Tocilizumab: Another medication related to osteonecrosis of the jaws? A case report and literature review.

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication in patients receiving antiresorptive medication, such as bisphosphonates and denosumab, for different oncologic and non-oncologic diseases. Here, we report a case of MRONJ in a patient treated with tocilizumab, a humanized anti-interleukin-6 receptor antibody that effectively treats moderate to severe rheumatoid arthritis in adults. Case description: A 45-year-old female patient diagnosed with severe rheumatoid arthritis, who had been undergoing intravenous tocilizumab therapy for three years without history of bisphosphonate use, was referred to our department. Four weeks previously, several teeth in the maxilla and mandible were removed under local anesthesia by her dentist. Two weeks after the extractions, she felt pain in both jaws. We diagnosed wound dehiscence and delayed healing of the alveolar bone after the tooth extractions. Digital volume tomography showed persistent dry alveolar sockets. The patient underwent surgical debridement of necrotic bone, and intravenous antibiotics were administered in hospital. Five months later, wound dehiscence reoccurred in the same regions. Histopathological analysis of bone biopsies revealed a diagnosis of MRONJ. Four months later, wound dehiscence occurred in the left maxillary alveolar ridge, and local bone resection was performed under antibiotic treatment. Twenty-four months after the last surgery, wound dehiscence had healed completely without signs of recurrence. Discussion: Osteomyelitis of the jaw in patients treated with tocilizumab has not been reported often. This case confirms the potential role of this interleukin-6 receptor inhibitor in the pathogenesis of MRONJ and shows that patients who receive tocilizumab with MRONJ-like symptoms should be closely monitored. The pathomechanism of MRONJ under tocilizumab therapy remains unclear, so dental practitioners, maxillofacial surgeons, and rheumatologists should look for signs of MRONJ in patients receiving tocilizumab to prevent MRONJ onset.

Eggerthia catenaformis infection originating from a dental abscess causes severe intestinal complications and osteomyelitis of the jaw.

Introduction: Odontogenic foci may result to generalized infections spreading the bacteria through contiguous anatomic cavities or hematogenous spread. The most reported secondary infections caused by oral pathogens are intracranial abscesses. Although, few reports in the literature describe the bacterial spread to extracranial locations. Case description: We describe the case of a 52-year-old male Caucasian patient who was admitted to our hospital suffering from severe sepsis caused by a submandibular abscess. Eggerthia catenaformis was detected in blood and abscess material (confirmed by MALDI-TOF mass spectrometry). The patient subsequently developed a perihepatic abscess and colon perforation, and was stabilized after several surgical interventions. He remained hospitalized for 66 days receiving intravenous antibiotics. Five months later, jaw osteonecrosis with Actinomyces contamination was detected in the left mandible, which also had to be treated surgically. Three years after the last surgery, no signs of recurrence have been detected. Discussion: Oral and maxillofacial surgeons should understand the characteristics of systemic infections, in which the potentially causal intraoral odontogenic foci often lack acute symptoms. If other origins of infection are not detected, elimination of the potentially causal odontogenic foci should be performed. However, the decision making criteria to eliminate suspected causal teeth is needed to be elucidated through more studies.

Formation of α clusters in dilute neutron-rich matter.

The surface of neutron-rich heavy nuclei, with a neutron skin created by excess neutrons, provides an important terrestrial model system to study dilute neutron-rich matter. By using quasi-free α cluster-knockout reactions, we obtained direct experimental evidence for the formation of α clusters at the surface of neutron-rich tin isotopes. The observed monotonous decrease of the reaction cross sections with increasing mass number, in excellent agreement with the theoretical prediction, implies a tight interplay between α-cluster formation and the neutron skin. This result, in turn, calls for a revision of the correlation between the neutron-skin thickness and the density dependence of the symmetry energy, which is essential for understanding neutron stars. Our result also provides a natural explanation for the origin of α particles in α decay.

Automatic Knowledge Extraction to build Semantic Web of Things Applications.

The Internet of Things (IoT) primary objective is to make a hyper-connected world for various application domains. However, IoT suffers from a lack of interoperability leading to a substantial threat to the predicted economic value. Schema.org provides semantic interoperability to structure heterogeneous data on the Web. An extension of this vocabulary for the IoT domain (iot.schema.org) is an ongoing research effort to address semantic interoperability for the Web of Things (WoT). To design this vocabulary, a central challenge is to identify the main topics (concepts and properties) automatically from existing knowledge in IoT applications. We designed KE4WoT (Knowledge Extraction for the Web of Things) to automatically identify the most important topics from literature ontologies of 3 different IoT application domains - smart home, smart city and smart weather - based on our corpus consisting of 4500 full-text conference and journal articles to utilize domain-specific knowledge encoded within IoT publications. Despite the importance of automatically identifying the relevant topics for iot.schema.org, up to know there is no study dealing with this issue. To evaluate the extracted topics, we compare the descriptiveness of these topics for the 10 most popular ontologies in the 3 domains with empirical evaluations of 23 domain experts. The results illustrate that the identified main topics of IoT ontologies can be used to sufficiently describe existing ontologies as keywords.

Similar regulation of human inducible nitric-oxide synthase expression by different isoforms of the RNA-binding protein AUF1.

The ARE/poly-(U) binding factor 1 (AUF1), a protein family consisting of four isoforms, is believed to mediate mRNA degradation by binding to AU-rich elements (ARE). However, evidence exists that individual AUF1 isoforms may stabilize ARE-containing mRNAs. The 3'-untranslated region of the human inducible nitric-oxide synthase (iNOS) contains five AREs, which promote RNA degradation. We have recently shown that the RNA-binding protein KSRP is critically involved in the decay of the iNOS mRNA. In this study we examined the effects of the individual AUF1 isoforms on iNOS expression. Overexpression of each AUF1 isoform reduces iNOS expression on mRNA and protein levels to the same extent by modulation of mRNA stability. Accordingly, knockdown of all or individual AUF1 isoforms by an RNA interference approach enhances iNOS expression. The AUF1 effect on iNOS expression is dependent on the iNOS 3'-untranslated region sequence, as demonstrated in transfection experiments with a reporter mRNA. Binding studies showed that all AUF1 isoforms interact with the same AU-rich region in the iNOS-3'-untranslated region. Cytokine stimulation altered intracellular AUF1 binding activities. These data demonstrate that AUF1 is an important factor that promotes iNOS mRNA degradation. Furthermore, all individual AUF1 isoforms act in a similar manner.