Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease associated with significant bone damage. Pathological bone remodeling in RA is primarily driven by persistent inflammation. Indeed, ...pro-inflammatory cytokines stimulate the differentiation of bone-resorbing osteoclasts and, in parallel, suppress osteoblast function, resulting in net loss of bone. Abating disease activity thus remains the major goal of any treatment strategy in patients with RA. Autoantibody-positive patients, however, often show a rapidly progressive destructive course of the disease, disproportionate to the level of inflammation. The epidemiological association between RA-specific autoantibodies, in particular anti-citrullinated protein autoantibodies, and poor structural outcomes has recently found mechanistic explanation in the multiple roles that B cells play in bone remodeling. In this review, we will summarize the substantial progress that has been made in deciphering how B cells and autoantibodies negatively impact on bone in the course of RA, through both inflammation-dependent and independent mechanisms.
Aims
To evaluate: (i) the propensity of paediatrics and emergency medicine residents to select different therapeutic options and (ii) the speed and administration success in a high-fidelity ...simulation of severe hypoglycaemia in a child with type 1 diabetes (T1DM).
Methods
In this single-centre high-fidelity simulation study, 51 paediatrics or emergency medicine residents were exposed to a scenario of severe hypoglycaemia in a T1DM child attending an ambulatory setting, before and after a training on the preparation and administration of both injectable and IN glucagon. Time for drug delivery and its effectiveness were collected.
Results
Before training, 45.1% of participants chose to administer injectable glucagon, 43.1% intravenous glucose solution, 5.9% intranasal (IN) glucagon, and 5.9% took no action. Administration was successful in 74% of injectable glucagon, 33.3% intravenous glucose solution, and 22.7% IN glucagon. After training, 58.8% of participants chose IN and 41.2% injectable glucagon, with 100% of successful administrations for IN glucagon and 90.5% for injectable glucagon. Time to successful administration was shorter for IN than injectable glucagon (23 ± 10 vs. 38 ± 7 s,
p
< 0.0001).
Conclusions
IN glucagon is an easy and effective option for severe hypoglycaemia treatment, with an almost zero possibility of failure provided that adequate training is imparted.
Group B Streptococcus (GBS) is the leading cause of invasive neonatal infection. In this study, we aimed to evaluate the analytical validation of qualitative real-time polymerase chain reaction ...(qPCR) as a means to detect GBS.
Genomic DNA (gDNA) was purified from 12 ATCC bacterial strains, two belonging to GBS and the remainder acting as negative controls. Additionally, gDNA was isolated from 21 strains of GBS from various serotypes (Ia, Ib and II-VIII). All gDNA was used to evaluate the analytical validation of the qPCR method employing a specific Taqman probe. Inclusivity, exclusivity, anticipated reportable range, the limit of detection and robustness were evaluated. The methods used are described in international guidelines and other existing reports. The performance of this qPCR method for detecting GBS was compared to other microbiological methods used with vaginal-rectal samples from pregnant women.
Our qPCR method for detecting GBS was analytically validated. It has a limit of detection of 0.7 GE/μL and 100% analytical specificity. It detects all strains of GBS with the same level of performance as microbiological methods.
Data suggest that this qPCR method performs adequately as a means to detect GBS in vaginal-rectal swabs from pregnant women.
Postprandial oxidative stress is characterized by an increased susceptibility of the organism towards oxidative damage after consumption of a meal rich in lipids and/or carbohydrates. Micronutrients ...modulate the immune system and exert a protective action by reducing low-density lipoproteins oxidation (ox-LDL) via induction of antioxidant enzymes.
The clinical study was a randomized and cross-over trial, conducted through the CONSORT flowchart. We evaluated the gene expression of 103 genes related to oxidative stress (HOSp) and human inflammasome pathways (HIp), and ox-LDL level at fasting and after 40 g raw "Tonda Gentile delle Langhe" hazelnut consumption, in association with a McDonald's® Meal (McDM) in 22 healthy human volunteers.
Ox-LDL levels significantly increased comparing no dietary treatment (NDT) vs. McDM, and decreased comparing McDM vs. McDM + H (p<0.05). Percentage of significant genes expressed after each dietary treatment were the follows: (A) NDT vs. McDM: 3.88% HIp and 17.48% HOSp; (B) NDT vs. McDM + H: 17.48% HIp and 23.30% HOSp; (C) McDM vs. McDM + H: 17.48% HIp and 33.98% HOSp.
Hazelnut consumption reduced post prandial risk factors of atherosclerosis, such as ox-LDL, and the expression of inflammation and oxidative stress related genes. Chronic studies on larger population are necessary before definitive conclusions.
To identify plants of the Alps through analysis of their roots is currently extremely difficult when using traditional identification methods such as dichotomous keys and/or illustrated atlases. ...Besides genetic analysis, other analytical methods, such as chromatographic analysis, could also be useful for root identification. Chromatographic fingerprints of root extracts of six species (Betula pendula, Picea abies, Fagus sylvatica, Larix decidua, Fraxinus excelsior and Corylus avellana) were analyzed in order to understand whether these species have a chromatographic fingerprint that identifies them, and hence to ascertain whether they can be identified by applying the method of analysis presented below. One hundred and sixty-two root samples were collected in various areas of the Alps and subjected to high-performance liquid chromatography (HPLC) analysis. Multivariate analysis techniques (e.g. cluster analysis) were employed for statistical analysis of chromatographic fingerprints. This study revealed that the chromatographic fingerprints of birch, spruce and larch samples were similar and that the method can therefore clearly identify the respective species. Instead, chromatographic fingerprint samples of beech, hazel and ash presented greater variability. Research proposals based on the results obtained in this study were also developed in order to implement and facilitate studies regarding plant roots.
The focused electron beam of an aberration-corrected scanning transmission electron microscope is used to create individual vacancies in predefined positions of carbon nanotubes. Vacancies in ...single-wall tubes are unstable and cause an immediate reconstruction of the lattice between 20 and 700 °C. In double-wall tubes, vacancies are stable and observable up to at least 235 °C, whereas above 480 °C a relaxation of the lattice occurs.
BackgroundThe afferent lymphatic network and the draining lymph node (LN) are fixed environments acting as remote complementary check-points through progressive phases of the inflammatory response. ...LN Power Doppler ultrasonography (PDUS) is a non-invasive and sensitive imaging technique commonly adopted in the preoperative diagnostic work-up of cancers. Whether the draining LN undergoes PDUS-sensitive dynamic modifications during chronic inflammation in humans and whether these modifications can be tracked to improve disease assessment is currently unclear.ObjectivesTo investigate axillary LN sono-morphology and Doppler activity in established RA, defining the existence of alterations compared to healthy individuals and dissecting their relationship with synovitis in peripheral joints.Methods40 RA patients refractory to conventional synthetic DMARDs (DAS28≥3.2) were evaluated through complete clinical and PDUS examination in hands/wrists and axillary LN. 20 healthy individuals served as controls. 31 patients starting anti-TNF treatment were followed-up prospectively with further assessments at weeks 4 and 24. Axillary LN PDUS characteristics were assessed according to 0–3 semi-quantitative scores for global LN volume, structure of the lymphocyte-rich cortex and local perfusion. Patient-related indices for each parameter were constructed for comparative, correlative, response-to-treatment and outcome analyses. Synovitis degree (PD and gray scale) was quantified according to 0–3 semi-quantitative scales and 12-joint cumulative indices.ResultsBaseline assessment of perfusion and sono-morphologic characteristics showed the existence of quantitative changes in a subset of RA axillary LN, collectively leading to a distinct sonotype differentiating patients and controls. Combining data derived from morpho-structural and vascularity indices, evidence for parameters exceeding the threshold of controls was restricted to 17 out of 40 patients (42.5%), indicating variable levels of LN response despite established active disease. No relationships were observed between LN parameters and ACPA-RF status, DAS28, acute phase reactants, tender-swollen joint counts. Significant correlations (at systemic and ipsilateral level) were instead consistently detected when sensitive PDUS imaging of the synovium was applied (LN-joint PD index correlation: r=0.35, p=0.03). Plasticity of the observed LN alterations was confirmed by responsiveness analyses showing clear-cut reduction at week 24 of both structural and perfusion scores in patients with LN alterations at baseline (LN PD index: p<0.002, LN cortical index: p<0.02, LN volume index: p<0.03). Patient stratification according to EULAR response at 6 months demonstrated the existence of specific differences in baseline LN scores (but not in clinical features and joint US parameters) with significant decrease in the moderate/non responder group (LN PD index median IQR 0 0–1 vs 2 1–4.25, p=0.01). At its lowest detectable threshold, the LN perfusion index was the only negative predictor of achievement of good response (OR=0.08, p=0.005).ConclusionsPDUS assessment of axillary LN allows detection of inflammatory-related changes in a subset of patients with active established RA. Lack of signs of LN challenge appears a negative predictor of clinical response.Disclosure of InterestNone declared
BackgroundEarly achievement and maintenance of disease remission improve long-term outcomes in patients with rheumatoid arthritis (RA), and eventually allow therapeutic withdrawal. Better knowledge ...of the prevalence and prognostic factors for sustained remission might improve patient care according to their individual profile. RA-specific autoantibodies are associated with a less favorable disease course, but their impact on the achievement and sustainability of remission upon treatment in early RA remains controversial.ObjectivesTo evaluate whether additional B cell-related markers, such as serum levels of the B-cell chemoattractant CXCL13, predict different remission outcomes in patients with early RA.MethodsWe evaluated 205 RA patients from the Pavia early arthritis inception cohort not in remission at baseline with at least 2 years of follow-up, for whom baseline serum was available. Patients had arthritis of short duration (<12 months) and were treatment-naïve at presentation. After diagnosis, patients were initiated a treat-to-target regimen with methotrexate aiming at low disease activity and were seen at 2-months intervals for the first six months and then trimestrally. Levels of rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and CXCL13 were determined on baseline sera. Point remission was defined as the achievement of DAS28 remission (<2.6) or SDAI remission (≤3.3) at any time within the first 12 months. Mean DAS28 <2.6 and mean SDAI ≤3.3 in the 3 visits following first remission (7–9 months) were regarded as sustained remission.Results95/205 (46.3%) patients achieved point DAS28 remission and 69/205 (33.7%) point SDAI remission, with a median (IQR) time to remission of 6 (2–9) and 6 (4–9) months respectively. Male gender, younger age, a lower TJC28, better functional status, absence of radiographic erosions and use of prednisone were independent predictors of point remission. No significant effects of the autoantibody status and CXCL13 levels, alone or in combination, were seen. Irrespective of the remission criterion, more than half of the patients lost remission at follow-up (54.7% for DAS28, 62.3% for SDAI). Shorter time to remission and deeper remission were independent predictors of sustained remission (Figure 1). The ACPA status did not significantly impact the chance of sustaining remission. In contrast, both DAS28 and SDAI remission showed a trend to be less frequently maintained in RF-positive patients and in patients with baseline serum levels of CXCL13 >100 pg/ml (Figure 1). The combination of RF-positivity and high CXCL13 independently predicted failure to sustain remission with an adjusted OR (95% CI) of 8.49 (1.95 to 36.91) for DAS28 and 4.61 (1.01 to 24.67) for SDAI (Figure 1).ConclusionsDisease remission is unfrequently maintained in early RA patients despite steered treatment strategies. B-cell autoimmunity does not significantly impact the chance of ever achieving remission. However, RF-positivity in combination with high CXCL13 identify a subgroup of patients at particularly high risk of losing remission in the short-term, irrespective of how early and how stringent remission is achieved.Disclosure of InterestNone declared
Group B
(GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending ...challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS.
is a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinant
strain secreting SIP from GBS (
-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized with
SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. Our
SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to naïve mice generated protection against GBS vaginal colonization. Moreover, the
-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion that
-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS.
We demonstrate that it is possible to encapsulate ferromagnetic nanowires of Fe, FeCo and FeNi inside carbon nanotubes via chemical vapor deposition methods. These wires exhibit extremely high ...coercive fields when compared with the bulk phases. We review the state-of-the art characterization carried out on these novel wires and discuss the importance of having aligned arrays of carbon nanotubes filled with ferromagnetic materials, towards the development of novel magnetic storage devices. In this context, we will show from the experimental and theoretical stand points, that the wire shape, aspect ratio and inter-wire distances play a crucial role in the fabrication of novel storage components. In addition, we theoretically show that pure carbon nanostructures such as carbon nanotori, perforated fullerenes and nanoporous graphitic structures, exhibiting negative Gaussian curvature introduced by the presence of non-hexagonal rings, behave as strong paramagnets experiencing large magnetic moments when an external magnetic field is applied. The latter results could explain some of the magnetic properties observed experimentally in carbon nanofoams and polymerized C
60 phases. We envisage that magnetism in different families of nanostructures will be playing a key role in the development of emerging technologies in the present century.
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