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Purpose Gastrointestinal symptoms are often related to antibiotic treatment. Their incidence, risk and protective conditions in children are not well defined and represent the aims of this study. Methods We prospectively enrolled inpatient children submitted to antibiotic treatment. Indication, type, dose and duration of treatment, probiotic supplementation and gastrointestinal symptoms were recorded at recruitment, after two and four weeks. Antibiotic-associated diarrhea (AAD) was defined as the presence of at least 3 loose/liquid stools within 14 days from antibiotic onset. Results AAD occurred in 59/289 (20.4%) of patients, with increased risk in children younger than 3 years (relative risk [RR]=4.25), in lower respiratory (RR=2.11) and urinary infections (RR=3.67), intravenous administration (RR=1.81) and previous AAD episodes (RR=1.87). Abdominal pain occurred in 27/289 (9.3%), particularly in children >6 years (RR=4.15), with previous abdominal pain (RR=7.2) or constipation (RR=4.06). Constipation was recorded in 23/289 (8.0%), with increased risk in children having surgery (RR=2.56) or previous constipation (RR=7.38). Probiotic supplementation significantly reduced AAD (RR=0.30) and abdominal pain (RR=0.36). Lactobacillus rhamnosus GG (LGG) and L. reuteri significantly reduced AAD (RR=0.37 and 0.35) and abdominal pain (RR=0.37 and 0.24). Conclusion AAD occurred in 20.4% of children, with increased risk at younger age, lower respiratory and urinary tract infections, intravenous treatment and previous AAD. LGG and L. reuteri reduced both AAD and associated abdominal pain.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In our institute, cell lines are stored after freezing procedure that provides for a constant temperature lowering by 1 degree/minute. This procedure is useful to minimizes ice crystals formation during freezing process, this allow to reduce the cells damage and, in turn increasing cells viability after thawing. After storage at -80°C or in liquid nitrogen (in relation to subsequent applications or the expected freezing time) cells are thawed rapidly in a water bath at 37°C and the cryopreserving-medium is immediately remove by gentle centrifugation in order to reduce as soon as possible, the DMSO toxic effect. Currently, in our institute, the freezing/thawing procedure is validated for the following cell lines: PC-12, Rat adrenal phaeochromocytoma, small irregularly shaped cells morphology, suspension growth mode. After freezing/thawing procedure, cells quality must be assessed by cell morphology evaluation (using Optical Microscopy technique) and time required to reach confluence in the T25 cm2 culture flask, which must not exceed the times indicated in the Table 1. After quality test cells must be resuspended according to specific protocols (for details see Table 2). List of published work by our institute that using this procedure Cosentino M, Marino F, Rasini E, Legnaro M, Bombelli R, Luini A, Pacchetti B. Improved solubility and increased biological activity of NeoSol™RCL40, a novel Red Clover Isoflavone Aglycones extract preparation. Biomed Pharmacother. 2019 Mar;111:91-98. doi: 10.1016/j.biopha.2018.12.065. Epub 2018 Dec 19. PMID: 30579257.

In our institute, cell lines are stored after freezing procedure that provides for a constant temperature lowering by 1 degree/minute. This procedure is useful to minimizes ice crystals formation during freezing process, this allow to reduce the cells damage and, in turn increasing cells viability after thawing. After storage at -80°C or in liquid nitrogen (in relation to subsequent applications or the expected freezing time) cells are thawed rapidly in a water bath at 37°C and the cryopreserving-medium is immediately remove by gentle centrifugation in order to reduce as soon as possible, the DMSO toxic effect. Currently, in our institute, the freezing/thawing procedure is validated for the following cell lines: MCF7, Human Caucasian breast adenocarcinoma, epithelial-like morphology, adherent growth mode. HUVEC, Human Umbilical Vein Endothelial Cells, endothelial morphology, adherent growth mode. A549, Human Caucasian lung carcinoma, epithelial-like morphology, adherent growth mode. Synovial fibroblasts, Human synoviocytes, fibroblast-like cells morphology, adherent growth mode. After freezing/thawing procedure, cells quality must be assessed by cell morphology evaluation (using Optical Microscopy technique) and time required to reach confluence in the T25 cm2 culture flask, which must not exceed the times indicated in the Table 1. After quality test cells must be resuspended according to specific protocols (for details see Table 2). List of published work by our institute that using this procedure Coelho M, Imperatori A, Chiaravalli AM, Franzi F, Castiglioni M, Rasini E, Luini A, Legnaro M, Marino F, Ribeiro L, Cosentino M. Beta1- and Beta2-Adrenoceptors Expression Patterns in Human Non-small Cell Lung Cancer: Relationship with Cancer Histology. J Neuroimmune Pharmacol. 2019 Dec;14(4):697-708. doi: 10.1007/s11481-019-09879-6. Epub 2019 Oct 16. PMID: 31620969. Marino F, Schembri L, Rasini E, Pinoli M, Scanzano A, Luini A, Congiu T, Cosentino M. Characterization of human leukocyte-HUVEC adhesion: Effect of cell preparation methods. J Immunol Methods. 2017 Apr;443:55-63. doi: 10.1016/j.jim.2017.01.013. Epub 2017 Feb 3. PMID: 28167274. Spagnuolo P, Rasini E, Luini A, Legnaro M, Luzzani M, Casareto E, Carreri M, Paracchini S, Marino F, Cosentino M. Isoflavone content and estrogenic activity of different batches of red clover (Trifolium pratense L.) extracts: an in vitro study in MCF-7 cells. Fitoterapia. 2014 Apr;94:62-9. doi: 10.1016/j.fitote.2014.01.027. Epub 2014 Feb 5. PMID: 24508860. Capellino S, Cosentino M, Luini A, Bombelli R, Lowin T, Cutolo M, Marino F, Straub RH. Increased expression of dopamine receptors in synovial fibroblasts from patients with rheumatoid arthritis: inhibitory effects of dopamine on interleukin-8 and interleukin-6. Arthritis Rheumatol. 2014 Oct;66(10):2685-93. doi: 10.1002/art.38746. PMID: 24965369. Cosentino M, Marino F, Ferrari M, Rasini E, Bombelli R, Luini A, Legnaro M, Delle Canne MG, Luzzani M, Crema F, Paracchini S, Lecchini S. Estrogenic activity of 7-hydroxymatairesinol potassium acetate (HMR/lignan) from Norway spruce (Picea abies) knots and of its active metabolite enterolactone in MCF-7 cells.Pharmacol Res. 2007 Aug;56(2):140-7. doi: 10.1016/j.phrs.2007.05.001. Epub 2007 May 22. PMID: 17572100.

Hundred and twenty years after its discovery, the Golgi complex still attracts the interest of cell biologists, and many yet open questions address both 'old' and 'new' aspects of its function. Over this long period, the field has shifted focus several times, giving rise to distinct eras of Golgi research. The initial descriptive era laid the basis for our present knowledge of the Golgi organization and transport function, whereas the subsequent reductionist era involved the identification of basic molecular machineries that execute fundamental and elementary trafficking steps. During the genomic era, we have observed a notable increase in the repertoire of molecular components known to contribute to the organization and function of the Golgi, as well as to the integration of Golgi functions with the global cell response. Presently, in the postgenomic era, we are faced with the challenge of incorporating available information into a coherent model of the morphological and functional organization of the Golgi that encompasses the diverse roles of this organelle in cargo transport, sorting and processing; in lipid metabolism; and as a relay or generator of signaling cascades. The diverse roles of the Golgi are the focus of the review articles collected in this FEBS Letters Special Issue on the Golgi complex. This Special Issue has been inspired by a FEBS special meeting held last October in Sorrento, namely the 2018 Golgi meeting: membrane trafficking in cell organization and homeostasis

Density estimation is a central topic in statistics and a fundamental task of machine learning. In this paper, we present an algorithm for approximating multivariate empirical densities with a piec...

Phosphatidic acid (PA) is the simplest cellular glycerophospholipid characterized by unique biophysical properties: a small headgroup; negative charge; and a phosphomonoester group. Upon interaction with lysine or arginine, PA charge increases from -1 to -2 and this change stabilizes protein-lipid interactions. The biochemical properties of PA also allow interactions with lipids in several subcellular compartments. Based on this feature, PA is involved in the regulation and amplification of many cellular signalling pathways and functions, as well as in membrane rearrangements. Thereby, PA can influence membrane fusion and fission through four main mechanisms: it is a substrate for enzymes producing lipids (lysophosphatidic acid and diacylglycerol) that are involved in fission or fusion; it contributes to membrane rearrangements by generating negative membrane curvature; it interacts with proteins required for membrane fusion and fission; and it activates enzymes whose products are involved in membrane rearrangements. Here, we discuss the biophysical properties of PA in the context of the above four roles of PA in membrane fusion and fission.

The sorting and distribution to different final destinations of roughly a third of the membrane and secreted proteins occurs at the level of the trans-Golgi network (TGN). This TGN mission involves efficient mechanisms of cargo recognition and activation of specific signalling pathways. This is important because protein localization is strictly connected with function, and many aberrant phenotypes may occur when a protein is missorted to the wrong cellular compartment. In this review, we briefly summarize the principal players known to be involved in TGN functions, highlighting the importance of regulatory signalling pathways and also the pathological outcomes of aberrant sorting and export events from the TGN compartment.

In order to keep up with the demand for new services, future satellite-to-ground communications will operate at higher frequencies, notably in the 20–50 GHz bands. Consequently, new challenges arise for system designers as the attenuation of the signal crossing the troposphere increases with frequency. Propagation experiments, such as the on-going Alphasat campaign, provide direct measurements of the attenuation. However, other data sources, such as collocated radiometers, are needed to recover the attenuation in nonrainy conditions. This paper uses the Weather Research and Forecasting (WRF) software and investigates Numerical Weather Prediction (NWP) models as an alternative source of nonrainy attenuation time series. Four months of measured Alphasat and radiometric signals collected at Spino d’Adda serve as the reference to assess the accuracy of NWP-derived attenuation. The best agreement between the NWP-derived and the radiometric nonrainy attenuations is achieved with the Tiedtke cumulus scheme. Considering the limits in accuracy inherent to the propagation and radiometric data, the resulting total attenuation statistics are acceptable. The results are expected to improve further with NWP simulation domains closer to the state of the art.

Summary Since May of 2014, NASA's Glenn Research Center has operated measurement campaigns for the Alphasat Aldo Paraboni Propagation Experiment alongside the European community of propagation expe...

A statistical model to predict the effects of both rain and clouds on the earth–space site diversity communication systems is presented. The methodology relies on the assumption, already widely considered in the literature, that both rain- and cloud-induced attenuations can be separately modeled, both in space and time, using log-normal distributions. The model is preliminarily tested against joint statistics of rain and cloud attenuations derived from the propagation data set collected in three Italian sites (Spino d’Adda and Milan, in the North, and Tito Scalo, in the South) during the ongoing Alphasat Aldo Paraboni propagation experiment. Although additional experimental data including attenuation induced by rain and clouds are required to further assess the accuracy of the proposed site diversity model, the obtained results, both for short (~20 km) and large (~760 km) site separation distances, are definitely encouraging and suggest that the proposed model is a step towards providing a more comprehensive and accurate prediction of tropospheric impairments for near future high-frequency earth–space systems implementing the site diversity.

The use of high-resolution Numerical Weather Prediction (NWP) data for electromagnetic wave propagation analysis along Extremely High Frequencies (EHF) is the focus of this work. The Weather Research and Forecast (WRF) model is coupled with the ERA5 meteorological data to produce NWP data, hence the link attenuation, at resolutions never explored for propagation purposes, i.e. 1 minute and 1 km x 1 km. By comparison with the Alphasat propagation data collected in Milan, light is shed on the best compromise between space-time resolution and computation time. Also, a statistical approach is proposed exploiting in a more reliable way the link attenuation forecasts to dynamically adapt the link parameters (e.g. modulation and coding scheme) and thus meet the target quality requirements (e.g. Bit Error Rate) in different weather conditions.

A new model for the application of Up-Link Power Control in satellite communication systems is presented. The model consists in the combination of an ARIMA model to forecast the rain rate (5 minutes in the future) and of the Enhanced Synthetic Storm Technique (E-SST) to generate time series of the rain attenuation at two frequencies, from which the frequency scaling ratio can be calculated for the real time application of Up-Link Power Control. The performance of the model, tested against the Alphasat Ka- and Q-band propagation data collected in Milan, indicate that the proposed frequency scaling approach is accurate enough to allow the real-time effective application of ULPC in EHF satellite communication systems.

Glycosphingolipids are important components of the plasma membrane where they modulate the activities of membrane proteins including signalling receptors. Glycosphingolipid synthesis relies on competing reactions catalysed by Golgi-resident enzymes during the passage of substrates through the Golgi cisternae. The glycosphingolipid metabolic output is determined by the position and levels of the enzymes within the Golgi stack, but the mechanisms that coordinate the intra-Golgi localisation of the enzymes are poorly understood. Here, we show that a group of sequentially-acting enzymes operating at the branchpoint among glycosphingolipid synthetic pathways binds the Golgi-localised oncoprotein GOLPH3. GOLPH3 sorts these enzymes into vesicles for intra-Golgi retro-transport, acting as a component of the cisternal maturation mechanism. Through these effects, GOLPH3 controls the sub-Golgi localisation and the lysosomal degradation rate of specific enzymes. Increased GOLPH3 levels, as those observed in tumours, alter glycosphingolipid synthesis and plasma membrane composition thereby promoting mitogenic signalling and cell proliferation. These data have medical implications as they outline a novel oncogenic mechanism of action for GOLPH3 based on glycosphingolipid metabolism.

The modeling of the earth-satellite propagation channel requires experimental data that is usually obtained by monitoring continuous wave (CW) signal sources installed in satellites (beacons). Although there is considerable experience in the development of beacon receivers for geostationary satellites, this is not the case for Medium Earth Orbit (MEO) or Low Earth Orbit (LEO) constellations. The main considerations for the development of propagation receivers for monitoring MEO satellites are addressed in this article. The target constellation is presented with a description of the satellite orbits, characteristics of the beacon payload and the project requirements. The receiver's requirements are then analyzed, starting with the antenna, satellite tracking, beacon detection and propagation data handling.