Publications by authors named "Kenichi Watanabe"

338 Publications

Artiodactyl livestock species have a uniform vomeronasal system with a vomeronasal type 1 receptor (V1R) pathway.

Tissue Cell 2022 Aug 30;77:101863. Epub 2022 Jun 30.

Department of Life and Food Sciences, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.

Artiodactyl livestock animals have a vomeronasal system that detects pheromones. Vomeronasal receptors comprise type 1 (V1R) coupled with G protein α-i2 (Gαi2) and type 2 (V2R) coupled with G protein α-o (Gαo). Laboratory rodents have two segregated V1R and V2R pathways that reach separately to the accessory olfactory bulb (AOB). In contrast, the AOBs of goats and sheep are entirely positive for Gαi2, indicating that they have only the V1R pathway. However, we detected a few V2R genes in the genome of cattle, goats, sheep and pigs by genome assembly. Thus, we immunohistochemically analyzed the AOBs of cattle and pigs to confirm which type of the vomeronasal system is present in artiodactyl livestock species. The glomerular layer of the AOB in cattle and pigs was entirely positive for anti-Gαi2 and weakly positive for anti-Gαo, as in the V1R uniform type of vomeronasal system in other mammal species. These findings indicated that artiodactyl livestock species have a uniform type of vomeronasal system composing the V1R pathway. Therefore, caution is advised when extrapolating knowledge of laboratory rodents with two vomeronasal pathways to livestock animals that have one.
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http://dx.doi.org/10.1016/j.tice.2022.101863DOI Listing
August 2022

Relationship Between Sacroiliac Joint-Related Pain and Spinopelvic Mobility.

Spine (Phila Pa 1976) 2022 Jun 29. Epub 2022 Jun 29.

Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

Study Design: A case-control study.

Objective: To evaluate the relationship between sacroiliac joint-related pain (SIJ-RP) and spinopelvic mobility.

Summary Of Background Data: No specific radiological findings are available for the diagnosis of SIJ-RP. A previous study reported that a higher pelvic incidence (PI) and sacral slope (SS) values were significantly associated with SIJP. The concept of spinopelvic mobility, which is evaluated by the differences between SS in the standing and sitting positions, has been the focus of hip and spine surgeries in recent years.

Methods: The SIJ-RP group comprised patients diagnosed with SIJ-RP based on physical findings and their response to analgesic injections. No other lumbar or hip joint diseases were observed. The non-SIJ-RP group comprised patients with lower back pain (LBP) for reasons other than SIJ-RP. Radiographs of the lateral view of the pelvis in the standing and sitting positions were evaluated for all patients. We compared and analyzed the backgrounds, SS in the two positions, and difference in SS between the two positions in both groups.

Results: In total, 245 patients were included in the study, with 49 and 196 patients in the SIJ-RP and non-SIJ-RP groups, respectively. More female patients experienced SIJ-RP than male patients (P=0.0361). There were significant differences between the groups for SS in standing (P=0.0076), sitting (P=0.0005), and those with a difference between sitting and standing of <5° (P=0.0278) in the univariate analyses. Logistic regression analyses, after adjustment for age and sex, revealed significant differences between the groups with an SS difference <5° (P=0.0088; 95% confidence interval, 1.280-5.519), with an odds ratio of 2.7.

Conclusions: On evaluating spinopelvic mobility, we found that SIJ-RP was related to hypomobility of the sacrum, which could indicate the hypermobility of the SIJ.
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http://dx.doi.org/10.1097/BRS.0000000000004390DOI Listing
June 2022

Bilateral Distal Transradial Approach for Coiling of Basilar Artery Aneurysm: A Technical Note.

Neurol Med Chir (Tokyo) 2022 Jun 24. Epub 2022 Jun 24.

Department of Neurosurgery, Okazaki City Hospital.

Distal transradial approach (dTRA) for neuroendovascular procedures has received much attention in recent years as a newer and less invasive alternative to the conventional transfemoral or transradial approaches. We present the case of an 89-year-old woman with a basilar artery aneurysm requiring simultaneous catheterization of the bilateral vertebral arteries who was successfully embolized using bilateral dTRA. The aneurysm was accessed from the right vertebral artery using the right dTRA. Control angiograms during the procedure were performed from the left vertebral artery via the left dTRA. The operator's posture was ergonomically comfortable, and the catheters were easy to handle during the procedure. To the best of our knowledge, this is the first case of a bilateral dTRA used for neuroendovascular procedures. Bilateral dTRA is a safe and minimally invasive method for patients and ergonomically comfortable for operators.
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http://dx.doi.org/10.2176/jns-nmc.2022-0083DOI Listing
June 2022

Impact on swallowing functions of arytenoid adduction in patients with unilateral vocal fold paralysis.

Auris Nasus Larynx 2022 Jun 9. Epub 2022 Jun 9.

Department of Otolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

Objective: Although the pathophysiology of swallowing dysfunction in patients with unilateral vocal fold paralysis (UVFP) remains uncertain, glottal insufficiency is known to be a possible major cause, and other factors due to vagus nerve or recurrent laryngeal nerve damage may contribute to dysphagia or aspiration. This study aimed to evaluate the effect of arytenoid adduction (AA) surgery on the swallowing functions of UVFP patients and to investigate the important role of glottic closure during swallowing.

Methods: We prospectively analyzed the data of thirteen patients with UVFP who underwent AA in combination with medialization laryngoplasty (ML) for improving voice quality. The subjects received a series of examinations for not only voice function but also swallowing function and cough strength both preoperatively and approximately 6 months after surgery. The evaluations of voice function included the Voice Handicap Index and aerodynamic measures; the evaluations of swallowing function included the Eating Assessment Tool-10, liquid aspiration, a videofluorographic examination of swallowing study, and high-resolution manometry; and the evaluation of cough strength included the measurement of cough peak flow. All measurements before and after surgery were statistically compared and examined.

Results: Considerable improvements in voice measures were observed after the procedure, as sufficient glottic closure was achieved during phonation and swallowing. In terms of swallowing evaluation, there were significant differences in the subjective assessment methods after the operation. Additionally, our intervention improved two cases of aspiration according to abnormal findings on the videofluorographic examination of swallowing. There was a significant difference in cough peak flow, with all participants having better values after surgery. High-resolution manometry revealed no significant differences between pre- and postsurgery in any parameters at the level of the mesopharynx or upper esophageal sphincter.

Conclusion: The findings of our study suggest an important effect on the dysphagia of UVFP patients who undergo AA combined with ML. In addition, we revealed improvements in swallowing by strengthening incomplete glottic closure; thus, we consider that sufficient glottic closure must play an important role in swallowing function in patients with UVFP.
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http://dx.doi.org/10.1016/j.anl.2022.05.015DOI Listing
June 2022

Significance of prostate/pancreatic/skin cancer family history for detecting BRCA2 pathogenic variant careers among patients with breast cancer.

Breast Cancer 2022 May 31. Epub 2022 May 31.

Department of Medical Genetics and Genomics, Sapporo Medical University School of Medicine, S1 W17, Chuo-ku, Sapporo, 060-8556, Japan.

Background: When considering BRCA1/2 genetic testing for diagnosis of hereditary breast and ovarian cancer (HBOC), family history (FH) of breast and ovarian cancer is commonly considered. However, FH of other HBOC-related cancers, such as prostate, pancreatic, and skin cancer (malignant melanoma), is often overlooked.

Methods: Among 945 patients who received genetic testing of BRCA1/2 at our hospital between October 2010 and September 2021, we compared the FH of 123 patients diagnosed with HBOC and 669 other patients who had breast cancer and had a documented FH. This study focused on the FH of HBOC-related cancers such as breast, ovarian, prostate, pancreatic, and skin cancer, as well as colorectal, gastric, liver, lung, and uterine cancers, which are common among Japanese, and other cancers.

Results: FH of prostate, pancreatic, and skin cancer was significantly higher in the BRCA2 pathogenic variant (PV) cases than in the wild-type (WT) cases. The mean number of family members are as follows: BRCA1 PV/ BRCA2 PV/ WT; prostate cancer: 0.05/ 0.34/ 0.09 (P < 0.0001, Kruskal-Wallis multiple comparisons test), pancreatic cancer: 0.13/ 0.21/ 0.10 (P = 0.01637), and skin cancer: 0.03/ 0.07/ 0.01 (P = 0.00129), respectively.

Conclusions: When considering BRCA1/2 genetic testing, FH of prostate, pancreatic, and skin cancers may also be examined as HBOC-related cancers to provide testing for patients who would benefit from it. However, further studies for the association between skin cancer and HBOC will be required because it has not been reported in Japan.
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http://dx.doi.org/10.1007/s12282-022-01360-2DOI Listing
May 2022

Bilateral Plaque-Like White Matter Degeneration in Cerebral Septal Regions of a Chapman's Zebra (Equus quaggachapmani).

J Comp Pathol 2022 Jun 6;194:54-57. Epub 2022 May 6.

Section of Pathology, Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. Electronic address:

Histopathological examination of an approximately 19-year-old female Chapman's zebra (Equus quagga chapmani) revealed multifocal bilateral plaque-like lesions in rostral septal regions of the cerebrum. The centre of these lesions consisted of radiating, acicular eosinophilic structures, which were surrounded by rare glial cells. Spheroids were also seen around the lesions. Luxol fast blue and Bodian staining revealed loss of normal myelin and axonal structures within the plaque-like lesions. The glial cells surrounding the lesions were considered reactive astrocytes due to their immunoreactivity to vimentin, glial fibrillary acidic protein and alpha-smooth muscle actin. Based on these findings, the lesions were consistent with focal white matter degeneration localized in bilateral, rostral septal regions; these lesions have not been previously reported. The cause of the lesions was not determined despite the application of various histochemical stains.
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http://dx.doi.org/10.1016/j.jcpa.2022.04.001DOI Listing
June 2022

Renal Dysplasia with Hydronephrosis and Congenital Ureteral Stricture in Two Holstein-Friesian Calves.

J Comp Pathol 2022 May 31;193:20-24. Epub 2022 Mar 31.

Laboratory of Veterinary Pathology, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan. Electronic address:

We investigated the pathological characteristics of renal dysplasia with hydronephrosis and congenital ureteral stricture in two calves. Macroscopically, the affected kidneys were enlarged and the renal calyces were dilated and associated with ureteral strictures. Histopathologically, multifocal regions of mesenchyme were observed in the renal medulla. This mesenchyme was weakly eosinophilic with haematoxylin and eosin, blue with Alcian blue and pale blue with Masson's trichrome, and was immunopositive for vimentin and smooth muscle actin, consistent with persistent mesenchyme. There was asynchronous differentiation of the renal cortex characterized by immature glomeruli, immature tubules and arteriolar proliferation. Similar persistent mesenchyme was observed in the ureteral walls with ureteral stricture, and the ureteral musculature or smooth muscle bundles had a disorganized arrangement. Congenital ureteral stricture appeared to have caused ureteral obstruction and hydronephrosis. The lesions may represent a new phenotype of renal dysplasia with concomitant congenital ureteral stricture in Holstein-Friesian calves.
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http://dx.doi.org/10.1016/j.jcpa.2022.02.006DOI Listing
May 2022

Meal Ingestion of Ceraceomyces tessulatus Strain BDM-X (Agaricomycetes) Protects against Nonalcoholic Steatohepatitis in Mice.

Int J Med Mushrooms 2022 ;24(1):41-52

Department of Hematology, Endocrinology, and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata 951-8510, Japan.

Nonalcoholic steatohepatitis (NASH) is becoming the most common cause of hepatocellular carcinoma (HCC) in developed countries. Oxidative stress plays a major role in the pathogenesis of NASH due to steatosis; hence, novel therapeutic approaches might include natural antioxidants. Ceraceomyces tessulatus strain Basidiomycetes-X (BDM-X), a novel edible mushroom, possesses potent antioxidant activity. This study aimed to investigate the hepato-protective effect of C. tessulatus BDM-X in a novel NASH-HCC mouse model. To prepare this animal model, 2-day-old C57BL/6J male pups were exposed to low-dose streptozotocin (STZ); at 4 weeks of age, they were randomly divided into two groups. The NASH group (NASH) received a high-fat diet (HFD32) up to 14 weeks of age; the C. tessulatus BDM-X group (BDM-X) received HFD32 up to age 10 weeks, followed by HFD32 + 20% BDM-X (percent weight per weight in the diet) up to age 14 weeks. Mice not treated with STZ and fed a normal diet served as a control group. We found that C. tessulatus BDM-X improved serum aminotransferase levels as well as histopathological features such as steatosis, inflammatory foci, and pericellular fibrosis in NASH mice. Hepatic protein expression of sterol regulatory element binding protein isoform SREBP-1 and peroxisome proliferator-activated receptor PPARα was significantly increased in NASH mice. C. tessulatus BDM-X treatment normalized the expression of both proteins. Our data suggest that C. tessulatus BDM-X may protect the liver against lipogenesis in NASH-HCC mice.
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http://dx.doi.org/10.1615/IntJMedMushrooms.2021041928DOI Listing
April 2022

Possibility for Prevention of Type 2 Diabetes Mellitus and Dementia Using Three Kinds of Brown Rice Blends after High-Pressure Treatment.

Foods 2022 Mar 12;11(6). Epub 2022 Mar 12.

Faculty of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1, Higashijima, Akiha-ku, Niigata 956-8603, Japan.

As it has been reported that type 2 diabetes mellitus increases the risk of Alzheimer's disease, we investigated how to prevent type 2 diabetes and dementia using biofunctional boiled rice. We adopted unpolished super-hard rice (SHBR) for diabetes and wax-free unpolished black rice (WFBBR) for dementia and blended those with ordinary non-polished rice (KBR) (blending ratio 4:4:2), adding 2.5% waxy black rice bran (WBB) and 0.3% rice oil after high-pressure treatment (HPT) (WFBSK) to improve its palatability. This boiled rice is rich in dietary fiber, anthocyanin, free ferulic acid and β-secretase inhibitory activity. A randomized, parallel-group comparison study was conducted for 12 weeks with 24 subjects, using Cognitrax to evaluate their cognitive function primarily. Furthermore, as the secondary purpose, we performed a single-dose test for postprandial blood glucose and insulin secretion at the end of the human intervention test. After 12 weeks, consumers of the WFBSK rice exhibited significant improvement in language memory by cognitive test battery compared with those who consumed the control white rice ( < 0.05). Moreover, subjects who consumed the WFBSK rice had lower insulin secretion levels than those who consumed the control polished rice ( < 0.05).
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http://dx.doi.org/10.3390/foods11060818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947517PMC
March 2022

Role of dense granule antigen 7 in vertical transmission of Neospora caninum in C57BL/6 mice infected during early pregnancy.

Parasitol Int 2022 Aug 15;89:102576. Epub 2022 Mar 15.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan. Electronic address:

Neosporosis is a parasitic disease affecting the health of dogs and cattle worldwide. It is caused by Neospora caninum, an obligate intracellular apicomplexan parasite. Dogs are its definitive host, it mostly infects livestock animals, especially cattle that acts as intermediate host. It is necessary to have well-established models of abortion and vertical transmission in experimental animals, in order to determine basic control measures for the N. caninum infection. We evaluated the role of N. caninum dense granule antigen 7 (NcGRA7) in the vertical transmission of N. caninum using the C57BL/6 pregnant mouse model. We inoculated mice on day 3.5 of pregnancy with parental Nc-1 or NcGRA7-deficient parasites (NcGRA7KO). Post-mortem analyses were performed on day 30 after birth and the surviving pups were kept until day 30 postpartum. The number of parasites in the brain tissues of offspring from NcGRA7KO-infected dams was significantly lower than that of the Nc-1-infected dams under two infection doses (1 × 10 and 1 × 10 tachyzoites/mouse). The vertical transmission rates in the NcGRA7KO-infected group were significantly lower than those of the Nc1-infected group. To understand the mechanism by which the lack of NcGRA7 decreases the vertical transmission, pregnant mice were sacrificed on day 13.5 of pregnancy (10 days after infection), although parasite DNA was detected in the placentas, no significant difference was found between the two parasite lines. Histopathological analysis revealed a greater inflammatory response in the placentas from NcGRA7KO-infected dams than in those from the parental strain. This finding correlates with upregulated chemokine mRNA expression for CCL2, CCL8, and CXCL9 in the placentas from the NcGRA7KO-infected mice. In conclusion, these results suggest that loss of NcGRA7 triggers an inflammatory response in the placenta, resulting in decreased vertical transmission of N. caninum.
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http://dx.doi.org/10.1016/j.parint.2022.102576DOI Listing
August 2022

Chronic otitis externa with heat shock protein 70-positive intranuclear inclusion bodies in the ceruminous gland epithelium of a Chihuahua dog.

J Toxicol Pathol 2022 Jan 28;35(1):83-87. Epub 2021 Aug 28.

Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, 2-11 Inada, Obihiro-shi, Hokkaido 080-8555, Japan.

A Chihuahua dog showed persistent itching in the right ear canal. Anti-inflammatory medicines and prednisolone were ineffective and total ear canal ablation was performed. Histological diagnosis was chronic otitis externa. Eosinophilic intranuclear inclusion bodies (Cowdry type A and full-type) were occasionally observed in the ceruminous gland epithelium. The inclusion bodies were negative for nucleic acid and ultrastructurally composed of fibrous structures (approximately 10 nm in width). Viral infection was initially suspected, but polymelase chain reaction tests did not detect the expected viral genes. Immunohistochemistry revealed that the inclusion bodies were positive for heat shock protein 70 (HSP70), suggesting that these bodies could be protein aggregates including HSP70. The etiology of this lesion has not been elucidated, but chronic inflammation may influence the cytoplasm-to-nuclear transportation of HSP70. To the best of our knowledge, this is the first report of canine chronic otitis externa with HSP70-positive intranuclear inclusion bodies.
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http://dx.doi.org/10.1293/tox.2021-0033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8828612PMC
January 2022

Characteristic computed tomographic myelography findings in 23 Thoroughbred horses.

J Vet Med Sci 2022 Apr 23;84(4):525-532. Epub 2022 Feb 23.

School of Veterinary Medicine, Azabu University, Kanagawa, Japan.

The purpose of this observational study was to determine the characteristic computed tomographic (CT) myelography findings of cervical vertebral stenotic myelopathy (CVSM) lesions in Thoroughbred horses. A total of 23 Thoroughbred horses (age range, 155-717 days on CT examination; mean, 410.9 days) were analyzed. All 23 Thoroughbred horses underwent unenhanced radiography, radiographic myelography, and CT myelography. Unenhanced radiographs were observed the presence of cervical vertebral malalignment and osseous lesions. Radiographic myelograms were observed for signs of cervical spinal cord compression; additionally, CT myelograms were used to detect cervical vertebral osseous lesions. Ventral compressions were frequently observed in the cranial cervical vertebrae (C2-C4), whereas dorsal compressions were frequently observed in the caudal cervical vertebrae (C5-C7). Furthermore, osseous lesions of the caudal articular process developed more frequently than those of the cranial articular process. CT myelography in Thoroughbred horses is a useful method for detecting CVSM changes.
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http://dx.doi.org/10.1292/jvms.22-0036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096043PMC
April 2022

A 7-year-old boy with central diabetes insipidus presenting with thickened pituitary stalk and anti-rabphilin-3A antibody positivity.

J Pediatr Endocrinol Metab 2022 May 4;35(5):687-690. Epub 2022 Feb 4.

Department of Paediatrics, Nagaoka Red Cross Hospital, Niigata, Japan.

Objectives: A highly invasive pathological diagnosis is necessary to differentiate central diabetes insipidus (CDI) with a thickened pituitary stalk. Lymphocytic infundibulo-hypophysitis (LIH) due to autoimmune involvement of the pituitary stalk is a differentiating disease, and anti-rabphilin-3A antibody (Rab3A-Ab) positivity was recently reported.

Case Presentation: A 7-year-old boy was diagnosed with CDI after having polyuria for two months. He showed growth hormone deficiency with reduced growth rate. Brain magnetic resonance imaging (MRI) revealed a thickened pituitary stalk. The placental alkaline phosphatase level of the cerebrospinal fluid, tumor marker for germ cell tumors, was below the level of sensitivity. No skin or bone findings suggestive of Langerhans cell histiocytosis were detected. Eight months after CDI onset, Rab3A-Ab was positive, and MRI showed shrinking of the thickened pituitary stalk, leading to the diagnosis with LIH.

Conclusions: Rab3A-Ab is a useful adjunctive diagnostic tool for childhood-onset LIH.
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http://dx.doi.org/10.1515/jpem-2021-0674DOI Listing
May 2022

Imaging Mass Spectrometry (IMS) for drug discovery and development survey: Results on methods, applications and regulatory compliance.

Drug Metab Pharmacokinet 2022 Apr 16;43:100438. Epub 2021 Dec 16.

Leader of Japan Association for Imaging Mass Spectrometry, Drug Metabolism and Pharmacokinetics, Laboratory for Drug Discovery and Development, Shionogi & Co., Ltd., 3-1-1, Futaba, Toyonaka, Osaka, 561-0825, Japan. Electronic address:

Imaging mass spectrometry (IMS) is increasingly used for drug discovery and development to understand target enagement, tissue distribution, drug toxicity, and disease mechanisms, etc. However, this is still a relatively new technique that requires further development validation before it will be an acceptable technique to support regulated development of new drugs. Thus, best practices will need to be established to build more confidence and gain wider acceptance by the scientific community, pharmaceutical industry, and regulatory authorities. The Imaging Mass Spectrometry Society (IMSS) and the Japan Association for Imaging Mass Spectrometry (JAIMS) have conducted a thorough survey to gather information on the current state of IMS and to identify key issues. The survey was sent to researchers or managers in the position who are currently using IMS techniques in support of their drug discovery and development efforts and/or who plan to use such tools as best practices are established. The survey probes questions related to details regarding technical aspects of IMS, which includes data acquisition, data analysis and quantitation, data integrity, reporting, applications, and regulatory concerns. This international survey was conducted online through the Survey Monkey (https://www.surveymonkey.com) in both English and Japanese from September 14 through September 30, 2020.
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http://dx.doi.org/10.1016/j.dmpk.2021.100438DOI Listing
April 2022

Retrieving a lost needle in the descending aorta during hemi-arch replacement.

Asian Cardiovasc Thorac Ann 2022 Sep 11;30(7):848-852. Epub 2022 Jan 11.

Department of Radiology, 13849Okazaki City Hospital, Japan.

A 73-year-old man diagnosed with moderate aortic insufficiency and dilatation of the aortic root and ascending aorta underwent a modified Bentall procedure and hemi-arch aortic replacement. During open distal anastomosis of the ascending aorta, the surgical needle was lost. Because of circulatory arrest, the operation was continued; before closing the chest, radiography and a transesophageal echo were located in the needle in the descending aorta. It was retrieved using a snare catheter via the graft branch under fluoroscopic guidance. Thus, locating the needle in the descending aorta and leaving the graft branch uncut led to its removal without a new incision.
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http://dx.doi.org/10.1177/02184923211072474DOI Listing
September 2022

Predictive ability of current machine learning algorithms for type 2 diabetes mellitus: A meta-analysis.

J Diabetes Investig 2022 May 28;13(5):900-908. Epub 2022 Jan 28.

Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Aims/introduction: Recently, an increasing number of cohort studies have suggested using machine learning (ML) to predict type 2 diabetes mellitus. However, its predictive ability remains inconclusive. This meta-analysis evaluated the current ability of ML algorithms for predicting incident type 2 diabetes mellitus.

Materials And Methods: We systematically searched longitudinal studies published from 1 January 1950 to 17 May 2020 using MEDLINE and EMBASE. Included studies had to compare ML's classification with the actual incidence of type 2 diabetes mellitus, and present data on the number of true positives, false positives, true negatives and false negatives. The dataset for these four values was pooled with a hierarchical summary receiver operating characteristic and a bivariate random effects model.

Results: There were 12 eligible studies. The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.81 (95% confidence interval [CI] 0.67-0.90), 0.82 [95% CI 0.74-0.88], 4.55 [95% CI 3.07-6.75] and 0.23 [95% CI 0.13-0.42], respectively. The area under the summarized receiver operating characteristic curve was 0.88 (95% CI 0.85-0.91).

Conclusions: Current ML algorithms have sufficient ability to help clinicians determine whether individuals will develop type 2 diabetes mellitus in the future. However, persons should be cautious before changing their attitude toward future diabetes risk after learning the result of the diabetes prediction test using ML algorithms.
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http://dx.doi.org/10.1111/jdi.13736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077721PMC
May 2022

Transcriptomic Analysis of the Effects of Chemokine Receptor CXCR3 Deficiency on Immune Responses in the Mouse Brain during Infection.

Microorganisms 2021 Nov 12;9(11). Epub 2021 Nov 12.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro 080-8555, Hokkaido, Japan.

The obligate intracellular parasite infects warm-blooded animals, including humans. We previously revealed through a whole-brain transcriptome analysis that infection with in mice causes immune response-associated genes to be upregulated, for instance, chemokines and chemokine receptors such as CXC chemokine receptor 3 (CXCR3) and its ligand CXC chemokine ligand 10 (CXCL10). Here, we describe the effect of CXCR3 on responses against infection in the mouse brain. In vivo assays using CXCR3-deficient mice showed that the absence of CXCR3 delayed the normal recovery of body weight and increased the brain parasite burden, suggesting that CXCR3 plays a role in the control of pathology in the brain, the site where chronic infection occurs. Therefore, to further analyze the function of CXCR3 in the brain, we profiled the gene expression patterns of primary astrocytes and microglia by RNA sequencing and subsequent analyses. CXCR3 deficiency impaired the normal upregulation of immune-related genes during infection, in astrocytes and microglia alike. Collectively, our results suggest that the immune-related genes upregulated by CXCR3 perform a particular role in controlling pathology when the host is chronically infected with in the brain.
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http://dx.doi.org/10.3390/microorganisms9112340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620038PMC
November 2021

Right ventricular failure: a comorbidity or a clinical emergency?

Heart Fail Rev 2021 Nov 26. Epub 2021 Nov 26.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Kolkata, Chunilal Bhawan, 168 Maniktala Main Road, Kolkata, 700054, West Bengal, India.

There has been ample data providing a convincing perception about the underlying mechanism pertaining to left ventricle (LV) hypertrophy progressing towards LV failure. In comparison, data available on the feedback of right ventricle (RV) due to volume or pressure overload is minimal. Advanced imaging techniques have aided the study of physiology, anatomy, and diseased state of RV. However, the treatment scenario of right ventricular failure (RVF) demands more attention. It is a critical clinical risk in patients with carcinoid syndrome, pulmonary hypertension, atrial septal defect, and several other concomitant diseases. Although the remodeling responses of both ventricles on an increase of end-diastolic pressure are mostly identical, the stressed RV becomes more prone to oxidative stress activating the apoptotic mechanism with diminished angiogenesis. This instigates the advancement of RV towards failure in contrast to LV. Empirical heart failure (HF) therapies have been ineffective in improving the mortality rate and cardiac function in patients, which prompted a difference between the underlying pathophysiology of RVF and LV failure. Treatment strategies should be devised, taking into consideration the anatomical and physiological characteristics of RV. This review would emphasize on the pathophysiology of the RVF and the differences between two ventricles in molecular response to stress. A proper insight into the underlying pathophysiology is required to develop optimized therapeutic management in RV-specific HF.
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http://dx.doi.org/10.1007/s10741-021-10192-9DOI Listing
November 2021

Congenital cutaneous fibropapillomatosis without evidences of papillomavirus infection in a Holstein-Friesian calf.

J Vet Med Sci 2021 Dec 4;83(12):1852-1854. Epub 2021 Nov 4.

Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.

A male Holstein-Friesian calf was born with multiple, cauliflower-like, pale pink cutaneous masses on the head and limbs. On histopathological examination, the cutaneous masses were diagnosed as congenital cutaneous fibropapillomatosis. Those lesions involved focal proliferation of sebaceous gland in the dermis. There were no histological findings to suggest bovine papillomavirus infection, such as the presence of intranuclear inclusion bodies, large keratohyalin granules, and koilocytosis. Furthermore, papillomaviral antigens and DNA were not detected by immunohistochemistry and polymerase chain reaction, respectively. These results suggested that there was no association between these cutaneous lesions and bovine papillomavirus infection, and the lesions were considered as harmartomatous changes.
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http://dx.doi.org/10.1292/jvms.21-0503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762411PMC
December 2021

Co-infection of SARS-CoV-2 and influenza virus causes more severe and prolonged pneumonia in hamsters.

Sci Rep 2021 10 28;11(1):21259. Epub 2021 Oct 28.

Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, Nagasaki, 852-8523, Japan.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently a serious public health concern worldwide. Notably, co-infection with other pathogens may worsen the severity of COVID-19 symptoms and increase fatality. Here, we show that co-infection with influenza A virus (IAV) causes more severe body weight loss and more severe and prolonged pneumonia in SARS-CoV-2-infected hamsters. Each virus can efficiently spread in the lungs without interference by the other. However, in immunohistochemical analyses, SARS-CoV-2 and IAV were not detected at the same sites in the respiratory organs of co-infected hamsters, suggesting that either the two viruses may have different cell tropisms in vivo or each virus may inhibit the infection and/or growth of the other within a cell or adjacent areas in the organs. Furthermore, a significant increase in IL-6 was detected in the sera of hamsters co-infected with SARS-CoV-2 and IAV at 7 and 10 days post-infection, suggesting that IL-6 may be involved in the increased severity of pneumonia. Our results strongly suggest that IAV co-infection with SARS-CoV-2 can have serious health risks and increased caution should be applied in such cases.
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http://dx.doi.org/10.1038/s41598-021-00809-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553868PMC
October 2021

Intake of Improves Defecation Frequency in Healthy Adults.

J Fungi (Basel) 2021 Sep 21;7(9). Epub 2021 Sep 21.

Niigata Bio-Research Park Inc., 316-2 Higashijima, Akiha-ku, Niigata City, Niigata 956-0841, Japan.

Reportedly, the intake of , a beverage made from steamed rice fermented by , improves defecation frequency. However, its functional ingredients and mechanism of action remain unclear. To compare the effects of and a placebo beverage on defecation frequency and to identify the functional ingredients and mechanism of action, a randomized, placebo-controlled, double-blind parallel-group comparative trial was performed on two groups. The had 302 ± 15.5 mg/118 g of cells, which was not in the placebo. Compared with the placebo group, the group showed a significant increase in weekly defecation frequency at 2 weeks (5.09 days vs. 4.14 days), 3 weeks (5.41 days vs. 4.18 days), and 4 weeks (5.09 days vs. 3.95 days), along with an increase in the weekly fecal weight at 4 weeks (724 g vs. 501 g). The intake of did not induce significant intergroup differences in the fecal SCFA concentration, whereas it significantly decreased the relative abundance of and significantly increased that of at 3 weeks. Therefore, intake improved defecation frequency, and cells played potentially important roles as functional ingredients.
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http://dx.doi.org/10.3390/jof7090782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470246PMC
September 2021

Soluble LR11 as a Novel Biomarker in Acute Kawasaki Disease.

Circ J 2022 05 16;86(6):977-983. Epub 2021 Sep 16.

Department of Clinical-laboratory and Experimental-Research Medicine, Toho University Sakura Medical Center.

Background: Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.Methods and Results: 106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0-24.9 ng/mL) than in controls (11.9 ng/mL, 10.4-14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7-16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity.

Conclusions: sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.
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http://dx.doi.org/10.1253/circj.CJ-20-1271DOI Listing
May 2022

Multiplatform metabolomic analysis of the R6/2 mouse model of Huntington's disease.

FEBS Open Bio 2021 10 14;11(10):2807-2818. Epub 2021 Sep 14.

Preclinical Research Unit, Sumitomo Dainippon Pharma Co., Ltd, Osaka, Japan.

Huntington's disease (HD) is a progressive, neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. To investigate the metabolic alterations that occur in HD, here we examined plasma and whole-brain metabolomic profiles of the R6/2 mouse model of HD. Plasma and brain metabolomic analyses were conducted using capillary electrophoresis-mass spectrometry (CE-MS). In addition, liquid chromatography-mass spectrometry (LC-MS) was also applied to plasma metabolomic analyses, to cover the broad range of metabolites with various physical and chemical properties. Various metabolic alterations were identified in R6/2 mice. We report for the first time the perturbation of histidine metabolism in the brain of R6/2 mice, which was signaled by decreases in neuroprotective dipeptides and histamine metabolites, indicative of neurodegeneration and an altered histaminergic system. Other differential metabolites were related to arginine metabolism and cysteine and methionine metabolism, suggesting upregulation of the urea cycle, perturbation of energy homeostasis, and an increase in oxidative stress. In addition, remarkable changes in specific lipid classes are indicative of dysregulation of lipid metabolism. These findings provide a deeper insight into the metabolic alterations that occur in HD and provide a foundation for the future development of HD therapeutics.
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http://dx.doi.org/10.1002/2211-5463.13285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487039PMC
October 2021

Spontaneous pulmonary adenocarcinoma in a common marmoset (Callithrix jacchus).

J Med Primatol 2021 12 26;50(6):335-338. Epub 2021 Aug 26.

Department of Marmoset Biology and Medicine, Central Institute for Experimental Animals, Kawasaki, Japan.

A seven-year-old female common marmoset (Callithrix jacchus) presented with weight loss. Imaging revealed a left thoracic mass, confirmed at necropsy. Histology and immunohistochemistry suggested a well-differentiated pulmonary adenocarcinoma. No evidence of local lymphovascular invasion or distant metastasis was observed. This is the first report of pulmonary adenocarcinoma in marmosets.
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http://dx.doi.org/10.1111/jmp.12540DOI Listing
December 2021

Characteristics of aspiration pneumonia patients in acute care hospitals: A multicenter, retrospective survey in Northern Japan.

PLoS One 2021 30;16(7):e0254261. Epub 2021 Jul 30.

Department of Otolaryngology, Sendai City Hospital, Sendai, Japan.

Background: Pneumonia is a common cause of illness and death of the elderly in Japan. Its prevalence is escalating globally with the aging of population. To describe the latest trends in pneumonia hospitalizations, especially aspiration pneumonia (AP) cases, we assessed the clinical records of pneumonia patients admitted to core acute care hospitals in Miyagi prefecture, Japan.

Methods: A retrospective multi-institutional joint research was conducted for hospitalized pneumonia patients aged ≥20 years from January 2019 to December 2019. Clinical data of patients were collected from the medical records of eight acute care hospitals.

Results: Out of the 1,800 patients included in this study, 79% of the hospitalized pneumonia patients were aged above 70 years. The most common age group was in the 80s. The ratio of AP to total pneumonia cases increased with age, and 692 out of 1,800 patients had AP. In univariate analysis, these patients had significantly older ages, lower body mass index (BMI), a lower ratio of normal diet intake and homestay before hospitalization, along with more AP recurrences and comorbidities. During hospitalization, AP patients had extended fasting periods, more swallowing assessments and interventions, longer hospitalization, and higher in-hospital mortality rate than non-AP patients. A total of 7% and 2% AP patients underwent video endoscopy and video fluorography respectively. In multivariate analysis, lower BMI, lower C-reactive protein, a lower ratio of homestay before hospitalization, a higher complication rate of cerebrovascular disease, dementia, and neuromuscular disease were noted as a characteristic of AP patients. Swallowing interventions were performed for 51% of the AP patients who had been hospitalized for more than two weeks. In univariate analysis, swallowing intervention improved in-hospital mortality. Lower AP recurrence before hospitalization and a lower ratio of homestay before hospitalization were indicated as characteristics of AP patients of the swallowing intervention group from multivariate analysis. Change in dietary pattern from normal to modified diet was observed more frequently in the swallowing intervention group.

Conclusion: AP accounts for 38.4% of all pneumonia cases in acute care hospitals in Northern Japan. The use of swallowing evaluations and interventions, which may reduce the risk of dysphagia and may associate with lowering mortality in AP patients, is still not widespread.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254261PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323917PMC
November 2021

Pleurography (thoracography) for pleural fistulas: A case series.

JTCVS Tech 2021 Jun 23;7:285-291. Epub 2021 Mar 23.

Department of Thoracic Surgery, Pneumothorax Research Center, Nissan Tamagawa Hospital, Tokyo, Japan.

Background: Pleurography (PG) has been described previously but has not gained popularity. PG can determine the exact air leak points in the lung, which is important for treating pneumothorax and pleural fistulas. We believe that the usefulness of PG should be reassessed, and here we describe the method, air leak detection rate, and common complications.

Methods: From the 1210 cases of pleural fistulas that were treated at our institution between March 2015 and October 2018, 275 patients with recurrent primary pneumothorax or secondary spontaneous pneumothorax were selected for this study. PG was performed in 127 patients with persistent air leakage during exhalation. In addition, 35 patients with postoperative complications of air leakage persisting for 7 days or longer were included.

Results: Air leak points were detected in 119 patients (73%), in the apex of the lung in 65 cases, in the basal segment in 13 cases, and in the middle lobe or lingular segment in 9 cases. There were 8 cases of hilar lesions, 12 cases of S6 lesions, 8 cases of upper lobe lesions other than apex, and 4 cases of upper mediastinal lesions. Complications within 30 days were observed in 10 cases (6.2%), with 8 grade 2 cases involving fever, 1 grade 3 case involving infection, and one grade 1 case with abdominal distension.

Conclusions: The incidence of grade ≥3 adverse events after PG was 0.6%, which is considered acceptable. Our findings suggest that PG is a safe examination method to identify air leaks before surgery for pleural fistulas.
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http://dx.doi.org/10.1016/j.xjtc.2021.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312103PMC
June 2021

Impact of focal apex angle on postoperative decompression status of the spinal cord and neurological recovery after cervical laminoplasty.

J Neurosurg Spine 2021 Jul 23;35(4):410-418. Epub 2021 Jul 23.

3Department of Orthopedics, Yokohama City University School of Medicine, Yokohama City, Japan.

Objective: Although anterior compression factors and cervical alignment affect neural decompression, cervical laminoplasty may be used to achieve indirect posterior decompression. The focal apex (FA) angle of the anterior compression factor of the spine represents the degree of anterior prominence toward the spinal cord. The authors investigated the mechanism underlying the influence of FA angle and cervical alignment on spinal cord alignment (SCA) after laminoplasty, including how high-intensity signal cord change (HISCC) on preoperative T2-weighted MRI (T2-MRI) may affect neurological improvement.

Methods: We performed a retrospective study of patients who underwent laminoplasty for CSM or OPLL at two hospitals (Kanto Rosai Hospital, Kawasaki City, and Yokohama Minami Kyousai Hospital, Yokohama City, Japan) between April 2004 and March 2015. In total, 109 patients (mean age 67.3 years) with cervical compression myelopathy were included. FA angle was defined as the preoperative angle between the lines from the top of the prominence to the upper and lower adjacent vertebrae. Preoperative cervical alignment was measured between the C2 and C7 vertebrae (C2-7 angle). MRI was used to classify SCA as lordosis (type-L SCA), straight (type-S), local kyphosis (type-LK), or kyphosis (type-K). Preoperative HISCC was investigated by using T2-MRI. Neurological status was evaluated by using the Japanese Orthopaedic Association score.

Results: The mean preoperative FA and C2-7 angles were 32.1° and 12.4°, respectively. Preoperative SCA was type-L or type-S in 53 patients. The neurological recovery rate (NRR) was significantly higher for patients with preoperative type-L and type-S SCA (51.4% for those with type-L and 45.0% for those with type-S) than for patients with other types (35.3% for those with type-LK and 31.7% for those with type-K). Among patients with preoperative type-L or type-S SCA, 87.3% maintained SCA; however, 5/12 (41.7%) patients with a preoperative average C2-7 angle < 12.4° and an average FA angle > 32.1° had postoperative type-LK or type-K SCA. SCA changed to type-L or type-S in 13.0% of patients with preoperative type-LK or type-K SCA. Moreover, in these patients, FA angle was significantly smaller and NRR was significantly higher than in other patients in whom postoperative SCA remained type-LK or type-K. Preoperative T2-MRI showed 73 patients with HISCC (43 with type-L and type-S, and 30 with type-LK and type-K SCA) and 36 without HISCC (20 with type-L and type-S, and 16 with type-LK and type-K SCA); the NRRs of these patients were 42.6% and 41.2%, respectively. No significant differences in SCA or NRR were observed between patients with and without HISCC.

Conclusions: NRR depends on preoperative SCA type; however, it is possible to change the type of SCA after laminoplasty. Preoperative FA and C2-7 angles influence change in SCA; therefore, they are important parameters for successful decompression with cervical laminoplasty.
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http://dx.doi.org/10.3171/2020.12.SPINE201831DOI Listing
July 2021

[Chemo-Resistant Breast Carcinoma with Cartilaginous Differentiation Manifestation after Neoadjuvant Chemotherapy-A Case Report].

Gan To Kagaku Ryoho 2021 Jul;48(7):951-953

Dept. of Surgery, Sapporo Century Hospital.

A 49-year-old woman was admitted to our hospital because of a tumor in her right breast. The tumor was localized to the C area and was approximately 3 cm in size. A right axillary lymphadenopathy was also found. Histopathological examination and needle biopsy of the breast tumor revealed invasive lobular carcinoma, and she was diagnosed with Stage ⅡB triple-negative breast cancer(cT2N1M0). Paclitaxel plus bevacizumab chemotherapy followed by ddAC chemotherapy was administered as neoadjuvant chemotherapy, but the tumor remained stable. Thus, she underwent mastectomy and lymph node dissection. Pathological findings of the resected specimen showed invasive carcinoma with cartilaginous differentiation. She was then treated with capecitabine 15 days after the surgery; however, multiple lung metastases were found on CT after 6 courses. Therefore, she was transferred to another hospital and received other chemotherapies, but died after 5 months.
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July 2021

Case report: The case of a 17 kg ovarian granulosa cell tumor in a Breton draft mare.

J Equine Sci 2021 Jun 18;32(2):67-72. Epub 2021 Jun 18.

United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan.

Granulosa cell tumor (GCT) is a benign tumor which affects the mare's ovaries. In this report, a case of unilateral GCT in an ovary, which weighed 17.04 kg, of a 9-year-old Breton draft mare is described. A transrectal ultrasonography exam revealed a unilateral multi-cystic enlarged ovary. Laparoscopic ovariectomy was difficult due to enlargement of blood vessels in the ovarian broad ligament. The mare was necropsied, and the pathological changes in the GCT-affected ovary and unaffected ovary were evaluated. The ovarian mass in the GCT-affected ovary had a cribriform pattern and was positive for anti-Müllerian hormone (AMH) and its receptor (AMHR2). The contralateral ovary showed no follicular development and was negative for AMH. AMHR2 was positively expressed in stromal cells. The AMH concentration in plasma was 4,210 ng/ml. This is the first report showing the presence of AMH (2,210 ng/ml) in ascites fluid, and it also shows that laparoscopic ovariectomy might not be suitable for larger ovaries affected by a GCT. Ultrasonographic, endocrine, and histopathological analyses were helpful for making a definitive diagnosis of GCT in this mare.
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http://dx.doi.org/10.1294/jes.32.67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240524PMC
June 2021

The Impact of Cefazolin Shortage on Surgical Site Infection Following Spine Surgery in Japan.

Spine (Phila Pa 1976) 2021 Jul;46(14):923-930

Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan.

Study Design: Retrospective study using prospectively collected data.

Objective: This study aimed to investigate the effect of alternative antimicrobial prophylaxis agents on surgical site infections (SSIs) after spine surgery.

Summary Of Background Data: Although the use of alternative antimicrobial prophylaxis agents might have a negative effect on SSI prevention, their association with SSI risk in spine surgery remains unclear.

Methods: We used the registry data of consecutive patients undergoing spine surgery from April 2017 to January 2020 in four institutions participating in the University of Tokyo Spine Group. Before March 2019, all institutions used cefazolin for antimicrobial prophylaxis. After March 2019, the institutions used broad-spectrum beta-lactam agents as an alternative due to a cefazolin shortage in Japan.

Results: Among the 3841 enrolled patients (2289 males), 2024 received cefazolin and 1117 received alternative agents. The risk of reoperation for deep SSI within 30 days of spine surgery was significantly higher in the alternative antimicrobial prophylaxis agent group (adjusted odds ratio [aOR] 1.96; 95% confidence interval [CI], 1.15-3.35; P = 0.014). In subgroup analyses, the SSI risk was significantly higher in the thoracolumbar surgery group (aOR 1.98; 95% CI, 1.06-3.73; P = 0.03). A nonsignificant consistent trend was found in all other subgroups: posterior decompression (aOR 1.91; 95% CI, 0.86-4.21; P = 0.11); posterior fixation (aOR 2.05; 95% CI, 0.99-4.24; P = 0.05); and cervical spine surgery (aOR 2.30; 95% CI, 0.82-6.46; P = 0.11).

Conclusion: Alternative antimicrobial prophylaxis agents increased the risk of reoperation for SSI after spine surgery compared with cefazolin. Our study supports the current practice of using first-generation cephalosporins as first-line antimicrobial prophylaxis agents in spine surgery as recommended in multiple guidelines.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003946DOI Listing
July 2021
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