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Purpose: This study assessed rotational mismatch between components after total knee arthroplasty (TKA) in the supine and standing positions and aimed to investigate the effect of rotational mismatch in the standing position on postoperative patient‐reported outcome measures (PROMs). Methods: Seventy‐one patients (71 knees) who underwent TKA for medial knee osteoarthritis were used to investigate rotational mismatches between components. Rotational mismatches between components were examined on postoperative standing whole‐leg and supine knee radiographs using a three‐dimensional‐to‐two‐dimensional model image registration technique, and the angles between the reference axes of the components were measured. Component alignment was evaluated using postoperative computed tomography images, and a questionnaire (2011 version of the Knee Society Score: [KSS 2011]) was mailed to investigate postoperative PROMs. Results: In the entire cohort, rotational mismatches in the supine and standing positions were similar (p = 0.9315). In 15% of patients, the mismatch was large (>5°) in the supine position but small (<5°) in the standing position (overestimated group). However, in 23% of patients, the mismatch was small (<5°) in the supine position and large (>5°) in the standing position (underestimated group). The underestimated group had severe preoperative varus deformity, resulting in external rotation of both femoral and tibial components. Rotational mismatch in the standing position (p = 0.0032) was a significant risk factor for unfavourable PROMs. Patients with a mismatch in the standing position had significantly lower scores than those without a mismatch (p = 0.0215), exceeding the minimal clinically important difference values. Conclusions: The underestimated group is clinically important because the surgical procedure and intraoperative assessment of component placement are performed in the supine position. In cases of severe preoperative varus deformity, care should be taken not to place the component in malrotation to avoid rotational mismatch in the standing position. Level of Evidence: Ⅳ, Case series. [ABSTRACT FROM AUTHOR]

Photographs and images in sustainability reports can affect readers' impressions of a company. This study conducts an exploratory analysis to investigate the impact of visual content on sustainability reporting and identify corporate reporting strategies. Using image recognition with deep learning technology, we analyse how 1025 global companies, publishing reports in English, incorporate images into their sustainability reports. The study also identifies factors influencing image selection and utilisation, assessing the images based on these factors' impact. Our findings highlight that economic development, cultural preferences and industry type contribute to variations in image usage. Moreover, these influences differ according to disclosure medium (i.e., integrated or sustainability reports), revealing industry‐specific image trends and providing insights into workforce characteristics. Leveraging deep learning, the study delves into facial expressions and demographic differences in the images, providing a comprehensive understanding of corporate communication strategies. [ABSTRACT FROM AUTHOR]

Background: A case of retropharyngeal abscess complicated by both artery and nerve injury has rarely been reported. Methods: A 36‐year‐old woman suddenly presented with right eye visual loss, dilated pupil, reduced direct light reflex, ptosis and ocular motility disorder on the side of inflammation progression, and was diagnosed with retropharyngeal abscess due to Fusobacterium necrophorum. The patient was treated only with antibiotics and, no further surgery was necessary but tracheotomy. Four months later, MRA showed right ICA occlusion and left ICA stenosis. MRI revealed continuous spread of inflammation due to the abscess from the retropharyngeal to the intracranial space. Results: These severe complications would be attributed to an endothelial damage to the arterial wall and an ischemic neuropathy caused by inflammation and thrombogenesis due to Fusobacterium necrophorum. Conclusions: This case should provide a better understanding of the mechanism of vascular and cranial nerve injury due to retropharyngeal infections, and highlights the need for early antibiotic therapy and repeated vascular evaluation. [ABSTRACT FROM AUTHOR]

This article discusses a case of cryoglobulinemic vasculitis complicating Sjögren's syndrome with IgA accumulation. The patient, a 90-year-old Japanese female, presented with bilateral lower limb purpura and joint pain. Laboratory investigations showed elevated levels of various markers, including immunoglobulin G (IgG), immunoglobulin A (IgA), and rheumatoid factor (RF). The patient was diagnosed with primary Sjögren's syndrome complicated by cryoglobulinemic vasculitis. Treatment with prednisolone and azathioprine improved the symptoms. The article highlights the importance of careful examination to identify underlying conditions such as Sjögren's syndrome or cryoglobulinemia in cases clinically diagnosed as IgA vasculitis. [Extracted from the article]

The association between immunoregulatory cytokines, such as interleukin (IL)‐10 or IL‐35, and dipeptidyl peptidase‐4 inhibitor (DPP4i)‐related bullous pemphigoid (BP) has not been evaluated. Serum IL‐10 and IL‐35 levels were measured in 39 patients with BP (24 males and 15 females; 6 DPP4i‐related and 33 DPP4i‐unrelated BP patients) and 10 healthy controls. The number of CD26+ cells in the dermis around bulla on sections was counted immunohistochemically for 12 patients (six patients with DPP4i‐related BP and six randomly sampled patients with DPP4i‐unrelated BP). Patients with DPP4i‐related BP had lower levels of serum eosinophils (DPP4i‐related vs. DPP4i‐unrelated BP: 476.1 ± 234.0 vs. 911.3 ± 948.8/μL; p = 0.537) and a higher rate of infiltrating CD26+ cells (32.9 ± 7.1% vs. 15.7 ± 4.4%; p = 0.01). There were no significant differences in serum IL‐10 (6.77 ± 0.24 vs. 6.84 ± 0.20 pg/mL), serum IL‐35 (2.63 ± 0.17 vs. 2.63 ± 0.21 pg/mL), serum anti‐BP180NC16a antibodies (67.31 ± 37.4 vs. 76.18 ± 54.59 U/mL) and Bullous Pemphigoid Disease Area Index before treatment in this study. Serum IL‐10 and IL‐35 levels do not increase in patients with BP and may not be a candidate for a therapeutic target for BP. An increase in CD26+ cells might be associated with DPP4i‐related BP. [ABSTRACT FROM AUTHOR]

Background: Clinical trials enroll patients with active fibrotic nonalcoholic steatohepatitis (NASH) (nonalcoholic fatty liver disease [NAFLD] activity score ≥ 4) and significant fibrosis (F ≥ 2); however, screening failure rates are high following biopsy. We developed new scores to identify active fibrotic NASH using FibroScan and magnetic resonance imaging (MRI). Methods: We undertook prospective primary (n = 176), retrospective validation (n = 169), and University of California San Diego (UCSD; n = 234) studies of liver biopsy‐proven NAFLD. Liver stiffness measurement (LSM) using FibroScan or magnetic resonance elastography (MRE), controlled attenuation parameter (CAP), or proton density fat fraction (PDFF), and aspartate aminotransferase (AST) were combined to develop a two‐step strategy—FibroScan‐based LSM followed by CAP with AST (F‐CAST) and MRE‐based LSM followed by PDFF with AST (M‐PAST)—and compared with FibroScan‐AST (FAST) and MRI‐AST (MAST) for diagnosing active fibrotic NASH. Each model was categorized using rule‐in and rule‐out criteria. Results: Areas under receiver operating characteristic curves (AUROCs) of F‐CAST (0.826) and M‐PAST (0.832) were significantly higher than those of FAST (0.744, p = 0.004) and MAST (0.710, p < 0.001). Following the rule‐in criteria, positive predictive values of F‐CAST (81.8%) and M‐PAST (81.8%) were higher than those of FAST (73.5%) and MAST (70.0%). Following the rule‐out criteria, negative predictive values of F‐CAST (90.5%) and M‐PAST (90.9%) were higher than those of FAST (84.0%) and MAST (73.9%). In the validation and UCSD cohorts, AUROCs did not differ significantly between F‐CAST and FAST, but M‐PAST had a higher diagnostic performance than MAST. Conclusions: The two‐step strategy, especially M‐PAST, showed reliability of rule‐in/‐out for active fibrotic NASH, with better predictive performance compared with MAST. This study is registered with ClinicalTrials.gov (number, UMIN000012757). [ABSTRACT FROM AUTHOR]

Patients with SSc often have anti-mitochondrial antibodies, as in our case.[4] Primary biliary cholangitis was excluded by hematological findings and a liver biopsy. We should think about the rare possibility that anti-mitochondrial antibodies occurred in her myositis.[7] Although the degree of serum CK was compatible, she did not have cardiac involvement, fibrosis or granulomatous change in the deltoid muscle biopsy. Limited cutaneous systemic sclerosis with myositis showing drug-induced liver injury and thrombotic microangiopathy. [Extracted from the article]

Background: Various physical and mental sequelae reduce the quality of life (QOL) of intensive care unit (ICU) patients. Current guidelines recommend multi‐angular approaches to prevent these sequelae. Some studies have demonstrated the clinical effectiveness of rehabilitation or the ICU diary against these sequelae, whereas others have not. Aim: The aims of the present study were to establish whether rehabilitation or the ICU diary was useful for reducing the severity of anxiety, depression, and post‐traumatic stress disorder (PTSD) in ICU patients. We also investigated whether these interventions improved the QOL of these patients. Study design: We conducted a systematic review and meta‐analysis of relevant randomized controlled trials published between January 1, 1985, and October 19, 2022, with the following search engines: PubMed, CHINAHL, all Ovid journals, and CENTRAL. The hospital anxiety and depression scale (HADS), the short‐form health survey (SF‐36), the EuroQol 5‐dimensions, 5‐levels (EQ‐5D‐5L), and the Impact of Event Scale‐Revised (IES‐R) were used as outcome measures. The quality of evidence across all studies was independently assessed using Review Manager software (v.5.4). Results: We included 12 rehabilitation studies and five ICU diary studies. Rehabilitation had no significant effects on HADS‐anxiety, HADS‐depression, or EQ‐5D‐5L, but significantly improved the physical component summary (PCS) [MD = 3.31, 95%CI (1.33 to 5.28), p =.001] and mental component summary (MCS) [MD = 4.31, 95%CI: (1.48 to 7.14), p =.003] of the SF‐36. The ICU diary significantly ameliorated HADS‐anxiety [MD = 0.96, 95%CI: (0.21 to 1.71), p =.01], but did not affect HADS‐depression, the IES‐R, or the PCS or MCS of the SF‐36. Conclusions: The present study showed that rehabilitation initiated after discharge from the ICU effectively improved SF‐36 scores. The ICU diary ameliorated HADS‐anxiety. Neither rehabilitation nor the ICU diary attenuated HADS‐depression or IES‐R in this setting. Rehabilitation and the ICU diary partially improved the long‐term prognosis of ICU patients. Relevance to clinical practice: The present study provides evidence for the beneficial effects of rehabilitation and the ICU diary for ICU patients. Rehabilitation alone does not ameliorate anxiety, depression, or PTSD symptoms, but may improve QOL. The ICU diary only appeared to ameliorate anxiety. [ABSTRACT FROM AUTHOR]

The Msp protein complex and the serine protease dentilisin are the best‐characterized virulence factors in Treponema denticola, the major etiological agent of chronic periodontitis. In addition to these outer sheath factors, the cysteine protease dentipain contributes to pathogenicity, but its secretion, processing, cellular localization, and role in T. denticola virulence are not fully understood. In this study, we found that full‐sized dentipain (74‐kDa) and the 52‐kDa truncated form of the enzyme are located, respectively, in the outer sheath derived from T. denticola dentilisin‐ and the Msp‐deficient mutants. Furthermore, dentipain was barely detected in the wild‐type strain. These results suggest that dentilisin and Msp, the major outer sheath proteins, are involved in the secretion and maturation of dentipain. Inactivation of the dentipain gene slowed the growth of T. denticola, and the effect was more profound in serum‐free medium than in serum‐containing medium. Several genes, including those encoding transporters and methyl‐accepting chemotaxis proteins, were differentially expressed in the dentipain‐deficient mutant. Furthermore, the mutant strain was more hydrophobic than the wild‐type strain. Finally, the mutant showed less autoaggregation activity and adhesion to IgG in a serum‐free medium than the wild‐type strain. These findings suggest that dentipain contributes to the virulence of T. denticola by facilitating adhesion and acquisition of nutrients essential for colonization and proliferation in the gingival crevice under serum‐rich conditions. [ABSTRACT FROM AUTHOR]

Objective: For patients with connective tissue disease‐associated interstitial lung disease (CTD‐ILD), early medical intervention would be desirable. This study analyzed the real‐world, single‐center use of nintedanib for CTD‐ILD patients. Methods: Patients with CTD who received nintedanib from January 2020 to July 2022 were enrolled. Medical records review and stratified analyses of the collected data were conducted. Results: Reduction in the percentage of predicted forced vital capacity (%FVC) was seen in the elderly group (>70 years; P =.210), males (P =.027), the late group who started nintedanib >80 months after confirmation of an ILD disease activity (P =.03), the severe %DLco (diffusing capacity for carbon monoxide as a percentage of predicted) group (<40%; P =.20), the group who had extensive pulmonary fibrosis at the beginning of nintedanib (pulmonary fibrosis score >35%), and the low‐dose group (nintedanib 50‐100 mg/d; P =.40). %FVC did not decrease by >5% in the young group (<55 years), the early group who started nintedanib within 10 months after confirmation of an ILD disease activity, and the group whose pulmonary fibrosis score at the beginning of nintedanib was <35%. Conclusion: It is important to diagnose ILD early and start antifibrotic drugs with proper timing for cases in need. It is better to start nintedanib early, especially for patients at risk (>70 years old, male, <40% DLco, and >35% areas of pulmonary fibrosis). [ABSTRACT FROM AUTHOR]

SUMMARY: The responses of photochemical efficiency to desiccation and salinity gradients in an intertidal edible brown macroalga, Sargassum fusiforme (Harvey) Setchell (Sargassaceae, Fucales), were determined using a pulse amplitude modulation (PAM)‐chlorophyll fluorometer. The effective quantum yields (ΔF/Fm'; = ΦPSII) of photosystem II (PSII) dropped to zero after 360‐min aerial exposure under low irradiance (20 μmol photons m−2 s−1) and 120‐min exposure under high irradiance (700 μmol photons m−2 s−1) for this species at 20°C and 50% relative humidity. Under these conditions, ΔF/Fm' failed to recover to initial levels even after 1‐day rehydration in seawater. In general, ΔF/Fm' decreased as desiccation reduced the absolute water content (AWC, %). Nevertheless, when AWC was above ca. 20%, ΔF/Fm' was mostly restored to initial levels after 1‐day rehydration in seawater, suggesting strong tolerance to dehydration. Furthermore, S. fusiforme appeared to tolerate a broad range of salinity (i.e. 15–50 psu) during six days of culture; however, ΔF/Fm' declined when salinity was <10 and 60 psu. Strong tolerance to dehydration and salinity stress likely provides S. fusiforme an advantage that allows it to flourish in the intertidal habitat. [ABSTRACT FROM AUTHOR]

Background: Tumors and tumor-like lesions of the foot and ankle are relatively rare and their postoperative clinical outcome has not been well reported. Methods: This study retrospectively reviewed medical records of all patients who underwent excision of tumors and tumor-like lesions of the foot and ankle from 2008 to 2020. Preoperative and postoperative clinical outcomes were evaluated by the Japanese Society for Surgery of the Foot (JSSF) scales (pain, function, and alignment). Results: A total of 117 consecutive patients were analyzed in this study. Bone lesions accounted for 51 patients (benign: 45, intermediate malignancy: 1, malignant: 5), and soft tissue lesions accounted for 66 patients (benign: 57, intermediate malignancy: 2, malignant: 7). Four patients (8%) presenting with bone tumor and six (9%) soft tissue tumors resulted in recurrence. Eight (67%) patients with malignant lesions were alive continuously disease free and followed for a median of 50.5 (range: 18 to 82) months. Amputation at the first operation was done for five cases (33%) of malignant or intermediate malignancy (below-knee amputation: 1, Chopart disarticulation: 1, forefoot amputation: 3). Postoperative JSSF scores resulted in a significant 'positive' increase (bone lesion, 75.9 ± 13.7 to 91.4 ± 14.9, p < 0.001; soft tissue lesion, 84.7 ± 14.8 to 91.9 ± 12.5, p < 0.001). The score improvement in bone lesions was significantly higher than in soft tissue lesions (p = 0.003). Conclusion: The surgical management of tumors and tumor-like lesions of the foot and ankle showed good post-operative functional outcomes with bone lesions exhibiting better results when compared to soft-tissue lesions. [ABSTRACT FROM AUTHOR]

Aim: Although malnutrition is an important prognostic factor in patients with chronic heart failure (CHF), no effective treatment for malnutrition has been established. Rikkunshito (RKT) is a Japanese herbal drug that has been used in daily practice for patients with loss of appetite. However, no data have demonstrated whether or not RKT can improve the body composition in patients with CHF. The aim of this study was to elucidate the effect of RKT on the nutritional status of patients with CHF. Methods: This single‐center retrospective observational study included 14 patients with CHF and loss of appetite who were treated with RKT. Body mass index (BMI) and body composition including fat‐free mass index (FFMI), skeletal muscle mass index (SMI) and fat mass index (FMI) were measured by the bioimpedance method. Body composition was measured at baseline and 12 weeks later. The primary endpoint was the change of BMI and body composition. Results: BMI was significantly improved from 23.7 (20.0–26.1) kg/m2 to 24.2 (20.3–27.3) kg/m2 (p = 0.0494). FFMI was significantly improved from 13.7 (11.3–14.9) kg/m2 to 14.2 (12.0–15.7) kg/m2 (p = 0.0002). SMI was also improved from 5.0 (3.0–6.2) kg/m2 to 5.3 (3.3–6.8) kg/m2 (p = 0.0085). On the other hand, FMI was not significantly changed (9.4 (7.2–12.0) kg/m2 to 10.3 (7.9–12.0) kg/m2, p = 0.8552). Conclusion: The Japanese herbal drug RKT was effective in improving the nutritional status of patients with CHF. [ABSTRACT FROM AUTHOR]

In this study, dermoscopy was applied to determine the site of skin biopsy in cases of palmoplantar pustulosis (PPP) with invisible tiny pustules or vesicles. Fifty‐two clinically diagnosed PPP patients (11 men and 41 women) were observed by a dermoscope and underwent skin biopsy. Nineteen patients had visible pustules, whereas 33 had no visible pustules. Pustules were detected by a dermoscope on palmoplantar lesions in 17 of the 33 PPP patients. In contrast, 16 patients showed no presence of pustules or vesicles observed by a dermoscope. In this group, biopsy specimens were taken from scaly lesions. Out of the 16 patients, 10 histologically showed pustules in the epidermis. We finally detected pustules for 46 patients among 52 who were clinically diagnosed with PPP. As a result, we detected pustules in PPP for 19 patients on "inspection", and 36 patients on "inspection and dermoscopy", and 46 patients on "inspection, dermoscopy, and biopsy". Dermoscopy is significantly useful comparing the detection rate (inspection, 0.41; inspection and dermoscopy, 0.78; p = 0.0003; using χ2‐test). In addition, we also should learn from the results that the detection rate goes down to 0.78 without a biopsy. Thus, dermoscopy is certainly a useful tool for invisible pustules and also undetectable pustules to detect pustules in PPP. Moreover, we objectively showed that "inspection, dermoscopy, and biopsy" are the best way to make a PPP diagnosis. [ABSTRACT FROM AUTHOR]

Treponema denticola, a helically shaped motile microorganism, is a major pathogen of chronic periodontitis. Major surface protein (Msp) and dentilisin are virulence factors of T. denticola that are located on the outer sheath. The motility of T. denticola is deeply involved in colonization on and invasion into the host tissue. The outer sheath is located at the interface between the environment and T. denticola, and its components may also contribute to its motility via interaction with the materials outside the cells. The study aimed to clarify whether Msp or dentilisin contributes to the motility of T. denticola on solid surfaces, termed crawling, by investigating their effects using Msp‐deficient and dentilisin‐deficient T. denticola strains. Motility was analyzed by measuring the colony size in agar plates and velocity was analyzed using dark‐field microscopy. The colony area of the mutant strains was smaller than that of the wild‐type strain. The crawling velocity of the mutant strains was lower than that of the wild‐type strain, with the lowest velocity observed in the dentilisin‐deficient strain. Additionally, the ratio of the crawling distance by one revolution to the protoplasmic cylinder pitch (an indicator of the crawling efficiency) in the dentilisin mutant was significantly lower than that in the wild type strain and the Msp mutant. Together, these results indicate that dentilisin facilitates the crawling‐dependent surface spreading of T. denticola. [ABSTRACT FROM AUTHOR]

Trimethoprim–sulfamethoxazole (TMP/SMX) combination is used for the prophylaxis of Pneumocystis pneumonia (PCP). Although TMP/SMX is frequently used in dermatology for cases treated with corticosteroids and/or immunosuppressants, it is often difficult to continue the administration of TMP/SMX due to adverse events. There are only a few reported studies on the prophylaxis of PCP in dermatology. This is the first review focused on adverse events of TMP/SMX among patients with dermatological diseases compared with previous reports. In this study, we retrospectively investigated 132 cases treated with TMP/SMX and examined the adverse events. Adverse events occurred in 32 cases (24.2%) and the incidence in this study was higher than in previous reports. Thrombocytopenia occurred in 17 cases (12.5%), which was the most frequent adverse event. The possible causes of adverse events were that the standard dose of TMP/SMX may be excessive for most Japanese, in addition to the long administration period, and the concomitant use of corticosteroids and/or immunosuppressants in almost all cases. We must consider the risks of PCP and adverse events of TMP/SMX in each case. It is desirable to examine possible administration methods that can be continued by adjusting the dose and interval of TMP/SMX. [ABSTRACT FROM AUTHOR]

Aim: Esophageal variceal ligation (EVL) is usually carried out to decrease the risk of hemorrhage. Several complications have been reported with the procedure, including bleeding from ligation‐induced esophageal ulcers or heartburn. However, there is scant evidence for gastroesophageal reflux caused by EVL. The aim of this study was to assess 24‐h pH monitoring in the esophagogastric junction before and after EVL and the bleeding rate for 18 months. Methods: We undertook this single‐center prospective trial in Kitasato University Hospital (Sagamihara, Japan). We included patients with cirrhosis who were Child–Pugh classification A or B, without uncontrollable hepatocellular carcinoma, and had F2 or larger esophageal varices, and/or were red color sign (RC) positive. The study period was from July 2012 through September 2017 for 32 patients enrolled in this study and followed up until March 2019. Results: Baseline characteristics were: median Child–Pugh score, 6; and mean age, 64.3 years. Before and after EVL, the median 24‐h under pH 4 holding time percentages of all patients were 0.6% (range, 0–5.6%) and 0.95% (range, 0–50.6%), respectively, without a significant difference (P = 0.107). We could not find any G3 or G4 adverse events during this study, and 75% of the patients who had already suffered from moderate gastroesophageal reflux became worse after EVL (P = 0.18) and required antacid therapies. There were no patients with hemorrhage from esophageal varices. Conclusions: Esophageal variceal ligation for esophageal varices did not significantly change gastroesophageal reflux. Therefore, acid suppressive therapy might be unnecessary for patients who do not suffer from gastroesophageal reflux after EVL. [ABSTRACT FROM AUTHOR]

Aim: Lenvatinib is an oral, multitargeted, tyrosine kinase inhibitor, which suppress tumor angiogenesis and tumor progression. It was non‐inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma (HCC). Sorafenib had a beneficial effect on portocollateral circulation with portal hypertension in translating and clinical studies. However, the hemodynamic effects of lenvatinib appear to be different from those of sorafenib because the efficacy of lenvatinib for vascular endothelial growth factor receptors and fibroblast growth factor receptors is different from that of sorafenib. This study was prospectively performed to evaluate the portal hemodynamic effect of lenvatinib in patients with advanced HCC using duplex Doppler ultrasonography. Methods: In total, 28 Child‐Pugh class A or B patients with advanced HCC received lenvatinib depending on body weight daily for 2 weeks. Primary outcomes were changes in the hemodynamics of the portal venous system using duplex Doppler ultrasonography before and after the 2‐week administration of lenvatinib. Results: The portal venous flow velocity (cm/s) significantly reduced (27 ± 12.1 vs. 22.6 ± 8.0, P = 0.019), while portal venous area (cm2) did not change after the 2‐week administration (0.80 ± 0.36 vs. 0.82 ± 0.27, P = 0.665). Therefore, the congestion index (portal venous area/portal venous flow velocity), which reflects the pathophysiological hemodynamics of the portal venous system significantly worsened (0.037 ± 0.025 vs. 0.043 ± 0.024, P = 0.045). Conclusions: Considering that this was a short‐term study, because lenvatinib could be an agent that aggravates portal hypertension, it will be necessary to verify its clinical effects for portal hypertension in future studies. [ABSTRACT FROM AUTHOR]

To identify the subsidence induced by an offshore earthquake, chemical compositions, fossil assemblages, and radiocarbon ages of organic materials were analyzed for Holocene sediments in the Miyazaki Plain, southwest Japan. The lower sedimentary facies (SF1) composed of sand‐ and pumice‐rich sediments and the upper sedimentary facies (SF2) composed of silt‐rich sediments were identified by stratigraphical description. Sharp facies changes and sediment disturbances are observed in the boundary between SF1 and SF2. Diatoms of brackish and marine water origins, foraminifers, ostracods, and mollusks are common in SF2, while fossils are rare, and most of them are diatoms of freshwater origins in SF1. The stratigraphical and paleontological evidences suggest an environmental change from the lower terrestrial to the upper shallow marine. The change is laterally continuous and seems to be inconsistent with Holocene uplift trends in the Miyazaki Plain. Radiocarbon ages of organic matters and the occurrence of the Sakurajima–Bunmei tephra (1471–1476 ad) show that the environmental change could be attributed to local subsidence due to the 1662 Kanbun Hyuganada Sea earthquake shown in historical records. The chemical analysis shows clear contrast between SF1 and SF2 in terms of concentrations of cations and anions commonly rich in seawater (i.e. Na+, Mg2+, K+, Ca2+, Cl−, and SO42−) in adsorbed water extracted from the sediments, and total S concentrations in bulk sediments, supporting the environmental change from terrestrial to shallow marine. However, the bulk chemical composition, except total sulfur, remains rather unclear for use as marine‐derived chemical markers compared to the adsorbed water, because it is more affected by the composition of the source sediments. [ABSTRACT FROM AUTHOR]

ABSTRACT: The acceleration of nerve regeneration remains a clinical challenge. We previously demonstrated that transcutaneous CO2 application using a novel hydrogel increases the oxygen concentration in local tissue via an “artificial Bohr effect” with the potential to prevent muscle atrophy. In this study, we investigated the effect of transcutaneous CO2 administration on limb function after peripheral nerve injury in a rat sciatic nerve injury model. In total, 73 Sprague–Dawley rats were divided into a sham group, a control group (crush injury to sciatic nerve and no treatment) or a CO2 group (crush injury with transcutaneous CO2 application). CO2 was administered percutaneously for 20 min five times per week. Scores for the sciatic function index and pinprick test were significantly higher in the CO2 group than control group. The muscle wet weight ratios of the tibialis anterior and soleus muscles were higher in the CO2 group than control group. Electrophysiological examination showed that the CO2 group had higher compound motor action potential amplitudes and shorter distal motor latency than the control group. Histological examination of the soleus muscle sections at postoperative week 2 showed shorter fiber diameter in the control group than in the CO2 group. The mRNA expression of Atrogin‐1 and MuRF‐1 was lower, mRNA expression of VEGF and myogenin and MyoD was higher in CO2 group at postoperative week 2 compared to the control group. Clinical significance: Transcutaneous CO2 application has the therapeutic potential to accelerate the recovery of muscle atrophy in peripheral nerve injury. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1653–1658, 2018. [ABSTRACT FROM AUTHOR]

GDC‐0853 is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) that is highly selective and noncovalent, leading to reversible binding. In double‐blind, randomized, and placebo‐controlled phase I healthy volunteer studies, GDC‐0853 was well tolerated, with no dose‐limiting adverse events (AEs) or serious AEs. The maximum tolerated dose was not reached during dose escalation (≤600 mg, single ascending dose (SAD) study; ≤250 mg twice daily (b.i.d.) and ≤500 mg once daily, 14‐day multiple ascending dose (MAD) study). Plasma concentrations peaked 1–3 hours after oral administration and declined thereafter, with a steady‐state half‐life ranging from 4.2–9.9 hours. Independent assays demonstrated dose‐dependent BTK target engagement. Based on pharmacokinetic/pharmacodynamic (PK/PD) simulations, a once‐daily dosing regimen (e.g., 100 mg, q.d.) is expected to maintain a high level of BTK inhibition over the dosing interval. Taken together, the safety and PK/PD data support GDC‐0853 evaluation in rheumatoid arthritis, lupus, and other autoimmune or inflammatory indications. [ABSTRACT FROM AUTHOR]

Objective: In the gingival crevice, the interaction between epithelial cells and periodontopathic bacteria is important for the development of periodontitis. Treponema denticola is a major pathogen of chronic periodontitis and possesses several virulence factors, such as major surface protein (Msp) and prolyl‐phenylalanine‐specific protease (dentilisin). Here, we investigated the behaviours of epithelial cells infected with T. denticola by measuring the expression of interleukin (IL)‐1β, IL‐6, β defensin 2 (BD‐2) and heat‐shock protein 70 (HSP70). Methods: Epithelial cells were infected with T. denticola wild‐type strain, Msp‐deficient mutant or dentilisin‐deficient mutant, and the expression levels of the above targets were analysed by polymerase chain reaction. Results: Infection with T. denticola wild‐type strain and mutants induced the production of IL‐6 and HSP70. The level of BD‐2 induced by T. denticola wild‐type strain at 24 hr was significantly higher than that of the dentilisin‐deficient mutant. The level of IL‐1β mRNA in the wild‐type strain and dentilisin‐deficient mutant was slightly lower than that in the uninfected control. Conclusion: These results suggest that the levels of BD‐2 were affected by Msp and dentilisin. This effect may contribute to the disruption of the response of epithelial cells to eradicate T. denticola. [ABSTRACT FROM AUTHOR]

Aim: To investigate the current status of portal vein thrombosis (PVT) in Japan, the Clinical Research Committee of the Japan Society of Portal Hypertension undertook a questionnaire survey. Methods: A questionnaire survey of 539 cases of PVT over the previous 10 years was carried out at institutions affiliated with the Board of Trustees of the Japan Society of Portal Hypertension. Results: The most frequent underlying etiology of PVT was liver cirrhosis in 75.3% of patients. Other causes included inflammatory diseases of the hepatobiliary system and the pancreas, malignant tumors, and hematologic diseases. The most frequent site was the main trunk of the portal vein (MPV) in 70.5%, and complete obstruction of the MPV was present in 11.5%. Among the medications for PVT, danaparoid was given to 45.8%, warfarin to 26.2%, heparin to 17.3%, and anti‐thrombin III to 16.9%. Observation of the course was practiced in 22.4%. Factors contributing to therapeutic efficacy were implementation of various medications, thrombi localized to either the right or left portal vein only, non‐complete obstruction of the MPV and Child–Pugh class A liver function. A survival analysis showed that the prognosis was favorable with PVT disappearance regardless of treatment. Conclusion: The questionnaire survey showed the current status of PVT in Japan. Any appropriate medication should be given to a patient with PVT when PVT is recognized. It is necessary to compile a large amount of information and reach a consensus on safe and highly effective management of PVT. [ABSTRACT FROM AUTHOR]

Aim: Portal vein thrombosis (PVT) is one of the most critical disorders in liver disease patients. These patients have the imbalance of coagulation and coagulation inhibition resulting from decreased levels of coagulation inhibitory factors, such as protein C, protein S, and antithrombin III (AT‐III). We designed this randomized, double‐blind, placebo‐controlled trial comparing the safety and efficacy of AT‐III for PVT in liver disease patients with those who received no treatment. Methods: Eligible patients were diagnosed with the association of thrombus, without tumor thrombus, and thrombus in more than 50% of the cross‐sectional lumen of the portal vein. Patients with 70% or less serum level of AT‐III were included. The study drug was given up to three times in a 5‐day consecutive infusion interval if the thrombus decreased in size. Efficacy was evaluated by contrast enhanced computed tomography using a five‐grade scale (complete response, partial response, slight response, no response, and progression). From October 2014 through to March 2016, 36 patients were randomly assigned to the AT‐III group and 37 patients to the placebo group. Results: The proportion of patients with complete response or partial response of PVT was significantly higher in the AT‐III group (55.6%; 20/36 patients; 95% confidence interval, 38.1–72.1) than in the placebo group (19.4%; 7/36 patients, 95% confidence interval, 8.2–36.0) (P = 0.003). The overall incidence of adverse events and adverse drug reactions did not differ significantly between the two groups. Conclusion: Antithrombin III is one of the essential therapies for patients with PVT in cases with lower concentration levels of AT‐III. [ABSTRACT FROM AUTHOR]

Aim: Transcatheter arterial chemoembolization (TACE) has been recognized as a treatment option for patients with intermediate hepatocellular carcinoma (HCC). This randomized, controlled study compared the local control efficacy of TACE with miriplatin (platinum monohydrate) or with epirubicin. Methods: The study group consisted of 200 Japanese patients with unresectable HCC treated at the Kitasato University East Hospital (Sagamihara, Japan) between July 2010 and June 2013. The primary end‐point of the study was time to tumor progression (TTP). Results: We analyzed 198 patients (99 in the miriplatin group and 99 in the epirubicin group) treated with TACE. The median TTP in the epirubicin group was 5.9 months (95% confidence interval [CI], 4.8–7.0) and 7.6 months (95% CI, 5.8–9.4) in the miriplatin group. There was a significant difference between the two groups (P = 0.021; risk ratio, 1.488; 95% CI: 1.061–2.086). In the epirubicin group, 53 patients (53%) had complete response, 24 patients (24%) had partial response, 12 patients (12%) had stable disease, and 10 patients (10%) had progressive disease. In the miriplatin group, 38 patients (38%) had complete response, 41 patients (41%) had partial response, 2 patients (2%) had stable disease, and 18 patients (18%) had progressive disease. There was no significant difference in the response rate (P = 0.862). Overall incidences of adverse events and adverse drug reactions did not differ significantly between the two groups. Conclusion: Miriplatin proved more effective than epirubicin in TACE for unresectable HCC. The trial described in this work has been registered under the trial number: UMIN000004790. [ABSTRACT FROM AUTHOR]

Aim The indocyanine green (ICG) finger-piece method (FPM), which allows measurement of the ICG concentration by mounting a light sensor onto a finger, is used to assess liver function. We compared the ICG FPM with the conventional ICG blood sampling method (BSM) in patients with liver disorders. Methods Ninety consecutive patients simultaneously underwent the ICG BSM and ICG FPM. After ICG administration, blood samples were collected at 5, 10, and 15 min for the ICG BSM. The ICG concentration was measured through the finger piece by an ICG clearance meter. Results Seventy-one patients (78.9%) had Child-Pugh class A liver disease, and 19 (21.1%) had class B or C. The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values ( r = 0.886, P < 0.001). Bland-Altman analysis showed good agreement between the two methods (mean difference, 0.012 ± 0.018). The FPM-measured ICG plasma disappearance rate was positively correlated with the BSM-measured values both in patients with Child-Pugh class A liver disease ( r = 0.821, P < 0.001) and class B or C liver disease ( r = 0.859, P < 0.001). Conclusion The ICG FPM may be an alternative to the ICG BSM for liver function assessment. [ABSTRACT FROM AUTHOR]

Aim To examine whether superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) can be used to assess the malignant potential of hepatic hypovascular nodules showing hypointensity during the hepatobiliary phase (HBP) on gadoxetic acid (Gd-EOB-DTPA)-enhanced MRI. Methods The study included 42 patients with chronic liver disease who had small hypovascular nodules (5-15 mm) showing hypointensity during the HBP on Gd-EOB-DTPA-enhanced MRI. The SPIO-enhanced T2-weighted MRI analyzed whether the signal intensity of each nodule was high. Nodules were prospectively followed up until hypervascularization by periodic Gd-EOB-DTPA-enhanced MRI. Initial MRI findings and clinical variables were used to analyze predictive factors for hypervascularization. Results We analyzed 77 nodules, of which 19 (25%) showed hypervascularization during the observation period. The cumulative rates for hypervascularization were 11% and 22% at 1 and 2 years, respectively. Hyperintensity was observed in 12 nodules (16%) on SPIO-enhanced T2-weighted MRI; among these, 7 (58%) showed hypervascularization, whereas 12 (18%) of the remaining 65 nodules without hyperintensity showed hypervascularization ( P = 0.007). A Cox model revealed that independent predictors of hypervascularization included hyperintense nodules on SPIO-enhanced MRI ( P < 0.001). The cumulative rates for hypervascularization in hyperintense nodules on SPIO-enhanced MRI were 52% at 1 year, whereas these rates were 3% for non-hyperintense nodules. Conclusion Superparamagnetic iron oxide-enhanced MRI is useful for predicting the malignant potential of vascular transformation of hypovascular nodules with hypointensity observed in the HBP on Gd-EOB-DTPA-enhanced MRI. [ABSTRACT FROM AUTHOR]

ABSTRACT Atrophy with fatty degeneration is often seen in rotator cuff muscles with torn tendons. PRP has been reported to enhance tissue repair processes after tendon ruptures. However, the effect of PRP on atrophy and fatty degeneration of the muscle is not yet known. The aim of this study is to examine the effect of PRP on degeneration change of rotator cuff muscles in vitro and in vivo. A murine myogenic cell line and a rat rotator cuff tear model were used in this study and PRP was administrated into subacromial space which is widely used in clinical practice. In in vitro study, administration of PRP to C2C12 cells stimulated cell proliferation while inhibited both myogenic and adipogenic differentiation. In in vivo study, administration of PRP suppressed Oil Red-O positive lipid droplet formation. The expression of adipogenic genes was also decreased by PRP administration. In conclusion, PRP promoted proliferation of myoblast cells, while inhibiting adipogenic differentiation of myoblast cells and suppressing fatty degeneration change in rat torn rotator cuff muscles. Further investigations are needed to determine the clinical applicability of the PRP. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1806-1815, 2017. [ABSTRACT FROM AUTHOR]

Simeprevir is a substrate for organic anion-transporting polypeptides (OATPs) that transport bilirubin. Hyperbilirubinemia is an adverse event reported during treatment of chronic hepatitis C patients with simeprevir plus pegylated interferon and ribavirin. Because gadoxetic acid is also a substrate of OATPs, pretreatment gadoxetic acid-enhanced magnetic resonance imaging (MRI) may predict hyperbilirubinemia during treatment. This prospective study therefore evaluated 11 consecutive patients with chronic hepatitis C who underwent gadoxetic acid-enhanced MRI prior to treatment with simeprevir plus pegylated interferon and ribavirin for 12 weeks, followed by pegylated interferon and ribavirin for an additional 12 weeks. Their contrast enhancement index (CEI), an index of liver parenchymal enhancement during the hepatobiliary phase, was assessed before treatment. Plasma trough concentrations (Ctrough) of simeprevir were determined 7 days after its administration, and serum bilirubin concentrations were measured throughout the course of treatment. Six patients (55%) developed hyperbilirubinemia (≥1.6 mg/dL) during treatment. Ctrough was significantly higher in patients with than without hyperbilirubinemia ( P = .009), with a strong inverse relationship between CEI and Ctrough ( r = -0.911, P < .001). CEI was significantly lower in patients with than without hyperbilirubinemia ( P = .009), but there were no significant differences between the 2 groups in pretreatment serum albumin concentrations and FIB-4 index, an index of liver fibrosis. Hepatic enhancement with gadoxetic acid was related to Ctrough of simeprevir. Gadoxetic acid-enhanced magnetic resonance imaging may predict the development of hyperbilirubinemia during treatment of hepatitis C patients with simeprevir plus pegylated interferon and ribavirin. [ABSTRACT FROM AUTHOR]

ABSTRACT To achieve biological regeneration of tendon-bone junctions, cell sheets of human rotator-cuff derived cells were used in a rat rotator cuff injury model. Human rotator-cuff derived cells were isolated, and cell sheets were made using temperature-responsive culture plates. Infraspinatus tendons in immunodeficient rats were resected bilaterally at the enthesis. In right shoulders, infraspinatus tendons were repaired by the transosseous method and covered with the cell sheet (sheet group), whereas the left infraspinatus tendons were repaired in the same way without the cell sheet (control group). Histological examinations (safranin-O and fast green staining, isolectin B4, type II collagen, and human-specific CD31) and mRNA expression (vascular endothelial growth factor; VEGF, type II collagen; Col2, and tenomodulin; TeM) were analyzed 4 weeks after surgery. Biomechanical tests were performed at 8 weeks. In the sheet group, proteoglycan at the enthesis with more type II collagen and isolectin B4 positive cells were seen compared with in the control group. Human specific CD31-positive cells were detected only in the sheet group. VEGF and Col2 gene expressions were higher and TeM gene expression was lower in the sheet group than in the control group. In mechanical testing, the sheet group showed a significantly higher ultimate failure load than the control group at 8 weeks. Our results indicated that the rotator-cuff derived cell sheet could promote cartilage regeneration and angiogenesis at the enthesis, with superior mechanical strength compared with the control. Treatment for rotator cuff injury using cell sheets could be a promising strategy for enthesis of tendon tissue engineering. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:289-296, 2017. [ABSTRACT FROM AUTHOR]

An evolutionarily conserved protein Tel2 regulates a variety of stress signals. In mammals, TEL2 associates with TTI1 and TTI2 to form the Triple T ( TTT: TEL2- TTI1- TTI2) complex as well as with all the phosphatidylinositol 3-kinase-like kinases ( PIKKs) and the R2 TP (Ruvbl1-Ruvbl2-Tah1-Pih1 in budding yeast)/prefoldin-like complex that associates with HSP90. The phosphorylation of TEL2 by casein kinase 2 ( CK2) enables direct binding of PIHD1 (mammalian Pih1) to TEL2 and is important for the stability and the functions of PIKKs. However, the regulatory mechanisms of Tel2 in fission yeast Schizosaccharomyces pombe remain largely unknown. Here, we report that S. pombe Tel2 is phosphorylated by CK2 at Ser490 and Thr493. Tel2 forms the TTT complex with Tti1 and Tti2 and also associates with PIKKs, Rvb2, and Hsp90 in vivo; however, the phosphorylation of Tel2 affects neither the stability of the Tel2-associated proteins nor their association with Tel2. Thus, Tel2 stably associates with its binding partners irrespective of its phosphorylation. Furthermore, the Tel2 phosphorylation by CK2 is not required for the various stress responses to which PIKKs are pivotal. Our results suggest that the Tel2-containing protein complexes are conserved among eukaryotes, but the molecular regulation of their formation has been altered during evolution. [ABSTRACT FROM AUTHOR]

SUMMARY The effects of photosynthetically active radiation (PAR) and temperature on the photosynthesis of two Vietnamese brown algae, Sargassum mcclurei and S. oligocystum (Fucales), were determined by field and laboratory measurements. Dissolved oxygen sensors and pulse-amplitude modulated (PAM) fluorometry were used for the measurements of photosynthetic efficiency. A Diving-PAM revealed that underwater measurements of the effective quantum yield ( Φ PSII) of both species declined with increasing incident PAR, with minimum Φ PSII occurring during noon to early afternoon. Φ PSII recovered in the evening, indicating photo-adaptation to excessive PAR. In laboratory experiments, Φ PSII also decreased under continuous exposure to 1000 μmol photons m−2 s−1; and full recovery occurred after 12 h of dark acclimatization. The net photosynthesis - PAR experiments of S. mcclurei and S. oligocystum conducted at 28°C revealed that the net photosynthetic rate quickly increased at PAR below the saturation irradiance of 361 and 301 μmol photons m−2 s−1 and nearly saturated to maximum net photosynthetic rates of 385 and 292 μg O2 gww − 1 min−1 without photoinhibition, respectively. Gross photosynthesis and dark respiration experiments determined over a range of temperatures (12-40°C), revealed that the maximum gross photosynthetic rates of 201 and 147 μg O2 gww − 1 min−1 occurred at 32.9 and 30.7°C for S. mcclurei and S. oligocystum, respectively. The dark respiration rates increased exponentially over the temperature ranges examined. The estimated maximum value of the maximum quantum yield occurred at 19.3 and 20.0°C and was 0.76 and 0.74, respectively. Similar to the natural habitat of the study site, these two species tolerated the relatively high temperatures and broad range of PAR. The ability of these species to recover from exposure to high PAR is one of the mechanisms that allow them to flourish in the shallow water environment. [ABSTRACT FROM AUTHOR]

Background and Objective Previous studies have shown that cigarette smoke (CS) and periodontal pathogens could alter wound healing responses of gingival epithelial cells. To elucidate molecular mechanisms leading to these epithelial changes, we studied the signaling pathway involved in the modulation of cell migration by CS condensate (CSC) and the infection by a prominent periodontal pathogen, Porphyromonas gingivalis. Material and Methods Human gingival epithelial cells (Ca9-22) were treated with CSC or vehicle control for 24 h. Activation of mitogen-activated protein kinases (MAPK) in cells with or without infection by P. gingivalis was assessed by polymerase chain reaction array and immunoblotting using phospho-specific antibodies. Cell migration was assessed using in vitro wound closure model, and specific pharmacologic inhibitors of MAPK pathways were used to characterize further the extent of involvement of the MAPK pathways. Results Polymerase chain reaction array showed that gene expression of several members of the MAPK, particularly p38 and JNK, was upregulated more than twofold in Ca9-22 cells stimulated with 10 μg/mL CSC. Coincubation with P. gingivalis induced a different pattern of gene expression for MAPK pathways, but it did not suppress the MAPK-related genes upregulated by CSC. A significant phosphorylation of ERK1/2 and p38 was observed in cells stimulated with 10 μg/mL CSC (p < 0.05), whereas coincubation with a higher concentration of CSC (250 μg/mL) evoked no such activation. P. gingivalis infection resulted in a tendency to reduce the phosphorylation of ERK1/2 and p38, which had been enhanced by stimulation with 10 μg/mL CSC. Incubation with ERK1/2 and p38 inhibitors significantly reduced the wound closure of CSC-stimulated cells, by approximately 43% and 46%, respectively (p < 0.05). Conclusion CSC exerts effects on the migration of human gingival epithelial cells through the activation of the MAPK ERK1/2 and p38 signaling pathways. P. gingivalis infection attenuates the CSC-induced migration at least partly by suppressing the phosphorylation of ERK1/2 and p38, but other pathways are likely to be involved in this modulatory process. [ABSTRACT FROM AUTHOR]

From November 17 to 20 in 2015, the Conference on Transposition and Genome Engineering 2015 ( TGE 2015) was held at Nara Kasugano International Forum- IRAKA-in Nara, Japan, located at the center of Nara Park. All of the presentations were carried out at Nohgaku hall in Nara Kasugano International Forum- IRAKA. Participation totaled 148 persons (30 international, 118 domestic), who were able to engage in lively scientific discussions over the 4-day period. The guest speaker list consisted of many top-notch international researchers, an achievement for which the conference received praise from the attendees. There were 36 oral presentations including the keynote lecture (22 presentations from guest speakers, complemented with 14 selected from abstract submissions). Additionally, there were 46 poster presentations. The conference uniquely combined research mainly from two different genomics approaches: (i) transposon technology allowing random genomic integration followed by gene discovery-related phenotypes and (ii) genome editing technology with designer nuclease allowing precise modification of a gene-of-interest. [ABSTRACT FROM AUTHOR]

Cancer stem cells ( CSCs) are maintained under special microenvironment called niche, and elucidation and targeting of the CSC niche will be a feasible strategy for cancer eradication. Tumor-associated macrophages ( TAMs) are known to be involved in cancer progression and thus can be a component of CSC niche. Although TAMs are known to play multiple roles in tumor progression, involvement of CSCs in TAM development fully remains to be elucidated. Using rat C6 glioma side population ( SP) cells as a model of glioma CSCs, we here show that CSCs induce the TAM development by promoting survival and differentiation of bone marrow-derived monocytes. CSC-induced macrophages can be separated into two distinct subsets of cells, CD11clow and CD11chigh cells. Interestingly, only the CD11chigh subset of cells have protumoral activity, as shown by intracranial transplantation into immune-deficient mice together with CSCs. These CD11chigh macrophages were observed in the tumor formed by co-transplantation with CSCs. Furthermore, CSCs produced GM- CSF and anti- GM- CSF antibody inhibited CSC-induced TAM development. In conclusion, CSCs have the ability to self-create their own niche involving TAMs through CSC-derived GM- CSF, which can thus be a therapeutic target in view of CSC niche disruption. [ABSTRACT FROM AUTHOR]

GASC1, also known as KDM4C/ JMJD2C, is a histone demethylase for histone H3 lysine 9 (H3K9) and H3K36. In this study, we observed an increase of GFAP-positive astrocytes in the brain of Gasc1 hypomorphic mutant mice at 2-3 months of age, but not at postnatal day 14 and day 30 by immunohistochemistry. Increases of GFAP-positive astrocytes were widely observed in the forebrain and prominent in such regions as cerebral cortex, caudate putamen, amygdala and diencephalon, but not obvious in hippocampus. Taken together with our observations to be published elsewhere that Gasc1 hypomorphic mutant mice exhibit abnormal behaviors including hyperactivity, persistence and many types of learning and memory deficits and abnormal synaptic functions such as prolonged long-term potentiation, the increase in GFAP-positive astrocytes may help understand their phenotypes, because astrocytes are known to affect synaptic plasticity. [ABSTRACT FROM AUTHOR]

Background and Objective Epithelial cells are recognized as the first line of defense against bacterial infection and environmental harmful stimuli such as cigarette smoke ( CS). Although previous studies explored the effects of nicotine on host cells, mechanisms by which CS affects cellular functions remain uncertain. The present study investigated the effects of CS condensate ( CSC) on in vitro wound closure of gingival epithelial cells and their potential interactions with a major periodontal pathogen, Porphyromonas gingivalis. Material and Methods Human gingival epithelial cells (Ca9-22) were treated with CSC for 24 h. Cell proliferation was determined using a WST-1 assay. Cell migration was assessed using a wound closure model. The expression of integrins was analyzed by confocal scanning laser microscopy and real-time PCR. Intracellular invasion of P. gingivalis was evaluated by confocal scanning laser microscopy and an antibiotic protection assay. Results Low concentrations (1-10 μg/mL) of CSC showed no significant effect on cell proliferation. CSC demonstrated dual effects on epithelial wound closure of Ca9-22 cells: high concentrations (i.e. 250 μg/mL) significantly inhibited the wound closure whereas low concentrations (i.e. 10 μg/mL) promoted it ( p < 0.01). CSC induced distinct changes in cytoskeleton. When CSC-exposed cells were infected with P. gingivalis for 2 h, a significant inhibition of wound closure was observed concurrent with a decrease in integrin α3 expression near the wound area. A significantly increased P. gingivalis invasion into Ca9-22 was observed when exposed to low concentrations of CSC. Conclusion Low concentrations of CSC increased invasion of human gingival epithelial cells by P. gingivalis and induced changes in cytoskeleton and integrin expression, thereby modulating the cell migration. [ABSTRACT FROM AUTHOR]

Aim To compare the pharmacokinetics of radiofrequency ( RF) ablation with chemolipiodolization using cisplatin ( CDDP) powder and miriplatin ( MPT) in a porcine liver. Methods Twelve pigs were divided equally into four groups. After each CDDP powder-lipiodol suspension ( n = 6; groups A and B) or MPT-lipiodol suspension ( n = 6; groups C and D) was injected into the lateral left artery, one RF ablation was performed at the lateral left lobe of each pig. Six pigs (groups A and C) were killed on the same day as treatment, whereas the other pigs (groups B and D) were killed 7 days after the treatment. The platinum concentrations in venous blood were assayed at 15, 60 and 120 min, and 7 days after treatment. The platinum concentrations in the ablated area and the surrounding liver were also examined. Results Plasma platinum concentrations of the CDDP group peaked at 15 min, and then gradually diminished over time (μg units), while plasma platinum levels in the MPT group gradually increased over time (ng units). Liver tissue platinum concentrations of the CDDP group were significantly lower in non-ablative areas than in ablated areas at days 0 and 7, while liver concentrations of the MPT group were significantly higher in non-ablative areas than in ablated areas at day 7. Conclusion MPT may be a suitable chemotherapeutic agent to stagnate platinum in the surrounding liver. [ABSTRACT FROM AUTHOR]

ABSTRACT Corticosteroid injections are widely used to treat enthesopathy and tendinitis, but are also associated with possible side effects, such as tendon degeneration or rupture. However, the mechanism of tendon degeneration or rupture after corticosteroid injection remains controversial. The purpose of this study was to reveal the mechanism of tendon degeneration or rupture after injection of triamcinolone acetonide (TA) or prednisolone (PSL). Forty-two rats were divided into 3 groups: A normal saline injection group (control group), a TA injection group, and a PSL injection group; the normal saline or corticosteroid was injected around the Achilles tendon. One or 3 weeks after injection, the tendons were subjected to biomechanical testing and histological analysis. At 1 week, the biomechanical strength was significantly lower in the corticosteroid groups. Histological analysis, at 1-week post-injection, showed collagen attenuation, increased expression of MMP-3 and apoptotic cells in the corticosteroid groups. The histological changes and biomechanical weaknesses of the tendon were not seen at 3 weeks. These alterations appeared to be involved in tendon degeneration or rupture after corticosteroid injection. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1297-1304, 2014. [ABSTRACT FROM AUTHOR]

CENP- A is a centromere-specific variant of histone H3 that is required for accurate chromosome segregation. The fission yeast Schizosaccharomyces pombe and mammalian Mis16 and Mis18 form a complex essential for CENP- A recruitment to centromeres. It is unclear, however, how the Mis16- Mis18 complex achieves this function. Here, we identified, by mass spectrometry, novel fission yeast centromere proteins Mis19 and Mis20 that directly interact with Mis16 and Mis18. Like Mis18, Mis19 and Mis20 are localized at the centromeres during interphase, but not in mitosis. Inactivation of Mis19 in a newly isolated temperature-sensitive mutant resulted in CENP- A delocalization and massive chromosome missegregation, whereas Mis20 was dispensable for proper chromosome segregation. Mis19 might be a bridge component for Mis16 and Mis18. We isolated extragenic suppressor mutants for temperature-sensitive mis18 and mis19 mutants and used whole-genome sequencing to determine the mutated sites. We identified two groups of loss-of-function suppressor mutations in non-sense-mediated m RNA decay factors ( upf2 and ebs1), and in SWI/ SNF chromatin-remodeling components ( snf5 , snf22 and sol1). Our results suggest that the Mis16- Mis18- Mis19- Mis20 CENP- A-recruiting complex, which is functional in the G1- S phase, may be counteracted by the SWI/ SNF chromatin-remodeling complex and non-sense-mediated m RNA decay, which may prevent CENP- A deposition at the centromere. [ABSTRACT FROM AUTHOR]

Background Inter-vendor discordance in three-dimensional speckle-tracking echocardiography (3 DS) remains uncharacterized. We aimed to examine inter-vendor discordance of left ventricular ( LV) volumes, and functional parameters and their reproducibilities between two commercially available 3 DS systems. Methods Echocardiographic examinations with 3 DS were performed in 26 healthy subjects (age 34 ± 13 years, 85% men) using a Vivid E9 system (V1) with 4V probe (GE Health Care) and Artida (V2) with PST-25 SX probe (Toshiba Medical Systems) on the same day. LV variables and global LV longitudinal, circumferential, radial, and area strains were measured by vendor-specific softwares, 4D strain Echo PAC BT11 (for V1) and 3D WMT (for V2), respectively. Reproducibility of data was assessed by an intra-class correlation coefficient ( ICC). Results The mean time required for 3 DS analysis was 5.4 ± 1.5 min for V1, being 21% less than that for V2 (6.8 ± 1.9 min, P < 0.01). Reproducibilities of all LV strains were comparable between V1 ( ICC 0.50-0.82) and V2 ( ICC 0.51-0.76), except for intra-observer and inter-observer reproducibilities of radial strain being lower in V2 ( ICC for V1 0.82 and 0.82 and ICC for V2 0.44 and 0.40, respectively). LV strains in all directions and area were significantly different between V1 and V2, though LV volumes and ejection fraction were comparable. Conclusions Global longitudinal, circumferential, and area LV strains are reproducible in both 3 DS vendors. However, values of three-dimensional LV strains by 3 DS are highly vendor-dependent. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate osteogenesis using an artificial fusion protein (AFP) composed of modified bone morphogenetic protein 2 (BMP-2) with a titanium (Ti)-binding peptide (TBP) motif on a Ti surface in vivo. In the in vivostudy, 5-μm thick Ti was coated with electron cyclotron resonance sputtering on a porous carbon scaffold which was then dipped in one of three different mixtures of collagen gel: (1) collagen gel only, (2) collagen gel with TBP, and (3) collagen gel with the AFP between BMP-2 and the TBP motif (AFP-TBP-BMP-2). These scaffolds were then implanted into rat abdominal muscles and were studied histologically at various times and the expression of several bone-related protein messenger RNAs (mRNAs) was also analyzed. The Ti-coated scaffold of the collagen gel with AFP-TBP-BMP-2 produced cartilage in the muscle and the expression of alkaline phosphatase, bone sialoprotein, and runt-related gene 2 mRNAs was significantly increased. These results suggest that the scaffold of the collagen gel with AFP-TBP-BMP-2 accelerates osteogenesis in vivo. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1180-1186, 2014. [ABSTRACT FROM AUTHOR]

Background and Aim: To examine the efficacy and outcomes of radiotherapy (RT) in patients who have hepatocellular carcinoma with invasion to intrahepatic large vessels (IHLVs). Methods: Sixty-seven patients who had advanced hepatocellular carcinoma with invasion to IHLVs received three-dimensional conformal RT. IHLV invasion was associated with portal venous tumor thrombosis in 40 patients, tumor thrombosis involving the hepatic vein in 17, and both findings in 10. A daily radiation dose of 1.8-2 Gy was administered using 6 or 10 MV X-rays to deliver a total dose of 30-56 Gy. Results: The overall objective response rate (complete response plus partial response) was 45% (n = 30). The median survival time was 13.7 months in the responder group and 5.9 months in the nonresponder group. An objective response was observed in 28 (56%) of 50 patients with Child-Pugh (C-P) class A and in 2 (12%) of 17 patients with C-P class B. Hepatic function of C-P class A was an independent factor for both RT responder and overall survival on Cox regression analysis (hazard ratio = 9.5, 95% confidence interval = 1.97-46.2, P = 0.005; and hazard ratio = 0.39, 95% confidence interval = 0.2-0.77, P = 0.007, respectively). Conclusion: RT is an effective treatment option without serious adverse events. RT should be considered for the patients with better hepatic function who have invasion to IHLVs. [ABSTRACT FROM AUTHOR]