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Supplementary Table 1 from Enhanced Spontaneous and Benzo(a)pyrene-Induced Mutations in the Lung of Nrf2-Deficient gpt Delta Mice

The lung is an organ that is sensitive to mutations induced by chemicals in ambient air, and transgenic mice harboring guanine phosphoribosyltransferase (gpt) gene as a target gene are a well-established model system for assessing genotoxicity in vivo. Transcription factor Nrf2 mediates inducible and constitutive expression of cytoprotective enzymes against xenobiotics and mutagens. To address whether Nrf2 is also involved in DNA protection, we generated nrf2+/−::gpt and nrf2−/−::gpt mice. The spontaneous mutation frequency of the gpt gene in the lung was approximately three times higher in nrf2-null (nrf2−/−) mice than nrf2 heterozygous (nrf2+/−) and wild-type (nrf2+/+) mice, whereas in the liver, the mutation frequency was higher in nrf2−/− and nrf2+/− mice than in nrf2+/+ wild-type mice. By contrast, no difference in mutation frequency was observed in testis among the three genotypes. A single intratracheal instillation of benzo(a)pyrene (BaP) increased the lung mutation frequency 3.1- and 6.1-fold in nrf2+/− and nrf2−/− mice, respectively, compared with BaP-untreated nrf2+/− mice, showing that nrf2−/− mice are more susceptible to genotoxic carcinogens. Surprisingly, mutation profiles of the gpt gene in BaP-treated nrf2+/− mice was substantially different from that in BaP-untreated nrf2−/− mice. In nrf2−/− mice, spontaneous and BaP-induced mutation hotspots were observed at nucleotides 64 and 140 of gpt, respectively. These results thus show that Nrf2 aids in the prevention of mutations in vivo and suggest that Nrf2 protects genomic DNA against certain types of mutations. [Cancer Res 2007;67(12):5643–8]

Supplementary Table 4 from Enhanced Spontaneous and Benzo(a)pyrene-Induced Mutations in the Lung of Nrf2-Deficient gpt Delta Mice

Supplementary Table 2 from Enhanced Spontaneous and Benzo(a)pyrene-Induced Mutations in the Lung of Nrf2-Deficient gpt Delta Mice

Supplementary Table 3 from Enhanced Spontaneous and Benzo(a)pyrene-Induced Mutations in the Lung of Nrf2-Deficient gpt Delta Mice

The COVID-19 pandemic has forced people to change many behaviours, including physical distancing, hygiene measures and lifestyles. This study aimed to evaluate the indirect impact of the COVID-19 pandemic on the incidence of non-COVID-19 infections and medical care costs/visits using health insurance claims.This was an observational study using patient-based administrative claims covering approximately 800,000 insured persons and their dependents in the Mie Prefecture in Japan.This study identified non-COVID-19 infectious disease incidences, number of outpatient visits and healthcare costs between 2017 and 2021. Each year was divided into quarters. The adjusted incidence rate ratios (IRRs) during the pandemic (January 2020 to September 2021) and during the prepandemic period (January 2017 to December 2019) were determined using Poisson regression.The adjusted influenza IRRs from April 2020 were close to zero. The incidence of upper respiratory tract infections and bacterial pneumonia was significantly reduced (IRRs range: 0.39-0.73 and 0.43-0.84, respectively). Gastrointestinal and urinary tract infection incidences decreased by approximately 30% and 10%, respectively. In contrast, sexually transmitted infections (STIs), including syphilis, gonococcal infection and Chlamydia trachomatis infection, did not decrease during the pandemic but increased significantly between April and June 2021 (adjusted IRR, 1.37; 95% confidence interval, 1.18-1.60). The adjusted IRRs for outpatient visits and healthcare costs were 0.86-0.93 and 0.91-0.97, respectively.In contrast to other infections, STIs did not decrease during the COVID-19 pandemic. The IRR of STIs during the pandemic period is an area of public health concern. Appropriate screening and medical consultations are strongly recommended.

We hypothesized that suppression of peripheral circulation

Hematological toxicities induced by pemetrexed plus platinum therapy remain a critical issue in clinical practice. We hypothesized that inhibition of the renin-angiotensin system (RAS) can ameliorate pemetrexed-induced hematological toxicities through drug-drug interactions involving organic anion transporters. Thus, this study aimed to clarify whether RAS inhibitors (RASIs) could prevent pemetrexed plus platinum-induced hematological toxicities. We retrospectively analyzed data from 305 consecutive patients with non-small cell lung cancer or malignant pleural mesothelioma who received their first cycle of a pemetrexed plus platinum regimen and were treated with or without RASIs. The primary endpoint was the incidence of severe myelosuppression after the first cycle. Propensity score (PS)-matched, PS-adjusted, and inverse probability of treatment weighting (IPTW) analyses were used. The number of patients with grade ≥3 hematological toxicities was 27 (8.9%). PS-matched analyses revealed that the concomitant use of RASIs was slightly associated with a lower risk of grade ≥3 hematological toxicities (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.20-2.32

Introduction and Purpose Surgical left ventricular (LV) septal myectomy in patients with obstructive hypertrophic cardiomyopathyhas been shown to reduce left ventricular outflow tract (LVOT) gradient and improve symptoms. We investigated changes in strain analysis, LA volume and LV systolic and diastolic function in patients with HOCM after surgical septal myectomy. Methods We enrolled consecutive 30 patients (age 63.7 ± 11.0 years, 47% Female), who underwent surgical LV septal myectomy for HOCM from 2012 to 2019. We evaluated LV dimension, LVOTG, LV-stroke volume, LV in flow pattern (E wave, A wave, Dct), e’(septal and lateral), LA volume, mitral regurgitation (MR), systolic anterior motion of mitral valve (SAM) and Global longitudinal strain. These parameters were evaluated at baseline and after LV myectomy at medium term (at least 6 months after surgery). Results They are followed for a mean of 3.4± 1.9 years after surgery. Eight patients underwent concomitant procedure; mitral valve repair and annuloplasty in 3 patients (10%), Maze surgery in 1 patient, LV aneurysmectomy in 2 patients and aortic valve replacement in 3 patients (10%). Patients with concomitant procedure were excluded from LV function analysis. Postoperative LVOTG were controlled in 10mmHg or less.Global longitudinal strain (GLS) improved but no significant change. Otherwise LA volume index decreased (from 52.5 ± 16.7 to 32.9 ± 14.6 ml/m2, p = 0.01) and LV diastolic function improved with an increase in lateral e" velocity (from 4.5 ± 2.8 to 9.2 ± 3.4 cm/sec, p = 0.001) and improved E/e’ (from 18.9 ± 5.6 to 10.6 ± 5.2, p Conclusion Excellent relief of LVOT obstruction in HOCM by surgical LV septal myectomy results in decreased LA volume and LV diastolic function with improved symptoms.

Objective Surgical septal myectomy is the gold-standard therapy for hypertrophic obstructive cardiomyopathy (HOCM). The aims of our study are to investigate anatomical characteristics and make clear effectiveness of transaortic extended left ventricular (LV) myectomy for HOCM. Methods This study enrolled 28 consecutive patients (age 66.7 ± 12.1 years, 46% Female) from 2012 to 2018 who met the following inclusion criteria: symptoms of heart failure persisting despite optimal medical therapy including beta blockers and Class I anti-arrhythmic agent, LV outflow tract gradient (LVOTG) > 50mmHg at rest or with provocation using stress echo (exercise TTE or low-dose dobutamine stress echo). We evaluated LV dimension, LVOTG, mitral regurgitation (MR), systolic anterior motion of mitral valve (SAM), Mitral complex morphology, high echoic region of endocardium and appearance of abnormal muscle bundles including apical-basal muscle bundle. These parameters were evaluated based on changes in LVOTG, MR and SAM at after LV myectomy. Also, intraoperative findings and cardiomyocytes pathological findings were evaluated. Stress echo were performed to investigate sustained reduction of LVOTG at medium term. Results All patients were successfully underwent transaortic extended LV myectomy. SAM was identified in all and moderate MR in 14 patients. The anterior mitral valve leaflet height was large in all patients and 16 patients had LV abnormal muscle bundles. Postoperative LVOTG were controlled in 10mmHg or less. SAM disappeared completely in all patients and MR were decreased mild or less. LVOTG were sustained good control in 10mmHg or less under stress echo at medium term. Conclusion LV myectomy provides excellent relief from LVOT obstruction. The appearance of mitral valve anterior leaflet and abnormal band may be important keys of LVOT obstruction.

Background Olanzapine (OLZ) 10 mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. Guidelines suggest that OLZ at a dose of 5 mg should be taken into consideration in patients at risk of sedation. OLZ 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5 mg in addition to standard antiemetic therapy for the prevention of CINV. Methods Patients receiving cisplatin (≥ 50 mg/m2) were randomly assigned to either OLZ 5 mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). As the secondary endpoints, frequency of sleepiness during daytime and appetite loss were assessed by patient reported outcome. Results A total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was significantly increased with OLZ than with placebo (79% vs. 66%, P Conclusions OLZ 5 mg can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Sleepiness during daytime due to OLZ 5 mg seems to be tolerable and addition of OLZ 5mg to the standard antiemetic therapy may reduce appetite loss. Legal entity responsible for the study Masakazu Abe. Funding Japan Agency for Medical Research and Development. Disclosure S. Iwasa: Honoraria (self): Taiho pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Ono Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Bristol-Myers Squib; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer. N. Yamamoto: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Merck Serono. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, An Immediate Family Member : Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: Celltrion; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho pharmaceutical; Honoraria (self): Kyowa Hakko Kirin; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Ignyta. All other authors have declared no conflicts of interest.

In today's highly globalised world, protecting human security is a core challenge for political leaders who are simultaneously dealing with terrorism, refugee and migration crises, disease epidemics, and climate change. Promoting universal health coverage (UHC) will help prevent another disease outbreak similar to the recent Ebola outbreak in west Africa, and create robust health systems, capable of withstanding future shocks. Robust health systems, in turn, are the prerequisites for achieving UHC. We propose three areas for global health action by the G7 countries at their meeting in Japan in May, 2016, to protect human security around the world: restructuring of the global health architecture so that it enables preparedness and responses to health emergencies; development of platforms to share best practices and harness shared learning about the resilience and sustainability of health systems; and strengthening of coordination and financing for research and development and system innovations for global health security. Rather than creating new funding or organisations, global leaders should reorganise current financing structures and institutions so that they work more effectively and efficiently. By making smart investments, countries will improve their capacity to monitor, track, review, and assess health system performance and accountability, and thereby be better prepared for future global health shocks.

Summary What is known and objective In Japan, although topiroxostat, a selective xanthine oxidoreductase inhibitor, has been used for the treatment of patients with hyperuricemia including gout, no published randomized controlled studies evaluating the dose-dependent relationship with respect to the serum urate-lowering efficacy have been reported. The aim of this study was to evaluate the dose-dependent relationship with serum urate-lowering efficacy and safety of topiroxostat in Japanese hyperuricemic patients including gout. Methods We conducted an exploratory, phase 2a, multicentre, randomized, double-blind, 8-week, placebo-controlled study in Japanese hyperuricemic patients with or without gout. The study arms were placebo and topiroxostat 40, 60, 80 or 120 mg/day. The primary efficacy endpoint was the per cent change in serum urate level from baseline to the final visit. Results and discussion One hundred and eighty-seven eligible patients were randomized and 186 received at least one dose of the study drug. The study results demonstrated a dose-dependent serum urate reduction effect ranging from 40 to 120 mg/day (P < 0·001, Jonckheere–Terpstra test). The mean per cent change in serum urate level from baseline at the final visit was −30·8% in the 120-mg group and 1·6% with placebo, with a between-group difference of −32·4% ([95% confidence interval, −38·9% to −25·9%]; P < 0·001). Incidences of overall adverse events (AEs) in the topiroxostat groups were comparable to those in the placebo group; however, the incidence of AEs in the 120-mg group was statistically lower than that in the placebo group. The incidences of gouty arthritis were not statistically but numerically higher in the topiroxostat 80- and 120-mg groups. What is new and conclusions A dose-dependent serum urate-lowering efficacy of topiroxostat was observed in Japanese hyperuricemic male patients with or without gout. Further clinical studies aimed at evaluating the long-term safety and clinical efficacy are warranted.

Heavy rain causes landslide and debris flow, which produce sediment and woody debris in the mountain river basin. During the process, woody debris and sediment are trapped by the obstacles. As a result, woody debris accumulations at bridges are formed. Trapped woody debris at the bridge caused inundation because the obstacle blocked the water flow in the river course. To get more information regarding the woody debris accumulation at a bridge, laboratory flume was used for experiments to investigate the characteristics of woody debris accumulation at a model bridge without a pier. As a result, the experiments show that the number of trapped wood pieces increases with the number of released pieces. Moreover, the trapped wood pieces caused wood accumulations at the model bridge and backwater rise in its upstream side region. Besides that, the backwater rise increase with a number of trapped wood pieces at the bridges.

This paper reports the structural and optical investigations of the structural colour of the weevil Lamprocyphus augustus . The photonic crystal structure within the weevil's scales was investigated using sequential focused ion-beam milling and scanning electron microscopy imaging. We carefully analysed the reconstructed three-dimensional structure to determine the unit cell of the photonic crystal. It was found that the cuticle network of the cubic unit cell perfectly matches the previously reported diamond-based network. However, different results were obtained for the crystal orientations of the small crystal domains that comprise the entire photonic crystal structure in the scales: directions are highly preferred along the surface normal of the scale. This finding explains the fact that the scale is almost uniformly coloured despite the multi-domain structure. It is confirmed experimentally and theoretically that the wavelength range of the reflection band corresponds to the gap of the photonic band.

Dose adjustment of vancomycin (VCM) is important in improving clinical outcomes and avoiding adverse effects such as nephrotoxicity. Although pharmacist-managed VCM therapy has been reported to optimize treatment, there are no studies focused on pharmacist expertise to date. In this study, we compared the contribution of pharmacists trained for infectious diseases and general pharmacists to dose adjustment of VCM.We retrospectively investigated VCM trough concentration after dose adjustment by both trained (n = 67) and general (without special training for infectious diseases; n = 85) pharmacists. We also compared the incidence of nephrotoxicity during VCM treatment in both groups.The rate of achieving therapeutic VCM trough concentration (10-20 μg/mL) was higher in the trained group than in the control group (80.6 vs. 54.1%, p0.001). No significant differences in incidence of nephrotoxicity were observed between the two groups (p = 0.744). Trained pharmacists could contribute more successfully to the achievement of therapeutic VCM concentration ranges without increasing the risk of nephrotoxicity.

A recent report described that sodium glucose cotransporter (SGLT) 1 and 2 were expressed in α cells, and dapagliflozin which is a specific SGLT2 inhibitor, increased plasma glucagon levels by inhibiting SGLT2 in α cells. However, it is still controversial whether SGLT2 inhibitors increase plasma glucagon levels in vivo. Here, we showed that dapagliflozin, but not canagliflozin which is a SGLT2/low-potency-SGLT1 inhibitor, increased plasma glucagon levels in mice fed a high-fat, high-sucrose diet (HFHSD) and diabetic db/db mice. A glucose clamp study revealed that the plasma glucagon increase associated with dapagliflozin could be explained as a response to acute declines in blood glucose. RT-PCR and whole RNA sequencing revealed that SGLT1 and glucose transporter 1 (GLUT1), but not SGLT2, were expressed in αTC1 cells and mouse islets. We showed that canagliflozin suppressed glucagon secretion by inhibiting SGLT1 in α cells; consequently, plasma glucagon did not increase with canagliflozin, even though blood glucose declined. We also showed that the SGLT1 effect on glucagon secretion depended on sodium/glucose cotransport, but not on metabolic effect of glucose. Islets from HFHSD and db/db mice displayed higher SGLT1 expression and lower GLUT1 expression than the islets from control mice. These expression levels were associated with glucagon secretion levels. Furthermore, SGLT1 inhibitor and siRNA against SGLT1 suppressed glucagon secretion in isolated islets. These data suggested that a novel mechanism regulated glucagon secretion, through SGLT1, in α cells. This finding explained the distinct effects of dapagliflozin and canagliflozin on plasma glucagon levels in mice. Disclosure T. Suga: None. O. Kikuchi: None. M. Kobayashi: None. S. Matsui: None. H.H. Hashimoto: None. T. Sasaki: None. S. Kakizaki: None. M. Yamada: None. T. Kitamura: None.

The outcomes of treatment for women with recurrent or advanced epithelial ovarian carcinoma previously treated with pacli- taxel plus platinum-based chemotherapy were analyzed.Retrospective analysis was performed in a total of 65 series of treatments provided for 35 patients with a history of paclitaxel plus platinum-based chemotherapy. The chemotherapy regimens used were classified into the following four types for analysis: conventional paclitaxel plus carboplatin therapy (TC arm), pegylated liposomal doxorubicin-containing regimens (PLD arm), CPT-11-containing regimens (CPT-11 arm), and others. Disease-control rates (DCRs) were compared and subjected to univariate analysis. Progression-free survival (PFS) was determined from the date of the first cycle of each chemotherapy with the Kaplan-Meier method, and comparisons were performed using the log-rank test.DCR was 80%, 71%, and 26% for the TC, PLD, and CPT-l arms, respectively. The median PFS was 286, 372, and 76 days for the TC, PLD, and CPT-11 arms, respectively. There was no discernible difference in PFS between the TC and the PLD arm. In contrast, PFS of the CPT- 11 arm was significantly shorter than that of the TC and PLD arms. In addition, three of seven (42.9%) treatments in the PLD arm maintained a progression-free period for longer than one year, while only one of 25 (4%) treatments in the TC arm maintained a progression-free period for more than one year.The PFS of PLD is similar to that of TC. PLD-containing regimens might have a potential benefit with a higher PFS over one year than the TC regimen.

Small hepatocytes have hepatocyte-like characteristics and high proliferation activity. Most small hepatocyte studies report on in vitro rat or human hepatocytes. Only a few studies of small hepatocytes after bile duct ligation have been reported, and none of these have focused on these cells in birds. In this study, small hepatocytes appearing in bile duct ligation chicken liver were examined using the morphological method with histological, immunohistochemical, and ultrastructural studies. Nine Boris Brown hens (over 744-d old) were used. In all chickens, both the common hepatoenteric duct and hepatocystic duct were ligated, and the livers were examined 1, 4, 6, 9, and 13 weeks after bile duct ligation. Histologically, the small cells were half the size of normal liver cells, and mitotic figures were often observed. The nuclei showed two forms: large and small. Many small cells were negative for periodic acid-Schiff stain, but positive cells were rarely observed. The cells existed in colonies on the side of the sinusoid of the hepatic lamina. Immunohistochemically, the small cells with large nuclei were strongly positive for CD44, albumin and proliferation cell nuclear antigen, and the cells with small nuclei were weakly positive. In the CD44-positive cell colony, negative cells were often observed to have mature hepatocyte-like morphology. Moreover, many of the cells were PAN cytokeratin negative. Ultrastructurally, the small cells had more nuclei with rich heterochromatin, poor cytoplasmic organelles, and narrow cytoplasm with a high electron density than mature hepatocytes. Moreover, cells having a middle ultrastructural characteristic existed between the small cells and mature hepatocytes. The small hepatocellular colony of the chicken appeared as a regeneration-related change in the liver after bile duct ligation. The cell had high cell proliferation activity and morphological, immunohistochemical, and ultrastructural characteristics similar to those of the mammalian small hepatocyte, as well as a similar progenitor cell.

Comparison of the unit cell structure between the theory (left) and experiment (right).

To determine the toxicological effect of ZnO nanoparticles (NPs), inflammatory responses, serum biological parameters and oxidative stress markers of Superoxide dismutase (SOD) were evaluated followed by intravenous treatment of ZnO NPs in mice.Inflammatory responses induced by a dose of 0.2 mg/kg ZnO NPs, followed by a single intravenous treatment were examined in mice. In addition, the serum biological parameters and oxidative stress markers were evaluated. Blood and spleen were collected following treatment. The mRNA transcript levels of inflammatory-related genes (TNF-α and IL1-β) were elevated in the spleen cells of mice treated with ZnO NPs at 12h.The elevated levels of TNF-α and IL1-β in supernatants of spleen cell cultures of mice treated with ZnO NPs were also observed at 24h. The serum aspartate aminotransferase, glutamate pyruvate alanine aminotransferase, and lactate dehydrogenase levels significantly increased at 6h and 12h in ZnO NPs treated group, indicating liver cell injury and tissue damage. On the other hand, no elevation was observed in BUN and Cre, biochemical markers of kidney damage. SOD activities were significantly elevated at 24 h and 48 h.This study shows the ZnO induced pro-inflammatory response in vivo, that this response may be related to oxidative stress, and to show hepatic damage at an early stage.

The dental follicle is an ectomesenchymal tissue that surrounds developing tooth germ and that contains osteoblastic-lineage-committed stem/progenitor cells. We examined the osteogenic potential of human dental follicle cells (hDFC) by microarray analysis. We first compared the characteristics of hDFC with those of human bone marrow mesenchymal stem cells (hMSC). Like hMSC, hDFC expressed stem cell markers such as STRO-1 and Notch-1 and differentiated not only into the osteoblastic lineage, but also into the adipogenic lineage. We analyzed the gene expression profiles of hDFC and hMSC that were not differentiated toward the osteogenic lineage. The expression of cell markers and growth factor receptors by hDFC and hMSC was similar, whereas the expression pattern of homeobox genes differed between hDFC and hMSC. Next, we investigated gene expression in hDFC during osteogenic differentiation. Gene expression profiles were analyzed in hDFC cultured in osteogenic induction medium (OIM) or in growth medium (GM) for 3 and 10 days. Many genes whose expression was regulated under these conditions were functionally categorized as "transcription" genes. Osteogenic markers were up-regulated in hDFC during osteogenic differentiation, whereas neurogenic markers were down-regulated. The genes whose expression was regulated in hDFC during osteogenic differentiation were further analyzed by ingenuity pathway analysis and real-time polymerase chain reaction. Bone morphogenetic protein and transforming growth factor-β signaling pathways were activated in hDFC cultured in OIM for 3 days. This study indicates that the dental follicle contains stem cells and/or osteoblastic progenitor cells and is a potential cellular resource for bone regeneration therapy.

We (JMAAV [Japanese patients with MPO-ANCA-associated vasculitis] Study Group) performed a prospective, open-label, multi-center trial to evaluate the usefulness of severity-based treatment in Japanese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA)-associated vasculitis. Patients with MPO-ANCA-associated vasculitis received a severity-based regimen according to the appropriate protocol: low-dose corticosteroid and, if necessary, cyclophosphamide or azathioprine in patients with mild form; high-dose corticosteroid and cyclophosphamide in those with severe form; and the severe-form regimen plus plasmapheresis in those with the most severe form. We followed up the patients for 18 months. The primary end points were the induction of remission, death, and end-stage renal disease (ESRD). Fifty-two patients were registered, and 48 patients were enrolled in this study (mild form, n = 23; severe form, n = 23; most severe form, n = 2). Among the 47 patients who received the predefined therapies, 42 achieved remission within 6 months, 5 died, and 1 developed ESRD. Disease flared up in 8 of the 42 patients with remission during the 18-month follow-up period. The JMAAV trial is the first prospective trial for MPO-ANCA-associated vasculitis to be performed in Japan. The remission and death rates were comparable to those in several previous clinical trials performed in western counties. The regimen employed in this trial was tailor-made based on patients’ disease severity and disease type, and it seems that standardization can be consistent with treatment choices made according to severity.

BACKGROUND: Conservative treatments have been proposed for people with shoulder impingement syndrome (SIS), such as strengthening of the rotator cuff and scapular muscles and stretching of the soft tissues of the shoulder. However, there is a lack of studies analyzing the effectiveness of eccentric training in the treatment of SIS. OBJECTIVES: To evaluate the effects of eccentric training for shoulder abductors on pain, function, and isokinetic performance during concentric and eccentric abduction of the shoulder in subjects with SIS. METHODS: Twenty subjects (7 females, 34.2 SD 10.2 years, 1.7 SD 0.1 m, 78.0 SD 16.3 kg) with unilateral SIS completed the study protocol. Bilateral isokinetic eccentric training at 60º/s for shoulder abductors was performed for six consecutive weeks, twice a week, on alternate days. For each training day, three sets of 10 repetitions were performed with a 3-minute rest period between the sets for each side. The range of motion trained was 60° (ranging from 80° to 20°). The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was used to evaluate functional status and symptoms of the upper limbs. Peak torque, total work and acceleration time were measured during concentric and eccentric abduction of the arm at 60º/s and 180º/s using an isokinetic dynamometer. RESULTS: DASH scores, peak torque, total work and acceleration time improved (pCONTEXTUALIZAÇÃO: Tratamentos conservadores têm sido propostos para pessoas com síndrome do impacto (SI) do ombro, como fortalecimento do manguito rotador e dos músculos escapulares e alongamento dos tecidos moles do ombro. No entanto, são escassos os estudos que analisaram a eficácia do treinamento excêntrico no tratamento da SI. OBJETIVOS: Avaliar os efeitos do treinamento excêntrico para abdutores do ombro na dor, função e desempenho isocinético durante a abdução concêntrica e excêntrica do ombro em indivíduos com SI. MÉTODOS: Vinte indivíduos (sete mulheres, 34,2 DP 10,2 anos, 1,7 DP 0,1 m, 78,0 DP 16,3 kg) com SI unilateral completaram o protocolo do estudo. Realizou-se treinamento isocinético excêntrico bilateral a 60º/s para abdutores do ombro durante seis semanas consecutivas, duas vezes por semana, em dias alternados. Para cada dia de treinamento, foram realizadas três séries de dez repetições, com um período de descanso de 3 minutos entre as séries para cada lado. A amplitude de movimento treinada foi de 60° (de 80° a 20°). O questionário Disabilities of the Arm, Shoulder and Hand (DASH) foi utilizado para avaliar a função e os sintomas dos membros superiores. O pico de torque, o trabalho total e o tempo de aceleração foram avaliados durante a abdução concêntrica e excêntrica do braço a 60º/s e 180º/s por meio de um dinamômetro isocinético. RESULTADOS: As pontuações do DASH, o pico de torque, o trabalho total e o tempo de aceleração melhoraram (p

1Center for Nuclear Study, University of Tokyo, Wako 351-0198, Japan 2Institute of Physics, VAST, Hanoi, Vietnam 3Japan Atomic Energy Agency, Tokai, Ibaraki 351-1195, Japan 4Department of Physics, Kyushu University, Fukuoka 812-8581, Japan 5Department of Physics, Tohoku University, Sendai 980-8578, Japan 6Department of Physics, Tsukuba University, Tsukuba 305-8571, Japan 7Faculty of Science, Yamagata University, Yamagata 990-8560, Japan 8Department of Physics, University of McMaster, Canada 9Universita di Catania and INFN-LNS, Catania, Italy 10Department of Physics, Seoul National University, Seoul, Korea 11Ewha Womans’ University, Seoul, Korea 12Institute of Modern Physics, Lanzhou, China 13Department of Physics, Chung Ang University, Seoul, Korea 14Max-Planck-Institut fur Astrophysik, D-85748 Garching, Germany