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In this study, we developed a simple method that enables iron(III) in environmental water to be directly determined via spectrophotometry. In water samples, iron(III) formed a yellowish complex with N-1-Naphthylethylenediamine dihydrochloride (NEDA) at pH 2.0-2.8, the maximum absorption wavelength of which was 462 nm. Detection sensitivity increased in the presence of chloride ions and remained constant for 2-24 h with 0.05-0.57 mol L -1 chloride. Therefore, NEDA solution containing chloride ions was used as a chromogenic reagent for the determination of iron(III). The determination range for this method was 0.1-20 mgFe(III) L -1 in a 5 cm glass cell. The developed method is highly selective for iron(III) and has been successfully applied to freshwater, brackish water, seawater, turbid water in rivers, as well as to riverbed and freshwater lake sediments. In addition, a combination of the proposed NEDA method and the 1,10-phenanthroline method enabled simultaneous determination of iron(III) and iron(II)., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Aim: Hypertensive disorders of pregnancy (HDP) are among the obstetric complications reportedly associated with later-life cardiovascular disease (CVD). This study examined physicians' recognition of reproductive history by elucidating their attitude and knowledge., Methods: This study included council members of the Japan Atherosclerosis Society. An Internet-based survey was conducted between August 9 and September 9, 2022., Results: A total of 137 council members completed the questionnaire (response rate: 36%). In terms of the internal medicine subspeciality of the participants, endocrinology was the most common (46%), followed by cardiology (38%). About 70% of the participants considered reproductive history to be important and obtained more information than those who considered it otherwise. In the questionnaire for knowledge about HDP and future diseases, physicians correctly answered 6.8 of 9 questions. Endocrinologists were more likely to ask regarding reproductive history at the initial visit than cardiologists (82.5% vs. 61.5%; p=0.012) and obtained more information from women below 50 years old. Contrarily, cardiologists obtained information on reproductive history from older women (those approaching menopause and those in their 60s and 70s)., Conclusion: We found that physicians had a high level of knowledge about HDP and the importance of reproductive information. However, the manner of obtaining information, including the target population, differed depending on the subspeciality. In the future, effective interventions for women with a history of HDP need to be developed in order to encourage physicians to obtain reproductive information to prevent CVD.

Objectives: Malnutrition and sarcopenia often co-exist in older patients. This condition, called co-MS, shows a worse prognosis than either condition alone but is often overlooked and undertreated. We aimed to clarify the prevalence of co-MS and its associated factors with a focus on prescription in a long-term nursing care facility in Japan., Methods: Patients aged >65 years who resided in a long-term nursing care facility in Hyogo, Japan, were recruited for this cross-sectional study, which was conducted from July 1 to July 30, 2022. Sarcopenia and malnutrition were diagnosed using the Asian Working Group for Sarcopenia and Global Leadership Initiative on Malnutrition criteria, respectively. Patients who met both criteria were classified as having co-MS. Potentially associated factors, including age, sex, length of stay, activities of daily living, comorbidity, oral function and hygiene, swallowing ability, and the number and type of prescriptions, were assessed., Results: The prevalence of sarcopenia was 92 % (72/78). All malnourished patients were sarcopenic (40.3 %) and were classified as having co-MS. Oral function and hygiene, swallowing ability, comorbidity, and the presence of potentially inappropriate medications showed significant associations in univariate analyses. Of particular note, potentially inappropriate medication was an independent factor in the multivariate analysis., Conclusions: Co-MS is prevalent in long-term nursing care facilities; thus, healthcare workers should pay attention to relevant factors to identify patients at risk of co-MS and to provide appropriate care and intervention., 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., (© 2023 The Authors.)

Aim: Hypertensive disorders of pregnancy (HDP) are estimated to occur in up to 10% of all pregnancies and are associated with an increased risk of future cardiovascular disease (CVD) and chronic hypertension (HT). Therefore, we examined the impact of a history of HDP on CVD possibility in middle- and older-aged Japanese women., Methods: We used the Tohoku Medical Megabank database to obtain the data of 26,024 menopausal women who were aged ≥ 50 years, had children, did not smoke, and did not have chronic kidney disease and to analyze the relationship between HDP history and CVD., Results: A history of HDP was found in 4.6% of women. We divided the women into four groups according to the presence or absence of HDP and HT. The percentage of women with dyslipidemia, diabetes mellitus, and body mass index of ≥ 25 kg/m 2 was the highest in the HDP＋ HT＋ group compared to the other groups (43.4%, 24.0%, and 45.2%, respectively). Adjusted odds ratio (OR) for the combined six CVD categories was higher for those with a history of HDP alone (OR [95% confidence interval [CI]]: 1.61 [1.03-2.53]). Moreover, the OR was significantly higher for those with combination with HDP history and HT (OR [95% CI]: 4.11 [3.16-5.35]). The prevalence of individual CVD was also the highest in the HT＋ HDP＋ group., Conclusion: An HDP history can influence the risk of CVD in Japanese women, indicating the importance of information about pregnancy outcomes in health management.

Emphysematous pyelonephritis (EPN) is a severe urinary tract infection common in patients with diabetes. Nephrectomy is recommended when the Huang classification is ≥3B. We herein report a case in which nephrectomy was avoided using antimicrobial agents and percutaneous drainage (PCD). A 59-year-old man was diagnosed with EPN (Huang classification 3B). The causative bacteria were Escherichia coli. Despite high-risk factors, EPN was cured with kidney preservation and PCD because the emphysema and abscess were not extensive. Thus, PCD should be considered in patients with Huang Class 3B EPN and high-risk factors if emphysema and abscess are not extensive.

A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases., (© 2023. The Author(s).)

The stratum corneum (SC), the outermost layer of the skin, has an important function to provide a barrier against dry environments. To evaluate the barrier function and the skin condition, it is crucial to investigate the ability of SC to absorb and retain water. In this study, we demonstrate stimulated Raman scattering (SRS) imaging of three-dimensional SC structure and water distribution when water is absorbed into dried SC sheets. Our results show that the process of water absorption and retention is dependent on the specific sample and can be spatially heterogeneous. We also found that acetone treatment leads to spatially homogeneous retention of water. These results suggest the great potential of SRS imaging in diagnosing skin conditions.

Idiopathic multicentric Castleman disease (iMCD) is a subtype of human herpesvirus type 8 (HHV-8)-related Castleman disease that causes multi-organ damage, including kidney damage due to polyclonal lymphoproliferation and interleukin (IL)-6-induced cytokine storm. However, its renal pathological findings are unclear. We report the case of a woman in her 80 s who was diagnosed with iMCD based on renal pathological findings. Five years ago, hypergammaglobulinemia was detected, and her renal function declined. Renal biopsy revealed plasma cells infiltrating the stroma. Immunostaining revealed numerous IgG4-positive plasma cells. The serum IgG4 level was high, and she was initially diagnosed with IgG4-related disease (IgG4-RD) and treated with steroids. However, the therapeutic effect was poor. On re-examination, computed tomography revealed lymphadenopathy around the aorta and spleen. Renal histopathology showed numerous IL-6-positive plasma cells. Anemia and C-reactive protein (CRP) positivity persisted despite steroid administration. HHV-8 was negative, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome was not suspected. Thus, iMCD was diagnosed. Based on previous reports, there is no significant difference in IgG4 levels between iMCD and IgG4-RD, and IgG4-positive plasma cell infiltrates were observed in iMCD-affected organs. Therefore, it may be difficult to distinguish iMCD from IgG4-RD. In this case, high-serum IL-6 and CRP were observed, which are usually not seen in IgG4-RD but are common findings in iMCD, leading to the diagnosis. Patients with deep lymphadenopathy may be diagnosed with iMCD based on renal pathological findings. Renal biopsy is recommended for patients with suspected iMCD and decreased renal function., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

Aim: Cardiovascular disease (CVD) is the second largest cause of death in Japanese women. Pregnancy and childbirth are events that put a strain on the cardiovascular system. When postpartum weight retention is insufficient, weight gain due to fat deposition during pregnancy might lead to obesity. Thus, we examined the effects of body mass index (BMI) in middle and older ages and the number of children on CVD and metabolic disorders., Methods: From the Tohoku Medical Megabank database, we used data from 32,000 women aged ≥ 50 years. This database contains obstetrical history, medical history, and laboratory data obtained once from 2013 to 2015., Results: The mean age of participants was 64.2 years, and 47.7% of women had two children. Compared with nulliparous women, those who had a higher number of children had higher BMI and systolic blood pressure. The prevalence of CVD was highest in obese class I (30 kg/m 2 ≤ BMI) women with three or more children and the prevalence of hypertension was high in pre-obese (25 kg/m 2 ≤ BMI ＜30 kg/m 2 ) and obese class I women with children. Conversely, the prevalence of diabetes and proportion of women whose HbA1c values were ＞6.5% was highest in obese class I women with no children., Conclusion: In this study, we found that not only BMI but also the number of children influenced the health status of middle- and older-aged women, suggesting the importance of childbirth history in the health management of women.

We have previously reported that a major quantitative trait locus (QTL) responsible for susceptibility to salt-induced stroke in the stroke-prone spontaneously hypertensive rat (SHRSP) is located in a 3-Mbp region on chromosome 1 covered by SHRSP.SHR-(D1Rat23-D1Rat213)/Izm (termed Pr1.31), a congenic strain with segments from SHRSP/Izm introduced into the stroke-resistant SHR/Izm. Here, we attempted to narrow down the candidate region on chromosome 1 further through analyses of subcongenic strains constructed for the target region. Simultaneously, salt-induced kidney injury was evaluated through the measurement of urinary albumin and the gene expression of renal tubular injury markers (Kim-1 and Clu) to explore a possible mechanism leading to the onset of stroke. All subcongenic strains examined in this study showed lower susceptibility to salt-induced stroke than SHRSP. Interestingly, Pr1.31 had the lowest stroke susceptibility when compared with newly constructed subcongenic strains harboring fragments of the congenic sequence in Pr1.31. Although Kim-1 and Clu expression after 1 week of salt loading in Pr1.31 did not differ significantly from those in SHRSP, the urinary albumin level of Pr1.31 was significantly lower than those of the other subcongenic strains and that of SHRSP. The present results indicated that, although the congenic fragment in Pr1.31 harbored the gene(s) related to salt-induced organ damages, further genetic dissection of the candidate region was difficult due to multiple QTLs suggested in this region. Further analysis using Pr1.31 will unveil genetic and pathophysiological mechanisms underlying salt-induced end organ damages in SHRSP.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins., (© 2021. The Author(s).)

Zn 2+ , Mg 2+ and Ca 2+ are essential divalent cations implicated in many metabolic processes and signalling pathways. An emerging new paradigm is that the organismal balance of these cations predominantly depends on a common gatekeeper, the channel-kinase TRPM7. Despite extensive electrophysiological studies and recent cryo-EM analysis, an open question is how the channel activity of TRPM7 is activated. Here, we performed site-directed mutagenesis of mouse TRPM7 in conjunction with patch-clamp assessment of whole-cell and single-channel activity and molecular dynamics (MD) simulations to show that the side chains of conserved N1097 form an inter-subunit Mg 2+ regulatory site located in the lower channel gate of TRPM7. Our results suggest that intracellular Mg 2+ binds to this site and stabilizes the TRPM7 channel in the closed state, whereas the removal of Mg 2+ favours the opening of TRPM7. Hence, our study identifies the structural underpinnings through which the TRPM7 channel is controlled by cytosolic Mg 2+ , representing a new structure-function relationship not yet explored among TRPM channels., (© 2022. The Author(s).)

Ninjin-yoei-to (NYT), a Kampo medicine, has ameliorative effects on cognitive dysfunction via enhancing cholinergic neuron activity. To explore an efficacy of NYT administration for prevention and cure of Alzheimer's disease, here we examined the effect of NYT on amyloid β 1-42 (Aβ 1-42 )-induced neurodegeneration in the dentate gyrus. A diet containing 3% NYT was administered to mice for 2 weeks and human Aβ 1-42 was intracerebroventricularly injected. Neurodegeneration in the dentate granule cell layer of the hippocampus, which was determined 2 weeks after the injection, was rescued by administration of the diet for 4 weeks. Aβ staining (uptake) was not modified in the dentate granule cell layer by pre-administration of the diet for 2 weeks, while Aβ 1-42 -induced increase in intracellular Zn 2+ was reduced, suggesting that pre-administration of NYT prior to Aβ injection is effective for reducing Aβ 1-42 -induced Zn 2+ toxicity in the dentate gyrus. As a matter of fact, Aβ 1-42 -induced neurodegeneration in the dentate gyrus was rescued by pre-administration of NYT. Interestingly, the level of metallothioneins, intracellular Zn 2+ -binding proteins, which can capture Zn 2+ from Zn-Aβ 1-42 complexes, was elevated in the dentate granule cell layer by pre-administration of NYT. The present study suggests that pre-administration of NYT prevents Aβ 1-42 -mediated neurodegeneration in the dentate gyurs by induced synthesis of metallothioneins, which reduces intracellular Zn 2+ toxicity induced by Aβ 1-42 .

To diagnose chronic kidney disease (CKD) at an early stage, it is important to promote appropriate health guidance and consultation recommendations through regular medical examinations and implementation of continuous high-quality and appropriate treatment. From fiscal year (FY) 2018, Izumo City has initiated the "Izumo City CKD Exacerbation Countermeasures" program. In this study, we aimed to report on the methods undertaken and the effects of this program. Residents aged 40-74 years who underwent specific health checkups from the Izumo City National Health Insurance in FY2018 and FY2019 were included. The rates of CKD re-examination candidates, re-examinations implementation, nephrologist referrals, and health guidance referrals between FY2018 and FY2019 were compared. The rate of CKD re-examination candidates in both years remained unchanged at approximately 7%. The rate of re-examination implementation in FY2019 significantly increased relative to that in FY2018 ( p < 0.001). Subsequent re-examination candidate trends showed that the rate of nephrologist referrals did not increase. However, the rate of city health guidance referrals significantly increased ( p < 0.001). Increase in the re-examination and health guidance examination rates indicate improved awareness of CKD among the public and family doctors, and it is expected to prevent CKD exacerbation in the future.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease. Although abdominal echography during medical checkup may be effective for the early detection of ADPKD, there are no reports of the early detection of ADPKD during medical checkup. We investigated whether there was a difference in renal function and total kidney volume (TKV) at the time of diagnosis due to differences in diagnostic triggers for ADPKD., Methods: A total of 34 patients diagnosed with ADPKD between January 1, 2010, and December 31, 2020, at the Department of Nephrology, Shimane University Hospital, were included. The triggers for diagnosis of the renal cyst(s) were usually unintentional findings. These included findings observed upon routine medical checkups, computed tomography, or abdominal echography during examination for other diseases (incidental detection group) and cases referred to our department for renal dysfunction (renal dysfunction group), and "other" group. We compared the renal dysfunction group and the incidental detection group., Results: The estimated glomerular filtration rate (eGFR) at diagnosis was significantly higher in the incidental detection group. The TKV was significantly lower in the incidental detection group than in the other group. The number of patients with eGFR > 45 mL/min/1.73 m 2 , for which tolvaptan was safe and effective, was significantly higher in the incidental detection group than in the renal dysfunction group., Conclusion: Our study shows that medical checkup enables early detection of ADPKD. This is important because ADPKD may have serious complications. The present study did not examine the age at which abdominal echography screening for the early detection of ADPKD was more useful or cost-effective; thus, further research is needed to ascertain this., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Fukunaga et al.)

Purpose: To assess the validity and reliability of the Japanese version of the Daily Record of Severity of Problems (J-DRSP, 24 items) for evaluating symptoms of premenstrual syndrome (PMS), and to develop a short form version of the J-DRSP., Methods: Using the "DRSP-JAPAN" smartphone app, we collected daily J-DRSP records from cycle day - 6 (CD - 6) to CD 10, with CD 1 representing the menstruation onset date. Factorial validity (exploratory factor analysis: EFA, confirmatory factor analysis: CFA) and criterion validity were examined, and test-retest reliability (intraclass correlation: ICC) evaluated. The short-form version of the J-DRSP was developed using classical test theory., Results: In total, 304 women participated and 243 recorded symptoms on at least 4 days spanning the week of the luteal phase (CD - 6 to CD 0) and 4 days spanning the week of the follicular phase (CD 4 to CD 10), with CD 0 set as the day before menstruation started. The EFA revealed a two-factor structure. Kaiser-Meyer-Olkin was 0.992, and Bartlett's test of sphericity chi-square was 3653.89 (P < 0.001). However, the model fitness of CFA was found to be suboptimal (comparative fit index (CFI): 0.83, root mean square error of approximation (RMSEA): 0.12). Total scores for J-DRSP and the sum scores for each subscale were higher on CD 0 than on CD 10 (p < 0.001), suggesting validity for some criteria. ICC values for the total J-DRSP score from CD 0 to CD - 1, and between CD 9 to CD 10, were 0.60 (95% CI: 0.48-0.72) and 0.76 (95% CI: 0.69-0.82), respectively. Having eliminated some original items after considering factor loading for each item, we developed an 8-item Short-Form J-DRSP (J-DRSP (SF)) comprising 2 factors (S-Psychological and S-Physical, 4 items for each). CFA showed a better model fit (CFI: 0.99, RMSEA: 0.048), and ICC values in the luteal and follicular phases were 0.61 (95%CI: 0.51-0.68) and 0.70 (95%CI: 0.62-0.77), respectively., Conclusion: The J-DRSP has moderate to good reliability and a certain level of validity. The 8-item J-DRSP (SF) has a two-factor structure and can be used effectively among Japanese women to assess their PMS symptoms.

Purpose: The effects of coffee intake on the ratio of stromal and luminal components in the choroid and the underlying mechanism remain unclear. This prospective cross-sectional study aimed to explore how coffee intake affects the choroidal component ratio and circulation., Methods: Forty-nine right eyes of healthy adult volunteers were evaluated as the coffee intake group. Thirty-two right eyes of healthy volunteers served as the control group. The participants consumed 185 mL of coffee or water, respectively, and the systemic hemodynamics, enhanced-depth imaging optical coherence tomographic (EDI-OCT) images, and foveal mean blur rate (MBR), an indicator of blood flow velocity, were recorded at baseline and after coffee or water intake. The EDI-OCT images were binarized using ImageJ software, and subfoveal choroidal thickness (SCT) and whole, luminal, and stromal choroidal areas were calculated., Results: In the coffee intake group, significant decreases in SCT and luminal area peaked at 60 minutes after intake (both P < 0.001), whereas a significant increase in MBR peaked at 30 minutes (P < 0.001). No significant stromal area fluctuations were observed. SCT and luminal area fluctuations exhibited a significant positive correlation (r = 0.978, P < 0.001). Significant negative correlations of luminal area fluctuations with MBR fluctuations were observed by stepwise regression analysis (r = -0.220, P < 0.001). The control group exhibited no significant fluctuations., Conclusions: Coffee-induced choroidal thinning may result mainly from a reduction in the choroidal vessel lumen, and this vessel lumen reduction correlated with an increased choroidal blood flow velocity after coffee intake. These coffee-induced changes in choroidal component ratio and circulation should be considered when evaluating choroids.

Nanomolar concentrations of NH 2 OH in natural water sources were determined using an Fe 3+ oxidation method. A pH of 2.35 - 2.50 was used, which was adjusted by adding a chloroacetate buffer. Equal amounts (1.0 mL) of the chloroacetate solution and ferric chloride solution were added to the water sample (70 mL) to oxidize NH 2 OH to N 2 O. The resulting N 2 O in the sample water was then quantified by headspace analysis using a gas chromatograph with an electron-capture detector (ECD), where a limit of detection of 0.2 μgN L -1 (14 nmol L -1 ) was achieved. This method was successfully applied to samples of freshwater, brackish water, and seawater, and despite the various salinities no interfering substances were observed. Furthermore, NH 2 OH was successfully detected in samples collected from the Hii River and Lakes Shinji and Nakaumi (Shimane Prefecture, Japan). In addition, the proposed method was also applicable to samples rich in organic substance derived from phytoplankton.

Background: The neutrophil-lymphocyte ratio (NLR) is a well-known prognostic marker in various cancers. However, its role as a predictive marker for the effectiveness of nivolumab in patients with metastatic RCC (mRCC) remains unclear. We evaluated the relationships between the NLR and progression-free survival (PFS) or overall survival (OS) in mRCC patients treated with nivolumab., Methods: The data of 52 mRCC patients who received nivolumab therapy were collected from seven institutes and evaluated. The median follow-up period from treatment with nivolumab was 25.2 months (IQR 15.5-33.2)., Results: The median duration of nivolumab therapy was 7.1 months (IQR 2.9-24.4). The objective response rate was 25% and the 1- and 2-year PFS rates were 46.2 and 25.2%, respectively. The median NLR values at baseline and 4 weeks were 3.7 (IQR 2.7-5.1) and 3.3 (IQR 2.4-5.7), respectively. In the multivariate analysis, an NLR of ≥3 at 4 weeks was an independent predictor of PFS (P = 0.013) and OS (P = 0.034). The 1-year PFS of patients with an NLR of < 3 at 4 weeks was better than that of those with an NLR of ≥3 (75% versus 29%, P = 0.011). The 1-year OS of patients with an NLR of < 3 at 4 weeks was also better than that of those with an NLR of ≥3 (95% versus 71%, P = 0.020)., Conclusions: Although the baseline NLR was not associated with PFS or OS, an NLR of ≥3 at 4 weeks after the initiation of therapy might be a robust predictor of poor PFS and OS in mRCC patients undergoing sequential treatment with nivolumab.

BRCA1/2 genetic testing to use PARP inhibitor for breast cancer has a possibility of the "secondary finding" among the younger nonaffected family members of the patient, which turns them into at-risk for hereditary breast cancer. Proper understanding of the background of the hereditary cancer is now required for appropriate acceptance of the risk. Therefore, we investigated the level of knowledge and attitudes of younger women on hereditary breast cancer in Japan. Study subject was Japanese university women between 20 and 30 years of age, without medical history of breast cancer. We conducted the anonymous self-answering questionnaire to them. We received responses from 353 women. The levels of knowledge, awareness, and interest were relatively high. Women with a family history of breast cancer were less likely to undergo testing than women without (92.8% vs. 74.5%, p < 0.001). The rates of positive response toward risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) was significantly high for medical majors compared with that for other majors (RRM: medical 71.6% vs. science 54.5% vs. humanities 53.8%, p = 0.008, RRSO: 35.4% vs. 36.3% vs. 48.4%, p = 0.027). Approximately half of respondents answered that they would hesitate to get married (45.3%) or to have children (55.4%), if they were a BRCA1/2 mutation carrier. The results may help to establish the methods for supporting the decision-making for reproduction of younger women who are unexpectedly labeled as being at-risk for HBOC.

This data article presents supplementary material for our report "Role of obstetricians in promoting pregnancy-related knowledge among women with epilepsy in Japan" (Egawa et al. 2020). To provide more effective preconception counseling and perinatal care, we surveyed the attitude of epileptologists and obstetricians about pregnancy-related issues in women with epilepsy (WWE). Obstetricians said they needed information from epileptologists about seizure for management of WWE. Half of epileptologists did not feel the need to communicate with obstetricians before their patients' pregnancy; they only contacted obstetricians after their patients became pregnant, and they only referred patients to an obstetrician if requested by the patient., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have, or could be perceived to have, influenced the work reported in this article., (© 2020 The Authors.)

Abstract: The influence of muscle fiber direction (parallel or perpendicular) in relation to the inoculation surface on migration of Salmonella Enteritidis, Staphylococcus aureus, and Escherichia coli into raw chicken breasts was examined. Chicken breast samples with two types of surface fibers (running parallel or perpendicular to the surface) were inoculated with cultures of each bacterium. Inoculated samples were stored for 5 min, 1 h, or 24 h at 4°C. After storage, the samples were divided into segments, and bacterial counts were determined in different regions (inoculation surface, inoculation surface to 1 cm, 1 to 2 cm, 2 to 4 cm, and 4 to 6 cm). The migration of bacteria did not change at 5 min or 1 h regardless of fiber direction. However, after 24 h each bacterium was detected at 4 to 6 cm in the pieces of sample with a perpendicular muscle fiber surface cut. Although these bacteria were detected at 4 to 6 cm in samples with muscle fibers perpendicular to the inoculated surface, these results do not clearly indicate that bacteria migrated into the chicken breast. To monitor actual migration of bacteria into the chicken breast, the tops of the perpendicular muscle fibers of the breast sample were inoculated with bioluminescent E. coli Xen-14. Various regions of the breast sample (inoculation surface and cut surfaces at 1, 2, 4, and 6 cm) were stamped directly on growth medium. Culture revealed that the bacteria migrated directly under the contaminated site and dispersed along the surface of the chicken breast segments. More bacteria distributed laterally than migrated directly below the contamination site. These results suggest that the direction of the muscle fibers is a major factor influencing migration of pathogenic bacteria into chicken breast., (Copyright ©, International Association for Food Protection.)

Background: Premenstrual syndrome (PMS) causes physical and mental symptoms in women during the luteal phase of the menstruation cycle. To confirm the relationship between symptoms and the menstruation cycle, daily symptom records are essential for diagnosing PMS. The daily record of severity of problems (DRSP) is currently the most validated tool for tracking symptoms to confirm and scale the severity of PMS, but there has been no validated Japanese version of this instrument. We developed a Japanese version of the DRSP and assessed its psychometric properties. Methods: A Japanese version of the DRSP was developed following the translation guidelines of the latest Patient-Reported Outcomes Consortium. We conducted a computational psychometric study among 119 women, all of whom completed the Japanese version of the DRSP, the Center for Epidemiologic Studies Depression Scale (CES-D), the Premenstrual Dysphoric Disorder (PMDD) scale, and a Numerical Rating Scale (NRS) for general health status. Each was filled out twice, 2 weeks apart, so that one set was completed in the luteal phase. Results: The Japanese version of the DRSP was developed with translation and cultural adaptation. The internal consistency coefficient for the total score was 0.93. The DRSP in the luteal phase correlated highly with the CES-D, PMDD scale, and NRS for general health status. Conclusions: Our Japanese version of the DRSP, developed as a PMS/PMDD diagnostic tool, was shown to provide substantial validity and reliability to rate premenstrual symptoms for Japanese women., Competing Interests: No competing financial interests exist., (© Yumie Ikeda et al. 2020; Published by Mary Ann Liebert, Inc.)

Background & Aims: Liver inflammation has been recognized as a hallmark of hepatocarcinogenesis. Although Forkhead Box M1 (FoxM1) is a well-defined oncogenic transcription factor that is overexpressed in hepatocellular carcinoma (HCC), its role in liver inflammation has never been explored., Methods: We generated hepatocyte-specific FoxM1 conditional transgenic (TG) mice by using the Cre-loxP and Tetracycline (Tet)-on systems to induce FoxM1 expression in a hepatocyte-specific and time-dependent manner., Results: After treatment of Tet-derivatives doxycycline (DOX) to induce FoxM1, TG mice exhibited spontaneous development of hepatocyte death with elevated serum alanine aminotransferase levels and hepatic infiltration of macrophages. The removal of DOX in TG mice completely removed this effect, suggesting that spontaneous inflammation in TG mice occurs in a hepatocyte FoxM1-dependent manner. In addition, liver inflammation in TG mice was associated with increased levels of hepatic and serum chemokine (C-C motif) ligand 2 (CCL2). In vitro transcriptional analysis confirmed that CCL2 is a direct target of FoxM1 in murine hepatocytes. After receiving FoxM1 induction since birth, all TG mice exhibited spontaneous HCC with liver fibrosis at 12 months of age. Hepatic expression of FoxM1 was significantly increased in liver injury models. Finally, pharmacologic inhibition of FoxM1 reduced liver inflammation in models of liver injury., Conclusions: Hepatocyte FoxM1 acts as a crucial regulator to orchestrate liver inflammation linking to hepatocarcinogenesis. Thus, hepatocyte FoxM1 may be a potential target not only for the treatment of liver injury but also for the prevention toward HCC., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A majority of women from all cultures and socioeconomic levels experience myriad symptoms known as premenstrual syndrome during the days prior to menstruation. The present study investigated commonly reported symptoms in the premenstrual phase among college students. The authors further scrutinized potential factors, including subjective perceptions of health, which may be related to the premenstrual-symptom constellation., Methods: We conducted a cross-sectional survey, which included 200 participants (mean age: 19.8 ± 0.1 years old). The subjects completed a rating of their premenstrual experiences relative to 46 symptoms in eight categories of the self-reporting menstrual distress questionnaire (MDQ) to evaluate the prevalence and severity of premenstrual symptoms. The participants also answered a standardized health questionnaire regarding subjective perceptions of health, self-rating stress, lifestyle, and demographic variables., Results: Regardless of severity, the 10 symptoms most often occurring among the participants included skin disorders, irritability, fatigue, mood swings, general aches and pains, lowered school or work performance, backache, painful breasts, weight gain, and swelling. Stepwise multiple regression analysis revealed subjective perception of health (β = 0.28; p  <  0.001) and self-rating stress (β = 0.18; p  = 0.008) as the factors most strongly related to the MDQ total scores. In addition, the 19 women who evaluated themselves as "unhealthy and stressed" had greater prevalence of severe or extremely severe physical (general aches and pains) and psychosocial symptoms (confusion, lowered school or work performance, decreased efficiency, loneliness, anxiety, restlessness, mood swings, and depression), compared to the healthy and non-stressed women., Conclusions: The present study indicates the prevalence of premenstrual symptoms, regardless of severity and number, among college students and suggests that negative subjective perceptions of health and stress may be related to the intensity of premenstrual symptomatology., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Epidermal keratinocyte (KC) differentiation, which involves the process from proliferation to cell death for shedding the outermost layer of skin, is crucial for the barrier function of skin. Therefore, in dermatology, it is important to elucidate the epidermal KC differentiation process to evaluate the symptom level of diseases and skin conditions. Previous dermatological studies used staining or labelling techniques for this purpose, but they have technological limitations for revealing the entire process of epidermal KC differentiation, especially when applied to humans. Here, we demonstrate label-free visualization of three-dimensional (3D) intracellular morphological changes of ex vivo human epidermis during epidermal KC differentiation using stimulated Raman scattering (SRS) microscopy. Specifically, we observed changes in nuclei during the initial enucleation process in which the nucleus is digested prior to flattening. Furthermore, we found holes left behind by improperly digested nuclei in the stratum corneum, suggesting abnormal differentiation. Our findings indicate the great potential of SRS microscopy for discrimination of the degree of epidermal KC differentiation.

Background: Peritoneal dialysis (PD)-associated infection caused by Mycobacterium spp. is rare. Mycobacterium abscessus is one of the most resistant acid-fast bacteria, and treatment is also the most difficult and refractory. Thus, we report a case of PD-associated peritonitis caused by Mycobacterium abscessus that was difficult to treat and led to PD failure., Case Presentation: We recently encountered a 56-year-old man who developed PD-associated infection. We initially suspected exit-site infection (ESI) and tunnel infection (TI) caused by methicillin-resistant coagulase-negative Staphylococcus. However, antibiotic therapy did not provide any significant improvement. Thus, we performed simultaneous removal and reinsertion of a PD catheter at a new exit site. The patient subsequently developed peritonitis and Mycobacterium abscessus was detected in the peritoneal effluent. Thus, the reinserted catheter was removed, hemodialysis was started, and the patient was eventually discharged., Conclusions: In cases of refractory ESI or TI, it is important to consider non-tuberculous mycobacteria as the potentially causative organism. Even if acid-fast bacterial staining is negative or not performed, detection of Gram-negative bacillus may lead to suspicion and early identification of Mycobacterium spp. In PD-associated infection by Mycobacterium abscessus, catheter removal is necessary in many cases. Simultaneous removal and reinsertion of the catheter is not recommended, even in cases of ESI or TI. Reinsertion should only be attempted after complete resolution of peritoneal symptoms. After removal of the catheter, careful follow-up is necessary, paying attention to complications such as wound infection, peritonitis, and ileus. In addition, the selection and treatment period of antibiotics in PD-associated infection by Mycobacterium abscessus remains unclear, and it is an important topic for future discussion.

Detecting the influence of psychological stress is particularly important in prolonged space missions. In this study, we determined potential markers of psychological stress in a confined environment. We examined 23 Japanese subjects staying for 2 weeks in a confined facility at Tsukuba Space Center, measuring salivary, skin, and facial image parameters. Saliva was collected at four points in a single day to detect diurnal variation. Increases in salivary cortisol were detected after waking up on the 4th and 11th days, and at 15:30 on the 1st and in the second half of the stay. Transepidermal water loss (TEWL) and sebum content of the skin were higher compared with outside the facility on the 4th and 1st days respectively. Increased IL-1β in the stripped stratum corneum was observed on the 14th day, and 7 days after leaving. Differences in facial expression symmetry at the time of facial expression changes were observed on 11th and 14th days. Thus, we detected a transition of psychological stress using salivary cortisol profiles and skin physiological parameters. The results also suggested that IL-1β in the stripped stratum corneum and facial expression symmetry are possible novel markers for conveniently detecting psychological stress.

Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of cholesterol biosynthesis in HCC. Inhibition of the mevalonate pathway by statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR), resulted in reduced expression of FoxM1 and increased cell death in human hepatoma cells. Re-exposure of mevalonate, a product of HMGCR, restored these effects. Likewise, knockdown of HMGCR reduced FoxM1 expression, indicating that FoxM1 expression was regulated by the mevalonate pathway in HCC. Mechanistically, protein geranylgeranylation was found to be responsible for FoxM1 expression and geranylgeranylated proteins, including RhoA, Rac1 or Cdc42, were shown to be involved in this process. In surgically resected human HCC tissues, the gene expression of FoxM1 had a positive correlation with that of the mevalonate pathway-related genes, such as HMGCR or sterol regulatory element-binding protein 2 ( SREBP2 ). Furthermore, the gene expression of FoxM1 along with that of HMGCR or SREBP2 defined prognosis of HCC patients, suggesting the clinical significance of the mevalonate-FoxM1 pathway in human HCC. Our data indicate that FoxM1 links the mevalonate pathway to oncogenic signals in HCC. Thus, we propose a novel therapeutic approach to inhibit FoxM1 by targeting the mevalonate pathway for HCC., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objective: This study aimed to evaluate clinically the effect of a novel dentifrice containing three kinds of bactericidal ingredients on periodontal disease., Results: This was a single-arm, prospective clinical study that enrolled patients with periodontitis undergoing supportive periodontal therapy. Periodontal examination, microbiological testing of saliva samples, and evaluation of inflammatory markers (IL-1β, IL-6, IL-8, TNF-α) in gingival crevicular fluid were performed. After 4 weeks of the use of test dentifrice, these parameters were re-evaluated. The use of dentifrice was also subjectively evaluated by clinicians and participants. Among 30 participants, there were significant improvements in the periodontal and microbiological parameters, and the level of interleukin-1β in the gingival crevicular fluid, following the use of the test dentifrice. In clinicians' subjective evaluation of the overall usefulness of the dentifrice, 'mild' and 'moderate' improvement accounted for 83% of the total responses. In the participants' subjective evaluation, the majority indicated their experience of the use as favorable. Within the limitations of this study, it is suggested that the progression of periodontal disease during the supportive periodontal therapy can be prevented by the use of the test dentifrice. Trial registration UMIN Clinical Trials Registry (UMIN-CTR) 000023175. Date of formal registration: July 14, 2016 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr&#95;view.cgi?recptno=R000026716 ).

Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide and has been identified as a risk factor for cirrhosis and hepatocellular carcinoma. However, there is no effective pharmacologic treatment for NAFLD. FABP1 is a liver-specific fatty acid-binding protein (FABP) that plays important roles in intracellular lipid metabolism in the liver. We investigated the effect of repression of FABP1 expression on NAFLD, using adenovirus-mediated silencing of FABP1. FABP1 knockdown in the liver decreased the liver weight and hepatic triglyceride (TG) accumulation. The expression of inflammatory and oxidative stress markers in the liver was also reduced. The level of thiobarbituric acid-reactive substances, a marker of lipid peroxidation, in the liver of FABP1 knockdown mice was significantly decreased. These results suggest that FABP1 reduction in the liver is an effective approach against NAFLD.

Background: This study aimed to evaluate, longitudinally, the outcome of periodontal regenerative therapy using a deproteinized bovine bone mineral (DBBM) in combination with a collagen barrier (CB) for the treatment of intrabony defects., Results: Patients with chronic periodontitis who have completed initial periodontal therapy participated in this study. They had at least one 2- or 3-wall intrabony periodontal defect of ≥3 mm in depth. During surgery, defects were filled with DBBM and covered with CB. Ten patients completed 2.5-year reevaluation. At baseline, mean clinical attachment level (CAL) of the treated site was 8.0 mm and mean probing depth (PD) was 7.5 mm. Mean depth of intrabony component was 4.6 mm. Mean gains in CAL at 6 months and 2.5 years were 2.8 ± 1.0 and 1.4 ± 1.5 mm, respectively, both showing a significant improvement from baseline. CAL gains at 1 and 2.5 years were significantly reduced from that at 6 months. A significant improvement in PD was also noted: mean reductions in PD at 6 months and 2.5 years were 4.0 ± 0.8 and 3.2 ± 0.8 mm, respectively., Conclusions: The combination therapy using DBBM and CB yielded statistically significant effects such as CAL gain and PD reduction, up to 2.5 years in the treatment of intrabony defects. However, the trend for decrease in CAL gain over time calls for the need for careful maintenance care.

We report a case of gingival recession in the mandibular incisor region requiring a connective tissue graft. The patient was a 17-year-old girl who visited the Tokyo Dental College Chiba Hospital in 2014 with the chief complaint of gingival recession in the lower incisor region. She had received orthodontic treatment for 5 years and noticed the gingival recession on completion of active orthodontic treatment in 2013. Gingival recession in tooth #31 extended 3 mm beyond the muco-gingival junction (MGJ) and was clinically diagnosed as Miller Class II recession; probing depth was 6 mm. Following initial periodontal therapy, a connective tissue graft procedure was implemented. The connective tissue was harvested from the left palate. Healing was uneventful, and the grafted site showed a favorable outcome at 6 months postoperatively. We are continuing to carefully monitor the condition of periodontal tissue.

A simple and rapid in situ method for the determination of hydrazine based on the concentration of aldazine compound formed by the reaction of hydrazine with p-dimethylaminobenzaldehyde was developed. This method was based on solid-phase extraction using a Sep-Pak C18 cartridge, followed by the quantification of hydrazine using a spectrophotometric method. To a sample solution of environmental water, p-dimethylaminobenzaldehyde solution was added to form aldazine by the reaction with hydrazine. The solution was passed through a Sep-Pak C18 cartridge for the adsorption of aldazine. In the laboratory, the aldazine adsorbed on the Sep-Pak C18 cartridge was eluted by passing a hydrochloric acid-ethanol (1:10) solution through the cartridge, and the color intensity of the solution was measured at 457 nm. The limit of detection for the new method was 0.2 mgN L -1 of hydrazine. The determination of hydrazine in solution was not influenced even by hydrogen sulfide and organic matter. This method was then applied to the brackish water of Lake Nakaumi in the eastern area of Shimane Prefecture, Japan. This method was used to determine hydrazine in freshwater, seawater and wastwater.

We developed a method for quantifying trace NH 2 OH in brackish- and sea-water samples. Previously reported methods applicable to fresh water cannot be applied to such samples. We determined that interference in seawater owing to the bromide ion can be removed by the addition of phenol. In our procedure, phenol and hypochlorite solutions were added to a sample solution to oxidize NH 2 OH to N 2 O. N 2 O in the sample was then quantified by headspace analysis. The method is not affected by the salt content or ammonia, nitrate, or nitrite at concentrations of 300 μgN L -1 or less. It has a limit of detection of 0.2 μgN L -1 , and can quantify NH 2 OH in natural water samples with a wide range of salinity. It was applied to samples from Lake Nakaumi, a brackish lake located in the eastern part of Shimane Prefecture, Japan.

Purpose: To determine the structural changes in the choroid after half-dose photodynamic therapy (hPDT) in eyes with chronic central serous chorioretinopathy (CSC)., Methods: This was a retrospective interventional study of 29 eyes of 29 patients who underwent hPDT for chronic CSC with serous retinal detachment (SRD) and were followed for ≥3 months. Enhanced depth imaging optical coherence tomographic (EDI-OCT) images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), the cross sectional subfoveal choroidal area, the hyporeflective and hyperreflective areas of the inner, outer, and whole choroid were determined at the baseline, and at 1, 3, and 12 months after the hPDT., Results: The SRDs were resolved in 26 (89.7%) eyes at 3 months after the hPDT. The mean CCT (P = 0.001), the total choroidal area (P = 0.001), and the hypo-reflective area (P = 0.003) of the whole choroid were significantly decreased from the baseline at 3 months. The hyperreflective area of whole choroid was not significantly changed during the study period (P = 0.083). The hyperreflective but not the hyporeflective area of the inner choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyporeflective but not the hyperreflective area of the outer choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively)., Conclusions: The hyperreflective area of the inner choroid and hyporeflective area of the outer choroid were significantly decreased after hPDT for chronic CSC. Because the hyperreflective and hyporeflective area correspond to the choroidal stroma and vessels, respectively, the decreased CCT and subfoveal choroidal area after hPDT may be attributed to a decrease in the exudative changes in the inner choroidal stroma and the reduction of the dilation of the outer choroidal vessels., Competing Interests: The authors have declared that no competing interests exist.

Visualization of epidermal cells is important because the differentiation patterns of keratinocytes (KCs) are considered to be related to the functions and condition of skin. Optical microscopy has been widely used to investigate epidermal cells, but its applicability is still limited because of the need for sample fixation and staining. Here, we report our staining-free observation of epidermal cells in both tissue and culture by stimulated Raman scattering (SRS) microscopy that provides molecular vibrational contrast. SRS allowed us to observe a variety of cellular morphologies in skin tissue, including ladder-like structures in the spinous layer, enucleation of KCs in the granular layer, and three-dimensional cell column structures in the stratum corneum. We noticed that some cells in the spinous layer had a brighter signal in the cytoplasm than KCs. To examine the relevance of the observation of epidermal layers, we also observed cultured epidermal cells, including KCs at various differentiation stages, melanocytes, and Langerhans cell-like cells. Their SRS images also demonstrated various morphologies, suggesting that the morphological differences observed in tissue corresponded to the cell lineage. These results indicate the possible application of SRS microscopy to dermatological investigation of cell lineages and types in the epidermis by cellular-level analysis.

A method for determination of hydrogen sulfide in microsamples (200 μL) was developed by modifying the methylene blue method. Samples were collected using a micropipette and were combined with sulfide coloring reagent and 5 mL of 0.1 M HCl in test tubes. Absorbance of the solution was measured spectrophotometrically at 667 nm. This modified method did not require any special labware or technique, and can be used in a variety of research fields.

Background: We report changes of choroidal structure determined by binarization of enhanced depth imaging optical coherence tomographic (EDI-OCT) images after treatment for primary intraocular lymphoma (PIOL)., Methods: Five eyes of four patients with PIOL were examined by EDI-OCT before and 6 months after intravitreal methotrexate injections. In addition, 15 eyes of 15 normal individuals controlled by age and refractive error were examined by EDI-OCT. Binarization of the EDI-OCT images was performed using publicly accessible software (ImageJ). The examined area of the subfoveal choroid was 1,500 μm wide, and the dark areas that represented the luminal areas were traced by the Niblack method. Wilcoxon signed rank test was used to determine the significance of changes in the subfoveal choroidal thickness, interstitial area, and luminal area. Mann-Whitney U test was used to compare the parameters in the eyes with pretreatment PIOL and normal control eyes., Results: The subfoveal choroidal thickness was significantly decreased after treatment (P = 0.0431). In the binarized images, the interstitial area was significantly decreased after treatment (P = 0.0431), while the luminal area was not significantly changed (P = 0.8927). After delayed onset of PIOL, increased interstitial area, thickened choroid and unchanged luminal area were observed in one eye. The interstitial area and choroidal thickness were significantly increased in the eyes with pretreatment PIOL compared with the normal control eyes (P = 0.0207, P = 0.0495, respectively), while the luminal area was not significantly different (P = 0.2752)., Conclusions: After treatment for PIOL, the EDI-OCT images showed a thinner choroid, and binarization of the EDI-OCT images showed significantly decreased interstitial areas compared with the luminal areas. The binarized EDI-OCT images can provide useful information on choroidal structure in eyes with PIOL, and combining these images with intraocular interleukin levels or fundus autofluorescence images should provide valuable information for determining the PIOL activity.

Grb2-associated binder 1 (Gab1) adaptor protein amplifies signals downstream of a broad range of growth factors/receptor tyrosine kinases. Although these signals are implicated in liver fibrogenesis, the role of Gab1 remains unclear. To elucidate the role of Gab1, liver fibrosis was examined in hepatocyte-specific Gab1-conditional knockout (Gab1CKO) mice upon bile duct ligation (BDL). Gab1CKO mice developed exacerbated liver fibrosis with activation of hepatic myofibroblasts after BDL compared with control mice. The antifibrotic role of hepatocyte Gab1 was further confirmed by another well-established mouse model of liver fibrosis using chronic injections of carbon tetrachloride. After BDL, Gab1CKO mice also displayed exacerbated liver injury, decreased hepatocyte proliferation, and enhanced liver inflammation. Furthermore, cDNA microarray analysis was used to investigate the potential molecular mechanisms of the Gab1-mediated signal in liver fibrosis, and the fibrosis-promoting factor chemokine (C-C motif) ligand 5 (Ccl5) was identified as upregulated in the livers of Gab1CKO mice following BDL. Interestingly, in vitro studies using primary hepatocytes isolated from control and Gab1CKO mice revealed that the loss of Gab1 resulted in increased hepatocyte CCL5 synthesis upon lipopolysaccharide stimulation. Finally, pharmacological antagonism of CCL5 reduced BDL-induced liver fibrosis in Gab1CKO mice. In conclusion, our results demonstrate that hepatocyte Gab1 is required for liver fibrosis and that hepatocyte CCL5 could be an important contributor to this process. Thus, we present a novel antifibrotic function of hepatocyte Gab1 in liver fibrogenesis., (Copyright © 2015 the American Physiological Society.)