Search

The present study investigated whether a single pretreatment with clofibric acid suppresses liver injury in rats after CCl 4 intoxication. Rats received a single pretreatment with clofibric acid (100 mg/kg, i.p.) 1 h prior to a CCl 4 (1 mL/kg, p.o.) challenge, and were euthanized 24 h after the CCl 4 administration. A single pretreatment with clofibric acid effectively suppressed increases in the serum aminotransferase activities and the severity of necrosis following the CCl 4 challenge, whereas the pretreatment did not protect against CCl 4 -induced fatty liver. The clofibric acid pretreatment did not affect blood concentrations of CCl 4 in the early stage after CCl 4 dosing, or the level of the CCl 4 reaching the liver 1 h after the CCl 4 challenge. Moreover, the clofibric acid pretreatment did not affect the intensity of the covalent binding of the [ 14 C]CCl 4 metabolite to microsomal proteins and lipids. The clofibric acid pretreatment did not alter microsomal cytochrome P450 2E1 activity. Based on these results, we conclude that protection against CCl 4 -induced hepatocellular necrosis by a clofibric acid pretreatment does not require its repeated administration, and that a single and brief pre-exposure to clofibric acid prior to CCl 4 dosing markedly suppresses necrosis without affecting the development and progression of steatosis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Although a "no-touch isolation" technique is used in colorectal cancer surgery to reduce the risk of metastatic induction, endoscopic resection (ER) prior to surgery may work against this aim. This study evaluated the effects of initial ER on short- and long-term outcomes in T1 colorectal cancer., Methods: This retrospective cohort study enrolled patients with pathological T1 colorectal cancer who underwent colorectal surgical resection at a Japanese tertiary cancer center between 2002 and 2012. A total of 548 eligible patients were divided into two groups: patients initially treated using surgical resection with lymph node dissection (LND) (primary group, n = 304) and patients treated using initial ER and additional surgical resection with LND (secondary group, n = 244). The inverse probability of treatment weighting (IPTW) method based on propensity score was used to compare postoperative complications and long-term recurrence., Results: The incidence of postoperative complications with Clavien-Dindo classification grade ≥ II was 10.9% and 7.4% in the primary and secondary groups, respectively (p = 0.16). Multivariate analysis with a logistic proportional hazard regression model using IPTW revealed no significant differences in postoperative complications between the two groups (p = 0.79). During a median follow-up after surgery of 61.4 months, recurrence was observed in 3 (1.0%) and 8 (3.3%) patients, respectively (p = 0.06). Multivariate analysis with a Cox proportional hazard regression model using IPTW revealed no significant differences in recurrence between the two groups (p = 0.07)., Conclusion: Our results suggest no significant adverse effects of initial ER prior to surgery on surgical complications and long-term recurrence in T1 colorectal cancer.

The aim of the study was to investigate the effect of chemo-radiation on the genetic and immunological status of rectal cancer patients who were treated with preoperative chemoradiotherapy (CRT). The expression of immune response-associated genes was compared between rectal cancer patients treated (n = 9) and not-treated (n = 10) with preoperative CRT using volcano plot analysis. Apoptosis and epithelial-to-mesenchymal transition (EMT) marker genes were analysed by quantitative PCR (qPCR). Other markers associated with the tumor microenvironment (TME), such as tumor-infiltrating lymphocytes (TIL) and immune checkpoint molecules, were investigated using immunohistochemistry (IHC). The clinical responses of preoperative CRT for 9 rectal cancer patients were all rated as stable disease, while the pathological tumor regression score (TRG) revealed 6 cases of grade2 and 3 cases of grade1. According to the genetic signature of colon cancers, treated tumors belonged to consensus molecular subtype (CMS)4, while not-treated tumors had signatures of CMS2 or 3. CRT-treated tumors showed significant upregulation of EMT-associated genes, such as CDH2, TGF-beta and FGF, and cancer stem cell-associated genes. Additionally, qPCR and IHC demonstrated a suppressive immunological status derived from the upregulation of inflammatory cytokines (IL-6, IL-10 and TGF-beta) and immune checkpoint genes (B7-H3 and B7-H5) and from M2-type macrophage accumulation in the tumor. The induction of EMT and immune-suppressive status in the tumor after strong CRT treatment urges the development of a novel combined therapy that restores immune-suppression and inhibits EMT, ultimately leading to distant metastasis control., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: There are few reports on the relationship between facial expression formation and mass of the muscle responsible for facial expression. We analyzed the facial expression using facial action coding system (FACS) and examined the muscle mass and characteristics of the facial expression muscles using multi-detector row computed tomography (MDCT) and magnetic resonance imaging (MRI). Moreover, the relation between these was statistically evaluated., Materials and Methods: Ten healthy women in their 40s (43.4 ± 3.0 years, 40-49) were enrolled. The expressive faces were analyzed by facial expression analysis software based on the FACS. The muscle mass and characteristics of the facial expression muscles were investigated using MDCT/MRI. The correlation between an integrated expression intensity value (IEIV) for FACS of the widest possible grin and muscle mass was analyzed. The mean values between the two categorized groups (G-1 and G-2) based on fat infiltration into the muscle were compared., Results: A positive correlation is found between the IEIV and the muscle mass. The IEIV of G-1 is significantly larger than the corresponding value of G-2. Hence, the results indicated that the subjects with high IEIV and expressive face had thicker facial expression muscles and little fat infiltration into the muscles., Conclusion: Our objective imaging diagnostic study using FACS, MDCT, and MRI corroborated the anti-aging medical science about the facial expression muscles related to youthful facial appearance. The results of this research could contribute to the elucidation of the mechanisms involved in the facial aging process and to the development of cosmetology., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Metabolomics is useful for analyzing the nutrients necessary for cancer progression, as the proliferation is regulated by available nutrients. We studied the metabolomic profile of gastric cancer (GC) tissue to elucidate the associations between metabolism and recurrence., Methods: Cancer and adjacent non-cancerous tissues were obtained in a pair-wise manner from 140 patients with GC who underwent gastrectomy. Frozen tissues were homogenized and analyzed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Metabolites were further assessed based on the presence or absence of recurrence., Results: Ninety-three metabolites were quantified. In cancer tissues, the lactate level was significantly higher and the adenylate energy charge was lower than in non-cancerous tissues. The Asp, β-Ala, GDP, and Gly levels were significantly lower in patients with recurrence than in those without. Based on ROC analyses to determine the cut-off values of the four metabolites, patients were categorized into groups at high risk and low risk of peritoneal recurrence. Logistic regression and Cox proportional hazard analyses identified β-Ala as an independent predictor of peritoneal recurrence (hazard ratio [HR] 5.21 [95% confidence interval 1.07-35.89], p = 0.029) and an independent prognostic factor for the overall survival (HR 3.44 [95% CI 1.65-7.14], p < 0.001)., Conclusions: The metabolomic profiles of cancer tissues differed from those of non-cancerous tissues. In addition, four metabolites were significantly associated with recurrence in GC. β-Ala was both a significant predictor of peritoneal recurrence and a prognostic factor.

Health risk behaviors practiced during adolescence often persist into adulthood and contribute to the leading causes of morbidity and mortality in the United States. Youth health behavior data at the national, state, territorial, tribal, and local levels help monitor the effectiveness of public health interventions designed to promote adolescent health. The Youth Risk Behavior Surveillance System (YRBSS) is the largest public health surveillance system in the United States, monitoring a broad range of health-related behaviors among high school students. YRBSS includes a nationally representative Youth Risk Behavior Survey (YRBS) and separate state, local school district, territorial, and tribal school-based YRBSs. This overview report describes the surveillance system and the 2019 survey methodology, including sampling, data collection procedures, response rates, data processing, weighting, and analyses presented in this MMWR Supplement. A 2019 YRBS participation map, survey response rates, and student demographic characteristics are included. In 2019, a total of 78 YRBSs were administered to high school student populations across the United States (national and 44 states, 28 local school districts, three territories, and two tribal governments), the greatest number of participating sites with representative data since the surveillance system was established in 1991. The nine reports in this MMWR Supplement are based on national YRBS data collected during August 2018-June 2019. A full description of 2019 YRBS results and downloadable data are available (https://www.cdc.gov/healthyyouth/data/yrbs/index.htm).Efforts to improve YRBSS and related data are ongoing and include updating reliability testing for the national questionnaire, transitioning to electronic survey administration (e.g., pilot testing for a tablet platform), and exploring innovative analytic methods to stratify data by school-level socioeconomic status and geographic location. Stakeholders and public health practitioners can use YRBS data (comparable across national, state, tribal, territorial, and local jurisdictions) to estimate the prevalence of health-related behaviors among different student groups, identify student risk behaviors, monitor health behavior trends, guide public health interventions, and track progress toward national health objectives., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The roles of cancer-associated fibroblasts (CAFs) have been studied in the tumor progression, and CAFs are expected to become the new targets for cancer pharmacotherapies. CAFs contribute to tumor cell survival and proliferation, tumor angiogenesis, immune suppression, tumor inflammation, tumor cell invasion and metastasis, and extracellular matrix remodeling. However, detailed mechanisms of how CAFs function in the living system remain unclear. CAFs include α-smooth muscle actin, expressing activated fibroblasts similar to myofibroblasts, and are highly capable of producing collagen. Several reports have demonstrated the contributions of extracellular-signal-regulated kinase 5 (ERK5) in fibroblasts to the fibrotic processes; however, the roles of CAF-derived ERK5 remain unclear. To investigate the roles of CAF-derived ERK5 in the tumor progression, we created mice lacking the ERK5 gene specifically in fibroblasts. Colon-26 mouse colon cancer cells were implanted into the mice subcutaneously, and the histological analyses of the tumor tissue were performed after 2 weeks. Immunofluorescence analyses showed that recipient-derived fibroblasts existed within the tumor tissue. The present study demonstrated that fibroblast-specific ERK5 deficiency exacerbated tumor progression and it was accompanied with thicker tumor vessel formation and the increase in the number of activated fibroblasts. We combined the results of The Cancer Genome Atlas (TCGA) database analysis with our animal studies, and indicated that regulating ERK5 activity in CAFs or CAF invasion into the tumor tissue can be important strategies for the development of new targets in cancer pharmacotherapies.

Background: Immune checkpoint inhibitors(nivolumab)have been recommended as third-line chemotherapy for advanced gastric cancer(AGC)according to the Guidelines of Gastric Cancer(5th edition). Therefore, they have been used in daily clinical practice. On the other hand, the neutrophil-lymphocyte ratio(NLR)has been reported to be associated with the prognosis of cancer patients., Methods: Twenty patients treated with nivolumab for AGC between January 2018 and November 2019 were retrospectively examined., Results: Median age of the 20 patients(18 males, 2 females)was 70 years(55- 84 years). Nivolumab was administered as second-, third-, fourth-, and fifth-line therapy in 1, 11, 7, and 1 case, respectively. The best tumor response evaluation was observed in PR 1, SD 7 and PD 10 cases. Median overall survival(OS)was 10 months, and median progression-free survival(PFS)was 3 months. No serious adverse events occurred. Compared to the NLR>2.0 group, OS significantly prolonged(2.2 months vs 21.9 months)and PFS tended to prolong(1.4 months vs 6.2 months)in the NLR≤2.0 group., Conclusion: NLR may be an effective prognostic factor in patients with AGC receiving nivolumab treatment.

Background/objective: Paraaortic lymph node (PALN) metastasis influences treatment strategy for colorectal cancer. The aims of this study were to elucidate the diagnostic value of computed tomography (CT) and positron emission tomography (PET) for PALN metastasis from left-sided colorectal cancer., Methods: A total of 108 patients who underwent radical surgery including PALN dissection were included. Size and morphology of PALN were evaluated using CT, and presence of higher FDG uptake was evaluated using PET. Findings of CT and PET were compared with pathological status., Results: The largest major axis ≥11 mm and heterogeneous internal density were predictive factors on multivariate analysis. Eighty five percent of the PALNs ≥11 mm with heterogeneous internal density were pathologically metastatic, whereas 94.1% without them were not metastatic. PET had an accuracy, sensitivity, and specificity of 85.7%, 66.7%, and 94.1%, respectively. In patients with PALNs <11 mm without heterogeneous internal density, the accuracy and specificity of PET improved to 93.8% and 96.6%, respectively. Conversely, in patients with some predictive CT findings, although the positive predictive value of PET increased from 83.3% to 88.9%, the accuracy and sensitivity remained at 70.6% and 66.7%, respectively, and 50.0% were false-negatives., Conclusion: CT had high NPV and relatively high PPV. PET had high specificity but low sensitivity. The addition of PET could be useful to confirm no PALN metastasis in patients with no predictive CT findings. Conversely, the improvement of diagnostic ability was limited in patients with some predictive CT findings., (Copyright © 2019. Published by Elsevier Taiwan LLC.)

A 78-year-old man with a history of surgical resection for ameloblastoma 31 years earlier visited our hospital for prolonged cough. Chest computed tomography showed multiple nodules in both lungs. Although there was no local recurrence in the mandible, the specimen taken from a transbronchoscopic bronchial biopsy showed recurrent ameloblastoma. Despite receiving no treatment, the disease in our patient remained clinically stable for 8.4 years. Chest physicians should be aware that pulmonary malignant ameloblastoma can first relapse several decades after curative surgery. In addition, pulmonary malignant ameloblastoma without local recurrence may be associated with a good prognosis.

Over the past two decades, the number of studies on work engagement has increased rapidly. Work engagement refers to a positive, affective-motivational state of high energy combined with high levels of dedication and a strong focus on work, leading to various work-related outcomes, including higher work performance. Several studies have indicated that training or coaching may increase work engagement, but other studies have shown contradicting results. These inconsistencies may be due to the indirectness between training/coaching and work engagement. Therefore, we investigated the relationship between training and brain structure as well as between brain structure and work engagement in cognitively normal participants. Brain structure was assessed using neuroimaging-derived measures, including the gray-matter brain healthcare quotient (GM-BHQ) and the fractional-anisotropy brain healthcare quotient (FA-BHQ), which are approved as the international standard (H.861.1) by ITU-T. Work engagement was assessed using the Utrecht Work Engagement Scale. To validate and enrich the analysis, we employed another two representative questionnaires, which are known to be close to but different from work engagement: The Social interaction Anxiety Scale and the Maslach Burnout Inventory-General Survey to gauge the levels of human relation ineffectiveness and burnout. The latter scale is subdivided into three variables including "Exhaustion," "Cynicism," and "Professional Efficacy." The results of the present study indicate that training is associated with an increase of FA-BHQ scores, and that an increase of the FA-BHQ scores is associated with an increase in Work Engagement and a decrease in Cynicism. On the other hand, the training with coaching was associated with a decrease in Interaction Anxiety. However, no correlation was observed for training with Work Engagement or the subscales of Burnout. Likewise, no correlation was observed for FA-BHQ with Exhaustion, Professional Efficacy, and Interaction Anxiety. The results of the current research provide the possibility to use brain information to evaluate training effectiveness from the viewpoint of neuroscience.

As the population ages worldwide, the prevalence of cognitive disorders including mild cognitive impairment (MCI) is increasing. MCI appears in 10-20% of adults aged 65 years and older and is generally referred to as an intermediate stage between normal cognitive aging and dementia. To develop timely prevention and early treatment strategies by identifying biological factors, we investigated the relationship between dietary consumption of fish, brain structure, and MCI in cognitively normal subjects. The brain structure was assessed using neuroimaging-derived measures including the "gray-matter brain healthcare quotient (GM-BHQ)" and "fractional-anisotropy brain healthcare quotient (FA-BHQ)," which are approved as the international standard (H.861.1) by the International Telecommunication Union Telecommunication Standardization Sector. Dietary consumption of fish was calculated using the brief self-administered diet history questionnaire (BDHQ), and MCI was assessed using the Memory Performance Index (MPI) of MCI screening method (MCI Screen). This study showed that fish intake was positively associated with both FA-BHQ and MPI, and FA-BHQ was more strongly associated with MPI than fish intake. Our findings are in line with those in previous studies, but our study further indicates that the condition of the whole brain integrity measured by the FA-BHQ may mediate the relationship between fish intake and MCI prevention in healthy people. In other words, FA-BHQ may be used to identify people at high risk of MCI to provide the appropriate intervention., (Copyright © 2020 Kokubun, Nemoto and Yamakawa.)

Appropriately handling and switching exploration of novel knowledge and exploitation of existing knowledge is a fundamental element of genuine innovation in society. Moreover, a mounting number of studies have suggested that such "ambidexterity" is associated not only with organizational performance but also with the human brain. Among these reports, however, there have not been any definitive MRI-based parameters that objectively and easily evaluate such ambidexterity. Therefore, an MRI-based index derived from gray matter volume, called the gray-matter brain healthcare quotient (GM-BHQ), was used to measure the association between ambidexterity and the entire human brain. For this purpose, 200 healthy adults were recruited as subjects to undergo structural T1-weighted imaging and to answer multiple psychological questionnaires. Ambidexterity was evaluated using two scales: the Curiosity and Exploration Inventory II and the Short Grit Scale, as exploration-exploitation indicators of curiosity and grit, respectively. Additionally, to enrich the understanding of these associations, three additional positive thinking scales were used-the General Self-Efficacy Scale, the Rosenberg Self-Esteem Scale, and the Life Orientation Test-to evaluate self-efficacy, self-esteem, and optimism, respectively. The authors discovered the GM-BHQ was weakly associated with curiosity, grit, and self-efficacy individually after controlling for age and sex. Furthermore, the GM-BHQ was directly associated with curiosity but indirectly associated with grit in the path model. However, no significant association was found between the GM-BHQ and the other outcome indicators (i.e., self-esteem and optimism). These results suggest that brain health is weakly associated with ambidexterity evaluated using psychological tests.

Absorption enhancement based on interaction between the localized surface plasmon (LSP) and molecular exciton is one of the most important phenomena for the development of high-performance solar devices. In this study, hybrids of plasmonic metal nanoparticles and dye molecules have been developed, which exhibit enhanced absorption at precisely tuned wavelengths in a visible region. The hybrids consist of a porphyrin derivative, which has four absorption peaks (Q-bands) in a range of 500-700 nm, and triangular silver nanoprisms (AgPRs), which are developed by us to exhibit precisely tuned LSP resonance wavelengths. Absorption enhancement over the whole Q-band range is induced by the combined use of three kinds of AgPRs of different aspect ratios. Furthermore, the quantitative evaluation of absorption enhancement based on the LSP-based fluorescence enhancement phenomenon has demonstrated that efficient absorption enhancement can be effected at multiple wavelengths.

Clinical studies have demonstrated that transtibial pullout repair led to favorable midterm outcomes in patients with medial meniscus posterior root tears (MMPRTs) although medial meniscal extrusion (MME) continued to be present. It has been unclear whether these residual postoperative MMEs existed after the pullout repair or had progressed at the very short-term evaluation after surgery. We sought to determine which characteristics of patients with MMPRTs influence the incidence of postoperative MME. The cases of 23 patients whose date of injury was known were analyzed. All patients underwent MMPRT pullout fixation. Preoperative and 3-month postoperative magnetic resonance imaging (MRI) examinations were performed. MME was retrospectively assessed on the mid-coronal plane of MRI scans. The preoperative and postoperative MME values were 4.2±1.2 mm and 4.3±1.5 mm, respectively (p=0.559). Pullout repair surgery was performed significantly earlier after the MMPRT-specific injury in patients whose postoperative MME improved compared to the patients whose MME did not improve (p<0.001). Our findings demonstrated that an early transtibial pullout repair of an MMPRT was more effective in reducing MME than a late repair. Surgeons should not miss the optimal timing for the pullout repair of an MMPRT, considering the period from the injury and the preoperative MME., Competing Interests: No potential conflict of interest relevant to this article was reported.

Aim: Neurological disorders are a major public health issue worldwide and are often associated with structural changes in the brain. We have previously demonstrated that iso-α-acids (IAAs), the hop-derived bitter components in beer, improve memory impairment in aged and Alzheimer's disease mouse models. In this study, we evaluated the effects of IAA intake on the brain structure in healthy middle-aged to older adults. This study was conducted under the Impulsing Paradigm Change through Disruptive Technologies Program (ImPACT) study launched by the Cabinet office of Japan., Method: This study employed an open-labeled, single-arm, before and after design. Healthy middle-aged to older adults consumed a beverage containing IAAs (3 mg/190 mL) for 4 weeks.Recently developed magnetic resonance imaging-based brain health indicators were used to evaluate the following brain conditions: the Brain Healthcare Quotient (BHQ) based on gray matter volume (GM-BHQ) and white matter fractional anisotropy (FA-BHQ)., Results: In total, 25 subjects were recruited, and GM-BHQ and FA-BHQ were measured before and after intervention. In all subjects, no significant differences in GM-BHQ and FA-BHQ were observed. In subjects aged ≥ 60 years (mean 54.5; standard deviation 3.9) (n = 8), GM-BHQ was significantly increased 4 weeks after intervention compared with that before intervention., Conclusion: Intake of beverages containing IAAs might affect brain aging, particularly in healthy older adults, which may prevent the development of neurological disorders. Future studies employing more robust designs can elucidate the effects of IAAs on GM-BHQ and cognitive functions., (© 2019. Research Laboratories for Health Science & Food Technologies, Kirin Company Limited. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Background: Plate fixation is one of the standard surgical treatments for distal femoral fractures. There are few reports on the relationship between the screw position and bone union when fixing by the bridging plate (relative stability) method., Methods: This retrospective study included 71 distal femoral fractures of 70 patients who were treated with the locking compression plate for distal femur (DePuy Synthes Co., Ltd, New Brunswick, CA, USA). The following measurements were evaluated and analyzed: (1) bone union rate, (2) bridge span length (distance between screws across the fracture), (3) plate span ratio (plate length/bone fracture length), (4) number of empty holes (number of screw holes not inserted around the fracture), and (5) medial fracture distance (bone fracture distance on the medial side of the distal femur). Patient demographics (age), comorbidities (smoking, diabetes, chronic steroid use, dialysis), and injury characteristics (AO type, open fracture, infection) were obtained for all participants. Univariate analysis was performed on them., Results: Of 71 fractures, 26 fractures were simple fractures, 45 fractures were comminuted fractures, and 7 fractures resulted in non-union. Non-union rate was significantly higher in comminuted fractures with bone medial fracture distance exceeding 5 mm. Non-union was founded in simple fractures with bone medial fracture distance exceeding 2 mm, but not significant (p = 0.06). In cases with simple fractures, one non-union case had one empty hole and one non-union case had four empty holes, whereas in cases with comminuted fractures, five non-union cases had two more empty holes., Conclusions: We concluded that bone fragment distance between fracture fragments is more important than bridge span length of the fracture site and the number of empty holes. Smoking and medial fracture distance are prognostic risk factors of nonunion in distal femoral fractures treated with LCP as bridging plate.

To better understand the risk factors and optimal therapeutic strategies of cerebral white matter hyperintensity (WMH), we examined a large population of adults with and without various vascular risk factors (VRFs) or vascular risk conditions (VRCs), such as hypertension (HT), diabetes mellitus (DM), and dyslipidemia (DLP), including the comorbidities. We assessed two participant groups having no medical history of stroke or dementia that underwent brain checkup using magnetic resonance imaging (MRI): 5541 participants (2760 men, 2781 women) without VRCs and 1969 participants (1169 men, 800 women) who had received drug treatments for VRCs and the combination of comorbidities. For data analysis, we constructed WMH-brain healthcare quotient (WMH-BHQ) based on the percentile rank of WMH volume. This metric has an inverse relation to WMH. Multiple linear regression analysis of 5541 participants without VRCs revealed that age, systolic blood pressure (SBP), Brinkman index (BI), and female sex were significant factors lowering WMH-BHQ, whereas body mass index (BMI), male sex, fasting blood sugar, and triglyceride levels were increasing factors. The Kruskal-Wallis test and Dunn tests showed that WMH-BHQs significantly increased or decreased with BMI or SBP and with BI classification, respectively. Regarding the impact of impaired fasting glucose and abnormal lipid metabolism, there were almost no significant relationships. For 1969 participants who had HT, DM, and DLP, as well as their comorbidities, we found that DLP played a substantial role in increasing WMH-BHQ for some comorbidities, whereas the presence of HT and DM alone tended to decrease it. Cerebral WMH can be used as a healthcare quotient for quantitatively evaluating VRFs and VRCs and their comorbidities.

Diet and nutrition play a key role in the promotion and maintenance of good health, as they are important modifiable risk factors for chronic diseases. A growing number of studies indicate that optimal food intake and optimal physical activity are essential for the gray matter volume (GMV). However, the precise definition of "optimal" is extremely difficult and a topic of several studies. In the current research, we used the magnetic resonance imaging (MRI)-based normalized GMV (nGMV), for monitoring brain conditions based on GMV. By analyzing the relationship between the nGMV of 171 healthy Japanese participants and the results of a brief self-administered diet history questionnaire (BDHQ), we found that while nGMV was high in the participants with high intake of milk and yogurt, it was low in the participants of "alcohol and animal foods dietary pattern" (high intake of alcohol and animal foods). On the other hand, another food pattern "vegetable-animal balanced dietary pattern" (balanced intake of vegetables and animal foods) has no significant association with nGMV, indicating that although a diet consisting of a good balance of vegetables and animal foods may not lead to brain atrophy, it might not positively contribute to a higher nGMV. nGMV, as an objective measure of the association between food intake and the brain, might provide useful information for "optimal" food intake for GMV., (Copyright © 2019 Kokubun and Yamakawa.)

Here, we investigated the clinicopathological and mutation profiles of colorectal cancer (CRC) with POLE mutations. Whole-exome sequencing was performed in 910 surgically resected primary CRCs. Tumors exceeding 500 counts of nonsynonymous single nucleotide variants (SNVs) were classified as hypermutators, whereas the remaining were classified as nonhypermutators. The hypermutators were subdivided into 2 groups. CRCs harboring more than 20% C-to-A and less than 3% C-to-G transversions were classified as POLE category tumors, whereas the remaining were classified as common-hypermutators. Gene expression profiling (GEP) analysis was performed in 892 (98.0%) tumors. Fifty-seven (6.3%) and 10 (1.1%) tumors were classified common-hypermutators and POLE category tumors, respectively. POLE category tumors harbored a significantly higher SNV count than common-hypermutators, and all POLE category tumors were associated with exonuclease domain mutations, such as P286R, F367C, V411L, and S297Y, in the POLE gene. Patients with POLE category tumors were significantly younger than those with nonhypermutators and common-hypermutators. All POLE mutations in the early-onset (age of onset ≤50 years old) POLE category (7 tumors) were P286R mutations. GEP analysis revealed that PD-L1 and PD-1 gene expression levels were significantly increased in both common-hypermutators and POLE category tumors compared with those in nonhypermutators. CD8A expression was significantly upregulated in POLE category tumors compared with that in nonhypermutators. Thus, we concluded that CRCs with POLE proofreading deficiency had characteristics distinct from those of other CRCs. Analysis of POLE proofreading deficiency may be clinically significant for personalized management of CRCs., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Spinopelvic fixation provides a strong fixation for unstable pelvic ring fractures. However, the technique is usually performed with the patient in the prone position, with the applied weight on the anterior superior iliac crests aggravating fracture displacement. We developed a novel approach for minimally invasive percutaneous spinopelvic fixation that is performed with the patient in a lateral (side lying) position. We describe the application of our technique for the treatment of a bilateral pelvic ring and acetabulum fracture in a 79-year-old woman injured in a traffic accident. Initial posterior fixation was performed with the patient in the left-side lying position, using bilateral pedicle screws at L3 and L4 and a left sacral-alar iliac screw and 2 right iliac screws inserted under navigation. The lateral and cranial displacement of the right pelvic ring was reduced percutaneously. One week after this initial surgery, we proceeded with an open anterior reduction and internal fixation of the left pelvic ring and acetabulum fracture. The postoperative course was uneventful and clinical outcomes were satisfactory. Reduction of a pelvic ring fracture in a lateral position, with subsequent spinopelvic fixation, is a reasonable option for the treatment of an unstable pelvic ring fracture.

Classical- (C-) and atypical L-type bovine spongiform encephalopathy (BSE) prions cause different pathological phenotypes in cattle brains, and the disease-associated forms of each prion protein (PrPSc) has a dissimilar biochemical signature. Bovine C-BSE prions are the causative agent of variant Creutzfeldt-Jakob disease. To date, human infection with L-BSE prions has not been reported, but they can be transmitted experimentally from cows to cynomolgus monkeys (Macaca fascicularis), a non-human primate model. When transmitted to monkeys, C- and L-BSE prions induce different pathological phenotypes in the brain. However, when isolated from infected brains, the two prion proteins (PrPSc) have similar biochemical signatures (i.e., electrophoretic mobility, glycoforms, and resistance to proteinase K). Such similarities suggest the possibility that L-BSE prions alter their virulence to that of C-BSE prions during propagation in monkeys. To clarify this possibility, we conducted bioassays using inbred mice. C-BSE prions with or without propagation in monkeys were pathogenic to mice, and exhibited comparable incubation periods in secondary passage in mice. By contrast, L-BSE prions, either with or without propagation in monkeys, did not cause the disease in mice, indicating that the pathogenicity of L-BSE prions does not converge towards a C-BSE prion type in this primate model. These results suggest that, although C- and L-BSE prions propagated in cynomolgus monkeys exhibit similar biochemical PrPSc signatures and consist of the monkey amino acid sequence, the two prions maintain strain-specific conformations of PrPSc in which they encipher and retain unique pathogenic traits., Competing Interests: The authors have declared that no competing interests exist.

Drug-induced block of the cardiac rapid delayed rectifying potassium current ( I Kr ), carried by the human ether-a-go-go-related gene (hERG) channel, is the most common cause of acquired long QT syndrome. Indeed, some, but not all, drugs that block hERG channels cause fatal cardiac arrhythmias. However, there is no clear method to distinguish between drugs that cause deadly arrhythmias and those that are clinically safe. Here we propose a mechanism that could explain why certain clinically used hERG blockers are less proarrhythmic than others. We demonstrate that several drugs that block hERG channels, but have favorable cardiac safety profiles, also evoke another effect; they facilitate the hERG current amplitude in response to low-voltage depolarization. To investigate how hERG facilitation impacts cardiac safety, we develop computational models of I Kr block with and without this facilitation. We constrain the models using data from voltage clamp recordings of hERG block and facilitation by nifekalant, a safe class III antiarrhythmic agent. Human ventricular action potential simulations demonstrate the ability of nifekalant to suppress ectopic excitations, with or without facilitation. Without facilitation, excessive I Kr block evokes early afterdepolarizations, which cause lethal arrhythmias. When facilitation is introduced, early afterdepolarizations are prevented at the same degree of block. Facilitation appears to prevent early afterdepolarizations by increasing I Kr during the repolarization phase of action potentials. We empirically test this prediction in isolated rabbit ventricular myocytes and find that action potential prolongation with nifekalant is less likely to induce early afterdepolarization than action potential prolongation with dofetilide, a hERG channel blocker that does not induce facilitation. Our data suggest that hERG channel blockers that induce facilitation increase the repolarization reserve of cardiac myocytes, rendering them less likely to trigger lethal ventricular arrhythmias., (© 2019 Furutani et al.)

Background: The clinical significance of contrast extravasation (CE) on computed tomography (CT) of the psoas major muscle after blunt torso trauma and the optimal management of patients requiring transcatheter arterial embolization (TAE) of the lumbar artery have not been well elucidated. The aim of this study was to investigate the impact of CE on CT to determine the need for TAE of the lumbar artery., Methods: We examined a single-center retrospective cohort of blunt torso trauma patients who underwent contrast-enhanced CT from 2008 to 2017. Basic demographics and clinical data were obtained, including the number of lumbar transverse process fractures (LTPFs) and maximum psoas major muscle hematoma (PMMH) size and ratio. Maximum PMMH size was analyzed by measuring the cross-sectional area of hematoma size at the level of CE. Psoas major muscle hematoma size ratio was obtained by dividing maximum PMMH size by psoas major muscle size of the unaffected side at the same slice level., Results: A total of 762 patients were included. One hundred seventeen patients had LTPFs and/or PMMH. Of 117 patients, 25 had CE on CT of the psoas major muscle and had significantly higher rates of older age and severe injury compared with those without CE. Of the 25 patients with CE, 13 required TAE of the lumbar artery. Patients who required TAE had a significantly higher number of LTPFs (4 vs. 2, p = 0.011) and higher PMMH size ratio (2.10 vs. 1.32, p = 0.016). Psoas major muscle hematoma size ratio revealed moderate accuracy (area under the receiver operating characteristic curve, 0.782)., Conclusions: Approximately half of the blunt torso trauma patients with CE on CT of the psoas major muscle will require TAE of the lumbar artery. Higher number of LTPFs and larger PMMH size can be a predictor of the need for TAE of the lumbar artery among patients with CE on CT., Level of Evidence: Therapeutic/care management, level IV.