Publications by authors named "Atsushi Saito"

450 Publications

Classification of large-scale image database of various skin diseases using deep learning.

Int J Comput Assist Radiol Surg 2021 Jul 26. Epub 2021 Jul 26.

Institute of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo, Japan.

Purpose: The purpose of this study was to develop a deep learning-based computer-aided diagnosis system for skin disease classification using photographic images of patients. The targets are 59 skin diseases, including localized and diffuse diseases captured by photographic cameras, resulting in highly diverse images in terms of the appearance of the diseases or photographic conditions.

Methods: ResNet-18 is used as a baseline model for classification and is reinforced by metric learning to boost generalization in classification by avoiding the overfitting of the training data and increasing the reliability of CADx for dermatologists. Patient-wise classification is performed by aggregating the inference vectors of all the input patient images.

Results: The experiment using 70,196 images of 13,038 patients demonstrated that classification accuracy was significantly improved by both metric learning and aggregation, resulting in patient accuracies of 0.579 for Top-1, 0.793 for Top-3, and 0.863 for Top-5. The McNemar test showed that the improvements achieved by the proposed method were statistically significant.

Conclusion: This study presents a deep learning-based classification of 59 skin diseases using multiple photographic images of a patient. The experimental results demonstrated that the proposed classification reinforced by metric learning and aggregation of multiple input images was effective in the classification of patients with diverse skin diseases and imaging conditions.
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http://dx.doi.org/10.1007/s11548-021-02440-yDOI Listing
July 2021

Primary Androgen-Depletion Therapy Prevails Not Only for Metastatic but Also for Nonmetastatic Hormone-Naïve Prostate Cancer in Japan-Recent Trends and Efficacy.

Gan To Kagaku Ryoho 2021 Jul;48(7):911-919

Dept. of Urology, International University of Health and Welfare Narita Hospital.

Objective: To investigate the real-world use of primary androgen-deprivation therapy(PADT; gonadotropin-releasing hormone agonists[leuprorelin/goserelin]and antagonists[degarelix]/surgical castration), its clinical effectiveness, and the characteristics of Japanese patients with hormone-sensitive prostate cancer treated with PADT.

Methods: In this retrospective, observational study, patients using PADT(≥1 record)in the 2016-2018 Japan Study Group of Prostate Cancer registry were followed up from their initial date of PADT until October 2018. The primary endpoints included prostate-specific antigen( PSA)response rate(PSA<4 ng/mL)and duration of initial treatment.

Results: Of 1,895 patients, 47.7%, 24.4%, and 22.0% received leuprorelin, goserelin, and degarelix, respectively; 5.9% underwent surgical castration. The degarelix group had the highest median PSA at diagnosis(116.7 ng/mL)and proportion of patients with clinical Stage Ⅳ prostate cancer (72.9%)and Gleason score 9-10(59.7%). A concomitant antiandrogen was used in >80% and 70% of patients in the leuprorelin/goserelin and degarelix groups, respectively; bicalutamide was used most commonly(99.0%). Median duration of initial treatment was 20.8 months in the degarelix group and not yet reached in the leuprorelin/goserelin groups; continuation rates at 24 months were 44.6% and 81.6%/87.3%, respectively. The PSA response rate was the highest in the leuprorelin group(93.7%); median percentage change in PSA was comparable across all treatment groups(-99.1% to -99.8%).

Conclusions: Real-world use of PADT in patients with hormone-sensitive prostate cancer is likely based on its specific therapeutic attributes and patient characteristics.
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July 2021

OASIS/CREB3L1 is a factor that responds to nuclear envelope stress.

Cell Death Discov 2021 Jun 29;7(1):152. Epub 2021 Jun 29.

Department of Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

The nuclear envelope (NE) safeguards the genome and is pivotal for regulating genome activity as the structural scaffold of higher-order chromatin organization. NE had been thought as the stable during the interphase of cell cycle. However, recent studies have revealed that the NE can be damaged by various stresses such as mechanical stress and cellular senescence. These types of stresses are called NE stress. It has been proposed that NE stress is closely related to cellular dysfunctions such as genome instability and cell death. Here, we found that an endoplasmic reticulum (ER)-resident transmembrane transcription factor, OASIS, accumulates at damaged NE. Notably, the major components of nuclear lamina, Lamin proteins were depleted at the NE where OASIS accumulates. We previously demonstrated that OASIS is cleaved at the membrane domain in response to ER stress. In contrast, OASIS accumulates as the full-length form to damaged NE in response to NE stress. The accumulation to damaged NE is specific for OASIS among OASIS family members. Intriguingly, OASIS colocalizes with the components of linker of nucleoskeleton and cytoskeleton complexes, SUN2 and Nesprin-2 at the damaged NE. OASIS partially colocalizes with BAF, LEM domain proteins, and a component of ESCRT III, which are involved in the repair of ruptured NE. Furthermore, OASIS suppresses DNA damage induced by NE stress and restores nuclear deformation under NE stress conditions. Our findings reveal a novel NE stress response pathway mediated by OASIS.
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http://dx.doi.org/10.1038/s41420-021-00540-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257603PMC
June 2021

Systemic administration of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation.

J Periodontal Res 2021 Jun 15. Epub 2021 Jun 15.

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Background/objectives: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule expressed on T cells. CTLA-4 also binds to the surfaces of monocytes and macrophages, precursors of osteoclasts. Research on rheumatoid arthritis demonstrated that CTLA-4 suppresses inflammation and bone resorption. However, its effects on alveolar bone have yet to be understood. The purpose of this study was to investigate the role and potential mechanism of CTLA-4 in bone resorption in periodontitis.

Materials And Methods: In vivo, the effects of systemic administration of CTLA-4 immunoglobulin fusion protein (CTLA-4-Ig) on alveolar bone resorption were investigated using a periodontitis mouse model. A total of 20 C57BL/6J mice were randomly assigned to two groups according to the administration modes. Periodontitis was induced by placing a ligature around the left maxillary second molar. The contralateral tooth was left un-ligated. In the CTLA-4-Ig (+) group, CTLA-4-Ig was administered by intraperitoneal injection at 1 and 3 days after ligature placement. Animals in the CTLA-4-Ig (-) group were given only phosphate-buffered saline each time. At 5 days after ligature placement, bone resorption was assessed by micro-computed tomography and histological examination, and the prevalence of osteoclast-like cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining. In vitro, the effects of CTLA-4-Ig on osteoclasts were evaluated. Viability of RAW 264.7 cells treated with receptor activator of nuclear factor-κB ligand (RANKL) and CTLA-4-Ig was tested by WST-1 assay. Osteoclast-like cells were enumerated by TRAP staining, and osteoclast activity was evaluated by resorption pit assay. Gene expression levels of osteoclast differentiation markers (macrophage-colony stimulating factor receptor, carbonic anhydrase II, cathepsin K, and Trap) and protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, were assessed by quantitative real-time polymerase chain reaction. The effect of CTLA-4-Ig on the nuclear factor-κB (NF-κB) activation was assessed by enzyme-linked immunosorbent assay.

Results: In vivo, ligature-induced bone resorption and the numbers of osteoclast-like cells were significantly decreased by the administration of CTLA-4-Ig. In vitro, treatment with RANKL and CTLA-4-Ig had no significant effect on cell viability. CTLA-4-Ig significantly reduced the prevalence and activation of osteoclast-like cells and decreased the expressions of osteoclast differentiation markers, compared with the RANKL-treated control. CTLA-4-Ig significantly suppressed RANKL-induced phosphorylation of NF-κB p65 but increased PP2A expression.

Conclusion: These results suggest that CTLA-4-Ig abrogates bone resorption in induced periodontitis, possibly via inhibition of osteoclast differentiation and activation. The regulation of the NF-κB pathway and PP2A expression may be one mechanism by which CTLA-4-Ig suppresses osteoclast behavior.
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http://dx.doi.org/10.1111/jre.12909DOI Listing
June 2021

Healing of Experimental Periodontal Defects Following Treatment with Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral.

Biomolecules 2021 May 29;11(6). Epub 2021 May 29.

Department of Periodontology, Tokyo Dental College, Chiyoda-ku, Tokyo 1010061, Japan.

The aim of this study was to investigate the effects of fibroblast growth factor (FGF)-2 used in combination with deproteinized bovine bone mineral (DBBM) on the healing of experimental periodontal defects. Periodontal defects created in rats were treated by FGF-2, DBBM, FGF-2 + DBBM, or left unfilled. Microcomputed tomography, histological, and immunohistochemical examinations were used to evaluate healing. In vitro cell viability/proliferation on DBBM with/without FGF-2 was assessed by WST-1. Cell behavior was analyzed using scanning electron and confocal laser scanning microscopy. Osteogenic differentiation was evaluated by staining with alkaline phosphatase and alizarin red. Bone volume fraction was significantly greater in FGF-2 and FGF-2 + DBBM groups than in other groups at 2 and 4 weeks postoperatively. In histological assessment, newly formed bone in FGF-2 and FGF-2 + DBBM groups appeared to be greater than other groups. Significantly greater levels of proliferating cell nuclear antigen-, vascular endothelial growth factor-, and osterix-positive cells were observed in FGF-2 and FGF-2 + DBBM groups compared to Unfilled group. In vitro, addition of FGF-2 to DBBM promoted cell viability/proliferation, attachment/spreading, and osteogenic differentiation. The combination therapy using FGF-2 and DBBM was similarly effective as FGF-2 alone in the healing of experimental periodontal defects. In certain bone defect configurations, the combined use of FGF-2 and DBBM may enhance healing via promotion of cell proliferation, angiogenesis, and osteogenic differentiation.
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http://dx.doi.org/10.3390/biom11060805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226676PMC
May 2021

Taxonomic and Gene Category Analyses of Subgingival Plaques from a Group of Japanese Individuals with and without Periodontitis.

Int J Mol Sci 2021 May 18;22(10). Epub 2021 May 18.

Department of Microbiology, Tokyo Dental College, Chiyoda-ku, Tokyo 101-0061, Japan.

Periodontitis is an inflammation of tooth-supporting tissues, which is caused by bacteria in the subgingival plaque (biofilm) and the host immune response. Traditionally, subgingival pathogens have been investigated using methods such as culturing, DNA probes, or PCR. The development of next-generation sequencing made it possible to investigate the whole microbiome in the subgingival plaque. Previous studies have implicated dysbiosis of the subgingival microbiome in the etiology of periodontitis. However, details are still lacking. In this study, we conducted a metagenomic analysis of subgingival plaque samples from a group of Japanese individuals with and without periodontitis. In the taxonomic composition analysis, genus and demonstrated significantly different compositions between healthy sites and sites with periodontal pockets. The results from the relative abundance of functional gene categories, carbohydrate metabolism, glycan biosynthesis and metabolism, amino acid metabolism, replication and repair showed significant differences between healthy sites and sites with periodontal pockets. These results provide important insights into the shift in the taxonomic and functional gene category abundance caused by dysbiosis, which occurs during the progression of periodontal disease.
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http://dx.doi.org/10.3390/ijms22105298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157553PMC
May 2021

Comprehensive treatment for severe periodontitis with pathologic tooth migration-related bimaxillary protrusion: A case report with 3-year follow-up.

J Am Dent Assoc 2021 Jun;152(6):471-482.e2

Background And Overview: Patients with severe periodontitis often experience pathologic tooth migration (PTM), which impairs esthetics and leads to occlusal disharmony (for example, premature contacts and traumatic occlusion) that can further exacerbate periodontitis. The authors describe a patient who exhibited severe periodontitis with PTM-related bimaxillary protrusion. This report includes 3-year clinical outcomes after periodontal regenerative therapy, implant-anchored orthodontic therapy, and implant prosthodontics intended to achieve both functional and esthetic improvements.

Case Description: A 63-year-old woman sought treatment with the chief complaint of maxillary anterior tooth mobility. Clinical examination revealed excessive tooth mobility, deep periodontal pockets, and infrabony defects in all teeth. All teeth exhibited PTM; the mandibular anterior teeth exhibited marked protrusion caused by the progression of periodontitis. After initial periodontal therapy, periodontal regenerative therapy was performed in all molar regions. At 6 and 9 months postoperatively, comprehensive orthodontic treatment was initiated for the mandible and maxilla, respectively, using orthodontic anchorage devices to achieve acceptable functional occlusion. After orthodontic treatment, staged guided bone regeneration was performed and dental implants were placed in the severely resorbed maxillary anterior ridge. This comprehensive treatment yielded favorable periodontal conditions, stable occlusion, and good esthetic outcomes.

Conclusions And Practical Implications: Favorable esthetics, stable occlusion, and highly cleansable periodontal tissues were achieved with well-planned interdisciplinary and comprehensive treatment, although the patient had severe periodontitis and PTM-related bimaxillary protrusion.
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http://dx.doi.org/10.1016/j.adaj.2021.02.017DOI Listing
June 2021

Surgical Periodontal Therapy with Recombinant Human Fibroblast Growth Factor-2 in Treatment of Chronic Periodontitis: A Case Report with 2-year Follow-up.

Bull Tokyo Dent Coll 2021 Jun 14;62(2):127-134. Epub 2021 May 14.

Department of Periodontology, Tokyo Dental College.

We report a case of generalized chronic periodontitis requiring periodontal regenerative therapy. The patient was a 53-year-old woman who presented with the chief complaint of gingival swelling. An initial examination revealed 31.5% of sites with a probing depth of ≥4 mm and 46.3% with bleeding on probing. Radiographic examination showed vertical bone resorption in tooth #33. Horizontal adsorption was also observed in other areas. Based on a clinical diagnosis of severe generalized chronic periodontitis, initial periodontal therapy consisting of plaque control, scaling and root planing, occlusal adjustment, caries treatment, and splint placement was performed. After re-evaluation, surgical periodontal treatment was performed at selected sites. Periodontal regeneration therapy with recombinant human fibroblast growth factor (rhFGF)-2 was performed at #33. Two other sites (#14, 15), which had residual periodontal pockets, were treated by open-flap debridement. After re-evaluation, the patient was placed on a maintenance program. Periodontal regenerative therapy with rhFGF-2 resulted in an improvement in angular bone resorption, which has been properly maintained for 2 years. Continued care is needed to maintain stable periodontal conditions.
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http://dx.doi.org/10.2209/tdcpublication.2020-0045DOI Listing
June 2021

Periodontal Regenerative Therapy with Recombinant Human Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral in Patient with Chronic Periodontitis: An 18-month Follow-up Report.

Bull Tokyo Dent Coll 2021 Jun 14;62(2):107-117. Epub 2021 May 14.

Department of Periodontology, Tokyo Dental College.

This report describes a case of generalized chronic periodontitis requiring periodontal regenerative therapy. The patient was a 62-year-old man who presented with the chief complaint of gingival swelling in the molar region. An initial examination revealed that 31.6% of sites had a probing depth of ≥4 mm and 18.5% bleeding on probing. Radiographic examination revealed vertical bone resorption in #14, 25, 26, 27, 32, 37, 45, and 47, and horizontal resorption in other regions. Based on a clinical diagnosis of moderate chronic periodontitis, initial periodontal therapy consisting of plaque control and scaling and root planing was performed. Occlusal adjustment of premature contact sites was performed after inflammation was suppressed. Surgical periodontal therapy was subsequently performed at selected sites. Periodontal regenerative therapy using recombinant human fibroblast growth factor (rhFGF)-2 was performed on #14, 25, 26, 32, and 37. Combination therapy with rhFGF-2 and deproteinized bovine bone mineral (DBBM) was performed on #45 and 47. Other sites with residual periodontal pockets were treated by open flap debridement, and #27 was extracted due to a bone defect exceeding the root apex. Progress was then reevaluated and the patient placed on supportive periodontal therapy. Periodontal regenerative therapy using rhFGF-2 in combination with DBBM resulted in an improvement in clinical parameters and vertical bone resorption. This improvement has been adequately maintained over an 18-month period. The periodontal treatment provided resulted in a marked improvement in the patient's oral health-related quality of life.
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http://dx.doi.org/10.2209/tdcpublication.2020-0034DOI Listing
June 2021

Integrated Structural Analysis of -Glycans and Free Oligosaccharides Allows for a Quantitative Evaluation of ER Stress.

Biochemistry 2021 Jun 13;60(21):1708-1721. Epub 2021 May 13.

Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.

Endoplasmic reticulum (ER) stress has been reported in a variety of diseases. Although ER stress can be detected using specific markers, it is still difficult to quantitatively evaluate the degree of stress and to identify the cause of the stress. The ER is the primary site for folding of secretory or transmembrane proteins as well as the site where glycosylation is initiated. This study therefore postulates that tracing the biosynthetic pathway of asparagine-linked glycans (-glycans) would be a reporter for reflecting the state of the ER and serve as a quantitative descriptor of ER stress. Glycoblotting-assisted mass spectrometric analysis of the HeLa cell line enabled quantitative determination of the changes in the structures of -glycans and degraded free oligosaccharides (fOSs) in response to tunicamycin- or thapsigargin-induced ER stress. The integrated analysis of neutral and sialylated -glycans and fOSs showed the potential to elucidate the cause of ER stress, which cannot be readily done by protein markers alone. Changes in the total amount of glycans, increase in the ratio of high-mannose type -glycans, increase in fOSs, and changes in the ratio of sialylated -glycans in response to ER stress were shown to be potential descriptors of ER stress. Additionally, drastic clearance of accumulated -glycans was observed in thapsigargin-treated cells, which may suggest the observation of ER stress-mediated autophagy or ER-phagy in terms of glycomics. Quantitative analysis of -glycoforms composed of -glycans and fOSs provides the dynamic indicators reflecting the ER status and the promising strategies for quantitative evaluation of ER stress.
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http://dx.doi.org/10.1021/acs.biochem.0c00969DOI Listing
June 2021

Prospective Longitudinal Changes in the Periodontal Inflamed Surface Area Following Active Periodontal Treatment for Chronic Periodontitis.

J Clin Med 2021 Mar 10;10(6). Epub 2021 Mar 10.

Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.

Periodontal disease is a chronic inflammatory disease of the periodontal tissue. The periodontal inflamed surface area (PISA) is a proposed index for quantifying the inflammatory burden resulting from periodontitis lesions. This study aimed to investigate longitudinal changes in the periodontal status as evaluated by the PISA following the active periodontal treatment. To elucidate the prognostic factors of PISA, mixed-effect modeling was performed for clinical parameters, tooth-type, and levels of periodontal pathogens as independent variables. One-hundred-twenty-five patients with chronic periodontitis who completed the active periodontal treatment were followed-up for 24 months, with evaluations conducted at 6-month intervals. Five-times repeated measures of mean PISA values were 130+/-173, 161+/-276, 184+/-320, 175+/-417, and 209+/-469 mm. Changes in clinical parameters and salivary and subgingival periodontal pathogens were analyzed by mixed-effect modeling. Plaque index, clinical attachment level, and salivary levels of were associated with changes in PISA at the patient- and tooth-level. Subgingival levels of and were associated with changes in PISA at the sample site. For most patients, changes in PISA were within 10% of baseline during the 24-month follow-up. However, an increase in the number of bleeding sites in a tooth with a deep periodontal pocket increased the PISA value exponentially.
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http://dx.doi.org/10.3390/jcm10061165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998532PMC
March 2021

A 3D analysis of growth trajectory and integration during early human prenatal facial growth.

Sci Rep 2021 Mar 25;11(1):6867. Epub 2021 Mar 25.

Department of Plastic and Reconstructive Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Significant shape changes in the human facial skeleton occur in the early prenatal period, and understanding this process is critical for studying a myriad of congenital facial anomalies. However, quantifying and visualizing human fetal facial growth has been challenging. Here, we applied quantitative geometric morphometrics (GM) to high-resolution magnetic resonance images of human embryo and fetuses, to comprehensively analyze facial growth. We utilized non-linear growth estimation and GM methods to assess integrated epigenetic growth between masticatory muscles and associated bones. Our results show that the growth trajectory of the human face in the early prenatal period follows a curved line with three flexion points. Significant antero-posterior development occurs early, resulting in a shift from a mandibular prognathic to relatively orthognathic appearance, followed by expansion in the lateral direction. Furthermore, during this time, the development of the zygoma and the mandibular ramus is closely integrated with the masseter muscle.
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http://dx.doi.org/10.1038/s41598-021-85543-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994314PMC
March 2021

Treatment of air leakage using the VIO soft coagulation system: a mouse pulmonary air leak model.

Surg Today 2021 Mar 20. Epub 2021 Mar 20.

Department of Thoracic Surgery, School of Medicine and Hospital, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan.

Purpose: We aimed to compare the efficacy of the VIO soft coagulation system (VSCS) for the treatment of air leaks by sealing with fibrin glue, and also assess the histological alterations that occur after soft coagulation.

Methods: A mouse pulmonary air leak model was designed. The pulmonary fistula was subsequently coagulated with the VSCS or sealed with fibrin glue with polyglycolic acid (PGA) sheets. The burst pressure at air leak recurrence was measured in each group, and the results were compared. We also evaluated the histological alterations in the mouse pulmonary air leak model after soft coagulation with the VSCS.

Results: The burst pressure in the soft coagulation group (80 W/Effect 5) (median 42.8; range 35.4-53.8 cmHO) was similar to that in the fibrin glue group (median 41.5; range 34.6-43.9 cmHO) (p = 0.21). Histological examinations revealed that the visceral pleura remained torn, the structure of the pulmonary alveolus was maintained, and the coagulated fistula was covered with a fibrin membrane in the soft coagulation group.

Conclusions: The pressure resistance following soft coagulation was equivalent to that after sealing using fibrin glue with PGA sheets. The air leaks were likely controlled by covering the fistula with a fibrin membrane after soft coagulation with the VSCS.
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http://dx.doi.org/10.1007/s00595-021-02251-3DOI Listing
March 2021

Estimation of the Periodontal Inflamed Surface Area by Simple Oral Examination.

J Clin Med 2021 Feb 12;10(4). Epub 2021 Feb 12.

Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.

The periodontal inflamed surface area (PISA) is a useful index for clinical and epidemiological assessments, since it can represent the inflammation status of patients in one contentious variable. However, calculation of the PISA is difficult, requiring six point probing depth measurements with or without bleeding on probing on 28 teeth, followed by data input in a calculation program. More simple methods are essential for screening periodontal disease or in epidemiological studies. In this study, we tried to establish a convenient partial examination method to estimate PISA. Cross-sectional data of 254 subjects who completed active periodontal therapy were analyzed. Teeth that represent the PISA value were selected by an item response theory approach. The maxillary second molar, first premolar, and lateral incisor and the mandibular second molar and lateral incisor were selected. The sum of the PISAs of these teeth was significantly correlated with the patient's PISA (R = 0.938). More simply, the sum of the maximum values of probing pocket depth with bleeding for these teeth were also significantly correlated with the patient's PISA (R = 0.6457). The simple model presented in this study may be useful to estimate PISA.
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http://dx.doi.org/10.3390/jcm10040723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917734PMC
February 2021

Relationship between Pathological Characteristics and Radiological Findings on Perfusion MR Imaging of Meningioma.

Neurol Med Chir (Tokyo) 2021 Mar 28;61(3):228-235. Epub 2021 Jan 28.

Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

Few studies have reviewed the roles of perfusion magnetic resonance (MR) imaging in the histopathological examination of meningiomas. We analyzed the relationships between radiological findings on perfusion MR imaging and pathological characteristics such as origin of the tumor, mitotic activity, pathological subtype, and perifocal edema formation. The subjects were 21 surgical cases of meningioma preoperatively evaluated by perfusion MR imaging. A region of interest (ROI) was set inside of the tumor, and perifocal edema of the same size, cerebral blood volume (CBV), and cerebral blood flow (CBF) on perfusion MR and diffusion-weighted (DW) imaging were analyzed. These radiological data were evaluated in comparison with histopathological characteristics. On perfusion MR imaging, the average ratio of CBV against the contralateral side was 6.43 (1.13-20.0) and that of CBF was 7.73 (1.34-11.3). There was no significant relationship with perfusion MR imaging data, tumor volume, or perifocal edema volume. However, the large peritumoral edema group often had a higher CBV and CBF than the non-large peritumoral edema group. The skull base group had a significantly higher CBV and lower signal intensity on DW images than the non-skull base group. Signal intensity on DW images was higher in grade II or III than in grade I. Perfusion MR imaging data revealed that the higher ratio of peritumoral edema against tumor size was associated with higher blood flow and blood volume under intratumoral circulatory conditions, and that skull base meningioma had a higher blood volume than non-skull base meningioma.
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http://dx.doi.org/10.2176/nmc.oa.2020-0131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966207PMC
March 2021

A large-scale observational study to investigate the current status of diabetic complications and their prevention in Japan (JDCP study 6): baseline dental and oral findings.

Diabetol Int 2021 Jan 15;12(1):52-61. Epub 2020 Oct 15.

Institution for Advanced Dental Sciences, Tokushinkai Group, Tokyo, Japan.

Japan Diabetes Complication and Prevention prospective (JDCP) study was conducted to examine the association between glycemic control and oral conditions in a large database of Japanese patients with diabetes. It included a total of 6099 patients with diabetes (range, 40-75 years) who had been treated as outpatients between 2007 and 2009. The mean number of present teeth at baseline was 19.8 and women with type 2 diabetes had fewer teeth than men with type 2 diabetes. Within the previous year, 17% of all patients had lost teeth. At baseline, 32% had experienced gingival swelling, 69% had brushed more than twice a day, 37% had used interdental cleaning aids, and 43% had undergone regular dental checkups. Multiple logistic regression analysis indicated that type 1 patients with HbA1c ≥ 7.0% were at higher risk of having fewer than 20 teeth (odds ratio [OR] 2.38; 95% confidence interval [CI] 1.25-4.78), and type 2 patients with HbA1c ≥ 8.0% also were at high risk of having fewer than 20 teeth (OR 1.16; 95% CI 1.00-1.34), after adjustment for nine possible confounding factors. In conclusion, patients with diabetes were found to be at high risk of tooth loss, and the poorer the glycemic control, the higher the risk of tooth loss in these patients.
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http://dx.doi.org/10.1007/s13340-020-00465-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790965PMC
January 2021

Characteristics of COVID-19 patients admitted into two hospitals in sapporo, Japan: Analyses and insights from two outbreak waves.

Respir Investig 2021 Mar 1;59(2):180-186. Epub 2021 Jan 1.

Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

Background: Coronavirus disease (COVID-19) emerged in January 2020 in Sapporo city, and the outbreak has shown two peaks.

Methods: A total of 260 COVID-19 patients were enrolled and categorized into three groups according to the pandemic pattern, jobs and situation, and disease severity. We compared clinical characteristics according to these categories.

Results: We found two pandemic peaks, and the proportion of patients and health providers who were infected in other hospitals had increased in the latter two periods (period 2: 49.6%, period 3: 32.7%). Particularly, the proportion of infected health providers was 27% in period 2, and they tended to be younger females with a mild condition. Severity of the disease (requirement of oxygen and/or mechanical ventilation) was associated with advanced age, and all the patients who died during admission were over 60 years old.

Conclusions: We reported the temporal dynamics and characteristics of the COVID-19 pandemic in Sapporo city, Japan. This survey from the viewpoint of the hospital provides a new insight into and a better guide for the further management of the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.resinv.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775652PMC
March 2021

Role of 5-HT receptor-mediated serotonergic transmission in the medial prefrontal cortex in acute restraint stress-induced augmentation of rewarding memory of cocaine in mice.

Neurosci Lett 2021 01 19;743:135555. Epub 2020 Dec 19.

Laboratory of Molecular Pharmacology, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 920-1192, Japan. Electronic address:

Stress enhances cocaine craving. We recently reported that acute restraint stress increases cocaine conditioned place preference (CPP) in mice; however, the underlying mechanisms remain unclear. This study aimed to examine the role of serotonergic transmission in the medial prefrontal cortex (mPFC) in cocaine CPP enhancement by acute restraint stress, which increases extracellular serotonin (5-HT) levels in the mPFC. Intra-mPFC infusion of the selective serotonin reuptake inhibitor (S)-citalopram prior to the test session significantly increased the cocaine CPP score under non-stressed conditions. This is indicative of the substantial role of increased mPFC 5-HT levels in cocaine CPP enhancement. Moreover, intra-mPFC and systemic administration of the 5-HT receptor antagonist WAY100635 immediately before restraint stress exposure significantly attenuated stress-induced cocaine CPP enhancement. Our findings suggest that enhanced serotonergic transmission via 5-HT receptors in the mPFC is involved in acute stress-induced augmentation of rewarding memory of cocaine; moreover, the 5-HT receptor could be a therapeutic target for stress-induced cocaine craving.
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http://dx.doi.org/10.1016/j.neulet.2020.135555DOI Listing
January 2021

Acute eosinophilic pneumonia accompanied with COVID-19: a case report.

Respirol Case Rep 2020 Dec 16;8(9):e00683. Epub 2020 Nov 16.

Department of Respiratory Medicine and Allergology Sapporo Medical University School of Medicine Sapporo Japan.

We report a case of acute eosinophilic pneumonia (AEP) triggered by coronavirus disease 2019 (COVID-19) infection. A 77-year-old man experienced left-sided chest pain and shortness of breath. Reverse transcription-polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) revealed a positive result, and he was treated with favipiravir, ciclesonide, and lascufloxacin, but he showed poor improvement. On the other hand, computed tomography (CT) images were atypical for COVID-19 infection, and the elevation of eosinophil was found in blood and the fluid obtained by bronchoscopy. So, we clinically diagnosed this case as AEP. Administration of prednisolone dramatically improved the patient's clinical condition and chest radiograph findings, which were consistent with the clinical course of AEP. This case suggests the importance of considering the complications of AEP when treating patients with COVID-19 infection.
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http://dx.doi.org/10.1002/rcr2.683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669372PMC
December 2020

Optimal Examination Sites for Periodontal Disease Evaluation: Applying the Item Response Theory Graded Response Model.

J Clin Med 2020 Nov 21;9(11). Epub 2020 Nov 21.

Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Tokyo 60-8582, Japan.

Periodontal examination data have a complex structure. For epidemiological studies, mass screenings, and public health use, a simple index that represents the periodontal condition is necessary. Periodontal indices for partial examination of selected teeth have been developed. However, the selected teeth vary between indices, and a justification for the selection of examination teeth has not been presented. We applied a graded response model based on the item response theory to select optimal examination teeth and sites that represent periodontal conditions. Data were obtained from 254 patients who participated in a multicenter follow-up study. Baseline data were obtained from initial follow-up. Optimal examination sites were selected using item information calculated by graded response modeling. Twelve sites-maxillary 2nd premolar (palatal-medial), 1st premolar (palatal-distal), canine (palatal-medial), lateral incisor (palatal-central), central incisor (palatal-distal) and mandibular 1st premolar (lingual, medial)-were selected. Mean values for clinical attachment level, probing pocket depth, and bleeding on probing by full mouth examinations were used for objective variables. Measuring the clinical parameters of these sites can predict the results of full mouth examination. For calculating the periodontal index by partial oral examination, a justification for the selection of examination sites is essential. This study presents an evidence-based partial examination methodology and its modeling.
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http://dx.doi.org/10.3390/jcm9113754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700480PMC
November 2020

Effects of green tea extract combined with brisk walking on lipid profiles and the liver function in overweight and obese men: A randomized, double-blinded, placebo-control trial.

An Acad Bras Cienc 2020 16;92(4):e20191594. Epub 2020 Nov 16.

Kyushu University, Faculty of Human-Environment Studies, 744 Motooka, Nishi-ku, 8190395, Fukuoka City, Japan.

This study was aimed to investigate the effect of green tea extract (GTE) combined with brisk walking on lipid profiles and the liver function in overweight and obese men. Twenty-four participants were randomized to either the GTE group or the placebo group for 12 weeks with a 4-week follow-up. The walking program consisted of four 60-min-sessions/week and all participants were asked to consume two GTE (150mg) or placebo tablets daily. After 12-week intervention, GTE group resulted in a significant difference in the low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels when compared to placebo group (P < 0.01). There was also a significant reduction in the aspartate aminotransferase levels (P < 0.01) in the GTE group, but no change in the placebo group (P >0.05). There was no change in the triglyceride or high-density lipoprotein cholesterol (HDL-C) levels in the placebo group, but a significant reduction was noted in the HDL-C levels in the GTE group (P < 0.05). GTE combined with brisk walking resulted in a significant change in the LDL-C and TC levels, however, a significant reduce in HDL-C in the GTE group. The study has a more positive effect on the liver function than brisk walking alone.
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http://dx.doi.org/10.1590/0001-3765202020191594DOI Listing
November 2020

Efficacy of arterial spin labeling magnetic resonance imaging with multiple post-labeling delays to predict postoperative cerebral hyperperfusion in carotid endarterectomy.

Neurol Res 2021 Mar 15;43(3):252-258. Epub 2020 Nov 15.

Department of Neurosurgery, Tohoku University Graduate School of Medicine , Sendai, Japan.

: Cerebral hyperperfusion (CHP) syndrome is one of the most deleterious complications after carotid endarterectomy (CEA). Arterial spin labeling (ASL) is a promising non-invasive method to evaluate various hemodynamic parameters in cerebrovascular diseases. The aim of this study was to clarify whether ASL with multiple post-labeling delays (PLDs) can predict postoperative CHP after CEA. : Sixty-one patients with carotid artery stenosis treated by CEA were retrospectively analyzed. The asymmetry index of the preoperative CBF was obtained from ASL using 3 PLDs (1525 ms, 2025 ms, and 2525 ms) and single-photon emission computed tomography (SPECT). Cerebrovascular reactivity (CVR) was measured from SPECT with acetazolamide challenge. The slope of the regression line obtained from the asymmetry index of three PLDs was defined as the slope index. : The CHP phenomenon was observed in seven patients (11.5%), one of whom developed CHP syndrome (1.6%). Using the CHP phenomenon as a reference standard, the area under the receiver operating characteristics (ROC) was 0.68 for the asymmetry index of the preoperative SPECT, 0.71 for the asymmetry index of the preoperative ASL,0.73 for CVR, and 0.78 for the slope index. Using the cutoff value obtained by ROC analysis, the slope index demonstrated a sensitivity of 85%, specificity of 74%, positive predictive value of 30% and the negative predictive value of 98% for predicting CHP. : The slope index calculated by ASL with multiple PLDs is a useful screening tool to predict postoperative CHP after CEA.
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http://dx.doi.org/10.1080/01616412.2020.1847529DOI Listing
March 2021

Surgical Treatment of Furcation Involvement Associated with Recurrence of Aggressive Periodontitis: A Case Report.

Bull Tokyo Dent Coll 2020 Dec 10;61(4):265-273. Epub 2020 Nov 10.

Department of Periodontology, Tokyo Dental College.

Here, we report a case of generalized chronic periodontitis with furcation involvement that was treated successfully by means of surgical intervention. The patient was a 43-year-old man requesting treatment for periodontal disease. An initial examination revealed 42% of sites with a probing depth of ≥4 mm and 42.9% of sites with bleeding on probing. The maxillary molars showed varying degrees of furcation involvement. Radiographic examination revealed bone resorption in the molar and mandibular anterior teeth regions. Microbiological examination of subgingival plaque revealed the presence of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Tannerella forsythia. The patient's oral health-related quality of life (OHRQL) was also assessed. Based on a clinical diagnosis of severe chronic periodontitis, initial periodontal therapy was performed. Plaque control, scaling and root planing, extraction, temporary fixed restoration, occlusal adjustment, and root canal treatment were implemented. Following reevaluation, open flap debridement was performed at selected sites. Root resection was performed on the distal root of #16. Prosthetic treatment was then initiated for recovery of oral function. After confirmation of appropriate occlusion and cleanability, the patient was placed on supportive periodontal therapy. Root resection improved cleanability. This clinical improvement has been adequately maintained over a 2-year period. The patient's OHRQL score showed a slight deterioration during the supportive periodontal therapy OK period, however. This indicates the need for further careful monitoring of periodontal conditions, as well as of how they are perceived by the patient themselves.
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http://dx.doi.org/10.2209/tdcpublication.2020-0020DOI Listing
December 2020

Root Coverage with Connective Tissue Graft in Patients with Thin Periodontal Biotype: A Case Series with 12-month Follow-up.

Bull Tokyo Dent Coll 2020 Dec 10;61(4):221-229. Epub 2020 Nov 10.

Department of Periodontology, Tokyo Dental College.

Preoperative gingival thickness is an important factor in the success of complete root coverage. Here, two cases are reported in which a biotype probe was used to assess the periodontal biotype before performance of a root coverage procedure. Clinical examinations were performed at baseline and at 3, 6, and 12 months postoperatively. The following clinical parameters were evaluated: probing depth, recession height, clinical attachment level, bleeding on probing, and width of keratinized gingiva. At baseline and at 12 months postoperatively, periodontal biotype was estimated using the biotype probe. The root coverage esthetic score was assessed to determine esthetic outcome at baseline and at 3, 6, and 12 months postoperatively. The periodontal biotypes in the mandibular central and lateral incisors were judged to be thin. These teeth presented with Miller Class II gingival recession after orthodontic therapy. Gingival recession was treated with a coronally advanced flap and autogenous connective tissue graft. In both cases, improvements in all clinical parameters and root coverage esthetic scores were evaluated at 3, 6, and 12 months postoperatively. The treated recession showed 100% root coverage. The periodontal biotype changed from one that was thin to one that was thick at the surgical sites. In both the present cases, objective preoperative assessment of the periodontal biotype allowed the appropriate surgical procedure to be selected.
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http://dx.doi.org/10.2209/tdcpublication.2020-0015DOI Listing
December 2020

Treatment of Chronic Periodontitis with Recombinant Human Fibroblast Growth Factor-2 and Deproteinized Bovine Bone Mineral in Wide Intrabony Defects:12-month Follow-up Case Series.

Bull Tokyo Dent Coll 2020 Dec 10;61(4):231-241. Epub 2020 Nov 10.

Department of Periodontology, Tokyo Dental College.

Clinical use of 0.3% recombinant human fibroblast growth factor (rhFGF)-2 for periodontal regeneration received formal approval in Japan in 2016. The combination of growth factor and bone graft material is used to enhance periodontal healing in regenerative therapy. The exact effects of combination therapy on periodontal healing remain unknown, however. Here, we report three cases of chronic periodontitis treated with the combination of rhFGF-2 and deproteinized bovine bone mineral (DBBM). Following initial periodontal therapy, periodontal regenerative therapy using rhFGF-2 in combination with DBBM was performed to treat wide intrabony defects. Periodontal parameters and radiographic bone fill were reevaluated at 3 months, 6 months, and 1 year postoperatively. Oral health-related quality of life (OHRQL) was assessed as a patient-reported measure of outcome. At 1 year postoperatively, probing pocket depth and clinical attachment level showed a significant improvement in comparison with at baseline. An improvement was also noted in radiographic evidence of bone fill and total OHRQL scores. Combination therapy yielded clinically favorable results in the present cases.
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http://dx.doi.org/10.2209/tdcpublication.2019-0050DOI Listing
December 2020

Periodontal surgery using rhFGF-2 with deproteinized bovine bone mineral or rhFGF-2 alone: 2-year follow-up of a randomized controlled trial.

J Clin Periodontol 2021 01 12;48(1):91-99. Epub 2020 Nov 12.

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Aim: To compare outcomes of rhFGF-2 + DBBM therapy with rhFGF-2 alone in the treatment of intrabony defects. This study provides 2-year follow-up results from the previous randomized controlled trial.

Materials And Methods: Defects were randomly allocated to receive rhFGF-2 + DBBM (test) or rhFGF-2 (control). Treated sites were re-evaluated at 2 years postoperatively, using original clinical and patient-centred measures.

Results: Thirty-eight sites were available for re-evaluation. At 2 years, both groups showed a significant improvement in clinical attachment level (CAL) from baseline. A gain in CAL of 3.4 ± 1.3 mm in the test group and 3.1 ± 1.5 mm in the control group was found. No significant inter-group difference was noted. Both groups showed a progressive increase in radiographic bone fill (RBF). The test treatment yielded greater RBF (56%) compared with the control group (41%). The control treatment performed better in contained defects in terms of CAL and RBF. There was no significant difference in patient-reported outcomes between groups.

Conclusions: At 2-year follow-up, the test and cotrol treatments were similarly effective in improving CAL, whereas the test treatment achieved a significantly greater RBF. In both treatments, favourable clinical, radiographic, and patient-reported outcomes can be sustained for at least 2 years.

Trial Registration: The University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) 000025257.
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http://dx.doi.org/10.1111/jcpe.13385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984167PMC
January 2021

Treatment with functionalized designer self-assembling peptide hydrogels promotes healing of experimental periodontal defects.

J Periodontal Res 2021 Jan 6;56(1):162-172. Epub 2020 Oct 6.

Department of Periodontology, Tokyo Dental College, Tokyo, Japan.

Background/objectives: It has been reported that self-assembling peptide (SAP) hydrogels with functionalized motifs enhance proliferation and migration of host cells. How these designer SAP hydrogels perform in the treatment of periodontal defects remains unknown. This study aimed to test the potential of local application of designer SAP hydrogels with two different functionalized motifs in the treatment of experimental periodontal defects.

Material And Methods: In vitro, viability/proliferation of rat periodontal ligament-derived cells (PDLCs) cultured on an SAP hydrogel RADA16 and RADA16 with functionalized motifs, PRG (integrin binding sequence) and PDS (laminin cell adhesion motif), was assessed. Cell morphology was analyzed by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In vivo, standardized periodontal defects were made mesially in the maxillary first molars of Wistar rats. Defects received RADA16, PRG, PDS or left unfilled. At 2 or 4 weeks postoperatively, healing was assessed by microcomputed tomography, histological and immunohistochemical methods.

Results: Viability/proliferation of PDLCs was significantly greater on PRG than on RADA16 or PDS at 72 hours. rPDLCs in the PRG group showed enhanced elongations and cell protrusions. In vivo, at 4 weeks, bone volume fractions in the PRG and PDS groups were significantly greater than the RADA16 group. Histologically, bone formation was more clearly observed in the PRG and PDS groups compared with the RADA16 group. At 4 weeks, epithelial downgrowth in the hydrogel groups was significantly reduced compared to the Unfilled group. In Azan-Mallory staining, PDL-like bundles ran in oblique direction in the hydrogel groups. At 2 weeks, in the area near the root, proliferating cell nuclear antigen (PCNA)-positive cells were detected significantly more in the PRG group than other groups. At 4 weeks, in the middle part of the defect, a significantly greater level of vascular endothelial growth factor (VEGF)-positive cells and α-smooth muscle actin (SMA)-positive blood vessels were observed in the PRG group than in other groups.

Conclusion: The results indicate that local application of the functionalized designer SAP hydrogels, especially PRG, promotes periodontal healing by increasing cell proliferation and angiogenesis.
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http://dx.doi.org/10.1111/jre.12807DOI Listing
January 2021

Toxic effects of endoplasmic reticulum stress transducer BBF2H7-derived small peptide fragments on neuronal cells.

Brain Res 2020 12 1;1749:147139. Epub 2020 Oct 1.

Department of Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. Electronic address:

Aggregation, fibril formation, and deposition of amyloid β (Aβ) protein are believed to be the central pathogeneses of Alzheimer's disease (AD). Numerous studies have shown that fibril formation is promoted by preformed seeds at the beginning of the aggregation process. Therefore, aggregated molecules that promote fibrillization of Aβ protein as seeds could affect the pathology. We recently found that approximately 40 amino acid hydrophobic peptides, BBF2H7-derived small peptide (BSP) fragments, are generated via intramembranous cleavage under endoplasmic reticulum (ER) stress conditions. Interestingly, similar to Aβ protein, the fragments exhibit a high aggregation propensity and form fibril structures. It has been noted that ER stress is involved in the pathogenesis of AD. In this study, we examined the effect of BSP fragments on aggregation and cytotoxicity of Aβ protein, which is generated as a major species of Aβ protein, but has a lower aggregative property than Aβ protein. We demonstrated that BSP fragments promote aggregation of Aβ protein. Aggregates of Aβ protein mediated by BSP fragments also exhibited potent neurotoxicity. Our findings suggest the possibility that BSP fragments affect accumulation of Aβ proteins and are involved in the pathogenesis of AD.
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http://dx.doi.org/10.1016/j.brainres.2020.147139DOI Listing
December 2020

Slowly progressive cerebral amyloid angiopathy-related inflammation: Characteristic findings of sequential magnetic resonance imaging.

Clin Neurol Neurosurg 2020 10 30;197:106198. Epub 2020 Aug 30.

Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.

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http://dx.doi.org/10.1016/j.clineuro.2020.106198DOI Listing
October 2020

A retrospective analysis of usefulness of impulse oscillometry system in the treatment of asthma.

Respir Res 2020 Aug 31;21(1):226. Epub 2020 Aug 31.

Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, S1W16 Chuoku, Sapporo, Hokkaido, 060-8543, Japan.

Background: Bronchial asthma (BA) has different phenotypes, and it requires a clinically effective subtype classification system. The impulse oscillometry system (IOS) is an emerging technique device used in respiratory functional tests. However, its efficacy has not been validated. Therefore, this study aimed to assess the relationship between BA and the IOS parameters, and the difference in the therapeutic effects of inhaled corticosteroids (ICSs) among the subtype classifications was evaluated using the IOS.

Methods: Of the 245 patients with bronchial asthma who were screened, 108 were enrolled in this study. These patients were divided based on three subtypes according to the IOS result as follows: central predominant type (n = 34), peripheral predominant type (n = 58), and resistless type (n = 16). Then, the following ICSs were randomly prescribed in daily medical care: coarse-particle ICS (fluticasone propionate [FP]), fine-particle ICS (mometasone furoate [MF]), and moderate-particle ICS (budesonide [BUD]). The treatment effects were assessed using the Asthma Health Questionnaire (AHQ) and the Asthma Control Test (ACT) and were compared among the three subtypes.

Results: In the central predominant type, the AHQ score of the MF group was significantly higher than that of the FP group (15.4 vs. 3.6, p < 0.01) and the BUD group (15.4 vs. 8.8, p < 0.05); the ACT score of the FP group was significantly higher than that of the MF and BUD groups (24.3 vs. 21.7, 22.3, respectively, p < 0.05) at 4 weeks after treatment. In the peripheral predominant type, the AHQ score of the FP group was significantly higher than that of the MF group (14.1 vs. 3.4, p < 0.05); the ACT score of the FP group was lower than that of the MF and BUD groups (22.8 vs. 24.6, 24.4, respectively, p < 0.01) at 4 weeks after treatment.

Conclusions: An association was observed between IOS subtype classification and ICS particle size in terms of therapeutic efficacy in BA. This result indicates that the IOS could be an effective tool in the selection of ICS and the evaluation of the BA phenotype.
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http://dx.doi.org/10.1186/s12931-020-01494-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457354PMC
August 2020
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