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Background: Colon cancer is the fourth leading cause of cancer deaths worldwide. The present study evaluated the chemopreventive effect of the combined treatment of Lactobacillus acidophilus, calcium citrate, and Moringa oleifera leaves extract against DMH (1,1-dimethylhydrazine hydrochloride) induced colon cancer., Material and Methods: Sprague Dawley rats were grouped into 10 different groups and treated with DMH 30 mg/kg s.c. for 8 weeks, Successful induction of colon cancer was confirmed with the help of symptoms, Individual and combined treatments of Lactobacillus acidophilus (10 9 cfu p.o.), calcium citrate (2 mg/kg p.o.) and Moringa oleifera (100 & 200 mg/kg p.o.) leaves extracts were used for 4 weeks., Result: After 4 weeks of treatment, it was observed that a significant reduction in aberrant crypt foci (ACFs) count, whereas liver and kidney function, AST (aspartate transaminase), ALT (alanine transaminase), urea and creatinine biomarkers were retained in its normal range. Upon DMH treatment, liver tissue loses histoarchitecture with mononuclear cell infiltration, nuclear enlargement, and hyperchromasia, this reverts due to the combined treatment of Lactobacillus acidophilus (LA), calcium citrate (CC) and hydroalcoholic extract of Moringa oleifera leaves (ME). From the results, it was revealed that individual and combined treatment of Lactobacillus acidophilus, calcium citrate, and hydroalcoholic extract of Moringa oleifera leaves shows beneficial effects against the carcinogen., Conclusion: Combined treatment of Lactobacillus acidophilus, calcium citrate, and hydroalcoholic extract of Moringa oleifera leaves showed positive effects against carcinogenesis and lowered aberrant crypt foci count and shows histoarchitectural improvements in liver histology with no nuclear enlargement and hyperchromasia in liver tissue., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Oral microbiota may be associated with serious local or systemic medical conditions resulting from chemotherapy. This study was conducted to evaluate the changes in the oral microbiota following the initiation of chemotherapy in patients with hematopoietic malignancies and to identify the characteristics of the oral microbiota associated with oral mucositis. Oral samples were collected from 57 patients with hematopoietic malignancies at 2 time points: before the start of chemotherapy and 8 to 20 days after the start of chemotherapy, when chemotherapy-induced oral mucositis often occurs, and 16S rRNA metagenomic analyses were performed. Comparative and linear discriminant analysis effect size (LEfSe) analyses were used to determine the characteristic bacterial groups before and after the initiation of chemotherapy and in those who developed oral mucositis. The alpha and beta diversities of oral microbiota before and after the initiation of chemotherapy differed significantly (operational taxonomic unit index, P  < .001; Shannon's index, P  < .001; unweighted UniFrac distances, P  = .001; and weighted UniFrac distances, P  = .001). The LEfSe analysis revealed a group of bacteria whose abundance differed significantly before and after the initiation of chemotherapy. In the group of patients who developed oral mucositis, a characteristic group of bacteria was identified before the start of chemotherapy. In conclusion, we characterized the oral microbiota associated with the initiation of chemotherapy in patients with hematopoietic malignancies. In addition, our findings suggest that oral microbiota composition before the start of chemotherapy may be associated with oral mucositis. The results of this study emphasize the importance of oral management focusing on the oral microbiota during chemotherapy in patients with hematologic malignancies.

Background: Brain astroglia are activated preceding the onset of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We characterized the effects of brain astroglia on spinal cord inflammation, focusing on astroglial connexin (Cx)43, because we recently reported that Cx43 has a critical role in regulating neuroinflammation., Methods: Because glutamate aspartate transporter (GLAST) + astroglia are enriched in the brain gray matter, we generated Cx43 fl/fl ;GLAST-CreER T2/+ mice that were brain gray matter astroglia-specific Cx43 conditional knockouts (Cx43 icKO). EAE was induced by immunization with myelin oligodendroglia glycoprotein (MOG) 35-55 peptide 10 days after tamoxifen injection. Cx43 fl/fl mice were used as controls., Results: Acute and chronic EAE signs were significantly milder in Cx43 icKO mice than in controls whereas splenocyte MOG-specific responses were unaltered. Histologically, Cx43 icKO mice showed significantly less demyelination and fewer CD45 + infiltrating immunocytes, including F4/80 + macrophages, and Iba1 + microglia in the spinal cord than controls. Microarray analysis of the whole cerebellum revealed marked upregulation of anti-inflammatory A2-specific astroglia gene sets in the pre-immunized phase and decreased proinflammatory A1-specific and pan-reactive astroglial gene expression in the onset phase in Cx43 icKO mice compared with controls. Astroglia expressing C3, a representative A1 marker, were significantly decreased in the cerebrum, cerebellum, and spinal cord of Cx43 icKO mice compared with controls in the peak phase. Isolated Cx43 icKO spinal microglia showed more anti-inflammatory and less proinflammatory gene expression than control microglia in the pre-immunized phase. In particular, microglial expression of Ccl2, Ccl5, Ccl7, and Ccl8 in the pre-immunized phase and of Cxcl9 at the peak phase was lower in Cx43 icKO than in controls. Spinal microglia circularity was significantly lower in Cx43 icKO than in controls in the peak phase. Significantly lower interleukin (IL)-6, interferon-γ, and IL-10 levels were present in cerebrospinal fluid from Cx43 icKO mice in the onset phase compared with controls., Conclusions: The ablation of Cx43 in brain gray matter astroglia attenuates EAE by promoting astroglia toward an anti-inflammatory phenotype and suppressing proinflammatory activation of spinal microglia partly through depressed cerebrospinal fluid proinflammatory cytokine/chemokine levels. Brain astroglial Cx43 might be a novel therapeutic target for MS.

In multiple sclerosis plaques, oligodendroglial connexin (Cx) 47 constituting main gap junction channels with astroglial Cx43 is persistently lost. As mice with Cx47 single knockout exhibit no demyelination, the roles of Cx47 remain undefined. We aimed to clarify the effects of oligodendroglia-specific Cx47 inducible conditional knockout (icKO) on experimental autoimmune encephalomyelitis (EAE) induced by myelin oligodendrocyte glycoprotein peptide (MOG35-55) in PLP/CreERT;Cx47fl/fl mice at 14 d after tamoxifen injection. Cx47 icKO mice demonstrated exacerbation of acute and chronic relapsing EAE with more pronounced demyelination than Cx47 flox (fl)/fl littermates. CD3+ T cells more abundantly infiltrated the spinal cord in Cx47 icKO than in Cx47 fl/fl mice throughout the acute to chronic phases. CXCR3-CCR6+CD4+ and IL17+IFNγ-CD4+ helper T (Th) 17 cells isolated from spinal cord and brain tissues were significantly increased in Cx47 icKO mice compared with Cx47 fl/fl mice, while MOG35-55-specific proliferation and proinflammatory cytokine production of splenocytes were unaltered. Microarray analysis of isolated microglia revealed stronger microglial activation toward proinflammatory and injury-response phenotypes with increased expressions of chemokines that can attract Th17 cells, including Ccl2, Ccl3, Ccl4, Ccl7, and Ccl8, in Cx47 icKO mice compared with Cx47 fl/fl mice. In Cx47 icKO mice, NOS2+ and MHC class II+ microglia were more enriched immunohistochemically, and A1-specific astroglial gene expressions and astroglia immunostained for C3, a representative A1 astrocyte marker, were significantly increased at the acute phase, compared with Cx47 fl/fl mice. These findings suggest that oligodendroglia-specific Cx47 ablation induces severe inflammation upon autoimmune demyelination, underscoring a critical role for Cx47 in regulating neuroinflammation., Competing Interests: Competing interest statement: R.Y. has received honoraria from Biogen Japan; N.I. has received grant support from Mitsubishi Tanabe Pharma, Bayer Yakuhin Ltd., and Japan Blood Products Organization. J.-i.K. is a consultant for Biogen Japan and Medical Review, and has received honoraria from Bayer Healthcare, Mitsubishi Tanabe Pharma, Nobelpharma, Otsuka Pharmaceutical, Sanofi K.K., Chugai Pharmaceutical Co. Ltd., Teijin Pharma, Novartis Pharma, and Medical Review. The remaining authors declare no conflicts of interest.

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. Although they have been reported to increase the risk of infection, the findings are controversial. Given that urinary tract infections (UTIs) are common in the elderly, we conducted a retrospective cohort study by using health care insurance claims data, to elucidate the association between the DPP-4 inhibitors and the incidence of UTI in latter-stage elderly patients., Methods: We analyzed 25,111 Japanese patients aged 75 years and older between the fiscal years 2011 and 2016. Patients using DPP-4 inhibitors and sulfonylureas (SUs) were matched at a 1:1 ratio using propensity scoring. The Incidence rate ratio (IRR) of UTI was compared between users of SUs and users of DPP-4 inhibitors by Poisson regression. Moreover, subgroup analyses stratified by sex were conducted to evaluate whether the combination of prostatic hyperplasia and DPP-4 inhibitors is associated with the incidence of UTI in male patients., Results: The use of DPP-4 inhibitors was associated with an increased risk of UTI (adjusted IRR 1.23, 95% CI [1.04-1.45]). After propensity score matching, the association remained significant (adjusted IRR 1.28, 95% CI [1.05-1.56]). Moreover, elderly male patients with prostatic hyperplasia who received DPP-4 inhibitors had a higher risk of UTI than SU users without prostatic hyperplasia (Matched: crude IRR 2.90, 95% CI [1.78-4.71]; adjusted IRR 2.32, 95% CI [1.40-3.84])., Conclusions: The long-term use of DPP-4 inhibitors by elderly patients, particularly male patients with prostatic hyperplasia, may increase the risk of UTI., (Copyright © 2018 John Wiley & Sons, Ltd.)

Few studies have evaluated the effects of lifestyle habits, such as eating behaviors, on the development of nonalcoholic fatty liver disease (NAFLD). It is known that NAFLD increases the risk of type 2 diabetes, prediabetes, cardiovascular disease, and chronic kidney disease. Therefore, a retrospective cohort study was conducted to evaluate the effect of eating behaviors and interactions between these behaviors on the development of NAFLD among health insurance beneficiaries without NAFLD. Study subjects were 2254 male and female insurance beneficiaries without NAFLD who had attended specific health checkups during fiscal years 2009 and 2012 among health insurance societies located in Fukuoka and Shizuoka Prefectures (Japan). The incidence of NAFLD was defined as Fatty Liver Index scores ≥60 or visiting medical organizations for fatty liver disease treatment according to claims data. Eating behaviors, including eating speed and eating before bedtime, were evaluated by a self-administered questionnaire. During the study period, 52 (2.3%) subjects progressed to NAFLD. Subjects who ate before bedtime but did not eat fast had a higher risk of NAFLD (adjusted odds ratio [AOR] = 2.15; 95% confidence interval [CI]: 1.03-4.46). Those with both negative eating habits had a significantly higher risk of NAFLD (AOR = 2.48; 95% CI: 1.09-5.63). Subjects who habitually ate before bedtime, and those who ate fast and before bedtime, tended to have an increased risk of NAFLD. Earlier intervention to modify these poor eating behaviors could be useful to prevent NAFLD. (Population Health Management 2016;19:279-283).

Background: Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease worldwide. Renin-angiotensin system (RAS) inhibitors are the first-line treatment for diabetic patients with hypertension. However, whether RAS inhibitors prevent the development of DKD remains controversial. We conducted a retrospective cohort study quantifying the preventive effect of antihypertensive treatment with RAS inhibitors on DKD, using data from specific health check-ups and health insurance claims., Methods: The study subjects were 418 patients with diabetes and hypertension, drawn from health insurance societies located in Fukuoka and Shizuoka prefectures in Japan. The subjects were divided into three groups, according to the type of antihypertensive treatment they received. They were then compared in terms of the development of DKD, using the diagnostic codes from ICD-10., Results: Thirty subjects (6.2%) developed DKD during the study period between April 2011 and September 2013. RAS inhibitor treated group showed a significantly lower risk of DKD [adjusted odds ratio (AOR) = 0.35; 95% confidential interval (CI): 0.16-0.76] compared with the no treatment group., Conclusion: We conclude that antihypertensive treatment with RAS inhibitors is potentially useful for preventing the development of DKD.

Aims/introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in developed countries, and it was required to monitor patients with prediabetes. However, there have been few reports establishing the risk for diabetes mellitus (DM) among patients with prediabetes. The purpose of the present study was to evaluate the effect of NAFLD on the progression of DM among insurance beneficiaries with prediabetes, using data from specific health check-ups and the fatty liver index (FLI)., Materials and Methods: We used a retrospective cohort study that enrolled 967 insurance beneficiaries with prediabetes who had rarely drunk or could not drink alcohol, or whose alcohol consumption was <19 g/day from two health insurance societies. We divided insurance beneficiaries into FLI <30, intermediates FLIs and FLI ≥60, and compared the incidence rate of DM among the groups after 3 years' follow up, using multiple logistic regression models., Results: During 3 years' follow up, progression of diabetes was seen in 65 men (11.5%) and 24 women (6.0%). Logistic regression analyses showed that those with NAFLD had significantly higher risks of developing DM; this was the case in both men (odds ratio 2.68, 95% confidential interval 1.29-5.56) and women (odds ratio 10.35, 95% confidential interval 3.22-33.31)., Conclusions: Among insurance beneficiaries with prediabetes, those with NAFLD had a significantly higher risk of DM than those without NAFLD. The FLI might be useful for detecting individuals who have an especially higher risk for DM, and developing more effective guidance for delivering healthcare services in Japan.

Aim: To examine the relationship between family structure and the risk of institutionalisation of disabled older people., Methods: The participants were 286 disabled older people aged 65 or older who were eligible to receive formal care services under the long-term care insurance system in a town in western Japan. Family structure was categorised as living alone, living only with a spouse, living with a son, living with a daughter and living other relatives. The risks of institutionalisation were estimated by logistic regression analyses., Results: Participants living with a daughter had a significantly low odds ratio (OR) for institutionalisation (OR: 0.35, 95% confidence interval (CI): 0.13-0.93) and those living alone had a significantly high OR (OR: 2.31, 95% CI: 1.02-5.20), when compared to participants living with a son (regarded as the reference). The ORs of participants living only with a spouse and living with other relatives were 1.50 (95% CI: 0.59-3.79) and 0.66 (95% CI: 0.15-2.82), respectively., Conclusion: Living with a daughter could reduce the risk of institutionalisation for disabled older people., (© 2013 ACOTA.)

A 36-year-old woman with a 4 year history of lower legs edema, hypermenorrhea and melena without medical treatment was admitted to our hospital. At 18 days before admission, anasarca and general fatigue appeared and she was admitted to another hospital. Her hemoglobin concentration was 1.4 g/dl and chest X-ray showed cardiomegaly. Heart failure with severe chronic anemia was diagnosed, and blood transfusion was performed. Her hemoglobin concentration increased to 10 g/dl and the anasarca disappeared. The day after discharge, she was referred to our hospital with generalized convulsion. We diagnosed posterior reversible encephalopathy syndrome (PRES) from the typical MRI imaging. We started treatment and her consciousness recovered steadily. At a week after admission, left hemiparesis appeared. Her brain imaging revealed multiple intracranial hemorrhages. In addition, her visual disturbance revealed vitamin A and vitamin K deficiency. PRES sometimes occur secondary to blood transfusion, but secondary brain hemorrhage is rare. Her fat-soluble vitamin deficiency, which resulted from a peculiar eating habit, may have contributed to the brain hemorrhage.

A 24-year-old woman was referred to our hospital because of impaired consciousness after influenza virus B infection. Neurological examination revealed mild disturbance of consciousness without other neurological abnormalities. Laboratory tests showed elevated serum CRP, IL-6 and TNF-α levels. The level of IL-6 in the cerebrospinal fluid was also slightly elevated. Electroencephalography (EEG) disclosed almost continuous generalized spike and wave complexes and multiple spikes and wave complexes at 1.5-3 Hz. Brain MRI was normal. She was diagnosed as having influenza encephalopathy presenting non-convulsive status epilepticus (NCSE), and commenced methylprednisolone pulse therapy followed by prednisolone with gradual tapering. She was also treated with intravenous phenytoin and oral sodium valproate for NCSE. The next day, her consciousness level had improved. Although she became alert, epileptic discharges on EEG were still observed on the seventh hospital day, and levetiracetam was added. Then, her epileptic discharges almost completely disappeared on the twelfth hospital day. She was discharged without any neurological deficit. We consider this patient to be a case of transient NCSE due to influenza encephalopathy; alternatively, she may have epileptic traits and her NCSE may have been provoked by influenza virus infection.

The purpose of this study was to clarify, through a prospective study, the relationship between leptin and adiponectin levels, and subsequent weight change. The study subjects were 2,485 male office workers aged 35-64 employed by a company in Fukuoka Prefecture, Japan. Of these men, 1,936 (77.9%) received health check-ups both in 2005-2007 and 3 years later, in 2008-2010. Of the subjects who received both health check-ups, 352 were excluded duo to cancer, cardiac infarction, stroke or diabetes mellitus, leaving a total of 1,584. We divided them into tertiles according to baseline leptin and adiponectin levels, and compared the subsequent change in body mass index (BMI) over 3 years. The subjects with the lowest leptin levels showed a significantly greater increase in BMI (difference in change in BMI=0.178 kg/m2, 95% CI:0.025-0.331 kg/m2) over 3 years when those with the highest leptin levels were regarded as the reference even after adjusting for age, baseline BMI, smoking status, drinking status and exercise. The subjects with the highest adiponectin levels showed a greater increase in BMI (difference in change in BMI=0.099 kg/m2, 95% CI: -0.034-0.231 kg/m2) over 3 years when those with the lowest adiponectin levels were regarded as the reference, but this association was not statistically significant after adjusting for age, baseline BMI, smoking status, drinking status and exercise. Our findings suggest that higher leptin levels may suppress weight gain in Japanese male workers.

Background: There are technical limitations to handling all the information mentioned in health insurance claims (HICs) in Japan. Therefore, conventional methods for estimating disease-specific medical expenditures assume that all medical care expenditures in a given HIC are spent on only one principal diagnosis even when the HIC contains multiple diagnoses., Objectives: To estimate the disease-specific medical expenditures that consider all diagnosis on a given HIC., Methods: Data were obtained from 169 622 outpatient HICs in May 2006 from health insurance provided by the employer. We compared the estimated disease-specific medical expenditures of the conventional method with a proportional distribution method (PDM), which considers all diagnoses on the HICs., Results: For diabetes mellitus and other diseases of the digestive system, the proportion of principal diagnoses among total diagnoses was 52.4% (4849/9251) and 19.6% (2614/13331), respectively. In addition, the ratio of the estimated disease-specific medical expenditures between the conventional method and the PDM method was 1.49 for diabetes mellitus and 0.64 for other diseases of the digestive system. The estimation of disease-specific medical expenditures using the conventional method may therefore have overestimated the expenditures on the disease category typically selected as the principal diagnosis and underestimated the expenditures on the disease category less likely to be selected as the principal diagnosis., Conclusions: The conventional method for estimation of disease-specific medical expenditures should be improved by utilizing all the diagnoses information on HICs., (© 2011 Blackwell Publishing Ltd.)

Background: According to the regulations concerning reimbursement rules for the uniform coverage scheme in Japan's health insurance system, rule-out diagnoses must be included in a health insurance claim (HIC) to ensure reimbursement for clinical procedures whose results show that a suspected disease is not present. However, estimations of disease-specific medical expenditure by conventional methods have not considered the information on rule-out diagnoses., Objectives: To estimate disease-specific medical expenditure for rule-out diagnoses., Methods: Data were obtained from 169,622 outpatient HICs in May 2006 from corporate health insurance societies. We used the proportional distribution method to estimate medical expenditure for each of the major disease categories defined by the Classification of Diseases for the use of Social Insurance, which is based on the International Statistical Classification of Diseases and Related Health Problems, 10th Revision., Results: There were 442,010 diagnoses on the HICs, of which 20,330 (4.60%) were rule-out diagnoses. Rule-out diagnoses accounted for 8.5% of total medical expenditure. The proportion of medical expenditure spent on rule-out diagnoses varied across the major diseases categories, and it was estimated that more than one-third (36.9%) of the medical expenditure on neoplasm is spent on rule-out diagnoses., Conclusions: The existence of rule-out diagnoses affects the estimation of disease-specific medical expenditure. Therefore, the estimation of disease-specific medical expenditure and evaluation of prevention and treatment programmes should be improved by utilizing information on rule-out diagnoses., (© 2011 Blackwell Publishing Ltd.)

Background: In many studies, high-molecular-weight (HMW) adiponectin has been considered the active form of adiponectin. However, whether HMW adiponectin is a good surrogate marker for coronary artery disease still needs to be elucidated., Methods: We conducted a hospital-based cross-sectional study to examine the relationship between total, HMW or non-HMW adiponectin concentrations and coronary stenosis in 83 male patients and 138 male controls., Results: Patients with coronary stenosis had significantly lower total adiponectin concentrations compared with controls. Non-HMW adiponectin concentrations in cases were significantly lower than the controls. However, there were no significant differences between cases and controls in HMW adiponectin concentrations. From the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) for total and non-HMW adiponectin was significantly larger than that for HMW adiponectin concentrations. Of the three models, that for non-HMW adiponectin showed the largest AUC (total adiponectin 0.74, HMW adiponectin 0.54, and non-HMW adiponectin 0.79)., Conclusions: Despite associations between total adiponectin levels and coronary stenosis, our data go against any apparent association between HMW adiponectin concentrations and coronary stenosis.