Publications by authors named "Yutaka Kobayashi"

147 Publications

Identification of malocclusion risk factors after closed treatment of condylar fractures using a novel three-dimensional computed tomography approach.

J Oral Sci 2021 Jun 2. Epub 2021 Jun 2.

Department of Dentistry and Oral Surgery, Tokyo Metropolitan Hiroo Hospital.

The condyle is the most common site of mandibular fracture. In the present study, an attempt was made to utilize three-dimensional computed tomography (3D-CT) images to evaluate mandibular condyle fractures and identify prognostic indicators of malocclusion after closed treatment. Accurate morphometric measurements were performed using 3D-CT images obtained before trauma, after trauma, and after healing. Morphometry revealed significant differences in loss of ramus height (LRH) and lateral movement length in patients with malocclusion, and significant LRH differences in patients with other maxillomandibular fractures after healing, or in those with dislocation-displacement. The present method of 3D-CT image analysis appears useful for evaluation of condylar fractures.
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http://dx.doi.org/10.2334/josnusd.20-0600DOI Listing
June 2021

Factors related to oxygen desaturation index during sleep 7 days after bilateral sagittal splitting ramus osteotomy in patients without previous obstructive sleep apnea.

Oral Maxillofac Surg 2021 May 15. Epub 2021 May 15.

Department of Oral and Maxillofacial Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan.

Purpose: The incidence of obstructive sleep apnea (OSA) immediately after surgery in patients with dentofacial deformities without previous OSA remains unknown. We aimed to perioperatively evaluate factors associated with oxygen desaturation index (ODI) during sleep, 7 days after bilateral splitting ramus osteotomy (BSSRO) in patients without previous OSA.

Methods: Fifty-one patients (15 males, 36 females) with dentofacial deformities, scheduled to undergo BSSRO, were included. Polysomnography was performed before orthognathic surgery. Perioperative OSA was evaluated with peripheral arterial tonometry on the day of surgery and 1, 2, 3, 4, and 7 days postoperatively. Rapid eye movement (REM) sleep periods and the ODI were measured. Factors associated with perioperative ODI after surgery were statistically analyzed.

Results: REM sleep periods were significantly decreased on the day of surgery and significantly increased at 4 and 7 days postoperatively, compared to the preoperative period. ODI increased on the day of surgery, decreased after 1 day, and increased again at 4 and 7 days postoperatively. ODI on the day of surgery was significantly increased due to increased preoperative ODI, overjet, and SN-MP angle and decreased SNA and SNB angle. ODI at 7 days postoperatively was significantly increased due to increased REM sleep periods and decreased SN-MP and gonial angle. ODI was increased in response to REM sleep periods 7 days after BSSO.

Conclusion: Airway management in patients with dentofacial deformity should be given more attention by preoperative assessment for OSA, even in the absence of previous OSA, until 7 days postoperatively due to REM rebound.
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http://dx.doi.org/10.1007/s10006-021-00972-wDOI Listing
May 2021

[On-pump Beating Pulmonary Embolectomy for Acute Pulmonary Thromboembolism].

Kyobu Geka 2021 Feb;74(2):94-98

Department of Cardiovascular Surgery, Uji-Tokushukai Medical Center, Uji, Japan.

Background: Acute massive pulmonary embolism is a life-threatening disease and the reported rate of mortality is 52%.It is often treated with anticoagulation therapy or thrombolysis, but in case of critically ill patients with shock or cardiac arrest, its effect is limited. Surgical embolectomy is a treatment option for patients with hemodynamic instability. We studied the outcomes of our patients who underwent on-pump beating pulmonary embolectomy for acute pulmonary embolism.

Method: We evaluated eight consecutive patients who underwent on-pump beating pulmonary embolectomy for acute pulmonary embolism since May 2012 to September 2016. Our surgical indications were hemodynamic instability, but one patient underwent pulmonary embolectomy without hemodynamic instability because the patient had floating thrombus in the right heart. Three patients experienced cardiac arrest, and two patients were treated with extracorporeal membrane oxygenation (ECMO). Four patients were treated with thrombolysis before surgical embolectomy.

Result: All patients underwent on-pump beating pulmonary embolectomy. One patient could not be weaned from cardiopulmonary bypass, and was treated with ECMO after pulmonary embolectomy. The patient died due to low output syndrome, while the other seven patients were rescued. One patient had gastrointestinal bleeding after surgery, but the other patients had developed no major complication including thrombosis, hemorrhage, and prolonged respiratory failure during follow-up of 11.4±16.1 months.

Conclusion: Pulmonary embolectomy is effective treatment for acute massive pulmonary embolism. On-pump beating pulmonary embolectomy is useful surgical procedure. Acute pulmonary embolism is often treated with anticoagulation therapy or thrombolysis, but in critically ill patients, surgical pulmonary embolectomy should be considered.
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February 2021

Time to extinction of a cultural trait in an overlapping generation model.

Theor Popul Biol 2021 02 19;137:32-45. Epub 2021 Jan 19.

Meiji University, Nakano 4-21-1, Nakano-ku, Tokyo 164-8525, Japan.

How long a newly emerging trait will stay in a population is a fundamental but rarely asked question in cultural evolution. To tackle this question, the distribution and mean of the time to extinction of a discrete cultural trait are derived for models with overlapping generations, in which trait transmission occurs from multiple role models to a single newborn and may fail with a certain probability. We explore two models. The first is a Moran-type model, which allows us to derive the exact analytical formula for the mean time to extinction of a trait in a finite population. The second is a branching process, which assumes an infinitely large population and allows us to derive approximate analytical formulae for the distribution and mean of the time to extinction in the first model under a large population size. We show that in the first model, the mean time to extinction apparently diverges (becomes so large that even numerical computation is impractical) under a certain parameter condition as the population size tends to infinity. Using the second model, we explain the underlying mechanism of the apparent divergence found in the first model and derive the mathematical condition for this divergence in terms of transmission efficiency and the number of role models per newborn. When this mathematical condition is satisfied in the second model, the probability of extinction is less than 1, and the mean extinction time does not exist. In addition, we find that in both models, the time to extinction of the trait becomes longer as the number of role models per individual increases and as cultural transmission becomes more efficient.
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http://dx.doi.org/10.1016/j.tpb.2021.01.002DOI Listing
February 2021

Cyclin-Dependent Kinase 1 Is Essential for Muscle Regeneration and Overload Muscle Fiber Hypertrophy.

Front Cell Dev Biol 2020 14;8:564581. Epub 2020 Oct 14.

Department of Orthopedic and Trauma Research, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

Satellite cell proliferation is an essential step in proper skeletal muscle development and muscle regeneration. However, the mechanisms regulating satellite cell proliferation are relatively unknown compared to the knowledge associated with the differentiation of satellite cells. Moreover, it is still unclear whether overload muscle fiber hypertrophy is dependent on satellite cell proliferation. In general, cell proliferation is regulated by the activity of cell cycle regulators, such as cyclins and cyclin-dependent kinases (CDKs). Despite recent reports on the function of CDKs and CDK inhibitors in satellite cells, the physiological role of Cdk1 in satellite cell proliferation remains unknown. Herein, we demonstrate that Cdk1 regulates satellite cell proliferation, muscle regeneration, and muscle fiber hypertrophy. Cdk1 is highly expressed in myoblasts and is downregulated upon myoblast differentiation. Inhibition of CDK1 activity inhibits myoblast proliferation. Deletion of in satellite cells leads to inhibition of muscle recovery after muscle injury due to reduced satellite cell proliferation . Finally, we provide direct evidence that Cdk1 expression in satellite cells is essential for overload muscle fiber hypertrophy . Collectively, our results demonstrate that Cdk1 is essential for myoblast proliferation, muscle regeneration, and muscle fiber hypertrophy. These findings could help to develop treatments for refractory muscle injuries and muscle atrophy, such as sarcopenia.
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http://dx.doi.org/10.3389/fcell.2020.564581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591635PMC
October 2020

Isostearyl Mixed Anhydrides for the Preparation of -Methylated Peptides Using -Terminally Unprotected -Methylamino Acids.

Org Lett 2020 10 2;22(20):8039-8043. Epub 2020 Oct 2.

PeptiDream, Inc. 3-25-23 Tonomachi, Kawasaki-ku Kawasaki, Kanagawa 210-0821, Japan.

Sustainable and efficient manufacturing methods for -methylated peptides remain underexplored despite growing interest in therapeutic -methylated peptides within the pharmaceutical industry. A methodology for the coupling of -terminally unprotected -methylamino acids mediated by an isostearic acid halide (ISTAX) and silylating reagent has been developed. This approach allows for the coupling of a wide variety of amino acids and peptides in high yields under mild conditions without the need for a -terminal deprotection step in the process of -terminal elongation. These advantages make this a useful synthetic method for the production of peptide therapeutics and diagnostics containing -methylamino acids.
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http://dx.doi.org/10.1021/acs.orglett.0c02984DOI Listing
October 2020

Second primary malignancy after rituximab-containing immunochemotherapy for diffuse large B cell lymphoma.

Leuk Lymphoma 2020 12 27;61(14):3378-3386. Epub 2020 Aug 27.

Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Extended post-therapy long-term survival of patients with diffuse large B cell lymphoma (DLBCL) may also lead to an increase of late adverse events. We retrospectively investigated the frequency and clinical manifestation of second primary malignancy (SPM) after rituximab-containing immunochemotherapy in patients with DLBCL treated at seven institutes belonging to the Kyoto Clinical Hematology Study Group (KOTOSG) from the perspective of the existence of past or synchronous cancer history. In a median follow-up period of 899 days, 69 SPMs were observed in 58 of 809 patients. The most frequent SPM was gastric cancer, followed by lung cancer and colorectal cancer. The cumulative incidence of SPM increased steadily over time and was not significantly influenced by the presence or absence of past or synchronous cancer history. Our study suggests the need for careful attention to SPM in patients with DLBCL in daily practice.
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http://dx.doi.org/10.1080/10428194.2020.1811862DOI Listing
December 2020

Postoperative lymphocyte percentage and neutrophil-lymphocyte ratio are useful markers for the early prediction of surgical site infection in spinal decompression surgery.

J Orthop Surg (Hong Kong) 2020 Jan-Apr;28(2):2309499020918402

Department of Orthopaedics, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

Purpose: Although the neutrophil-lymphocyte ratio (NLR) is a simple biomarker for inflammation, its diagnostic value for predicting surgical site infection (SSI) after spinal decompression surgery has not been extensively investigated. We aimed to determine the predictive value of NLR for SSI in patients undergoing spinal decompression surgery.

Methods: We performed a retrospective observational study of patients who underwent spinal decompression surgery. Consecutive 254 patients were divided into an SSI group and a non-SSI group based on the presence of SSI. We evaluated which markers, including NLR, differed significantly between groups. We then determined the diagnostic cutoff values of these markers for the prediction of SSI based on the significance in the univariate analysis.

Results: The incidence of SSI was 7 of 254 patients (2.8%). Univariate analysis showed that there were significant differences in the C-reactive protein (CRP) level at 1 day postoperatively; neutrophil and lymphocyte percentage and NLR at 3-4 days postoperatively; and CRP level, white blood cell count, neutrophil count and percentage, lymphocyte percentage, and NLR at 6-7 days postoperatively between SSI and non-SSI groups. Among these markers, the cutoff values of lymphocyte percentage and NLR at 3-4 days postoperatively for the prediction of SSI were ≤15.1% and ≥4.91, respectively. The cutoff values of lymphocyte percentage and NLR at 6-7 days postoperatively were ≤19.8% and ≥3.21, respectively.

Conclusions: Lymphocyte percentage and NLR at 3-4 and 6-7 days postoperatively were useful markers for the early prediction of SSI in patients who had undergone spinal decompression surgery. These parameters may aid in identifying patients at higher risk of SSI after spinal decompression surgery.
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http://dx.doi.org/10.1177/2309499020918402DOI Listing
March 2021

Relationship between pharyngeal airway depth and ventilation condition in mandibular setback surgery: A computational fluid dynamics study.

Orthod Craniofac Res 2020 Aug 4;23(3):313-322. Epub 2020 Mar 4.

Department of Pediatric Dentistry, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima-City, Japan.

Objectives: This study aimed to determine the anteroposterior depth (APD) of the pharyngeal airway (PA) where post-operative PA obstruction was predicted, using computer fluid dynamics (CFD), in order to prevent obstructive sleep apnoea after mandibular setback surgery.

Settings And Sample Population: Nineteen skeletal Class III patients (8 men; mean age, 26.7 years) who required mandibular setback surgery had computed tomography images taken before and 6 months after surgery.

Methods: The APD of each site of the four cross-sectional reference planes (retropalatal airway [RA], second cervical vertebral airway, oropharyngeal airway and third cervical vertebral airway) were measured. The Maximum negative pressure (Pmax) of the PA was measured at inspiration using CFD, based on a three-dimensional PA model. Intersite differences were determined using analysis of variance and the Friedman test with Bonferroni correction. The relationship between APD and Pmax was evaluated by Spearman correlation coefficients and non-linear regression analysis.

Results: The smallest PA site was the RA. Pmax was significantly correlated with the APD of the RA (r  = .628, P < .001). The relationship between Pmax and the APD-RA was fitted to a curve, which showed an inversely proportional relationship of Pmax to the square of the APD-RA. Pmax substantially increased even with a slight reduction of the APD-RA. In particular, when the APD-RA was 7 mm or less, Pmax increased greatly, suggesting that PA obstruction was more likely to occur.

Conclusions: The results of this study suggest that APD-RA is a useful predictor of good PA ventilation after surgery.
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http://dx.doi.org/10.1111/ocr.12371DOI Listing
August 2020

Procalcitonin and Neutrophil Lymphocyte Ratio After Spinal Instrumentation Surgery.

Spine (Phila Pa 1976) 2019 Dec;44(23):E1356-E1361

Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Study Design: This was a retrospective observational study.

Objective: To assess the diagnostic value of procalcitonin (PCT) and neutrophil lymphocyte ratio (NLR) for predicting surgical site infection (SSI) in patients undergoing spinal instrumentation surgery, we analyzed a large consecutive cohort of patients who had undergone spinal instrumentation surgery.

Summary Of Background Data: Although PCT and NLR are commonly used as markers for bacterial infection, the diagnostic value of these factors for predicting SSI in the context of spinal instrumentation surgery has not been extensively investigated.

Methods: We retrospectively investigated 242 patients who underwent spinal instrumentation surgery and evaluated the significance of various postoperative measures for predicting SSI, including PCT and NLR. We then determined the diagnostic cut-off values for these markers in the prediction of SSI using receiver operating characteristic curve analysis.

Results: Among the 242 patients analyzed, 10 were diagnosed with infection. Even though univariate analysis showed that neutrophil percentage and NLR at 6 to 7 days postoperatively were significant predictors for SSI, PCT at 6 to 7 days postoperatively did not differ significantly between the SSI and non-SSI groups. The cut-off value used for neutrophil percentage at 6 to 7 days postoperatively was more than 69.0% [sensitivity, 80.0%; specificity, 70.0%; area under the curve, 0.737]. The cut-off value used for NLR at 6 to 7 days postoperatively was 3.87 (sensitivity, 70.0%; specificity, 73.2%; area under the curve, 0.688).

Conclusion: Neutrophil percentage and NLR at 6 to 7 days postoperatively were more useful markers than PCT at 6 to 7 days postoperatively for early prediction of SSI in patients who had undergone spinal instrumentation surgery. Therefore, routine use of PCT as a predictor of postoperative infection is not supported by the results of this study.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003157DOI Listing
December 2019

The popularity spectrum applied to a cross-cultural question.

Theor Popul Biol 2020 06 28;133:104-116. Epub 2019 Oct 28.

School of Economics and Management, Kochi University of Technology, 2-22 Eikokuji, Kochi City, Kochi 780-8515, Japan. Electronic address:

We investigate a new approach for identifying the contribution of horizontal transmission between groups to cross-cultural similarity. This method can be applied to datasets that record the presence or absence of artefacts, or attributes thereof, in archaeological and ethnographic assemblages, from which popularity spectra can be constructed. Based on analytical and simulation models, we show that the form of such spectra is sensitive to horizontal transmission between groups. We then fit the analytical model to existing datasets by Bayesian MCMC and obtain evidence for strong horizontal transmission in oceanic as opposed to continental datasets. We check the validity of our statistical method by using individual-based models, and show that the vertical transmission rate tends to be underestimated if the datasets are obtained from lattice-structured rather than island-structured meta-populations. We also suggest that there may be more borrowing of functional than stylistic traits, although the evidence for this is currently ambiguous.
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http://dx.doi.org/10.1016/j.tpb.2019.10.003DOI Listing
June 2020

The long noncoding RNA Crnde regulates osteoblast proliferation through the Wnt/β-catenin signaling pathway in mice.

Bone 2020 01 14;130:115076. Epub 2019 Oct 14.

Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address:

In the past decade, a growing importance has been placed on understanding the significance of long noncoding RNAs (lncRNAs) in regulating development, metabolism, and homeostasis. Osteoblast proliferation and differentiation are essential elements in skeletal development, bone metabolism, and homeostasis. However, the underlying mechanisms of lncRNAs in the process of osteoblast proliferation and differentiation remain largely unknown. Through comprehensive analysis of lncRNAs during bone formation, we show that colorectal neoplasia differentially expressed (Crnde), previously viewed as a cancer-related lncRNA, is an important regulator of osteoblast proliferation and differentiation. Crnde was found to be expressed in osteoblasts, and its expression was induced by parathyroid hormone. Furthermore, Crnde knockout mice developed a low bone mass phenotype due to impaired osteoblast proliferation and differentiation. Overexpression of Crnde in osteoblasts promoted their proliferation, and conversely, reduced Crnde expression inhibited osteoblast proliferation. Although ablation of Crnde inhibited osteoblast differentiation, overexpression of Crnde restored it. Finally, we provided evidence that Crnde modulates bone formation through Wnt/β-catenin signaling. Therefore, our data suggest that Crnde is a novel regulator of bone metabolism.
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http://dx.doi.org/10.1016/j.bone.2019.115076DOI Listing
January 2020

Is Modified K-line a Powerful Tool of Surgical Decision Making for Patients With Cervical Spondylotic Myelopathy?

Clin Spine Surg 2019 11;32(9):351-356

Department of Orthopedic Surgery, Tokyo Medical and Dental University, Bunkyo-Ku, Tokyo, Japan.

Study Design: Prospective observational single-center study.

Objective: To evaluate anterior decompression and fusion (ADF) or posterior surgery (PS) for patients with cervical spondylotic myelopathy (CSM) using the modified K-line (mK-line) and to compare clinical and radiologic outcomes between these 2 techniques.

Summary Of Background Data: The authors have previously reported that insufficient posterior decompression is often seen after laminoplasty for CSM in patients with preoperative anterior clearance of the spinal cord <4 mm on the basis of the mK-line. However, to our knowledge, no study has investigated the role, if any, of the mK-line in surgical decision making for patients with CSM.

Methods: A total of 87 patients were enrolled who underwent surgery for treatment of CSM between 2011 and 2015 at our hospital and who could be followed up for at least 2 years. ADF was selected as a more favorable procedure than PS in patients with anterior spinal clearance of <4 mm on preoperative midsagittal magnetic resonance imaging. On the basis of the Japanese Orthopedic Association (JOA) scoring system for cervical myelopathy, the rate of recovery of the JOA scores at 2 years after surgery was investigated as a clinical outcome to compare these 2 groups.

Results: Mean age was 65.1 (±12.9) years in the ADF group (n=26) and 70.5 (±8.6) years in the PS group (n=61). In the PS group, 10 patients underwent posterior decompression with fusion. Mean preoperative and postoperative JOA scores were 10.5 and 14.1 points in the ADF group and 9.8 and 13.1 points in the PS group, respectively, showing no significant difference in recovery rate of JOA score between the ADF (58.9%) and PS (47.1%) groups. However, patients with a minimum interval between the mK-line and the anterior compression factor on the midsagittal image (minimum interval of the spinal cord) <4 mm tended to have unsatisfactory outcomes (recovery rate 29.6%) compared with patients with minimum interval of the spinal cord >4 mm (53.6%, P=0.07) in the PS group.

Conclusion: Preoperative intervention using the mK-line is useful to predict residual cord compression and might homogenize postoperative clinical outcomes in both anterior surgery and PS.
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http://dx.doi.org/10.1097/BSD.0000000000000899DOI Listing
November 2019

Body Mass Index and Modified Glasgow Prognostic Score Are Useful Predictors of Surgical Site Infection After Spinal Instrumentation Surgery: A Consecutive Series.

Spine (Phila Pa 1976) 2020 Feb;45(3):E148-E154

Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Study Design: Retrospective observational study.

Objective: To analyze a large consecutive cohort of patients who had undergone spinal instrumentation surgery, to characterize a patient population with surgical site infections (SSI), and to identify preoperative risk factors associated with SSI.

Summary Of Background Data: Malnutrition is a risk factor for SSI in many health conditions; however, the evidence connecting preoperative malnutrition with SSI in spinal instrumentation surgery is limited because of the small number of retrospective studies. While the modified Glasgow prognostic score (mGPS), C-Reactive protein (CRP)-albumin ratio (CAR), controlling nutritional status index (CONUT), prognostic nutritional index (PNI), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR) are established methods for evaluating nutritious status, little has been reported on the predictive value of these indicators with respect to postoperative spinal infection.

Methods: We retrospectively investigated 384 patients who underwent spinal instrumentation surgery. We evaluated the significance of risk factors, including mGPS, CAR, CONUT, PNI, PLR, and NLR. We then performed stepwise logistic regression analysis to analyze the concurrent effects of various factors on the prevalence of SSI.

Results: Of the 384 patients analyzed, 14 were diagnosed with SSIs. Univariate analysis showed that preoperative BMI, lymphocyte count, albumin, erythrocyte sedimentation rate, CRP, CONUT, mGPS, CAR, and PNI were risk factors for SSI. Stepwise logistic regression analysis revealed that higher mGPS and lower BMI before surgery were independent risk factors for SSI. A receiver operating characteristic curve showed that the cut-off values of mGPS and BMI were 1 and 20.39, respectively.

Conclusion: The risk factors for SSI after spinal instrumentation surgery were mGPS more than or equal to 1 and BMI less than or equal to 20.39 kg/m. These findings could help to identify patients at higher risk of SSI after spinal instrumentation surgery.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003226DOI Listing
February 2020

Polyethyleneimine-Modified Polymer as an Efficient Palladium Scavenger and Effective Catalyst Support for a Functional Heterogeneous Palladium Catalyst.

ACS Omega 2019 Jun 13;4(6):10243-10251. Epub 2019 Jun 13.

Laboratory of Organic Chemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.

The polyethyleneimine-modified polymers, polystyrene-divinylbenzene-based (TAs) and polymethacrylate-based polymers (TAm), were used as palladium scavengers to eliminate residual palladium species after palladium on carbon-catalyzed Sonogashira-type coupling reaction. Since both TAs and TAm indicated relatively favorable elimination abilities toward residual palladium species in the reaction mixture, the affinities of TAs and TAm for palladium species were used as supports for palladium catalysts. The TAm-supported palladium catalyst (Pd/TAm) indicated better catalyst properties for the chemoselective hydrogenation compared to those of the corresponding TAs-supported palladium catalyst (Pd/TAs). Aromatic benzyl ethers; aromatic and aliphatic -Cbzs; and aromatic carbonyl groups were smoothly hydrogenated in the presence of 1-5 mol % of Pd/TAm in MeOH or 2-PrOH. In contrast, the hydrogenation of aromatic ketones was selectively suppressed in morpholine which act as appropriate catalyst poison and solvent. Furthermore, Pd/TAm-catalyzed chemoselective hydrogenation was applicable to continuous-flow reaction.
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http://dx.doi.org/10.1021/acsomega.9b00707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649293PMC
June 2019

Significance of FLT3-tyrosine kinase domain mutation as a prognostic factor for acute myeloid leukemia.

Int J Hematol 2019 Nov 20;110(5):566-574. Epub 2019 Aug 20.

Department of Hematology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo, 113-8603, Japan.

The prognostic significance of FLT3-tyrosine kinase domain (TKD) mutations remains unknown. To investigate the prognostic impact of FLT3-TKD, 676 de novo acute myeloid leukemia (AML), we retrospectively analyzed cases and conducted a review of the literature. Of the 676 de novo AML cases, 34 (5.0%) were FLT3-TKD-positive; both FLT3-TKD and FLT3-ITD were noted in only two cases (0.3%). Although no significant differences in relapse-free survival (RFS) were noted, FLT3-TKD-positive cases showed better prognoses than FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.152). For overall survival (OS), although FLT3-TKD-positive cases showed prognoses similar to those for FLT3-WT cases, their prognoses were significantly better than those of FLT3-ITD-positive cases (FLT3-TKD versus FLT3-ITD, p = 0.032). Moreover, the 5-year OS for FLT3-TKD-positive cases was 46.1%, indicating that this as an intermediate prognosis group. Although no reports from Asia have indicated a frequency of FLT3-TKD-positive cases > 10%, several reports from Europe and the United States have indicated frequencies > 10%. This suggests the possibility that FLT3-TKD-positive cases are less common in Asia than in Europe and the United States. We anticipate that in the future, the appearance of targeting agents, such as FLT3 inhibitors, will improve the prognosis of FLT3-TKD-positive AML relative to that of FLT3-WT AML.
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http://dx.doi.org/10.1007/s12185-019-02720-zDOI Listing
November 2019

Selectively high efficacy of eribulin against high-grade invasive recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Oncol Lett 2019 Jun 19;17(6):5064-5072. Epub 2019 Mar 19.

Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.

Patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have a poor prognosis. Over the past decade, a major development in the first-line treatment of R/M SCCHN was the introduction of cetuximab in combination with platinum plus 5-fluorouracil chemotherapy. Currently, a promising novel treatment option in R/M SCCHN has emerged, termed immune checkpoint inhibitors. However, only a few patients presenting with R/M SCCHN have exhibited meaningful tumor regression with these agents. Therefore, novel agents are required to order improve the overall survival of patients with R/M SCCHN. Recently, we demonstrated that R/M SCCHN cells are highly sensitive to eribulin. In the present study, the effects of eribulin, paclitaxel and vinblastine were investigated in R/M SCCHN (OLC-01 and OSC-19) and locally advanced SCCHN (OSC-20) cells. Tumour-inhibitory activities of eribulin against R/M SCCHN were evaluated in orthotopic xenograft models. The data revealed that eribulin has sub-nM growth inhibitory activities against OLC-01 cells, and that it is more potent than paclitaxel and vinblastine. The reduced expression of Tubulin Beta 3 Class III (TUBB3) following treatment was correlated with a high sensitivity to eribulin. Histological analysis of OLC-01 cells in NOD-SCID mice demonstrated that they had a higher invasiveness in the tissue around the alveolar cancer when compared with the histology of OSC-19 cells, which has been reported in our previous study. Treatment with eribulin revealed marked inhibitory activities at 0.125 mg/kg against OLC-01 cells orthotopic xenografts. In conclusion, the results highlight the existence of invasive-type heterogeneity in R/M SCCHN with respect to eribulin sensitivity. Eribulin is already an approved clinical agent; therefore, the continued investigation of its preclinical antitumor attributes may contribute significantly to the future process of identifying novel uses of eribulin against R/M SCCHN.
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http://dx.doi.org/10.3892/ol.2019.10165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507455PMC
June 2019

Combined rituximab, bendamustine, and dexamethasone chemotherapy for relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma: a multicenter phase II study.

Int J Hematol 2019 Jul 24;110(1):77-85. Epub 2019 May 24.

Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

This multicenter phase II study (UMIN000008145) aims to investigate the efficacy and safety of six cycles of combination therapy (RBD) comprising rituximab, bendamustine, and dexamethasone (DEX) for relapsed or refractory (RR) indolent B-cell non-Hodgkin lymphoma (B-NHL) and mantle cell lymphoma (MCL). Although the initial study protocol comprised 20 mg/body DEX on days 1 and 2, and 10 mg/body on days 3-5 [high-dose (HD-) DEX group], the dose of DEX was later decreased to 8 mg/body on days 1 and 2 [low-dose (LD-) DEX group] due to frequent cytomegalovirus (CMV) antigenemia and recurrent retinitis. We enrolled 33 patients, and LD-DEX and HD-DEX were administered in 15 and 18 patients, respectively. The overall response and the 3-year progression-free survival rates were 88% and 75.5%, respectively. The leading adverse event was myelosuppression. Incidence of grade 3-4 leukocytopenia, neutropenia, and lymphocytopenia was 55%, 67%, and 91%, respectively. The most frequent nonhematological adverse events were CMV antigenemia and rash (33% and 30%, respectively). Incidence of CMV antigenemia over 10/100,000 white blood cells was significantly lower with LD-DEX than that with HD-DEX (P = 0.0127). In conclusion, RBD showed significant effectiveness for RR indolent B-NHL and MCL.
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http://dx.doi.org/10.1007/s12185-019-02650-wDOI Listing
July 2019

Evolution of cumulative culture for niche construction.

J Theor Biol 2019 07 12;472:67-76. Epub 2019 Apr 12.

SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa 240-0193, Japan.

A mathematical model of the joint evolution of learning and niche construction in a spatially subdivided population is described, in which culture is used to practice niche construction and can evolve by accumulating small improvements over generations. Individuals allocate their lifetimes to social learning, individual learning, niche construction to improve the environment, and exploitation of resources according to their genetically determined strategies. The coordinated optimal strategy (COS) is defined as the allocation strategy which maximizes the equilibrium fecundity of the population, as opposed to the convergence stable strategy (CSS), which is the strategy favored by natural selection. Both the COS and CSS are analytically derived and compared. It turns out that, although the levels of the CSS in terms of culture and the environmental quality can be high in a highly viscous population, they are in general much lower than those of the COS. It is argued that the discrepancy between the CSS and COS stems from the producer-scrounger structure inherent in the model. Analysis of transient dynamics reveals that the level of culture and the environmental quality may temporarily undergo drastic increases after sudden changes in parameter values, although they eventually drop down to low values due to the genetic adaptation of the time allocation strategy to the new cultural and environmental backgrounds. Implications of the results for human evolution are discussed.
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http://dx.doi.org/10.1016/j.jtbi.2019.04.013DOI Listing
July 2019

Genetic Incompatibilities Between Mitochondria and Nuclear Genes: Effect on Gene Flow and Speciation.

Front Genet 2019 13;10:62. Epub 2019 Feb 13.

School of Economics and Management, Kochi University of Technology, Kami, Japan.

The process of speciation is, according to the biological species concept, the reduction in gene flow between genetically diverging populations. Most of the previous theoretical studies analyzed the effect of nuclear genetic incompatibilities on gene flow. There is, however, an increasing number of empirical examples suggesting that cytoplasmically inherited genetic elements play an important role in speciation. Here, we present a theoretical analysis of mitochondrial driven speciation, in which genetic incompatibilities occur between mitochondrial haplotypes and nuclear alleles. Four population genetic models with mainland-island structure were analyzed that differ with respect to the type of incompatibility and the underlying genetics. Gene flow reduction was measured on selectively neutral alleles of an unlinked locus and quantified by the effective migration rate. Analytical formulae for the different scenarios were derived using the fitness graph method. For the models with haploid genetics, we found that mito-nuclear incompatibilities (MtNI) are as strong as nuclear-nuclear incompatibilities (NNI) in reducing gene flow at the unlinked locus, but only if males and females migrate in equal number. For models with diploid genetics, we found that MtNI reduce gene flow stronger than NNI when incompatibilities are recessive, but weaker when they are dominant. For both haploid and diploid MtNI, we found that gene flow reduction is stronger if females are the migrating sex, but weaker than NNI when males are the migrating sex. These results encourage further examination on the role of mitochondria on genetic divergence and speciation and point toward specific factors (e.g., migrating sex) that could be the focus of an empirical test.
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http://dx.doi.org/10.3389/fgene.2019.00062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396729PMC
February 2019

Immunosuppressive therapy with rabbit antithymocyte globulin therapy for acquired aplastic anemia: a multi-institutional retrospective study in Japanese adult patients.

Int J Hematol 2019 Mar 9;109(3):278-285. Epub 2019 Jan 9.

Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan.

We retrospectively analyzed efficacy and safety of therapy with rabbit antithymocyte globulin (rATG) in combination with cyclosporine A (CsA) in 30 Japanese adult patients with acquired aplastic anemia (AA) in the Kyoto Clinical Hematology Study Group. The median observation period was 31 months and the median age of the patients was 54 years. The objective response rates (ORRs) to rATG plus CsA increased over time until 18 months after the start of treatment; the rate of achievement of better than partial response at 18 months was 66.7%. The 2-year overall survival (OS) rate was 79% in all patients. In eight patients aged ≥ 75 years old, the ORR was 62.5% and the 2-year OS rate of 50% was not significantly inferior to that in patients aged ≤ 74 years old. The overall mortality rate was 16.7% in our cohort, while the mortality rate in patients aged ≥ 75 years old was 37.5%, which was higher than that in patients aged ≤ 74 years old (9.1%), although the difference was not statistically significant. Collectively, rATG combined with CsA is an effective and feasible treatment for AA, while patients should be appropriately selected.
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http://dx.doi.org/10.1007/s12185-018-02583-wDOI Listing
March 2019

Corrigendum to "Topographical distribution of neurovascular canals and foramens in the mandible: avoiding complications resulting from their injury during oral surgical procedures" [Heliyon 4 (9) (September 2018) e00812].

Heliyon 2018 12 6;4(12):e00946. Epub 2018 Dec 6.

Department of Radiology, Tokyo Metropolitan Hiroo Hospital, 2-34-10 Ebisu, Shibuya-ku, Tokyo, 150-0013, Japan.

[This corrects the article DOI: 10.1016/j.heliyon.2018.e00812.].
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http://dx.doi.org/10.1016/j.heliyon.2018.e00946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287082PMC
December 2018

Clinicopathological Significance of the ET Axis in Human Oral Squamous Cell Carcinoma.

Pathol Oncol Res 2019 Jul 31;25(3):1083-1089. Epub 2018 Oct 31.

Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.

The interaction between cancer cells and the surrounding microenvironment in malignant tumor tissue is known to be closely associated with cancer cell invasion and proliferation. Endothelin (ET) present in the microenvironment surrounding tumors has been reported to play a role in cancer cell invasion and proliferation by binding to receptors on the cell membrane of cancer cells. Here, we immunohistologically detected the expression of ET-1 and its receptor ETR in oral squamous cell carcinoma (OSCC) and evaluated the association between the expression of each as well as their co-expression (ET-axis expression) and clinicopathological factors. A significant difference was observed between the invasion pattern as a parameter of cancer cell malignancy and the expressions of ET-1 and ETR. The survival rates were significantly lower among the patients who were strongly positive for ET-1 and the ETR-positive patients compared to negative patients. There was also a significant difference between ET-axis expression and the degree of histological differentiation and mode of invasion, and the survival rate of the positive cases was significantly lower than that of the negative cases. Our findings suggested that ET-axis assessments are important for assessing the malignancy of cancer cells and predicting the prognoses of OSCC patients.
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http://dx.doi.org/10.1007/s12253-018-0514-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614151PMC
July 2019

Loss of cyclin-dependent kinase 1 impairs bone formation, but does not affect the bone-anabolic effects of parathyroid hormone.

J Biol Chem 2018 12 26;293(50):19387-19399. Epub 2018 Oct 26.

From the Department of Orthopedics, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan,

Bone mass is maintained by a balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Although recent genetic studies have uncovered various mechanisms that regulate osteoblast differentiation, the molecular basis of osteoblast proliferation remains unclear. Here, using an osteoblast-specific loss-of-function mouse model, we demonstrate that cyclin-dependent kinase 1 (Cdk1) regulates osteoblast proliferation and differentiation. Quantitative RT-PCR analyses revealed that Cdk1 is highly expressed in bone and is down-regulated upon osteoblast differentiation. We also noted that Cdk1 is dispensable for the bone-anabolic effects of parathyroid hormone (PTH). Cdk1 deletion in osteoblasts led to osteoporosis in adult mice due to low bone formation, but did not affect osteoclast formation Cdk1 overexpression in osteoblasts promoted proliferation, and conversely, Cdk1 knockdown inhibited osteoblast proliferation and promoted differentiation. Of note, we provide direct evidence that PTH's bone-anabolic effects occur without enhancing osteoblast proliferation Furthermore, we found that Cdk1 expression in osteoblasts is essential for bone fracture repair. These findings may help reduce the risk of nonunion after bone fracture and identify patients at higher risk for nonresponse to PTH treatment. Collectively, our results indicate that Cdk1 is essential for osteoblast proliferation and that it functions as a molecular switch that shifts osteoblast proliferation to maturation. We therefore conclude that Cdk1 plays an important role in bone formation.
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http://dx.doi.org/10.1074/jbc.RA118.004834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302182PMC
December 2018

Prognostic impact of low allelic ratio ITD and mutation in acute myeloid leukemia.

Blood Adv 2018 10;2(20):2744-2754

Department of Hematology, Nippon Medical School, Tokyo, Japan.

In the opinion of the European LeukemiaNet (ELN), nucleophosmin member 1 gene mutation ( mut)-positive acute myeloid leukemia (AML) with an fms-like kinase 3-internal tandem duplication (-ITD) allele ratio (AR) <0.5 (low AR) has a favorable prognosis, and allogeneic hematopoietic stem cell transplant (allo-HSCT) in the first complete remission (CR1) period is not actively recommended. We studied 147 patients with -ITD gene mutation-positive AML, dividing them into those with low AR and those with AR of ≥0.5 (high AR), and examined the prognostic impact according to allo-HSCT in CR1. Although -ITD AR and mut are used in the prognostic stratification, we found that mut-positive AML with -ITD low AR was not associated with favorable outcome (overall survival [OS], 41.3%). Moreover, patients in this group who underwent allo-HSCT in CR1 had a significantly more favorable outcome than those who did not (relapse-free survival [RFS] = .013; OS = .003). Multivariate analysis identified allo-HSCT in CR1 as the sole favorable prognostic factor (RFS < .001; OS < .001). The present study found that prognosis was unfavorable in mut-positive AML with -ITD low AR when allo-HSCT was not carried out in CR1.
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http://dx.doi.org/10.1182/bloodadvances.2018020305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199656PMC
October 2018

Topographical distribution of neurovascular canals and foramens in the mandible: avoiding complications resulting from their injury during oral surgical procedures.

Heliyon 2018 Sep 21;4(9):e00812. Epub 2018 Sep 21.

Department of Radiology, Tokyo Metropolitan Hiroo Hospital, 2-34-10 Ebisu, Shibuya-ku, Tokyo 150-0013, Japan.

Purpose: Certain oral surgical procedures can injure neurovascular canals and foramens in the mandible. Hence, before performing surgical procedures, it is important to assess the distribution of the bifid mandibular canal (BMC), accessory mental foramen (AMF), medial lingual canal (MLC), lateral lingual canal (LLC), buccal foramen (BF), and lingual alveolar canal (LAC). This study aimed to assess the distribution of different types of canals and foramens. Furthermore, we investigated the limitations associated with finding these structures in panoramic images.

Methods: Fifty-eight patients who had undergone panoramic radiography and computed tomography (CT) scans at our hospital were randomly selected for this study. Imaging data obtained from these patients were retrospectively reviewed.

Results: We found that the occurrence of BMC was 60.3%, AMF was 6.9%, MLC was 98.2%, LLC was 75.9%, BF was 43.1%, and LAC was 98.3%. Edge-contrasted inverted panoramic images revealed BMCs in 21.7% and AMFs in 25%; however, most of these canals could not be detected. In the panoramic images, the average diameter of the BMC was significantly different between the detected group and not detected group. The number of canals and foramens in the anterior region to the molar region decreased on the buccal and lingual sides, and most BMCs were in the retromolar to the ramus region.

Conclusion: Our results indicated different distributions and occurrence rates of each type of neurovascular canal and foramens.
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http://dx.doi.org/10.1016/j.heliyon.2018.e00812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153467PMC
September 2018

Genealogies and ages of cultural traits: An application of the theory of duality to the research on cultural evolution.

Theor Popul Biol 2018 09 9;123:18-27. Epub 2018 May 9.

SOKENDAI (The Graduate University for Advanced Studies), Hayama, Kanagawa 240-0193, Japan.

A finite-population, discrete-generation model of cultural evolution is described, in which multiple discrete traits are transmitted independently. In this model, each newborn may inherit a trait from multiple cultural parents. Transmission fails with a positive probability unlike in population genetics. An ancestral process simulating the cultural genealogy of a sample of individuals is derived for this model. This ancestral process, denoted by M, is shown to be dual to a process M describing the change in the frequency of a trait. The age-frequency spectrum is defined as a two-dimensional array whose (i,k) element is the expected number of distinct cultural traits introduced k generations ago and now carried by i individuals in a sample of a particular size n. Numerical calculations reveal that the age-frequency spectrum and related metrics undergo a critical transition from a phase with a moderate number of young, rare traits to a phase with numerous very old, common traits when the expected number of cultural parents per individual exceeds one. It is shown that M and M converge to branching or deterministic processes, depending on the way population size tends to infinity, and these limiting processes bear some duality relationships. The critical behavior of the original processes M and M is explained in terms of a phase transition of the branching processes. Using the results of the limiting processes in combination, we derive analytical formulae that well approximate the age-frequency spectrum and also other metrics.
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http://dx.doi.org/10.1016/j.tpb.2018.04.007DOI Listing
September 2018

Usefulness of BCOR gene mutation as a prognostic factor in acute myeloid leukemia with intermediate cytogenetic prognosis.

Genes Chromosomes Cancer 2018 08;57(8):401-408

Department of Hematology, Nippon Medical School, Tokyo, Japan.

BCOR gene is a transcription regulatory factor that plays an essential role in normal hematopoiesis. The wider introduction of next-generation sequencing technology has led to reports in recent years of mutations in the BCOR gene in acute myeloid leukemia (AML), but the related clinical characteristics and prognosis are not sufficiently understood. We investigated the clinical characteristics and prognosis of 377 de novo AML cases with BCOR or BCORL1 mutation. BCOR or BCORL1 gene mutations were found in 28 cases (7.4%). Among cases aged 65 years or below that were also FLT3-ITD-negative and in the intermediate cytogenetic prognosis group, BCOR or BCORL1 gene mutations were observed in 11% of cases (12 of 111 cases), and this group had significantly lower 5-year overall survival (OS) (13.6% vs. 55.0%, P = 0.0021) and relapse-free survival (RFS) (14.3% vs. 44.5%, P = 0.0168) compared to cases without BCOR or BCORL1 gene mutations. Multivariate analysis demonstrated that BCOR mutations were an independent unfavorable prognostic factor (P = 0.0038, P = 0.0463) for both OS and RFS. In cases of AML that are FLT3-ITD-negative, aged 65 years or below, and in the intermediate cytogenetic prognosis group, which are considered to have relatively favorable prognosis, BCOR gene mutations appear to be an important prognostic factor.
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http://dx.doi.org/10.1002/gcc.22542DOI Listing
August 2018

Synthesis and Evaluation of Antibacterial Activity of Bottromycins.

J Org Chem 2018 07 16;83(13):7135-7149. Epub 2018 Apr 16.

Kitasato Institute for Life Sciences , Kitasato University , 5-9-1 Shirokane , Minato-ku, Tokyo 108-8641 , Japan.

Total synthesis of bottromycin A can be accomplished through a diastereoselective Mannich reaction of a chiral sulfinamide, mercury-mediated intermolecular amidination, and cyclization of a constrained tetracyclic peptide. Exploitation of this process allowed the synthesis of several novel bottromycin analogs. The antimicrobial activity of these analogs was evaluated in vitro against Gram-positive bacteria, such as methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE). Structure-activity relationships were explored taking into consideration the unique three-dimensional structure of the compounds. Notably, one of the new analogs devoid of a methyl ester, which is known to lower the in vivo efficacy of bottromycin, exhibited antibacterial bioactivity comparable to that of vancomycin.
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http://dx.doi.org/10.1021/acs.joc.8b00045DOI Listing
July 2018

Tooth loss-related dietary patterns and cognitive impairment in an elderly Japanese population: The Nakajima study.

PLoS One 2018 15;13(3):e0194504. Epub 2018 Mar 15.

Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Although several studies have demonstrated a potential correlation of dietary patterns with cognitive function, the relationship between tooth loss and dietary patterns and cognitive function have not been identified. In this cross-sectional study, we used a reduced rank regression (RRR) analysis, a technique used previously to observe dietary patterns based on the intakes of nutrients or levels of biomarkers associated with the condition of interest, to identify tooth loss-related dietary patterns and investigate the associations of such patterns with cognitive impairment in 334 community-dwelling Japanese subjects aged ≥ 60 years. According to Pearson correlation coefficients, the intakes of six nutrients (ash content, sodium, zinc, vitamin B1, α- and β-carotene) correlated significantly with the number of remaining teeth. Using RRR analysis, we extracted four dietary patterns in our subject population that explained 86.67% of the total variation in the intakes of these six nutrients. Particularly, dietary pattern 1 (DP1) accounted for 52.2% of the total variation. Food groups with factor loadings of ≥ 0.2 included pickled green leafy vegetables, lettuce/cabbage, green leaves vegetables, cabbage, carrots/squash; by contrast, rice had a factor loading of <-0.2. In a multivariate regression analysis, the adjusted odds ratios regarding the prevalence of cognitive impairment for the lowest, middle and highest tertiles of the DP1 score were 1.00 (reference), 1.224 (95% confidence interval [CI]: 0.611-2.453) and 0.427 (95% CI: 0.191-0.954), respectively. To our knowledge, this is the first report to show that tooth loss-related dietary patterns are associated with a high prevalence of cognitive impairment. These results may motivate changes in dental treatment and the dietary behaviours and thereby lower the risk of cognitive impairment.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0194504PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854423PMC
July 2018