Analysis of gut microbiota in rheumatoid arthritis patients. Disease-related dysbiosis and modifications induced by etanercept

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota

Perceived weight discrimination, changes in health, and daily stressors

Objective  To examine whether perceived weight discrimination is associated with change in health markers over time and whether it is associated with daily stressors, physical symptoms, and affect.  Methods  Participants were selected from the Midlife in the United States (MIDUS) study if they had data on perceived weight discrimination and health markers at MIDUS II (2004–2006), health markers at MIDUS III (2013–2014), and a body mass index ≥25 kg/m2(N = 1,841). A subset of these participants (N = 1,153) reported on their experiences daily for 8 days as part of the second National Study of Daily Experiences.  Results  Perceived weight discrimination was associated with declines in mental and physical health over time (medianβ =0.06). Participants who reported weight discrimination experienced more daily stressors (β =0.13), physical symptoms (β =0.13), and negative affect (β =0.13) and less positive affect (β =−0.12) over the 8 days of the second National Study of Daily Experiences. Weight discrimination was most strongly associated with interpersonal stressors (medianβ =0.14), feelings of anger (β =0.16) and frustration (β =0.14), lower attention (β =−0.14) and activity (β =−0.16), and more nonspecific physical symptoms (e.g., fatigue;β =0.10).  Conclusions  This research replicates the association between perceived weight discrimination and worse health over time and extends this literature to show that people who experience weight discrimination have more daily stressors, physical symptoms, and negative emotions

In-room test results at CNAO of an innovative PT treatments online monitor (Dose Profiler)

The use of C, He and O ions as projectiles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of their enhanced relative biological effectiveness and oxygen enhancement ratio, when compared to the protons one. The advantages related to the incoming radiation improved efficacy are requiring an accurate online monitor of the dose release spatial distribution. Such monitor is necessary to prevent unwanted damage to the tissues surrounding the tumour that can arise, for example, due to morphological changes occurred in the patient during the treatment with respect to the initial CT scan. PT treatments with ions can be monitored by detecting the secondary radiation produced by the primary beam interactions with the patient body along the path towards the target volume. Charged fragments produced in the nuclear process of projectile fragmentation can be emitted at large angles with respect to the incoming beam direction and can be detected with high efficiency in a nearly background-free environment. The Dose Profiler (DP) detector, developed within the INSIDE project, is a scintillating fibre tracker that allows an online reconstruction and backtracking of such secondary charged fragments. The construction and preliminary in-room tests performed on the DP, carried out using the 12C ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution. The impact of the secondary fragments interactions with the patient body will be discussed in view of a clinical application. Furthermore, the results implications for a pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed

Healthcare workers training courses on vaccinations: A flexible format easily adaptable to different healthcare settings.

Since 2017, Italy has expanded the compulsory vaccination from 4 to 10 for those aged 0 to 16 years. Because of the great organizational effort required for the immunization services, minor attention was given to the vaccinations not included among the mandatory ones. This situation led to a real difficulty in harmonizing the vaccination procedures even inside a single region. In the Lazio region, the Laboratory of Vaccinology of the University of Rome Tor Vergata established a working group to create a new training model for healthcare professionals. The course program proposed an update of three vaccinations which are not mandatory but actively offered. It included the same part of scientific updating and a variable part based on local experiences. A specific anonymous questionnaire on knowledge and attitude was administered. The study aimed to propose a general format of training courses for vaccination centers adaptable to the individual local health units (ASLs) and to evaluate through questionnaires. The results show differences in knowledge and attitudes toward non‐mandatory vaccinations among the ASLs of Lazio, confirming the usefulness of a support to make knowledge and procedures homogeneous. This model could be adapted to any healthcare setting and exported to other services

Gastrointestinal strongyles burden monitoring in a flock of Zerasca sheep treated with homeopathy

Introdution The widespread use of conventional drugs in farm animals has resulted in anthelmintic resistance as well as the contamination of deleterious molecules in animal products and in the environment. Researchers are thus focusing on production systems that rely less on chemicals. The aim of this study was to monitor the gastrointestinal strongyle burden, blood count, body condition scores (BCS), and FAffa MAlan CHArt (FAMACHA) in a local Italian breed of sheep reared in natural conditions. Methods The study was carried out in a farm where homeopathy was utilised. Over a one-year period, faeces were sampled six times from ten Zerasca ewes to evaluate the fecal eggs count using a modified McMaster technique. At the same time, blood samples were collected to evaluate white blood cells, red blood cells, hemoglobin, packed cell volume, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red cell distribution width. BCS and FAMACHA were also recorded. Results Results showed low parasite levels in most of the samples with the highest value in the spring. Blood parameters were within the normal range, with significant fluctuations during the sampling period. BCS values corresponded to an adequate nutritional condition of the animals and FAMACHA scores did not suggest a worrying state of anemia. Conclusions In this farm, a thorough monitoring of the gastrointestinal parasite burden together with a BCS and FAMACHA evaluation allowed the amount of chemical treatments to be limited, normally administered twice a year without laboratory tests

Discovery of new molecular entities able to strongly interfere with Hsp90 C-terminal domain

Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone deeply involved in the complex network of cellular signaling governing some key functions, such as cell proliferation and survival, invasion and angiogenesis. Over the past years the N-terminal protein domain has been fully investigated as attractive strategy against cancer, but despite the many efforts lavished in the field, none of the N-terminal binders (termed “classical inhibitors”), currently in clinical trials, have yet successfully reached the market, because of the detrimental heat shock response (HSR) that showed to induce; thus, recently, the selective inhibition of Hsp90 C-terminal domain has powerfully emerged as a more promising alternative strategy for anti-cancer therapy, not eliciting this cell rescue cascade. However, the structural complexity of the target protein and, mostly, the lack of a co-crystal structure of C-terminal domain-ligand, essential to drive the identification of new hits, represent the largest hurdles in the development of new selective C-terminal inhibitors. Continuing our investigations on the identification of new anticancer drug candidates, by using an orthogonal screening approach, here we describe two new potent C-terminal inhibitors able to induce cancer cell death and a considerable downregulation of Hsp90 client oncoproteins, without triggering the undesired heat shock response