Serological surveillance of rubella in Europe: European Sero-Epidemiology Network (ESEN2)

Serological surveillance is an important resource to evaluate vaccine programmes, especially for diseases such as rubella, where a sub-optimal programme can lead to an increase in morbidity. A coordinated vaccine policy in Europe is needed and the aim of the European Sero-Epidemiology Network (ESEN2) is to standardise serological surveillance in 22 countries for eight diseases, including rubella.     

Intracellular Adenosine Inhibits IgE-Dependent Degranulation of Human Skin Mast Cells

Purpose

Adenosine (ADO) can enhance and inhibit mast cell degranulation. Potentiation of degranulation occurs at relatively low concentrations of ADO (10^?6–10^?5 M) through triggering of A3AR, whereas, inhibition occurs at higher concentrations of ADO reportedly through triggering of A2aAR. However, the discrepancy in the concentration of ADO that inhibits degranulation and that required to trigger ADORs suggests a different mechanism. The purpose of this study is to determine the mechanism by which ADO inhibits human mast cell degranulation.

Methods

We compare the effectiveness of A2aAR specific antagonist ZM241385 and equilibrative nucleoside transporter inhibitors Dipyridamole and NBMPR in preventing ADO-mediated inhibition of FcεRI-induced degranulation of human skin mast cells (hSMCs). Western blotting is done to analyze the effect of ADO on FcεRI-induced Syk phosphorylation.

Results

Dipyridamole and NBMPR completely and dose-dependently prevented ADO from inhibiting FcεRI-induced degranulation in all hSMC preparations. In contrast, ZM241385 at 10^?5 M was effective in only 3 of 10 hSMC preparations. Moreover, NBMPR was effective even in those hSMC preparations not responsive to ZM241385. ADO inhibited degranulation induced by FcεRI crosslinking, but not that induced by complement component 5a (C5a), Substance P or calcium ionophore. Accordingly, ADO significantly attenuated FcεRI-induced phosphorylation of Syk at the critical activating tyrosine (Y525).

Conclusion

Blocking the influx of ADO, but not A2aAR signals, is necessary and sufficient to prevent ADO from inhibiting FcεRI-induced mast cell degranulation. Thus, ADO specifically inhibits FcεRI-induced degranulation of hSMCs primarily by an intracellular mechanism that requires its influx via equilibrative nucleoside transporter 1 (ENT1).     

Evaluation of the commercial AD fosfomycin test for susceptibility testing of multidrug-resistant Enterobacterales and Pseudomonas aeruginosa

ObjectivesTo compare fosfomycin susceptibility testing with the commercial agar dilution (AD) test, AD Fosfomycin (Liofilchem, Roseto degli Abruzzi, Italy) and the reference AD method, using a collection of multidrug-resistant (MDR) Enterobacterales and Pseudomonas aeruginosa clinical isolates.MethodsThe collection included 119 carbapenemase-producing Enterobacterales, 53 Enterobacterales producing acquired AmpC-type and/or extended-spectrum β-lactamases and 38 carbapenemase-producing P. aeruginosa, including representatives of different high-risk clones. AD Fosfomycin and AD reference method (ISO 20776-1:2019) were performed starting from the same microbial suspension. Results were interpreted according to EUCAST clinical breakpoints (10.0). Essential agreement (EA), category agreement (CA) and error rates were calculated as described by the International Organization for Standardization.ResultsOf 172 Enterobacterales, 143 (83.1%, including 92.9% (52 of 56) of the NDM-producers and 84.2% (48 of 57) of the KPC-producers) were susceptible to fosfomycin using reference AD. A CA of 91.9% (158 of 172; 95% CI 87.1%–95.3%) and an EA of 92.5% (136 of 147; 95% CI 87.4%–96.0%), respectively, were calculated for the commercial AD Fosfomycin test, with 9.8% (14 of 143) of major errors and no very major errors (0 of 29). Overall, 86.8% (33 of 38) of P. aeruginosa showed a fosfomycin MIC ≤128 mg/L using reference AD. An EA of 84.8% (95% CI 66.3%–92.0%) was calculated for the commercial AD Fosfomycin test, with a CA of 100% (95% CI 93.6%–100%) when considering a tentative breakpoint at 128 mg/L.ConclusionsAD Fosfomycin showed an overall good concordance compared with reference AD.     

Peak width of skeletonized mean diffusivity (PSMD) and cognitive functions in relapsing-remitting multiple sclerosis

Peak width of skeletonized mean diffusivity (PSMD) is a new MRI marker, which has shown clinical relevance in some neurological conditions and, in preliminary data, in multiple sclerosis (MS). We aimed here to investigate, in a group of relapsing-remitting MS (RRMS) patients, the relationship between PSMD and cognitive performances, in comparison with other MRI measures. RRMS patients (n = 60) and normal controls (n = 15) underwent a 3 T MRI examination. MRI-based white matter (WM) lesion volume, microstructural integrity (assessed with Tract-Based Spatial Statistics of diffusion tensor imaging [DTI] images) and brain volumes (i.e., total brain, grey matter [GM] and WM) were computed. In addition, PSMD was calculated through “skeletonization” of WM tracts and diffusion histograms. Cognition was evaluated with Rao’s Brief Repeatable Battery (BRB), which incorporated tests of verbal and visual memory, attention, concentration, information processing speed and verbal fluency. PSMD closely correlated with symbol digit modalities test (SDMT) (r = −0.70, p < 0.001) and, to a lesser extent, with verbal and visual memory tests. Multiple regression analysis showed that PSMD explained SDMT variance (R² = 0.54, p < 0.001) more than other MRI measures. Results point out the relevance of microstructural damage, as assessed by PSMD, as a reliable marker of cognition in MS, especially in explaining dysfunction in information processing speed.

     

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism: Multicentre prospective study by the ‘Nutritional Problems in Gastroenterology’ Section of the Italian Society of Gastroenterology (SIGE)

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.     

Mechanical flutter stimulation induces a lasting response in the sensorimotor cortex as revealed with BOLD fMRI

It has been recently shown that 20 min of mechanical flutter stimulation induces lasting motor cortical excitability changes, as assessed by transcranial magnetic stimulation in relaxed hand muscles. The present functional magnetic resonance imaging (fMRI) study aims to examine if such neuromodulatory changes are reflected in the BOLD signal during a motor test. Therefore, two groups were recruited: one group receiving whole‐hand flutter stimulation with a frequency of 25 Hz (FSTIM group, n = 22) and a second group receiving no stimulation (NOSTIM group, n = 22). As motor test finger‐to‐thumb tapping was performed to activate a wide sensorimotor network during the fMRI measurements. Three fMRI measurements were obtained with this test: before stimulation (PRE), after stimulation (POST1), and 1 h after stimulation (POST2). Three regions of interest (ROIs) were defined: primary motor area (M1), primary somatosensory area (S1), and supplementary motor area. In the absence of baseline differences between both groups, the FSTIM group showed increased movement‐related brain activations compared with the NOSTIM group, both at POST1 and POST2. ROI analysis revealed increased blood‐oxygenation‐level‐dependent (BOLD) responses within contralateral S1 (+20%) and M1 (+25%) at POST1, which lasted until POST2. These poststimulatory effects within S1 and M1 obviously reflect neuroplastic changes associated with augmented cortical excitability. These findings are of high clinical relevance, for example, to improve the treatment of stroke patients. Hum Brain Mapp 34:2767–2774, 2013. © 2012 Wiley Periodicals, Inc.     

Primary visual cortex excitability in migraine: a systematic review with meta-analysis

The objective is to update and extend previous results of a systematic review of the literature with meta-analysis performed to determine the prevalence of phosphenes and the phosphene threshold (PT) values obtained during single-pulse transcranial magnetic stimulation (TMS) in adults with migraine. Both published and unpublished controlled studies measuring PT by single-pulse TMS in adults with migraine with or without aura (MA, MwA) were systematically reviewed. Prevalence of phosphenes and PT values were assessed calculating mean difference (MD) and odds ratio (OR) with 95 % confidence intervals (CI). Fifteen trials (369 migraine patients and 269 controls), were included. Patients with MA had a statistically significant lower PT compared with controls when a circular coil was used (MD: ?22.27, 95 % CI ?33.44 to ?11.10); with a figure-of-eight coil the difference was not statistically significant. There was a significant higher phosphene prevalence in MA compared with controls (OR: 3.57, 95 % CI 1.16–10.94). No significant differences were found either in phosphene reporting between patients with MwA and controls, or in PT values obtained by figure-of-eight coil in subjects with MwA versus controls. In general, these results slightly support the hypothesis of a primary visual cortex hyper-excitability in MA, providing not enough evidence for MwA. A significant heterogeneity across studies probably reflects relevant clinical and methodological heterogeneity.