Survival time analysis of remaining teeth following replacement of unilateral free-end missing teeth: A comparison between fixed implant-supported prostheses and removable partial dentures.

OBJECTIVES: This retrospective study aimed to investigate the differences in tooth loss rate between fixed implant-supported prostheses (FISPs) and removable partial dentures (RPDs) in cases of unilateral free-end missing teeth. MATERIALS AND METHODS: The data of 324 patients who underwent treatment with FISPs or RPDs for unilateral free-end missing teeth and satisfied the applicable criteria, were evaluated (47 in the FISPs group and 277 in the RPDs group). After propensity score (PS) matching, which was used to extract patients with similar background factors related to prosthetic selection at baseline, survival time analyses were performed with tooth loss as the endpoint. The adjusted variables were age, sex, number of restored teeth, periodontal status, and the practicing dentist's experience in years. The remaining teeth were classified into subcategories in relation to the missing molars. RESULTS: Overall, 58 patients (29 in each group) selected by PS matching were evaluated in the final analysis. The total number of lost teeth was 35 (FISPs group: n = 10; RPDs group: n = 25). The mean (±SD) period to tooth loss and the 10-year survival rates in the FISPs and RPDs groups were 51.6 (±30.1) months and 42.3 (±29.7) months, 70.5% and 16.4%, respectively. The log-rank test showed that significantly longer survival time in FISPs compared with RPDs. CONCLUSIONS: After adjustments for confounding factors using PS matching, replacing unilateral free-end missing teeth with FISPs may exhibit a lower tooth loss rate in adjacent and contralateral teeth compared to replacing with RPDs.

Telepathology in intraoperative frozen section consultation of breast cancer sentinel node biopsy in Fukushima, Japan following the 2011 triple disaster: diagnostic accuracy and required time during the early implementation phase.

In breast cancer surgery, some medical facilities lack the necessary resources to conduct sentinel lymph node biopsy and its intraoperative frozen section consultation. In the coastal rural area of Fukushima, Japan, which has suffered from physician undersupply following the 2011 triple disaster of earthquake, tsunami and nuclear disaster, we explored the feasibility of telepathology by evaluating the diagnostic accuracy in remote intraoperative frozen section consultation of sentinel lymph node biopsy and its required time. Although examination time has room for improvement, telepathology can be one possible solution in resource-limited areas.

Electronic structure of dense solid oxygen from insulator to metal investigated with X-ray Raman scattering.

Electronic structures of dense solid oxygen have been investigated up to 140 GPa with oxygen K-edge X-ray Raman scattering spectroscopy with the help of ab initio calculations based on density functional theory with semilocal metageneralized gradient approximation and nonlocal van der Waals density functionals. The present study demonstrates that the transition energies (Pi*, Sigma*, and the continuum) increase with compression, and the slopes of the pressure dependences then change at 94 GPa. The change in the slopes indicates that the electronic structure changes at the metallic transition. The change in the Pi* and Sigma* bands implies metallic characteristics of dense solid oxygen not only in the crystal a-b plane but also parallel to the c axis. The pressure evolution of the spectra also changes at ∼40 GPa. The experimental results are qualitatively reproduced in the calculations, indicating that dense solid oxygen transforms from insulator to metal via the semimetallic transition.

Spermine Suppresses Adipocyte Differentiation and Exerts Anti-Obesity Effects In Vitro and In Vivo.

Endogenous polyamines such as putrescine (Put), spermidine (Spd), and spermine (Spm) affect adipocyte differentiation. In this study, we investigated the effect of exogenously supplemented polyamines on mouse adipocyte differentiation and anti-obesity actions in vitro and in vivo. The preadipocyte cell line, 3T3-L1, was cultured with Put, Spd, or Spm, and lipid accumulation in the cells was measured by Oil Red O staining. Lipid accumulation was significantly suppressed by Spm. Suppression of CCAAT/enhancer binding protein α mRNA by Spm suggested that the decreased lipid accumulation was due to delaying the cell differentiation. The body weight and fat of obese mice induced with a high-fat diet were reduced by oral ingestion of Spm. In conclusion, oral supplementation of Spm has the ability to prevent obesity through inhibition of adipocyte differentiation.

Pharmaceutical good manufacturing practice: Leuplin® production in Japan identifies major international shortcomings.

In Japan, the production of Leuplin®, a key drug for the treatment of prostate cancer and breast cancer, was temporarily suspended in 2020 by the manufacturer. The incident illustrated several significant failings, namely the lack of uniformity in international GMP (Good Manufacturing Practice) regulations, the lack of mechanisms to resolve disputes between PIC/S (Pharmaceutical Inspection Co-operation Scheme) member countries, and the importance of maintaining a stable supply of safe GMP-compliant essential medicines.

Two- and ten-year follow-up of patients responding and non-responding to the surgical treatment of peri-implantitis: A retrospective evaluation.

OBJECTIVES: To report a follow-up of patients following the surgical anti-infective treatment of peri-implantitis and to identify possible risk indicators for the progression of disease during supportive peri-implant therapy. MATERIAL AND METHODS: Following peri-implant surgery, 41 patients (213 implants) were enrolled in a supportive peri-implant therapy. At the 2-year follow-up, two groups of patients were identified, with or without residual peri-implant pockets (responding and non-responding group). Eighteen patients (85 implants) of the non-responding group were followed for further 8 years. RESULTS: At the 2-year examination, 73 of the 117 treated implants (62.4%) presented healthy peri-implant condition, while 44 (37.6%) presented persisting peri-implantitis associated with substantial bone loss before treatment. The 10-year examination of the non-responding group revealed that 1) 84% of the implants that regained health following surgery remained healthy during the entire observation period; 2) 66% of the implants with residual pockets following surgery maintained stable peri-implant condition; and 3) 29% of all treated implants showed disease progression, and 11 of those were extracted. Presence of pockets at 3-4 sites of the implants was identified as risk indicator for progression of peri-implantitis. CONCLUSION: The peri-implant health achieved following therapy was maintained for most of the implants during the follow-up. Residual pockets were a frequent finding at implants with substantial bone loss before treatment. Presence of pockets around the entire circumference of the implants resulted as a risk indicator for further disease progression. The probability of progression of peri-implant disease increased with increased observation time.

Two New Halogenated Compounds from the Marine Red Alga Laurencia nipponica Yamada from the Kunashiri and Etorofu Islands.

The red alga Laurencia nipponica comprises various chemical races distributed relative to the ocean current in Japanese coastal areas. We investigated the chemical compositions and chemical races of L. nipponica distributed from the Kunashiri and Etorofu Islands, the confluence of the Soya warm current and Oya-shio cold current. Two new halogenated secondary metabolites, deacetylneonipponallene (1) and neopacifenol (2), along with four known compounds, deoxyprepacifenol (3), pacifenol (4), halo-chamigrene diether (5), and isolaurallene (6) were isolated from L. nipponica collected at Chikappunai, Kunashiri Island, while Zaimokuiwa (Kunashiri Island) and Sana (Etorofu Island) populations contained 3, 7-hydroxylaurene (7), 2,10-dibromo-3-chloro-9-hydroxy-α-chamigrene (8), and (3Z)-laurefucin (9). The structures of 1 and 2 were established using spectroscopic methods. The chemical races of L. nipponica distributed in this area were divided into 6- and 9-producing races. Interestingly, both races contained 4 as an additional race-index, as well as its derivatives, 2 and 5. To the best of our knowledge, this is the first example of a race comprising a mixture of two race-index compounds, suggesting that the convergence of two currents causes the production of new and diverse chemical races in this species.

Prevalence of peri-implant disease and risk indicators in a Japanese population with at least 3 years in function-A multicentre retrospective study.

OBJECTIVES: The aim of this study was to evaluate the prevalence of peri-implant disease and analyze risk indicators in Japanese subjects with ≥3 years of implant function. MATERIAL AND METHODS: Five hundred and forty-three subjects treated with 1,613 implants were evaluated. Information was collected about the patients' physical and dental history, as well as implant details. Peri-implant evaluation included probing depth, bleeding on probing (BoP), suppuration (Sup), and keratinized tissue width. Bone loss was calculated from intra-oral radiographs taken after 1 year and more than 3 years of function. Implants were classified into three groups: healthy, peri-implant mucositis (BoP without bone loss), and peri-implantitis (BoP and/or Sup with bone loss >1 mm). These data were analyzed by multivariable multinomial logistic regression. RESULTS: The prevalence of peri-implant mucositis and peri-implantitis at the subject level was 23.9% and 15.8%, respectively. An association was found between peri-implant mucositis and plaque control record (PCR) >20% and keratinized tissue width <2 mm. Peri-implantitis was associated with PCR >20%, smoking, insertion in the maxilla, and keratinized tissue width <2 mm. CONCLUSIONS: Within the limitations of this study, the prevalence of peri-implant diseases was elucidated in a Japanese population. Peri-implant mucositis was associated with poor oral hygiene and less keratinized tissue. Poor oral hygiene, smoking, insertion in the maxilla, and less keratinized tissue were risk indicators for peri-implantitis.

Short communication: Milk basic protein promotes proliferation and inhibits differentiation of mouse chondrogenic ATDC5 cells.

It has been reported that the intake of milk basic protein (MBP) increases bone density by promoting bone formation and suppressing bone resorption. However, few studies have been done on MBP in cartilage, the tissue adjacent to bone. We therefore investigated the effect of MBP on a chondrocyte cell line, ATDC5. In a proliferative assay using the WST-1 method, the addition of 10, 100, and 1,000 µg/mL of MBP to ATDC5 cells significantly increased the cell number by about 1.2-, 1.5-, and 1.7-fold, respectively, compared with the control cells. The cell cycle analysis using flow-cytometry revealed that the proportion of S- and G2/M-phase cells was increased but that of G0/G1 phase was decreased in a dose-dependent manner with MBP addition. We measured the alkaline phosphatase activity of MBP-treated ATDC5 cells to examine the differentiation stage of the cells. Alkaline phosphatase activity was suppressed in a dose-dependent manner with MBP addition and was especially drastic at higher doses of MBP (100 and 1,000 µg/mL). The Alizarin Red S staining intensity, the indicator for calcification of cells, was lower in the MBP-treated (100 µg/mL) cells than in nontreated control cells. In the reverse-transcription PCR experiment, the mRNA level of SRY-box containing gene 9 (Sox9) and type II collagen (Col2) was significantly increased in the MBP-treated cells compared with the control cells. A significant decrease of the mRNA level of runt-related transcription factor 2 (Runx2) and type X collagen (Col10) was also observed in the MBP-treated cells. These results suggested that MBP promoted the proliferation of chondrocytes by suppressing their differentiation toward calcification.

Gonial Angle Measured by Orthopantomography as a Predictor of Maximum Occlusal Force.

PURPOSE: To establish the accuracy of measuring the gonial angle on an orthopantomogram (GAO), as defined by the anatomic relationship between the inferior and posterior borders of the mandible. Furthermore, to examine the relationship between GAO and maximum occlusal force (MOF) in the premolar and molar regions of healthy young adults. MATERIALS AND METHODS: Orthopantomograms of dry mandibles were obtained in three orientations in the sagittal plane, to represent variation in image acquisition in clinical settings. The GAO was measured using image-processing software, and reliability was analyzed using the intraclass correlation coefficient. Then, GAO, MOF, gender, and body mass index (BMI) were measured in a cohort of healthy young adult volunteers. MOF was measured using an Occlusal Force Meter GM 10 device. The relationships between GAO, MOF, sex, and BMI were examined using the Pearson correlation coefficient and multiple regression analysis. RESULTS: In five dry mandibles, there was a high correlation between the GAOs measured in the different orientations (p < 0.001). In 58 healthy volunteers (31 women and 27 men, mean age 24.6 years), the mean GAO was 123.3° ± 7.5°. The mean MOFs at the first premolar, second premolar, and first molar teeth were 256.4 N ± 128.3 N, 319.0 N ± 171.7 N, and 487.5 N ± 227.2 N, respectively. Men had significantly greater MOF than women at all teeth. The GAO was significantly inversely correlated with MOF at the second premolar (r = -0.376, p = 0.005) and first molar teeth (r = -0.479, p < 0.001). Multiple regression analysis showed that GAO was a significant explanatory factor for MOF at the second premolar and first molar teeth (p = 0.012 and 0.001, respectively). CONCLUSIONS: GAOs were measured accurately on the orthopantomograms taken in this study and were a reliable predictor of MOF between the second premolar and first molar teeth. A smaller GAO was associated with a greater MOF at the second premolar and first molar teeth.

Phase II trial of eribulin mesylate as a first- or second-line treatment for locally advanced or metastatic breast cancer: a multicenter, single-arm trial.

BACKGROUND: Eribulin mesylate is currently indicated as a sequential monotherapy to be administered after two chemotherapeutic regimens, including anthracycline and taxane treatments, for treatment of metastatic breast cancer. This open-label, multicenter phase II study was designed to evaluate the efficacy and safety of eribulin as a first- or second-line treatment for patients with metastatic breast cancer. METHODS: The primary objective was to determine the overall response rate. Secondary objectives were to evaluate progression-free survival and the safety profile. Patients were scheduled to receive eribulin mesylate 1.4 mg/m2 intravenously on days 1 and 8 of a 21-day cycle. Patients received the study treatment unless disease progression, unacceptable toxicity, or a request to discontinue from the patient and/or investigator eventuated. RESULTS: Between December 2012 and September 2015, 32 patients with metastatic breast cancer were enrolled at 10 participating clinical institutions in Japan, and toxicity and response rates were evaluated. The overall response rate was 43.8% (95% confidence interval [CI] 26.5-61.0). The clinical benefit and tumor control rates were 56.3% (95% CI 39.0-73.5) and 78.1% (95% CI 63.8-92.5), respectively. Median progression-free survival was 8.3 months (95% CI 7.1-9.4). A subgroup analysis did not identify any factors affecting the efficacy of eribulin. The most common adverse events were neutropenia (71.9%), alopecia (68.7%), and peripheral neuropathy (46.9%). As a first- or second-line therapy, eribulin showed sufficient efficacy for metastatic breast cancer compared with taxane and capecitabine treatment in previous clinical trials. The safety profile of eribulin was acceptable. CONCLUSIONS: Eribulin may be another option for first-line chemotherapeutic regimens for metastatic breast cancer. TRIAL REGISTRATIONS: This trial was retrospectively registered at the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (ID number: UMIN000010334 ). Date of trial registration: April 1st, 2013.

Supplemented Chondroitin Sulfate and Hyaluronic Acid Suppress Mineralization of the Chondrogenic Cell Line, ATDC5, via Direct Inhibition of Alkaline Phosphatase.

Chondroitin sulfate (CS) is a sulfated polysaccharide produced by chondrocytes. Alkaline phosphatase (ALP) is an important enzyme involved in the mineralization of chondrocytes. In recent years, it has been reported that CS regulates the differentiation of various cells. In this study, we investigated the effect of supplemented CS on ALP activity and mineralization of the chondrogenic cell line, ATDC5. In addition, hyaluronic acid (HA), a non-sulfated and acidic polysaccharide, was used in comparison to CS. CS and HA significantly suppressed ALP activity without affecting ATDC5 cell proliferation. In addition, although the inhibition of ALP activity was observed at every time point, Alp mRNA expression level was not affected by CS. The suppressive effect of CS on ALP activity was abrogated by pre-treatment with chondroitinase ABC (CSase). CS and L-homoarginine (hArg), an inhibitor of ALP, significantly suppressed mineralization in ATDC5 cells. In conclusion, supplemented CS directly inhibits ALP to prevent the progression of chondrocytes from differentiation to mineralization.

Collagen-derived dipeptide prolyl-hydroxyproline promotes osteogenic differentiation through Foxg1.

Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. We previously reported that Pro-Hyp promotes the differentiation of osteoblasts by increasing Runx2, osterix and Col1α1 mRNA expression levels. Here, to elucidate the mechanism of Pro-Hyp promotion of osteoblast differentiation, we focus on the involvement of Foxo1 in osteoblast differentiation via Runx2 regulation and the role of Foxg1 in Foxo1 regulation. The addition of Pro-Hyp had no effect on MC3T3-E1 cell proliferation in Foxo1- or Foxg1-knockdown cells. In Foxo1-knockdown cells, the addition of Pro-Hyp increased ALP activity, but in Foxg1-knockdown cells, it had no effect on ALP activity. An enhancing effect of Pro-Hyp on the Runx2 and osterix expression levels was observed in Foxo1-knockdown cells. However, no enhancing effect of Pro-Hyp on osteoblastic gene expression was observed when Foxg1 was knocked down. These results demonstrate that Pro-Hyp promotes osteoblastic MC3T3-E1 cell differentiation and upregulation of osteogenic genes via Foxg1 expression.

Glucosamines Attenuate Bone Loss Due to Menopause by Regulating Osteoclast Function in Ovariectomized Mice.

The effect of glucosamine (GlcN) and N-acetylglucosamine (GlcNAc) on bone metabolism in ovariectomized (OVX) mice was studied. After 12 weeks of feeding with 0.2% GlcN and 0.2% GlcNAc, the femoral bone mineral density in OVX mice was significantly increased compared with that in OVX mice fed the control diet. Histomorphometric analysis of the tibia indicated that the rates of osteogenesis and bone resorption were reduced due to the GlcN diet. The erosion depth of osteoclasts on the tibia in GlcN- and GlcNAc-fed OVX mice was significantly lower than that in the control OVX mice. The number of tartrate-resistant acid phosphatase-positive osteoclasts induced from bone marrow stem cells isolated from GlcN-fed OVX mice was significantly lower than that from control OVX mice. A loss of uterine weight and higher serum calcium concentration in the GlcN- and GlcNAc-fed OVX mice were observed. The results suggest that the intake of GlcN suppresses bone loss by inhibiting osteoclast differentiation and activity in a nonestrogenic manner.

Oral collagen-derived dipeptides, prolyl-hydroxyproline and hydroxyprolyl-glycine, ameliorate skin barrier dysfunction and alter gene expression profiles in the skin.

Oral supplementation with collagen hydrolysate (CH) has been shown to improve the condition of the skin in humans and experimental animals. Several hydroxyproline-containing oligo-peptides were previously detected in human peripheral blood after the ingestion of CH, and the two dipeptides, prolyl-hydroxyproline (PO) and hydroxyprolyl-glycine (OG), have been proposed to have beneficial effects on human health. When HR-1 hairless mice were fed a HR-AD diet, which lacked magnesium and zinc, transepidermal water loss (TEWL) increased and water content of stratum corneum decreased. In the present study, we investigated the effects of dietary PO and OG on skin barrier dysfunction in HR-1 hairless mice. Mice were fed a HR-AD diet with or without PO (0.15%) and OG (0.15%) for 35 consecutive days. The administration of PO and OG significantly decreased TEWL, and significantly increased water content of stratum corneum. A DNA microarray analysis of the dorsal skin revealed differences in gene expression between the group administered PO and OG and the control group. We also identified muscle-related Gene Ontology as a result of analyzing the up-regulated genes. These results suggested that the administration of PO and OG improved skin barrier dysfunction and altered muscle-related gene expression.

Age-related decrease of IF5/BTG4 in oral and respiratory cavities in mice.

An IF5 cDNA was isolated by expression cloning from a mouse oocyte cDNA library. It encoded a protein of 250 amino acids, and the region of it encoding amino acids 1-137 showed 86.8% alignment with the anti-proliferative domain of BTG/TOB family genes. This gene is also termed BTG4 or PC3B. Transiently expressed IF5/BTG4 induced alkaline phosphatase activity in human embryonic kidney (HEK293T) and 2T3 cells. IF5/BTG4 mRNA was detected by reverse transcription polymerase chain reaction in pharynx, larynx, trachea, oviduct, ovary, caput epididymis, and testis, but not in lung, intestine, or liver. Immunohistochemistry showed the IF5/BTG4 protein to be present in epithelial cells of the tongue, palate, pharynx, internal nose, and trachea. Both protein and mRNA levels of IF5/BTG4 were reduced by aging when comparing 4-week-old mice with 48-week-old mice. Our findings suggest that IF5/BTG4 may be an aging-related gene in epithelial cells.

Collagen-derived dipeptide prolyl-hydroxyproline promotes differentiation of MC3T3-E1 osteoblastic cells.

Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. The objective of this study was to investigate the effects of Pro-Hyp on the proliferation and differentiation of MC3T3-E1 osteoblastic cells. Addition of Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization but alkaline phosphatase activity was significantly increased. Furthermore, cells treated with Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. These results indicate that Pro-Hyp promotes osteoblast differentiation. This study demonstrates for the first time that Pro-Hyp has a positive effect on osteoblast differentiation with upregulation of Runx2, Osterix, and Collα1 gene expression.

Endoscopic ultrasound with double-balloon endoscopy in the evaluation of small-bowel disease.

BACKGROUND: Double-balloon endoscopy (DBE) has become a new standard in enteroscopy. However, it may be difficult to make a diagnosis or plan treatment strategy with endoscopic visualization alone. The addition of endoscopic ultrasonography (EUS) has the potential to improve the ability to establish the diagnosis and develop a treatment strategy. The present study was conducted to assess the feasibility and usefulness of EUS with DBE. METHODS: EUS with DBE was performed in 31 of 891 patients who underwent DBE from July 2004 to March 2011 at Jichi Medical University Hospital. We analyzed the EUS findings for lesions and evaluated the usefulness of EUS considering the following three factors: qualitative diagnostic value for lesions, depth grading of lesions, and evaluation of the structure of severe strictures prior to endoscopic balloon dilation. RESULTS: EUS was performed for 31/32 lesions (97%) in 31 patients. EUS findings were informative for 29/32 lesions (91%). EUS findings were useful for establishing a qualitative diagnosis in 15/25 lesions (60%). EUS findings for depth grading provided useful information for determining the therapeutic strategy in 11/13 lesions (85%). EUS with DBE was useful in the evaluation of strictures for all six lesions (100%). The overall usefulness of EUS with DBE on decision making was 72% (23/32) in this study. CONCLUSIONS: EUS with DBE is feasible and useful. It provides additional information on small-bowel disease and contributes to establishing a precise diagnosis and selection of an appropriate therapeutic strategy.

Formation of long-chain N-vanillyl-acylamides from plant oils.

Long-chain N-vanillyl-acylamides (LCNVAs) were generated from plant oils and vanillylamine (VA) by nucleophilic amidation without any catalytic reagents. The resulting LCNVAs varied according to the fatty acid composition of the plant oil used. Therefore, the LCNVAs contained in Capsicum oleoresins were products that were spontaneously generated from the oleoresin during storage.