± 5.5 years, and 76.1% of the participants were women. The mean grip strength was greater in men (β: 6.6 ± 0.62, P &lt;.001) and was directly related to the Short Portable Mental Status Questionnaire results (P &lt;.001), Basic Activities of Daily Living results (P &lt;.001), serum vitamin D levels (P =.03), and time before surgery (P &lt;.001), whereas it was inversely related to age (P &lt;.001), Geriatric Depression Scale score (P &lt;.001), and Charlson Index (P &lt;.001). After adjusting for confounders, the grip strength was directly associated with the probability of both incident and persistent walking recovery (odds ratio highest tertile vs lowest tertile, 2.84, confidence interval, 1.76-4.59 and 2.79, confidence interval, 1.35-5.79, respectively). Conclusions In older patients with hip fractures, early grip strength evaluation might provide important prognostic information regarding the patient's future functional trajectory. © 2013 Elsevier Inc. All rights reserved

The aflatox® project: Approaching the development of new generation, natural‐based compounds for the containment of the mycotoxigenic phytopathogen Aspergillus flavus and aflatoxin contamination

The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre‐ and post‐harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox® Project was aimed at the development of new‐generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti‐aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi‐genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem