A myeloma paraprotein with specificity for platelet glycoprotein IIIa in a patient with a fatal bleeding

Abstract Impaired platelet aggregation, normal shape change, and agglutination and normal ATP secretion and thromboxane synthesis in response to high concentrations of thrombin or arachidonic acid were found in a patient with multiple myeloma and hemorrhagic tendency. The purified IgG1 kappa or its F(ab'}2 fragments induced similar changes when added in vitro to plateletrich plasma from normal subjects. In addition, the paraprotein inhibited adhesion to glass microbeads, fibrin clot retraction, and binding of radiolabeled fibrinogen or von Willebrand factor to platelets exposed to thrombin or arachidonic acid without affecting intraplatelet levels of cAMP. The radiolabeled paraprotein bound to an average of 35,000 sites on normal platelets but it bound to <2,000 sites on the platelets from a patient with Glanzmann's thrombasthenia. Immunoprecipitation studies showed that the platelet antigen identified by the paraprotein was the glycoprotein IlIa. Furthermore, binding of radiolabeled prostaglandin El (PGEI) to resting platelets as well as binding of von Willebrand factor to platelets stimulated with ristocetin were entirely normal in the presence of patient's inhibitor. These studies indicate that bleeding occurring in dysproteinemia may be the result of a specific interaction of monoclonal paraproteins with platelets. In addition, our data support the concept that the interaction of fibrinogen and/or von Willebrand factor with the platelet glycoprotein Ilb-IIla complex is essential for effective hemostasis

Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum TimeCourse

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.This research was partially funded by FOREUM—Foundation for Research in Rheumatolog

La dimensione territoriale dello sviluppo tra competitività e sostenibilità

Il capitolo presenta una rassegna della letteratura che offre importanti spunti di riflessione sul ruolo strategico che sta assumendo la dimensione territoriale dello sviluppo nell’attuale contesto di competizione globale. Inoltre, evidenzia come i mutamenti dell’economia mondiale hanno modificato anche le fonti del vantaggio competitivo e intensificato la complessità delle relazioni che caratterizzano un territorio. Nella prospettiva delineata, i sistemi territoriali sono al centro della competitizione globale e si trovano a dover fronteggiare la sfida di uno sviluppo competitivo ma sostenibile

Qualità alimentare e competitività di sistema

Food quality and competitive system The changes in the competitive scenario which agribusiness companies must deal with have determined the transition to an economic model in which the territory assumes an increasingly more important role. The objective of this work is to contribute to the broad debate on sustainable competitive development in a local key, to understand what could be the possible repositioning strategies for the agribusiness sector. This study, starting with the traditional determinants that, according to Porter, differentiate the competitive advantage of a country/territory system, aims to identify "particular" variables which will allow the focalization on a "sustainable" competitiveness in a territory. Furthermore, given the centrality of agribusiness in a strategy of competitive sustainable development, the most significant elements that characterize the baseline scenario are presented and possible strategic options for the sector are analyzed. Finally, a possible strategy is proposed for the overall development of agribusiness to enable this sector to contribute to a sustainable competitive development orientated on a "quality of system" approach.

Climate change, rural systems and innovation: the role of Internet

Climate change can compromise the development of the territorial systems with rural vocation. Nevertheless, these last can influence, both positively than negatively, the factors that determine climate change. Starting from this dichotomous vision of the relationship between climate change and rural development, this study focuses on the role that Internet and the web marketing strategies can develop in the mitigation and in the adaptation to climate change trough the spread of information on virtuous behaviour by individuals and firms. In such optics, the study, looking over agritourism as multifunctional farm with an orientation to sustainability, provides a survey to evaluate the diffusion of Internet in the Campania Region and the propensity of firms to use the web in order to promote responsible behaviour among the users of websites (suggesting virtuous behaviours) or to valorize their commitment in the fight against climate change

Sonic hedgehog pathway for the treatment of inflammatory diseases: implications and opportunities for future research

The Sonic hedgehog (Shh) signaling pathway is an essential pathway in the human body that plays an important role in embryogenesis and tissue homeostasis. Aberrant activation of this pathway has been linked to the development of different diseases, ranging from cancer to immune dysregulation and infections.Uncontrolled activation of the pathway through sporadic mutations or other mechanisms is associated with cancer development and progression in various malignancies, such as basal cell carcinoma, medulloblastoma, pancreatic cancer, breast cancer and small-cell lung carcinoma. Targeted inhibition of the pathway components has therefore emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Currently, two main components of the pathway, the smoothened receptor and the glioma-associated oncogene homolog transcriptional factors, have been investigated for the development of targeted drugs, leading to the marketing authorization of three smoothened receptor inhibitors for the treatment of basal cell carcinoma and acute myeloid leukemia.The Shh pathway also seems to be involved in regulating the immune response, possibly playing a role in immune system evasions by tumors, development of autoimmune diseases, such as rheumatoid arthritis and Crohn’s disease, airway inflammation, and diseases related to aberrant activation of T-helper 2 cellular response, such as allergy, atopic dermatitis, and asthma.Finally, the Shh pathway is involved in pathogen-mediated infection, including influenza-A and, more recently, SARS-CoV-2 viruses. Therefore, agents that inhibit the Shh signaling pathway might be used to treat pathogenic infections, shifting the therapeutic approach from strain-specific treatments to host-based strategies that target highly conserved host targets

Anatomic Examination of the Upper Head of the Lateral Pterygoid Muscle Using Magnetic Resonance Imaging and Clinical Data

The aim of this work was to ascertain the different kinds of insertion of the upper head of the lateral pterygoid muscle (LPM) on the temporomandibular joint and to clarify its physiology to understand its possible role in the dysfunction at the temporomandibular joint. Magnetic resonance imaging examinations were used in this work to achieve a direct view of the LPM on a large number of selected patients with dysfunction at the temporomandibular joint. The study population was composed of 92 patients, of whom 74 were women and 18 were men. Their age range was from 19 to 53 years (mean age, 31 years). The images were analyzed using the following parameters: symmetry of morphologic insertions of the upper head of the LPM, types of muscular insertion divided into 3 groups (A, single bundle on the capsule and condyle; B, one bundle on the disk and a second bundle on the condyle; and C, one bundle only on the disk), and relationship between disk position regarding the condyle in patients with disk dislocations with or without reduction and upper head of the LPM. The chi-square test was used to measure the magnitude of the results. It is possible to impute to the C-type insertion morphology a negative prognostic value for a long-term improvement of disk pathology and to consider the possibility that this muscle may contribute to dislocating the disk when its insertion was directed only on the disk itself. When the upper head of the LPM was inserted on the disk, the percentage of disk dislocation without reduction was greater

MEDUSA: a real-time multi-parameter marine monitoring research infrastructure

MEDUSA stands for Multiparametric Elastic-beacon Devices and Underwater Sensors Acquisition system. It is a marine monitoring research infrastructure based on instrumented geodetic-buoys with cabled seafloor multi-parametric modules operating in the Gulf of Pozzuoli (Naples, Italy) within the Campi Flegrei caldera. It mainly monitors the local seismicity and the seafloor movements (bradyseisms). MEDUSA consists of four buoys and as many submarine cabled modules, at water depth ranging from 38 to 96 meters, equipped with geophysical and oceanographic sensors. The infrastructure has been present since 2016 and allows the acquisition and transmission of all data in real time at the INGV (Istituto Nazionale di Geofisica e Vulcanologia, Italy) monitoring center in Naples, where they are integrated with those acquired by the on land networks. This new and augmented implementation is based on the previous experience gained during the realization of CUMAS (Cabled Underwater Multidisciplinary Acquisition System), the first prototype of instrumented buoy operating in the Gulf of Pozzuoli since 2008. CUMAS has allowed the acquisition of new skill in the design and management of fixed marine monitoring systems in shallow waters, making possible to reach precious reference points in the field of geophysical monitoring technologies. Each of buoys is equipped with a standard geodetic GNSS receiver (Leica GR10 and AR10 radome antenna), a heading (±1°), pitch and roll (±0.1°) monitoring system, the power-supply monitoring of the overall system (current, voltage and PV panel’s power), and, for only-one of this, a meteorological station (air pressure and temperature, wind velocity and direction), an IP web-enabled camera (nel visibile), and a pulsed K-band radar tide-gauge. Each seafloor modules is equipped with a Bottom Pressure Recorder (Paroscientific, 8CDP-130I), a low-frequency and broad-band Hydrophones, a tri-axial broad-band (120s ÷ 25Hz) Ocean Bottom Seismometer with auto-leveling system, a tri-Axial Micro Electro-Mechanical Systems accelerometer (DC ÷ 100Hz), the clock synchronization (1PPS and NMEA) with absolute GPS time reference on RS-422 interface, a heading, pitch and roll monitoring system, the power-supply monitoring system (current, voltage, water detector and on-off power control), and, for only-one of this, a 3-D Current-meter with water temperature sensor . Recently, a sea floor borehole precision tiltmeter (LILY, Jewell Instruments) has been installed to extend to the Gulf of Pozzuoli the on land tiltmeter network. The overall marine monitoring research infrastructure therefore acquires 152+ channels with sampling frequencies variable from 60 seconds to 200 Hz. All the data are stored in a relational database and the complete time series are visible on a dedicated website, where all data can be downloaded as files, in various formats available.PublishedVienna3A. Geofisica marina e osservazioni multiparametriche a fondo mar