Medication-Related Osteonecrosis of the Jaw

Osteonecrosis of the jaw (ONJ) is a common side effect of antiresorptive drugs that are administered to cancer patients for bone metastasis, multiple myeloma, and osteoporosis. Since both bisphosphonate (BP) and denosumab show anti-bone resorption effects with ONJ, antiresorptive agent-related ONJ (ARONJ) has been suggested as a comprehensive term encompassing both BP-related osteonecrosis of the jaw (BRONJ) and denosumab-related osteonecrosis of the jaw (DRONJ). The term medication-related osteonecrosis of the jaw (MRONJ) is proposed as ARONJ with the antiangiogenic inhibitors or molecularly targeted drugs-related ONJ. Suppression of bone remodeling may contribute to the development of osteonecrosis and results in inadequate osteoclast activity to allow healing of the extraction socket. Infection is a major factor in the development of MRONJ. The major treatment goals for patients at risk of developing or who have MRONJ are prioritization and support of continued oncologic treatment in patients receiving antiresorptive and antiangiogenic therapy. To minimize the development of MRONJ in patients at risk, regular dental examinations are encouraged. Oral hygiene should be improved and local infection is managed as early as possible. The use of antibiotics before and after oral surgical procedures has been demonstrated to lower the risk of MRONJ

The isolation and identification of the higher bone differentiation of mesenchymal stem cell from the pulp of human teeth and the application for the jaw bone regeneration.

科学研究費助成事業 研究成果報告書：基盤研究(C)2012-2014課題番号:2459298

Proton Beam Therapy for Ameloblastic Carcinoma of the Maxilla: Report of a Rare Case

Ameloblastic carcinoma (AC) is a rare malignant odontogenic tumor that combines the histologic features of ameloblastoma with those of cytologic atypia. The standard treatment for this lesion is wide local excision. Proton beam therapy (PBT) can deliver high irradiation doses to the target and avoid irradiation to surrounding normal tissues, but no reports of PBT for AC have been published thus far. This report describes the case of a 70-year-old woman with a pathologic diagnosis of maxillary AC who refused surgical resection and received hypofractionated PBT at a total dose of 69 Gy in 23 fractions. She has been alive for more than 5 years after PBT without any evidence of recurrence and side effects. This is the first reported case of successful treatment after curative radiation therapy for maxillary AC

Displacement-noise-free interferometeric gravitational-wave detector using unidirectional neutrons with four speeds

For further gravitational wave (GW) detections, it is significant to invent a technique to reduce all kinds of mirror displacement noise dominant at low frequencies for ground-based detectors. The neutron displacement-noise-free interferometer (DFI) is one of the tools to reduce all the mirror displacement noise at lower frequencies. In this paper, we describe a further simplified configuration of a neutron DFI in terms of neutron incidence direction. In the new configuration, neutrons enter the interferometer with unidirectional incidence at four speeds as opposed to two bidirectional incidences of opposite directions at two speeds as reported previously. This simplification of the neutron DFI is significant for proof-of-principle experiments

14-3-3 proteins stabilize LGI1-ADAM22 levels to regulate seizure thresholds in mice

新たなてんかん治療戦略を提案 --脳の過剰興奮を阻止するタンパク質ADAM22の量が鍵--. 京都大学プレスリリース. 2021-12-15.What percentage of the protein function is required to prevent disease symptoms is a fundamental question in genetic disorders. Decreased transsynaptic LGI1-ADAM22 protein complexes, because of their mutations or autoantibodies, cause epilepsy and amnesia. However, it remains unclear how LGI1-ADAM22 levels are regulated and how much LGI1-ADAM22 function is required. Here, by genetic and structural analysis, we demonstrate that quantitative dual phosphorylation of ADAM22 by protein kinase A (PKA) mediates high-affinity binding of ADAM22 to dimerized 14-3-3. This interaction protects LGI1-ADAM22 from endocytosis-dependent degradation. Accordingly, forskolin-induced PKA activation increases ADAM22 levels. Leveraging a series of ADAM22 and LGI1 hypomorphic mice, we find that ∼50% of LGI1 and ∼10% of ADAM22 levels are sufficient to prevent lethal epilepsy. Furthermore, ADAM22 function is required in excitatory and inhibitory neurons. These results suggest strategies to increase LGI1-ADAM22 complexes over the required levels by targeting PKA or 14-3-3 for epilepsy treatment

The effects of perioperative oral management on perioperative serum albumin levels in patients treated surgically under general anesthesia : A multicenter retrospective analysis in Japan

The purpose of the present study was to investigate the efficacy of perioperative oral managements (POMs) on perioperative nutritional conditions in patients undergoing surgery with general anesthesia. Medical records were retrospectively reviewed and the effects of POMs were investigated based on a large number of cases using a multicenter analysis. The profile of serum albumin levels was assessed and compared between patients with and without POMs using the multivariate analysis. Seventeen Eleven thousand and one hundred sixty patients (4,873 males and 6,287 females) were reviewed. Of these, 2710 patients (24.3%) had undergone POMs. The results of a multivariate analysis revealed the significant positive effect of POMs on perioperative serum albumin level (change between at admission and discharge, (Estimate: 0.022, standard error: 0.012, P < .0001). Patient gender, age, surgical site, performance status, the American Society of Anesthesiologists (ASA) physical status classification, operation time, amount of blood loss, and serum albumin level at admission were also significant predictors. Adjusted multivariate analysis of the effects of POMs on perioperative change of serum albumin level in all subjects reveled the significance of POMs intervention (estimate: 0.022, standard error: 0.012, P < .0001). These results suggest that POMs exerts significant positive effects on perioperative serum albumin levels in patients underwent surgery under general anesthesia

Deletion of both p62 and Nrf2 spontaneously results in the development of nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is one of the leading causes of chronic liver disease worldwide. However, details of pathogenetic mechanisms remain unknown. Deletion of both p62/Sqstm1 and Nrf2 genes spontaneously led to the development of NASH in mice fed a normal chow and was associated with liver tumorigenesis. The pathogenetic mechanism (s) underlying the NASH development was investigated in p62:Nrf2 double-knockout (DKO) mice. DKO mice showed massive hepatomegaly and steatohepatitis with fat accumulation and had hyperphagia-induced obesity coupled with insulin resistance and adipokine imbalance. They also showed dysbiosis associated with an increased proportion of gram-negative bacteria species and an increased lipopolysaccharide (LPS) level in feces. Intestinal permeability was elevated in association with both epithelial damage and decreased expression levels of tight junction protein zona occludens-1, and thereby LPS levels were increased in serum. For Kupffer cells, the foreign body phagocytic capacity was decreased in magnetic resonance imaging, and the proportion of M1 cells was increased in DKO mice. In vitro experiments showed that the inflammatory response was accelerated in the p62:Nrf2 double-deficient Kupffer cells when challenged with a low dose of LPS. Diet restriction improved the hepatic conditions of NASH in association with improved dysbiosis and decreased LPS levels. The results suggest that in DKO mice, activation of innate immunity by excessive LPS flux from the intestines, occurring both within and outside the liver, is central to the development of hepatic damage in the form of NASH