Infliximab to treat Crohn's disease: an update

Abstract: Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract characterized by recurring flares followed by periods of inactive disease and remission. The etiology is unknown, although the common opinion is that the disease arises from a disordered immune response to the gut contents in genetically predisposed individuals. Infliximab (IFX), a chimeric immunoglobulin G1 monoclonal antibody to tumor necrosis factor, has dramatically changed the approach to managing patients with CD and improving their treatment, by achieving treatment goals, such as mucosal healing, and decreasing the need for hospitalizations and surgeries. This review provides an update on existing evidence for the use of IFX in CD, taking into account the safety profile in clinical practice and special situations such as pregnancy. Antitumor necrosis factor therapy has been evaluated as an induction and maintenance therapy in CD in several randomized controlled trials and meta-analyses, showing efficacy in both clinical settings. Early use of biologics may improve patient outcomes in active CD. However, a widespread use of a “top-down” approach in all CD patients cannot be recommended. Clinical factors at diagnosis may predict poor outcome in CD, and should be taken into account when determining the initial therapeutic approach. Keywords: Crohn’s disease, infliximab, adul

Total solar irradiance during the last five centuries

The total solar irradiance (TSI) varies on timescales of minutes to centuries. On short timescales it varies due to the superposition of intensity fluctuations produced by turbulent convection and acoustic oscillations. On longer timescales, it changes due to photospheric magnetic activity, mainly because of the facular brightenings and dimmings caused by sunspots. While modern TSI variations have been monitored from space since the 1970s, TSI variations over much longer periods can only be estimated either using historical observations of magnetic features, possibly supported by flux transport models, or from the measurements of the cosmogenic isotope (e.g., 14C or 10Be) concentrations in tree rings and ice cores. The reconstruction of the TSI in the last few centuries, particularly in the 17th/18th centuries during the Maunder minimum, is of primary importance for studying climatic effects. To separate the temporal components of the irradiance variations, specifically the magnetic cycle from secular variability, we decomposed the signals associated with historical observations of magnetic features and the solar modulation potential Φ by applying an empirical mode decomposition algorithm. Thus, the reconstruction is empirical and does not require any feature contrast or field transport model. The assessed difference between the mean value during the Maunder minimum and the present value is ≃2.5 W m−2. Moreover it shows, in the first half of the last century, a growth of ≃1.5 W m−2, which stops around the middle of the century to remain constant for the next 50 years, apart from the modulation due to the solar cycle

UMTS rapid response real-time seismic networks: implementation and strategies at INGV

The benefits of portable real-time seismic networks are several and well known. During the management of a temporary experiment from the real-time data it is possible to detect and fix rapidly problems with power supply, time synchronization, disk failures and, most important, seismic signal quality degradation due to unexpected noise sources or sensor alignment/tampering. This usually minimizes field maintenance trips and maximizes both the quantity and the quality of the acquired data. When the area of the temporary experiment is not well monitored by the local permanent network, the real-time data from the temporary experiment can be fed to the permanent network monitoring system improving greatly both the real-time hypocentral locations and the final revised bulletin. All these benefits apply also in case of seismic crises when rapid deployment stations can significantly contribute to the aftershock analysis. Nowadays data transmission using meshed radio networks or satellite systems is not a big technological problem for a permanent seismic network where each site is optimized for the device power consumption and is usually installed by properly specialized technicians that can configure transmission devices and align antennas. This is not usually practical for temporary networks and especially for rapid response networks where the installation time is the main concern. These difficulties are substantially lowered using the now widespread UMTS technology for data transmission. A small (but sometimes power hungry) properly configured device with an omnidirectional antenna must be added to the station assembly. All setups are usually configured before deployment and this allows for an easy installation also by untrained personnel. We describe here the implementation of a UMTS based portable seismic network for both temporary experiments and rapid response applications developed at INGV. The first field experimentation of this approach dates back to the 2009 L’Aquila aftershock sequence and since then it has been customized and refined to overcome most reliability and security issues using an industry standard VPN architecture that allows to avoid UMTS provider firewall problems and does not expose to the Internet the usually weak and attack prone data acquisition ports. With this approach all the devices are protected inside a local network and the only exposed port is the VPN server one. This solution improves both the security and the bandwidth available to data transmission. While most of the experimentation has been carried out using the RefTek units of the INGV Mobile Network this solution applies equally well to most seismic data loggers available on the market. Overall the UMTS data transmission has been used in most temporary seismic experiments and in all seismic emergencies happened in Italy since 2010 and has proved to be a very cost effective approach with real-time data acquisition rates usually greater than 97% and all the benefits that result from the fast integration of the temporary data in the National Network monitoring system and in the EIDA data bank

UMTS rapid response real-time seismic networks: implementation and strategies at INGV

<abstract> <p>Universal Mobile Telecommunications System (UMTS) and its evolutions are nowadays the most affordable and widespread data communication infrastructure available almost world wide. Moreover the always growing cellular phone market is pushing the development of new devices with higher performances and lower power consumption. All these characteristics make UMTS really useful for the implementation of an â easy to deployâ temporary real-time seismic station. Despite these remarkable features, there are many drawbacks that must be properly taken in account to effectively transmit the seismic data: Internet security, signal and service availability, power consumption. <list list-type="bullet"><list-item> <p>Internet security: exposing seismological data services and seismic stations to the Internet is dangerous, attack prone and can lead to downtimes in the services, so we setup a dedicated Virtual Private Network (VPN) service to protect all the connected devices.</p></list-item><list-item> <p>Signal and service availability: while for temporary experiment a carefull planning and an accurate site selection can minimize the problem, this is not always the case with rapid response networks. Moreover, as with any other leased line, the availability of the UMTS service during a seismic crisis is basically unpredictable. Nowadays in Italy during a major national emergency a Committee of the Italian Civil Defense ensures unified management and coordination of emergency activities. Inside it the telecom companies are committed to give support to the crisis management improving the standards in their communication networks.</p></list-item><list-item> <p>Power consumption: it is at least of the order of that of the seismic station and, being related to data flow and signal quality is largely unpredictable. While the most secure option consists in adding a second independent solar power supply to the seismic station, this is not always a very convenient solution since it doubles the cost and doubles the equipment on site. We found that an acceptable trade-off is to add an inexpensive Low Voltage Disconnect (LVD) circuit to the UMTS router power supply that switches off the data transmission when the power is low. This greatly reduces the probability of data loss but lowers the real-time data availabilty. This approach guarantees on the average a satisfactory data acquistion rate, only in very few cases and when the real-time data is extremely important for a particular site we needed to double the power supply on the site.</p></list-item></list></p> <p>Overall the UMTS data transmission has been used in most temporary seismic experiments and in all seismic emergencies happened in Italy since 2010 and has proved to be a very cost effective approach with real-time data acquisition rates usually greater than 97â ¯% and all the benefits that result from the fast integration of the temporary data in the National Network monitoring system and in the EIDA data bank.</p> </abstract

UMTS rapid response real-time seismic networks: implementation and strategies at INGV

The benefits of portable real-time seismic networks are several and well known. During the management of a temporary experiment from the realtime data it is possible to detect and fix rapidly problems with power supply, time synchronization, disk failures and, most important, seismic signal quality degradation due to unexpected noise sources or sensor alignment/tampering. This usually minimizes field maintenance trips and maximizes both the quantity and the quality of the acquired data. When the area of the temporary experiment is not well monitored by the local permanent network, the real-time data from the temporary experiment can be fed to the permanent network monitoring system improving greatly both the real-time hypocentral locations and the final revised bulletin. All these benefits apply also in case of seismic crises when rapid deployment stations can significantly contribute to the aftershock analysis. Nowadays data transmission using meshed radio networks or satellite systems is not a big technological problem for a permanent seismic network where each site is optimized for the device power consumption and is usually installed by properly specialized technicians that can configure transmission devices and align antennas. This is not usually practical for temporary networks and especially for rapid response networks where the installation time is the main concern. These difficulties are substantially lowered using the now widespread UMTS technology for data transmission. A small (but sometimes power hungry) properly configured device with an omnidirectional antenna must be added to the station assembly. All setups are usually configured before deployment and this allows for an easy installation also by untrained personnel

Organoids of Human Endometrium: A Powerful In Vitro Model for the Endometrium-Embryo Cross-Talk at the Implantation Site

Embryo implantation has been defined as the "black box" of human reproduction. Most of the knowledge on mechanisms underlining this process derives from animal models, but they cannot always be translated to humans. Therefore, the development of an in vitro/ex vivo model recapitulating as closely and precisely as possible the fundamental functional features of the human endometrial tissue is very much desirable. Here, we have validated endometrial organoids as a suitable 3D-model to studying epithelial endometrial interface for embryo implantation. Transmission and scanning electron microscopy analyses showed that organoids preserve the glandular organization and cell ultrastructural characteristics. They also retain the responsiveness to hormonal treatment specific to the corresponding phase of the menstrual cycle, mimicking the in vivo glandular-like aspect and functions. Noteworthy, organoids mirroring the early secretive phase show the development of pinopodes, large cytoplasmic apical protrusions of the epithelial cells, traditionally considered as reliable key features of the implantation window. Moreover, organoids express glycodelin A (GdA), a cycle-dependent marker of the endometrial receptivity, with its quantitative and qualitative features accounting well for the profile detected in the endometrium in vivo. Accordingly, organoids deriving from the eutopic endometrium of women with endometriosis show a GdA glycosylation pattern significantly different from healthy organoids, confirming our prior data on endometrial tissues. The present results strongly support the idea that organoids may closely recapitulate the molecular and functional characteristics of their cells/tissue of origin

MESENCHIMAL STEM CELLS IN INFLAMMATORY BOWEL DISEASES: CLINICAL EVIDENCES AND POTENTIAL INSIGHTS FOR THE CLINICIANS

Mesenchimal stem cells (MSCs) have been used experimentally and clinically in the treatment of a wide variety of pathologies MSCs can be safely transplanted in autologous and allogenic ways as they are non-immunogenic, and consequently represent a therapeutic option for refractory connective tissue diseases, fibrosing diseases like scleroderma and fistulizing colitis like in Crohn's disease (CD). The immunomodulatory properties of MSCs have already shown promise when used as therapy for otherwise medically refractory CD. Accumulating evidence suggests that the properties may also be exploited of several other conditions. The currently available experimental and clinical data indicate that, similar to previously obtained data in the setting of HSCT, MSC treatment for IBD is feasible and safe. aim of this review is to analyze the pathophysiological insights for the use of MSCs in inflammatory bowel diseases, and to summarize the clinical evidences about the efficacy and safety of stem cell therapy in such disorders