Risk factors for dental findings of the development of medication-related osteonecrosis of the jaw: Investigation of 3734 teeth in cancer patients receiving high dose antiresorptive agents.

Background/purpose: Local infection is a risk factor for medication-related osteonecrosis of the jaw (MRONJ), along with invasive dental treatment of the bone; the tooth that is the source of infection should be extracted prior to the administration of bone resorption inhibitors. However, which teeth should be extracted remains unclear. This study aimed to determine the relationship between dental findings prior to high-dose antiresorptive agent (ARA) administration and the subsequent development of MRONJ. Materials and methods: Patients with cancer who were scheduled to receive high-dose ARAs and referred to our hospital between 2011 and 2020 were included in this retrospective study. Apical lesions, enlargement of the periodontal space, thickening of the lamina dura, alveolar bone resorption of >1/3, periapical osteosclerosis, and local infection symptoms in each tooth were investigated using medical records and panoramic radiographs. Results: A total of 172 patients, 329 jaws, and 3734 teeth were registered. MRONJ developed in 68 teeth in 33 jaws of 32 patients. In tooth-by-tooth analysis, fewer teeth (P < 0.001), apical lesions (P < 0.001), periapical osteosclerosis (P < 0.001), local infection symptoms (P = 0.002), and one or more dental findings (P < 0.001) were significant factors for MRONJ development. In jaw-by-jaw analysis, old age, local infection symptoms, and number of radiographic abnormalities per tooth were significant. In patient-by-patient analysis, patients with diabetes and those with fewer teeth developed MRONJ. Conclusion: Patients with fewer teeth, apical lesions, periapical osteosclerosis, and local infection were more likely to develop MRONJ. Therefore, these teeth should be treated as much as possible before ARA administration.

Extranodal Extension and Epithelial Cell Adhesion Molecule Over-expression in Oral Squamous Cell Carcinoma.

BACKGROUND/AIM: Concomitant chemoradiotherapy (CCRT) with cisplatin is commonly administered after neck dissection in patients with oral squamous cell carcinoma (OSCC) showing extranodal extension (ENE). This study investigated whether the efficacy of CCRT differed depending on the degree of ENE and whether the expression of epithelial cell adhesion molecule (EpCAM) was associated with prognosis. PATIENTS AND METHODS: Patients with OSCC who underwent neck dissection and had histologically proven neck metastasis (pN+) were investigated retrospectively. ENE was divided into ENE minor (ENEmi; <2 mm) and ENE major (ENEma; ≥2 mm). The expression of EpCAM was also immunohistochemically examined using tissues obtained during neck dissection. RESULTS: One hundred and seventy pN+ cases [ENE(-), n=89; ENEmi, n=23; ENEma, n=58] were included. Multivariate analysis revealed that advanced T stage and ENEma were significantly correlated with poor prognosis. The 5-year disease-specific survival rates in ENE(-), ENEmi, and ENEma groups were 73.7%, 75.5%, and 28.0% respectively. An add-on effect of postoperative CCRT was not seen in the ENEmi group; however, postoperative CCRT improved the survival of patients in the ENEma group. In the ENEma group, the prognosis was significantly worse in EpCAM-positive patients than in EpCAM-negative patients. CONCLUSION: Postoperative CCRT may improve prognosis in ENEma cases. EpCAM expression may be a poor prognostic factor in ENEma cases. On the other hand, postoperative CCRT did not have a significant effect on prognosis in ENEmi cases. Among them, although there was no significant difference in the survival rate, postoperative CCRT could be omitted in ENEmi/EpCAM(-) cases.

Complete response of recurrent oral squamous cell carcinoma treated with cetuximab in combination with radiotherapy: A case series.

Salvage surgery for recurrent oral squamous cell carcinoma (OSCC) often leads to a poor quality of life (QOL). The present study described three cases that resulted in favorable locoregional control with cetuximab in combination with radiotherapy (Cmab + RT). Case 1 had regional recurrence of OSCC at the lower right mastoid area 4 months after primary surgery. Case 2 had regional recurrence of OSCC at the parotid area 7 months after primary surgery. Case 3 had local recurrence of OSCC at the masticatory muscle and Rouviere's lymph nodes 1 year and 3 months after primary surgery. In all cases, Cmab + RT was performed, and disease-free survival was confirmed 4 months, 2 years and 6 months, and 10 months after Cmab + RT, respectively. Immunohistochemically, all resected tumors had no expression of 110-kDa catalytic subunit of class IA phosphatidylinositol 3-kinase (PI3Kp110α). In conclusion, if salvage surgery for recurrent OSCC results in a significantly low QOL, then shifting to chemoradiotherapy may be appropriate as a treatment strategy. In addition, strong evidence indicated that PI3Kp110α expression is associated with Cmab therapy efficacy.

Metal leaching test of commercially available faucets in the Japanese market in 2016-2020.

In this study, metal leaching was investigated in commercially available faucets in Japan to clarify their compliance to Japanese regulations. We purchased 37 faucets from the market and analyzed the leaching of cadmium, mercury, selenium, lead (Pb), arsenic, hexavalent chromium, boron, zinc (Zn), copper, manganese, and nickel. The leaching tests were performed with and without a conditioning treatment, that simulated approximately 1-month intermittent use of faucets on weekdays, and the results were compared to estimate the changes in metal leaching during the use of faucets. The results revealed that metal leaching from most of the faucets complied with Japanese regulations. However, the levels of Pb leaching from several faucets produced by certain manufacturers exceeded the Japanese standard. The conditioning treatment was generally effective in reducing metal leaching. However, the reductions in Pb and Zn leaching tended to be lower than those of the other metals. Nickel is not legally regulated in Japan; although the number of cases where nickel concentration in leachate exceeded the water quality management target value was greater, such cases were limited to faucets primarily made of copper alloys. We believe that these results will be helpful to improve the public health associated with metal leaching from faucets.

Semi-fixed versus fixed oral appliance therapy for obstructive sleep apnea: A randomized crossover pilot study.

BACKGROUND/PURPOSE: Although mandibular advancement oral appliances (OAs) are the most widely used and accepted therapeutic modality for obstructive sleep apnea (OSA), whether these maxillary and mandibular appliances should be semi-fixed or fixed remains uncertain. This randomized crossover pilot study compared the efficacy, side effects, and patient preference of semi-fixed and fixed OAs for the treatment of OSA. MATERIALS AND METHODS: Patients with mild to moderate OSA were recruited and randomly assigned to either the semi-fixed or fixed OA group, whereby they used their assigned OA for the first 4 weeks, followed by assessments for sleep parameters (including the Apnea-Hypopnea Index [AHI]) and temporomandibular joint pain as a side effect. After a two-week washout period, patients were switched to the alternative OA for 4 weeks, followed by repeated assessments. Patient preference was assessed at the end of the completed treatment period. RESULTS: Fifteen patients were enrolled and completed the full study protocol. Both types of OAs were efficient in reducing the patient's AHI in comparison to baseline (i.e., without OA). However, there was no significant difference in AHI reduction between the semi-fixed and fixed OA devices. Regarding the side effect of temporomandibular joint pain and patient preference, the semi-fixed OA device was superior to the fixed OA device on both measures. CONCLUSION: While both semi-fixed and fixed OAs are effective in treating patients with OSA, semi-fixed OAs are superior in regards to both patient preference and reduced side effects. Thus, semi-fixed OAs may be the preferred therapeutic modality for OSA.

[Gingival squamous cell carcinoma diagnosed on the occasion of osteonecrosis of the jaw in a patient with chronic GVHD].

A 44-year-old male was diagnosed with acute myeloid leukemia with a complex karyotype. He underwent bone marrow transplantation using an HLA 6/6 antigen-matched sibling donor, but developed chronic graft-versus-host disease (cGVHD) with skin erythema and oral and esophageal lichen planus changes. Treatment with a combination of prednisolone and cyclosporine was initiated on day 646 after transplantation, but oral symptoms persisted. The patient developed bilateral osteonecrosis of the lower jaw after extraction of the lower left and right molars on days 2,861 and 3,339, respectively. As the disease gradually progressed, segmental mandibular osteotomy was performed. Biopsy specimens demonstrated proliferation of squamous epithelial carcinoma cells in the bilateral gingiva and lower jaw bone, which confirmed the diagnosis of bilateral gingival squamous cell carcinoma. Thus, gingival squamous cell carcinoma should be considered as a differential diagnosis in post-transplant patients with refractory osteonecrosis of the jaw during the course of cGVHD.

Preparation of robust braid-reinforced poly(vinyl chloride) ultrafiltration hollow fiber membrane with antifouling surface and application to filtration of activated sludge solution.

Braid-reinforced hollow fiber membranes with high mechanical properties and considerable antifouling surface were prepared by blending poly(vinyl chloride) (PVC) with poly(vinyl chloride-co-poly(ethylene glycol) methyl ether methacrylate) (poly(VC-co-PEGMA)) copolymer via non-solvent induced phase separation (NIPS). The tensile strength of the braid-reinforced PVC hollow fiber membranes were significantly larger than those of previously reported various types of PVC hollow fiber membranes. The high interfacial bonding strength indicated the good compatibility between the coating materials and the surface of polyethylene terephthalate (PET)-braid. Owing to the surface segregation phenomena, the membrane surface PEGMA coverage increased upon increasing the poly(VC-co-PEGMA)/PVC blending ratio, resulting in higher hydrophilicities and bovine serum albumin (BSA) repulsion. To compare the fouling properties, membranes with similar PWPs were prepared by adjusting the dope solution composition to eliminate the effect of hydrodynamic conditions on the membrane fouling performance. The blend membranes surface exhibited considerable fouling resistance to the molecular adsorption from both BSA solution and activated sludge solution. In both cases, the flux recovered to almost 80% of the initial flux using only water backflush. Considering their great mechanical properties and antifouling resistance to activated sludge solution, these novel membranes show good potential for application in wastewater treatment.

Discrepant membrane fouling of partial nitrification and anammox membrane bioreactor operated at the same nitrogen loading rate.

In this study, two times more serious membrane fouling was found in anammox membrane bioreactor, compared to partial nitrification membrane bioreactor (PN-MBR) operated at the same nitrogen loading rate. By protein, polysaccharide, amino acids and functional groups analysis, it was found that the discrepancy in membrane fouling was virtually due to the difference in microbial products of nitrifiers and anammox bacteria. Protein and polysaccharide were main foulants on membrane surface; meanwhile theirs content and ratio in the EPS, supernatant and membrane surface were significantly different in PN-MBR and anammox-MBR. The anammox metabolism products contained much more hydrophobic organics, hydrophobic amino acids, and hydrophobic functional groups than nitrifiers. A mass of anammox bacteria as well as hydrophobic metabolism products deposited on the hydrophobic membrane surface and formed serious fouling. In further, hydrophilic modification is more urgently needed to mitigate membrane fouling when running anammox-MBR, than PN-MBR.

Progress toward the Total Synthesis of Goniodomin A: Stereocontrolled, Convergent Synthesis of the C12-C36 Fragment.

Goniodomin A is a marine polyether macrolide natural product isolated from the dinoflagellate Alexandrium hiranoi. In this paper, we report stereocontrolled, convergent synthesis of a fully functionalized C12-C36 fragment of goniodomin A. The synthesis of the C12-C25 vinylstannane involved a Wittig reaction and a reductive cycloetherification for the construction of the dihydropyran ring. The C26-C36 thioester was synthesized via a Nozaki-Hiyama-Kishi reaction of an aldehyde and an iodoalkyne, the former of which was easily prepared from (R)-malic acid as a chiral source by taking advantage of substrate-controlled diastereoselective reactions. Finally, a palladium-catalyzed coupling of the C12-C25 vinylstannane and the C26-C36 thioester completed the synthesis of the target compound.

Mitigated membrane fouling of anammox membrane bioreactor by microbiological immobilization.

In this study, membrane fouling behavior of anammox MBR with or without carriers made by magnetic porous carbon microspheres was investigated. The results show that Trans Membrane Pressure was an order of magnitude lower after 50days due to use of carriers, which did not directly contact with membrane surface. Scanning Electron Microscope analysis indicates that abundance of anammox bacteria formed biofilm on membrane surface. Fourier transform infrared spectroscopy combined with amino acids contents analysis for membrane surface deposition show that metabolite released by anammox bacteria contains more hydrophobic groups than hydrophilic, which was considered as important reason for its abundant existence on hydrophobic membrane surface. Microbiological immobilization not only reduces biological membrane fouling, but also mitigates organic fouling including organic matter containing COO, hydrophobic groups (CH3, CH2 and CH etc), as well as inorganic deposition. Our finding provides an effective method for mitigating MBR membrane fouling in anammox process.

Proteins causing membrane fouling in membrane bioreactors.

In this study, the details of proteins causing membrane fouling in membrane bioreactors (MBRs) treating real municipal wastewater were investigated. Two separate pilot-scale MBRs were continuously operated under significantly different operating conditions; one MBR was a submerged type whereas the other was a side-stream type. The submerged and side-stream MBRs were operated for 20 and 10 days, respectively. At the end of continuous operation, the foulants were extracted from the fouled membranes. The proteins contained in the extracted foulants were enriched by using the combination of crude concentration with an ultrafiltration membrane and trichloroacetic acid precipitation, and then separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). The N-terminal amino acid sequencing analysis of the proteins which formed intensive spots on the 2D-PAGE gels allowed us to partially identify one protein (OmpA family protein originated from genus Brevundimonas or Riemerella anatipestifer) from the foulant obtained from the submerged MBR, and two proteins (OprD and OprF originated from genus Pseudomonas) from that obtained from the side-stream MBR. Despite the significant difference in operating conditions of the two MBRs, all proteins identified in this study belong to ß-barrel protein. These findings strongly suggest the importance of ß-barrel proteins in developing membrane fouling in MBRs.

Application of glyco-blotting for identification of structures of polysaccharides causing membrane fouling in a pilot-scale membrane bioreactor treating municipal wastewater.

A new approach for the analysis of polysaccharides in membrane bioreactor (MBR) is proposed in this study. Enrichment of polysaccharides by glyco-blotting, in which polysaccharides are specifically collected via interactions between the aldehydes in the polysaccharides and aminooxy groups on glycoblotting beads, enabled MALDI-TOF/MS analysis at a high resolution. Structures of polysaccharides extracted from fouled membranes used in a pilot-scale MBR treating municipal wastewater and those in the supernatant of the mixed liquor suspension in the MBR were investigated. It was found that the overlap between polysaccharides found in the supernatants and those extracted from the fouled membrane was rather limited, suggesting that polysaccharides that dominate in supernatants may not be important in membrane fouling in MBRs. Analysis using a bacterial carbohydrate database suggested that capsular polysaccharides (CPS) and/or lipo-polysaccharides (LPS) produced by gram-negative bacteria are key players in the evolution of membrane fouling in MBRs.

Toxicity assessment of chlorinated wastewater effluents by using transcriptome-based bioassays and Fourier transform mass spectrometry (FT-MS) analysis.

Effects of chlorination on the toxicity of wastewater effluents treated by activated sludge (AS) and submerged membrane bioreactor (S-MBRB) systems to HepG2 human hepatoblastoma cells were investigated. In addition to the cytotoxicity and genotoxicity assays, the DNA microarray-based transcriptome analysis was performed to evaluate the change in types of biological impacts on HepG2 cells of the effluents by chlorination. Effluent organic matter (EfOM) and disinfection by-products (DBPs) were also characterized by using Fourier transform mass spectrometry (FT-MS). Although no significant induction of genotoxicity was observed by chlorination for both effluents, the chlorination elevated the cytotoxicity of AS effluent but reduced that of S-MBRB effluent. The FT-MS analyses revealed that more DBPs including nitrogenated DBPs (N-DBPs) were formed in the AS effluent than in the S-MBRB effluent by chlorination, supporting the increased cytotoxicity of AS effluent. The lower O/C ratio of S-MBRB EfOM suggests that a large number of organic molecules were detoxified by chlorination, which consequently decreased the cytotoxicity of S-MBRB effluent. Integration of all the results highlights that both cytotoxicity and biological impacts of chlorinated wastewater effluents were clearly dependent on the EfOM characteristics such as DBPs and O/C ratio, namely, on types of treatment systems.

Evaluation of whole wastewater effluent impacts on HepG2 using DNA microarray-based transcriptome analysis.

DNA microarray-based transcriptome analysis with human hepatoma HepG2 cells was applied to evaluate the impacts of whole wastewater effluents from the membrane bioreactors (MBRs) and the activated sludge process (AS). In addition, the conventional bioassays (i.e., cytotoxicity tests and bioluminescence inhibition test), which were well-established for the evaluation of the overall effluent toxicity, were also performed for the same samples. Transcriptome analysis revealed that 2 to 926 genes, which were categorized to 0 to 225 biological processes, were differentially expressed after exposure to the effluents and the raw wastewater. Among the tested effluents, the effluent from a MBR operated at a relatively long solid retention time (i.e., 40 days) and small membrane pore size (i.e., 0.03 µm) showed the least impacts on the HepG2 even at the level comparable to tap water. The observed gene expression responses were in good agreement with the results of cytotoxicity tests, and provided additional molecular mechanistic information on adverse effects occurred in the sublethal region. Furthermore, the genes related to "lipid metabolism", "response to endogenous stimulus", and "response to inorganic substance" were selected as potential genetic markers, and their expression levels were quantified to evaluate the cellular impacts and treatability of wastewater effluents. Although the harmful impacts and innocuous impacts could not be distinguished at present, the results demonstrated that the DNA microarray-based transcriptome analysis with human HepG2 cells was a powerful tool to rapidly and comprehensively evaluate impacts of whole wastewater effluents.

Further examination of polysaccharides causing membrane fouling in membrane bioreactors (MBRs): Application of lectin affinity chromatography and MALDI-TOF/MS.

Membrane fouling remains a major obstacle for wider application of membrane bioreactors (MBRs) to wastewater treatment. Polysaccharides in mixed liquor suspensions in the reactors are thought to be mainly responsible for the evolution of membrane fouling in MBRs. However, details of polysaccharides causing membrane fouling in MBRs are still unknown. In this study, polysaccharides in a mixed liquor suspension of a pilot-scale MBR treating municipal wastewater were fractionated by using lectins, special proteins that bind to specific polysaccharides depending on their properties. Fouling potentials of the fractionated polysaccharides were assessed by bench-scale dead-end filtration tests. It was clearly shown that the degrees of fouling caused by fractionated polysaccharides were significantly different. The amounts of polysaccharides in each fraction could not explain the variations in the fouling, indicating the presence of polysaccharides with high specific fouling potentials. To investigate structures and origins of the polysaccharides with high fouling potentials, matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF)/mass spectrometry (MS) analysis was applied to the fractionated polysaccharides after partial hydrolysis. Several mass peaks obtained could be assigned to fragments of structures of polysaccharides (i.e., oligosaccharides) reported in a database/literature. This is the first report showing the plausible structures of polysaccharides in MBRs based on MS. A deeper understanding and effective control of membrane fouling in MBRs could be achieved with information obtained by the approach used in this study.

Seasonal variation in membrane fouling in membrane bioreactors (MBRs) treating municipal wastewater.

We investigated seasonal variation in membrane fouling in membrane bioreactors (MBRs) treating municipal wastewater regarding the difference between physically reversible and irreversible fouling. Two separate MBRs with different solid retention times (SRTs) operated in parallel for about 200 days including high- and low-temperature periods to evaluate the effect of operating conditions on seasonal variation of membrane fouling. Seasonal variations of both types of membrane fouling (i.e., physically reversible and irreversible fouling) were observed for the MBR with short SRT (13 days). However, in the MBR with long SRT (50 days), there were no significant seasonal variations in both types of membrane fouling. In the MBR with short SRT, the trends in the seasonal variation in the development rates of physically reversible and irreversible fouling were different. Physically reversible fouling was more significant in the low-temperature period, while physically irreversible fouling developed more rapidly in the high-temperature period. The development rates of physically reversible fouling can be related to the concentration of dissolved organic matter in the mixed liquor suspension of MBRs; whereas those of physically irreversible fouling could not be explained by the concentration of dissolved organic matter. The characteristics of dissolved organic matter differed depending on the temperature period, and the trends of dissolved organic matter variation in mixed liquor were similar with those of foulants that caused physically irreversible fouling. The results obtained in this study indicated that seasonal variation in physically reversible and irreversible fouling is related to changes in quantity and quality of organic matter, respectively.

Baffled membrane bioreactor (BMBR) for efficient nutrient removal from municipal wastewater.

Submerged membrane bioreactors (MBRs) are now widely used for various types of wastewater treatment. One drawback of submerged MBRs is the difficulty in removing nitrogen because intensive aeration is usually carried out in the tank and the MBRs must therefore be operated under aerobic conditions. In this study, the feasibility of treating municipal wastewater by a baffled membrane bioreactor (BMBR), particularly in terms of nitrogen removal, was examined. Simultaneous nitrification/denitrification in a single and small reaction tank was possible by inserting baffles into a normal submerged MBR as long as wastewater was fed in the appropriate way. To examine the applicability of the BMBR, pilot-scale experiments were carried out using real municipal wastewater. Although neither external carbon addition nor mixed liquor circulation was carried out in the operation of the BMBR, average removal rates of total organic carbon (TOC), total phosphorus (T-P) and total nitrogen (T-N) reached 85%, 97% and 77%, respectively, with the hydraulic retention time (HRT) of 4.7h. Permeability of the membrane could be maintained at a high level throughout the operation. It was found that denitrification was the limiting step in removal of nitrogen in the BMBR in this study. Various types of monitoring carried out in the BMBR also demonstrated the possibility of further improvements in its performance.