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In order to optimize the biogas recovery from the co-digestion of food waste (FW) and paper waste (PW), the effect of PW content on two-phase anaerobic digestion (TPAD) was investigated. The mixtures of FW and PW, with the ratios of 10:0, 8:2, 6:4 and 5:5 (total solids), were fed into TPAD to recover biomethane. After the long-term expriment, it is elucidated that the methanogenesis in TPAD was stable for PW ≤ 40%. When PW = 50%, NH 4 HCO 3 was added to the methanogenic phase to provide nitrogen. As the indicators of the stability of the anaerobic process, the ammonia and alkalinity in the methanogenic phase were simulated for their decreasing trend. The simulation results quantified the nitrogen deficiency in the methanogenic phase for PW = 50%. Also, the comparison of alkalinity and ammonia revealed that ammonia was the major contributor to the alkalinity. Furthermore, via stoichiometric calculations, high C/N ratios were found to increase the microbial yield and exacerbated the nitrogen deficiency. In the energy estimation, adding PW showed significant increase only when PW ≥ 40%. It was concluded that 40% was the optimal PW content for bioenergy augmentation from co-digestion of FW and PW using TPAD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We sought to determine the influence of age on cardiorespiratory kinetics during sinusoidal walking in two groups: 13 healthy young subjects (YG; 7 men and 6 women, age 21 ± 2 years) and 15 healthy elderly subjects (ELD; 9 men and 6 women, age 67 ± 5 years). A treadmill's speed was sinusoidally changed between 3 and 6 km h -1 in the YG and between 3 and 5 km h -1 in the ELD during periods of 1, 2, 5, and 10 min, and in a stepwise manner. We compared the groups' heart rate (HR), ventilation ( V ˙ E ), and gas exchange (CO 2 output ( V ˙ CO 2 ) and O 2 uptake ( V ˙ O 2 )) responses. We determined the phase shift ( PS ) and the normalized amplitude ( Amp ) ratio of these kinetics in relation to the sinusoidal change in walking speed in response to the magnitude from the maximum to minimum speeds as revealed by a Fourier analysis in all cardiorespiratory variables. Both the Amp ratio and PS in the V ˙ E , V ˙ CO 2 , and V ˙ O 2 responses were very similar between the ELD and YG, and being independent of the periods of sinusoidal oscillations. In marked contrast, the PS of the HR kinetics was significantly slowed in the ELD compared to the YG. The Amp ratio of HR was not related to the covariance variation of HR (CVHR) at standing rest in the ELD. The HR kinetics during sinusoidal walking may not be attributable to parasympathetic nerve activity into the heart in the ELD. The slope of the Amp of V ˙ E related to the Amp of V ˙ CO 2 ( V ˙ E / V ˙ CO 2 slope) was steeper in the ELD (0.0258) compared to the YG (0.0132), suggesting that exercise hyperpnea could be greatly induced during walking in the ELD. These findings suggest that aging influences the alterations of autonomic nervous system-dependent slower HR kinetics and exercise hyperpnea during walking in the ELD.

The usefulness of a radiotelemetric pedometer for estrus detection in standing (ST) heat, or in silent heat without ST events, but in which ovulation is observed, in Japanese Black cattle was investigated. The duration of an increase in steps in ST heat was 11.8 ± 1.3 hr, and it was similar to that of ST events (duration: 10.1 ± 0.8 hr). Even in silent heat, the change pattern and the duration (11.6 ± 0.2 hr) of the period with an increase in steps during estrus were not different compared with ST heat. When artificial insemination (AI) was performed at 15.5 ± 0.6 hr from the onset of estrus detected by the pedometer in ST heat cases, the conception rate was 57.1% (8/14). Furthermore, fertility in cattle that underwent silent heat was evaluated. When AI was performed at 14.4 ± 2.0 hr from the onset of estrus detected by the pedometer, the conception rate was 60% (3/5) in silent heat cases. The overall results suggest that the radiotelemetric pedometer is a valid device for detecting estrus and it can even detect silent heat in Japanese Black cattle. Moreover, even silent heat cattle are fertile when AI is performed at the appropriate time., (© 2018 Japanese Society of Animal Science.)

Oral surgery can be difficult in patients with chorea-like dyskinesia, which is common in those on long-term levodopa medication for Parkinson's disease, and we know of no conclusive evidence to indicate whether conscious sedation with midazolam is effective in such cases. We report a patient in whom levodopa-induced chorea-like dyskinesia disappeared when midazolam was given intravenously for conscious sedation., (Copyright © 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

We evaluated the utility of the continuous measurement of vaginal temperature by a wireless sensor and wireless connection for predicting the onset of calving and for clarifying the relationships among dystocia, calf conditions, and temperature changes at a commercial beef cattle farm in Japan. A total of 625 effective delivery data was collected. The temperature sensor inserted to the vagina on 7 days before the expected due date and collected the vaginal temperature every 5 min. The sensor detected two alerts according to the temperature change, one was the vaginal temperature of 4 h moving average compared to the same time temperature of last two days decreased more than 0.4 °C (Alert 1) and the other was the rupture of the allantoic sac and the dropped sensor temperature reached to the ambient temperature (Alert 2). The detection rates of Alert 1 and Alert 2 were 88.3% and 99.4%, respectively. The average time between Alert 1 and Alert 2 (Time 1) was 22 h, and that between Alert 2 and delivery (Time 2) was 2 h. These results indicated that the continuous measurement of vaginal temperature is effective for predicting the calving time. The necessity of assistance was correlated with dystocia, calf birth weight (BW), sex, and gestation periods. Interestingly, the durations of Times 1 and 2 were also associated with dystocia. The calf BW, sex, and gestation periods affected the length of Time 2. Our findings indicate that the BW of the calf is the most important factor for dystocia risk, and that the continuous measurement of vaginal temperature could become a good indicator for predicting not only the onset of calving, but also the necessity of assistance., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We investigated the electrical impedance of the reproductive tracts (vagina and uterine endometrial tissues) and the expression of mucus-related genes to identify the stage of the estrous cycle in mares. We first examined vaginal impedance in native Hokkaido mares during their estrous cycle and found no significant differences. However, impedance levels tended to decrease towards ovulation. Furthermore, we investigated the estrous cycle by measuring the electrical impedance of the uterine endometrial tissues obtained from carcasses of mares. We found that impedance levels in the endometrial tissues decreased in the regressed phase of the corpus luteum (CL). Expression of mucus-related genes (ATP1A1, CFTR, AQP3, and AQP5) varied at different stages of the estrous cycle. Among them, AQP3 expression was consistent with previous reports. We concluded that electrical impedance in the uterine endometrial tissues of mares could be potentially used to verify the presence of active CL in horses for experimental purposes. However, further studies are needed to determine the reference value and to identify the day of the estrous cycle in mares.

Selection of functional spermatozoa plays a crucial role in assisted reproduction. Passage of spermatozoa through the female reproductive tract requires progressive motility to locate the oocyte. This preferential ability to reach the fertilization site confers fertility advantage to spermatozoa. Current routine sperm selection techniques are inadequate and fail to provide conclusive evidence on the sperm characteristics that may affect fertilization. We therefore developed a selection strategy for functional and progressively motile bovine spermatozoa with high DNA integrity based on the ability to cross laminar flow streamlines in a diffuser-type microfluidic sperm sorter (DMSS). The fluid dynamics, with respect to microchannel geometry and design, are relevant in the propulsion of spermatozoa and, consequently, ultrahigh-throughput sorting. Sorted spermatozoa were assessed for kinematic parameters, acrosome reaction, mitochondrial membrane potential, and DNA integrity. Kinematic and trajectory patterns were used to identify fertility-related subpopulations: the rapid, straighter, progressive, nonsinuous pattern (PN) and the transitional, sinuous pattern (TS). In contrast to the conventional notion that the fertilizing spermatozoon is always vigorously motile and more linear, our results demonstrate that sinuous patterns are associated with fertility and correspond to truly functional spermatozoa as supported by more live births produced from predominant TS than PN subpopulation in the inseminate. Our findings ascertain the true practical application significance of microfluidic sorting of functional sperm characterized by sinuous trajectories that can serve as a behavioral sperm phenotype marker for fertility potential. More broadly, we foresee the clinical application of this sorting technology to assisted reproduction in humans., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Greenhouse gas emissions from different sewage treatment plants: oxidation ditch process, double-circulated anoxic-oxic process and anoxic-oxic process were evaluated based on the survey. The methane and nitrous oxide characteristics were discussed based on the gaseous and dissolved gas profiles. As a result, it was found that methane was produced in the sewer pipes and the primary sedimentation tank. Additionally, a ventilation system would promote the gasification of dissolved methane in the first treatment units. Nitrous oxide was produced and emitted in oxic tanks with nitrite accumulation inside the sewage treatment plant. A certain amount of nitrous oxide was also discharged as dissolved gas through the effluent water. If the amount of dissolved nitrous oxide discharge is not included, 7-14% of total nitrous oxide emission would be overlooked. Based on the greenhouse gas calculation, electrical consumption and the N 2 O emission from incineration process were major sources in all the plants. For greenhouse gas reduction, oxidation ditch process has an advantage over the other advanced systems due to lower energy consumption, sludge production, and nitrogen removal without gas stripping., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In order to investigate the phase separation and microbial distribution in the TPAD, the conventional thermophilic-mesophilic type (TM-TPAD) and the hyperthermophilic-mesophilic type (HM-TPAD) were operated with a single-stage mesophilic anaerobic digestion (MAD) as control. HM-TPAD accomplished the volatile solids destruction 14.5% higher than MAD. Calculating conversion efficiencies distinguished the separation of acidogenic and methanogenic phases in HM-TPAD, which was not found in TM-TPAD. The differences on microbial distributions also reflected the phase separation in HM-TPAD. The protein degraders, Coprothermobacter had higher abundance in the first stage than the second stage of HM-TPAD but it had similar abundance between the two stages of TM-TPAD. Also, the archaeal communities from the two stages of HM-TPAD shared the least similarity but those from the two stages of TM-TPAD were closely similar., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16.8 ± 3.5 mL/min/kg and 18.4 ± 12.2% for TMD-322, respectively. The area under the plasma concentration-time curves of cetrozole and TMD-322 after oral administration was markedly lower than that of anastrozole because of their high hepatic clearance. Two subjects out of six exhibited 4- and 17-fold larger exposure of cetrozole than the others following intravenous and oral administration, respectively. Such variation was not observed for TMD-322 and anastrozole. Extensive metabolism of cetrozole and TMD-322 was observed in the CYP2C19 expression system among the test CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). We report the first clinical investigation of our aromatase inhibitors by a cassette microdose strategy in healthy Japanese subjects. This strategy offers an optional approach for candidate selection as a phase zero study in drug development., (Copyright © 2017. Published by Elsevier Ltd.)

A novel single-stage partial nitritation-anammox process equipped with porous functional suspended carriers was developed at 25°C in a CSTR by controlling dissolved oxygen <0.3mg/L. The nitrogen removal performance was almost unchanged over a nitrogen loading rate ranging from 0.5 to 2.5kgNH 4 + -N/m 3 /d with a high nitrogen removal efficiency of 81.1%. The specific activity of AOB and anammox bacteria was of 3.00g-N/g-MLVSS/d (the suspended sludge), 3.56g-N/g-MLVSS/d (the biofilm sludge), respectively. The results of pyrosequencing revealed that Nitrosomonas (5.66%) and Candidatus&#95;Kuenenia (4.95%) were symbiotic in carriers while Nitrosomonas (40.70%) was predominant in the suspended flocs. Besides, two specific types of heterotrophic filamentous bacteria in the suspended flocs (Haliscomenobacter) and the functional carrier biofilm (Longilinea) were shown to confer structural integrity to the aggregates. The novel single-stage partial nitritation-anammox process equipped with functional suspended carriers was shown to have good potential for the nitrogen-rich wastewater treatment., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Nickel(0)-catalyzed cross-coupling of methoxyarenes through C-O bond activation has been the subject of considerable research because of their favorable features compared with those of the cross-coupling of aryl halides, such as atom economy and efficiency. In 2008, we have reported nickel/PCy 3 -catalyzed cross-coupling of methoxyarenes with arylboronic esters in which the addition of a stoichiometric base such as CsF is essential for the reaction to proceed. Recently, we have also found that the scope of the substrate in the Suzuki-Miyaura-type cross-coupling of methoxyarenes can be greatly expanded by using 1,3-dicyclohexylimidazol-2-ylidene (ICy) as the ligand. Interestingly, a stoichiometric amount of external base is not required for the nickel/ICy-catalyzed cross-coupling. For the mechanism and origin of the effect of the external base to be elucidated, density functional theory calculations are conducted. In the nickel/PCy 3 -catalyzed reactions, the activation energy for the oxidative addition of the C(aryl)-OMe bond is too high to occur under the catalytic conditions. However, the oxidative addition process becomes energetically feasible when CsF and an arylboronic ester interact with a Ni(PCy 3 ) 2 /methoxyarene fragment to form a quaternary complex. In the nickel/ICy-catalyzed reactions, the oxidative addition of the C(aryl)-OMe bond can proceed more easily without the aid of CsF because the nickel-ligand bonds are stronger and therefore stabilize the transition state. The subsequent transmetalation from an Ar-Ni-OMe intermediate is determined to proceed through a pathway with lower energies than those required for β-hydrogen elimination. The overall driving force of the reaction is the reductive elimination to form the carbon-carbon bond.

Reactive oxygen species (ROS) are unstable molecules that activate oxidative stress. Because of the insufficient blood flow in tumors, the tumor microenvironment is often exposed to hypoxic condition and nutrient deprivation, which induces ROS accumulation. We isolated tumor endothelial cells (TECs) and found that they have various abnormalities, although the underlying mechanisms are not fully understood. Here we showed that ROS were accumulated in tumor blood vessels and ROS enhanced TEC migration with upregulation of several angiogenesis related gene expressions. It was also demonstrated that these genes were upregulated by regulation of Nuclear factor erythroid 2-related factor 2 (NRF2). Among these genes, we focused on Biglycan, a small leucine-rich proteoglycan. Inhibition of Toll-like receptors 2 and 4, known BIGLYCAN (BGN) receptors, cancelled the TEC motility stimulated by ROS. ROS inhibited NRF2 expression in TECs but not in NECs, and NRF2 inhibited phosphorylation of SMAD2/3, which activates transcription of BGN. These results indicated that ROS-induced BGN caused the pro-angiogenic phenotype in TECs via NRF2 dysregulation.

The operation performance of a novel micro-granule based syntrophic system of nitritation and anammox was studied by controlling the oxygen concentration and maintaining a constant temperature of 25°C. With the oxygen concentration of around 0.11 (<0.15)mg/L, the single-stage nitritation-anammox system was startup successfully at a nitrogen loading rate (NLR) of 1.5kgN/m 3 /d. The reactor was successfully operated at volumetric N loadings ranging from 0.5 to 2.5kgN/m 3 /d with a high nitrogen removal of 82%. The microbial community was composed by ammonia oxidizing bacteria (AOB) and anammox bacteria forming micro-granules with an average diameter of 0.8mm and good settleability. Results from pyrosequencing analysis revealed that Ca. Kuenenia and Nitrosomonas were selected and enriched in the community over the startup period, and these were identified as the dominant anammox bacteria and AOB species, respectively., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Review, safety, and relief services of the Pharmaceuticals and Medical Devices Agency are primarily focused on scientifically evaluating pharmaceuticals, medical devices, and cellular and tissue-based products referring to their quality, efficacy, and safety, which requires a variety of scientific knowledge and methods. Pharmaceutical regulation should be established based on the most advanced scientific expertise at all times. In order to evaluate products that use cutting-edge technology such as induced pluripotent stem cells and information and communication technology adequately, since fiscal year 2012 the Science Committee has been established as a platform to exchange opinions among members from top-ranking domestic and international academia and to enhance personnel exchanges through the Initiative to Facilitate Development of Innovative Drugs. In addition, the Regulatory Science Center will be established in 2018 to increase the integrity of our services for product reviews and safety measures. In particular, requiring electronic data submissions for clinical trial applications followed by an advanced approach to analysis should not only enhance the quality of reviews of individual products but should also support the development of pharmaceuticals and medical devices by providing pharmaceutical affairs consultations on research and development strategies with various guidelines based on new insights resulting from product-bridging data analysis. Moreover, a database including electronic health records with comprehensive medical information collected mainly from 10 cooperating medical institutions will be developed with the aim of developing safety measures in a more timely manner using methods of pharmacoepidemiological analysis.

Iguchi, J, Watanabe, Y, Kimura, M, Fujisawa, Y, Hojo, T, Yuasa, Y, Higashi, S, and Kuzuhara, K. Risk factors for injury among Japanese collegiate players of American football based on performance test results. J Strength Cond Res 30(12): 3405-3411, 2016-The purpose of this study was to identify how risk factors for injury during American football are related to players' physical strength as determined using typical performance tests. One hundred 53 Japanese collegiate players of American football were recruited for this study. Eight potential risk factors were evaluated: position (skill vs. lineman), body mass index, back squat one-repetition maximum, vertical jump height, power, height, body weight, and previous injury. Using multivariate Cox regression, we examined how these factors were associated with knee sprain, ankle sprain, and hamstring strain. We recorded 63 injuries (17 knee sprains, 23 ankle sprains, and 23 hamstring strains). Players with higher power were at significantly greater risk for knee sprains (p = 0.04), those with low power had a significantly higher incidence of ankle sprain (p = 0.01), and vertical jump height was a significant predictor of hamstring strain (p = 0.02). We identified several independent predictors of injuries associated with American football. Our findings may contribute to the development of effective screening tests and prevention exercises.

The accumulation of soluble microbial production (SMP) in an anammox attached film expanded bed (AAFEB) and its effect on the reactor performance were investigated in this study. During the long-term experiment, an extended HRT resulted in the accumulation of SMP and the change of treatment performance. When the SMP increased from 10.5±1.5mgL -1 to 31.7±6.4mgL -1 with the increase of influent TN concentration from 313mgL -1 to 2500mgL -1 , the TN removal efficiency was stable. However, when the influent TN concentration was 3500mgL -1 , the SMP concentration increased higher than 100mgL -1 , the reactor soon became inhibited. Bath tests indicated that both the specific anammox activity (SAA) and the substrate tolerance ability decreased during the stable operation phases, whereas the specific denitrification activity (SDA) was significantly enhanced. In addition, N 2 O emissions in the anammox-denitrifier symbiotic system were greater than in the conventional nitrogen removal process., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

It has been described that tumor progression has many similarities to inflammation and wound healing in terms of the signaling processes involved. Among biological responses, angiogenesis, which is necessary for tumor progression and metastasis, is a common hallmark; therefore, tumor blood vessels have been considered as important therapeutic targets in anticancer therapy. We focused on pentraxin 3 (PTX3), which is a marker of cancer-related inflammation, but we found no reports on its expression and function in tumor blood vessels. Here we showed that PTX3 is expressed in mouse and human tumor blood vessels based on immunohistochemical analysis. We found that PTX3 is upregulated in primary mouse and human tumor endothelial cells compared to normal endothelial cells. We also showed that PTX3 plays an important role in the proliferation of the tumor endothelial cells. These results suggest that PTX3 is an important target for antiangiogenic therapy., (© 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Programmed necrosis (necroptosis) is an alternative form of programmed cell death that is regulated by receptor-interacting protein kinase (RIPK) 1 and 3-dependent, but is a caspase (CASP)-independent pathway. In the present study, to determine if necroptosis participates in bovine structural luteolysis, we investigated RIPK1 and RIPK3 expression throughout the estrous cycle, during prostaglandin F2α (PGF)-induced luteolysis in the bovine corpus luteum (CL), and in cultured luteal steroidogenic cells (LSCs) after treatment with selected luteolytic factors. In addition, effects of a RIPK1 inhibitor (necrostatin-1, Nec-1; 50 μM) on cell viability, progesterone secretion, apoptosis related factors and RIPKs expression, were evaluated. Expression of RIPK1 and RIPK3 increased in the CL tissue during both spontaneous and PGF-induced luteolysis (P < 0.05). In cultured LSCs, tumor necrosis factor α (TNF; 2.3 nM) in combination with interferon γ (IFNG; 2.5 nM) up-regulated RIPK1 mRNA and protein expression (P < 0.05). TNF + IFNG also up-regulated RIPK3 mRNA expression (P < 0.05), but not RIPK3 protein. Although Nec-1 prevented TNF + IFNG-induced cell death (P < 0.05), it did not affect CASP3 and CASP8 expression. Nec-1 decreased both RIPK1 and RIPK3 protein expression (P < 0.05). These findings suggest that RIPKs-dependent necroptosis is a potent mechanism responsible for bovine structural luteolysis induced by pro-inflammatory cytokines.

Objective: To determine the effect of acupuncture performed at the synovial and ligamentous tendon sheath (A1 pulley site) on pain during snapping and the severity of the snapping phenomenon in patients with trigger finger., Methods: In this observational study, changes in the patients' condition were compared before and after acupuncture treatment. Acupuncture was performed on 19 fingers of 15 patients. Acupuncture needles were inserted into the radial and ulnar sides of the flexor tendon at the A1 pulley of the affected finger. Treatment was performed daily up to a maximum of five times. Before and after each treatment, pain during snapping and the severity of snapping were evaluated using a visual analogue scale (VAS)., Results: VAS scores for pain and snapping severity were significantly improved immediately after the first treatment (p<0.001). Pain during snapping, assessed before each treatment, improved over time, reaching statistical significance from the second treatment onwards (p<0.001); similarly, a significant improvement in the severity of snapping was observed, also from the second treatment (p<0.001). Patients with clinically significant improvements (≥50%) in pain and snapping severity had a significantly shorter duration of the disorder than those with <50% improvement (p<0.05)., Conclusions: Acupuncture at the impaired A1 pulley site may be an effective treatment for trigger finger. We postulate that acupuncture may reduce inflammation/swelling of the synovial membrane of the tendon sheath, which predominates when the disorder is of short duration. Further research is required to confirm the efficacy/effectiveness of acupuncture for trigger finger and its mechanisms of action., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Preoperatively diagnosed ductal carcinoma in situ (DCIS) has the potential to have occult invasion. The predictors of invasive carcinoma underestimation in patients with DCIS diagnosed by preoperative percutaneous biopsy were identified and the effects of underestimation on axillary management were evaluated., Methods: Medical records of 280 patients preoperatively diagnosed as DCIS who underwent surgery were retrospectively analyzed. The patients were divided into non-invasive and invasive carcinoma groups according to the final pathological diagnosis. Risk predictors of invasive carcinoma underestimation and axillary lymph node (ALN) metastasis were analyzed. The axillary status estimated by pathological diagnosis and one-step nucleic acid amplification (OSNA) assay was evaluated., Results: The presence of an invasive carcinoma was overlooked in 104 (37.1 %) patients. A clinically palpable mass was an independent risk predictor of invasive carcinoma underestimation by multivariate analysis. There was no risk predictor of ALN metastasis. No ALN metastasis was seen in non-invasive carcinoma group. Six (6.2 %) patients in invasive carcinoma group had macro- or micrometastasis in sentinel lymph nodes (SLNs). Non-SLN metastasis was observed in 3 patients of them. Fourteen patients with only isolated tumor cells (ITCs) or only OSNA-positive SLNs had no metastasis in non-SLNs., Conclusions: SLN biopsy and, if necessary, subsequent ALN dissection (ALND) should be performed in patients with DCIS who have a risk predictor of underestimation. ALND can be avoided in patients who have histologically negative or ITC-positive SLNs, regardless of the presence of invasion on final pathological diagnosis.

Background: Breast angiosarcomas are rare neoplasm. Due to its rarity, our therapeutic strategy is extremely limited. Therefore, we investigated the clinicopathologic features and examined the treatment for angiosarcoma compared with some literatures., Methods: We conducted a retrospective chart and slide review of all patients in our division seen from 1997 to 2012 with a diagnosis of primary or secondary breast angiosarcoma at the National Cancer Center Hospital (Tokyo, Japan)., Results: Nine patients were diagnosed with breast angiosarcoma (six primary and three secondary cases). The median age of patients with primary angiosarcoma was 39 years (range 27-65 years). The median tumor size was 6.78 cm (range 3.0-8.8 cm). In the primary tumor, 4 patients had total mastectomy and 2 had a breast conserving surgery. 3- and 5-year disease-free survival (DFS) of the patients with primary angiosarcoma was 20 and 0 %. 5-year surviving rate of primary angiosarcoma was 50 %. In all patients with secondary angiosarcoma, recurrence was observed in all cases. But one case obtained long-term survival in local control therapy., Conclusions: Our study demonstrates breast angiosarcoma exhibits high recurrence rates. Tumor size and surgical margin may be important factor to obtain long-term survival. In this point of view, total mastectomy with adequate tumor margin with early detection is desired. In case of recurrence, if it is local, surgery may be potentially curative.

Background: Various posterior elbow problems cause posterior elbow pain among baseball players. We aimed to determine the prevalence and diagnoses associated with posterior elbow problems and post-treatment recovery time for returning to sports in Japanese high school baseball players when treated in the off-season., Methods: A total of 576 Japanese high school baseball players who participated in baseball skill training camp during the off-season were enrolled in the study. The elbow of each player's throwing arm was assessed by use of a questionnaire and physical examination. Players with abnormal results were advised to visit the hospital. Players who visited the hospital were initially treated conservatively and underwent surgery if necessary. Retrospectively, players with positive physical examination results associated with posterior elbow pain, defined as olecranon tenderness and/or a positive elbow extension impingement test, were selected. Information about their position, elbow pain, physical examination results, diagnosis, treatment, and recovery time before returning to playing sports was assessed., Results: Olecranon tenderness and/or positive elbow extension impingement test results were found in 76 players (13.2%). Of these, 33 agreed to visit the hospital for further diagnostic imaging and 25 players (75.8%) were diagnosed with posteromedial elbow impingement. By the next spring, 87.9% of players returned to sport, and 100% of players returned to sport before the next summer. The average recovery period was 77 ± 47 days., Conclusion: Physical examinations related to posterior elbow injuries were positive in 13.2% of high school baseball players. The most common diagnosis for posterior elbow pain was posteromedial elbow impingement. All players returned to competitive sports activity levels within 77 ± 47 days., (Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

A lab-scale upflow anaerobic sludge blanket (UASB) has been run for 250days to investigate the influence of influent COD/SO4(2-) ratios on the biodegradation behavior of starch wastewater and process performance. Stepwise decreasing COD/SO4(2-) ratio enhanced sulfidogenesis, complicating starch degradation routes and improving process stability. The reactor exhibited satisfactory performance at a wide COD/SO4(2-) range ⩾2, attaining stable biogas production of 1.15-1.17LL(-1)d(-1) with efficient simultaneous removal of total COD (73.5-80.3%) and sulfate (82.6±6.4%). Adding sulfate favored sulfidogenesis process and diversified microbial community, invoking hydrolysis-acidification of starch and propionate degradation and subsequent acetoclastic methanogenesis; whereas excessively enhanced sulfidogenesis (COD/SO4(2-) ratios <2) would suppress methanogenesis through electrons competition and sulfide inhibition, deteriorating methane conversion. This research in-depth elucidated the role of sulfidogenesis in bioenergy recovery and sulfate removal, advancing the applications of UASB technology in water industry from basic science., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: We investigated the effects of electrical stimulation therapy on cutaneous and muscle blood flow in critical limb ischemia patients following regenerative therapy., Methods: Three groups were studied: 10 healthy young subjects, 10 elderly subjects, and 7 critical limb ischemia patients after regenerative therapy. After 5 min rest, electrical stimulation was applied at 5 Hz on the tibialis anterior muscle for 10 min. We estimated the relative changes in oxyhemoglobin and total hemoglobin compared to the basal values at rest (Δ[HbO2], Δ[Hbtot]), which reflected the blood flow in the skin and muscle layer, and we simultaneously measured the tissue O2 saturation (StO2) throughout the electrical stimulation and recovery phase by near-infrared spectroscopy., Results: The Δ[HbO2] and Δ[Hbtot] values of the muscle layer in critical limb ischemia patients increased gradually and remained significantly higher at the 5-min and 10-min recovery periods after the electrical stimulation without reducing the StO2, but there is no significant change in the other two groups. Skin blood flow was not influenced by electrical stimulation in three groups., Conclusion: This improvement of the peripheral circulation by electrical stimulation would be beneficial as the adjunctive therapy after regenerative cell therapy.

Background: Ipsilateral breast tumor recurrence (IBTR) after partial breast resection and contralateral breast tumor recurrence (CBTR) have been shown to occur relatively frequently in patients with ductal carcinoma in situ (DCIS). However, there is only limited data from Japanese institutes to support this., Methods: Of 301 consecutive DCIS patients, 179 patients underwent a mastectomy, and the other 122 underwent partial resection in the National Cancer Center Hospital, Tokyo, with a median follow-up period of 2,106 days. We reviewed clinicopathological parameters including age, menopausal status, body mass index, family history (FH) of breast cancer, tumor size, histological subtype, nuclear grade (NG), hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, treatment, and the surgical margin status of partially resected specimens. The risk associated with each of these parameters for IBTR in 122 patients who underwent partial resections, and for CBTR in a total of 301 patients were calculated using Cox proportional hazard general linear models., Results: Of the 122 patients who underwent partial breast resection, IBTR occurred in 7 (5.7%). The risk of IBTR was higher or tended to be higher in younger patients or those with lower NG tumors, but did not change significantly with respect to margin status or irradiation. Amongst the entire cohort of 301 patients, CBTR occurred in 18 cases (6.0%). CBTR occurred significantly more frequently in patients with a FH of breast cancer and with HR+/HER2- subtype tumors by univariate analyses, and tumor subtype was an independent risk factor for CBTR by multivariate analysis., Conclusions: The local recurrence rate was low following partial resection of DCIS. Younger age was a risk factor for IBTR, whereas the HR+/HER2- tumor subtype and a FH of breast cancer were risk factors for CBTR.

This Phase III trial aims to determine the superiority of intensive follow-up to standard follow-up in terms of overall survival in high-risk breast cancer patients, who are expected to have recurrence rates of over 30% within 5 years after surgery. Eligible patients are randomized either to the intensive follow-up group or to the standard follow-up group; the former will undergo physical examination, bone scintigraphy, chest computed tomography, abdominal computed tomography, brain magnetic resonance imaging/computed tomography and frequent tumor marker evaluations, whereas the latter will undergo physical examination at the same frequency and tumor markers will be evaluated once a year. Mammography once a year is planned for both groups. The primary endpoint is overall survival. Patient accrual was started in November 2013. A total of 1700 patients will be enrolled for 3 years and followed up for 7 years after closure of accrual. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000012429., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Recent clinical trials have shown that axillary lymph node dissection can be omitted even with positive sentinel nodes (SN) unless the patient undergoes total mastectomy without irradiation. The aim of our study was to identify predictive factors for non-SN metastasis among patients with solitary or multiple breast cancer treated with total mastectomy., Patients and Methods: Clinically node-negative breast cancer patients with pathologically node-positive disease treated with total mastectomy and axillary dissection after SN biopsy were retrospectively analyzed. Significant pathologic predictive factors for positive non-SN metastasis were also examined., Results: There were 47 multiple and 143 solitary breast cancer patients. Pathologic diagnosis demonstrated that smaller invasion size but larger tumor size, including adjacent noninvasive cancer, was observed in multiple breast cancer. The number of involved SNs and the rate of non-SN metastasis were similar between the multiple and solitary groups. Regarding predictive factors for non-SN metastasis, lymphatic invasion and SN macrometastasis were significant factors in the solitary group, and pathologic invasion size > 2 cm was the only significant factor in the multiple group., Conclusion: Larger pathologic invasion size was important for predicting non-SN metastasis in multiple breast cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to retrospectively assess the oncological safety of breast-conserving surgery (BCS) after primary systemic chemotherapy (PST) in terms of local recurrence (LR) in cT3-4 patients., Methods: The subjects were 146 cT1-2 patients who underwent BCS after PST, and 169 patients with cT3-4 primary breast cancer. Of the 169 patients with cT3-4 disease, 20 underwent surgery first, and 149 underwent surgery after PST (mastectomy: 101 patients; BCS: 48 patients). The LR-free survival (LRFS) was analyzed using a Kaplan-Meier analysis. We evaluated the predictors using Cox proportional hazards modeling for LR after PST., Results: There was no significant difference in 5-year LRFS between the cT1-2 and cT3-4 groups that underwent BCS after PST (98.6 vs. 92.5 %; P = 0.074). The 5-year LRFS was 94.7 % in the group that underwent initial surgery and 93.0 % in the PST group (P = 0.845) in the cT3-4 patients, while the 5-year LRFS rates were 93.2 % in the BCS subgroup and 92.5 % in the mastectomy subgroup (P = 0.958). In a multivariate analysis, the histological type, hormone negativity and a higher histological grade were independent predictors of LR after PST., Conclusions: BCS after PST may be oncologically acceptable for cT3-4 breast cancers in terms of the LR compared with initial surgery or mastectomy after PST.

Intraductal papillary lesions of the breast constitute a heterogeneous entity, including benign intraductal papilloma (IDP) with or without atypia and malignant papillary carcinoma. Differentiating between these diagnoses can be challenging. We re-evaluated core biopsy specimens that were diagnosed as IDP and the corresponding surgical excision specimens, and assessed the potential risk for the diagnosis to be modified to malignancy based on excision. By sorting the pathology database of the National Cancer Center Hospital, Tokyo, we identified 146 core biopsy cases that were histologically diagnosed as IDP between 1997 and 2013. The re-evaluated diagnosis was IDP without atypia in 79 (54%) patients, IDP with atypia in 66 (45%), and ductal carcinoma in situ (DCIS) in 1 (1%). Among the 34 patients (23%) who underwent surgical excision subsequent to core biopsy, histological diagnosis was upgraded to carcinoma, excluding lobular carcinoma in situ (LCIS), in 14 (41%) cases, including 4 (33%) of 12 IDPs without atypia and 10 (45%) of 22 IDPs with atypia. Complete surgical excision should be kept in mind for all IDPs diagnosed on core biopsy, not only IDPs with atypia but IDPs without atypia, especially when clinical or imaging diagnosis findings cannot rule out the possibility of malignancy, because papillary lesions comprise a variety of morphological appearances., (© 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

At onset of muscle contraction, myoglobin (Mb) immediately releases its bound O2 to the mitochondria. Accordingly, intracellular O2 tension (PmbO2) markedly declines in order to increase muscle O2 uptake (mVO2). However, whether the change in PmbO2 during muscle contraction modulates mVO2 and whether the O2 release rate from Mb increases in endurance-trained muscles remain unclear. The purpose of this study was, therefore, to determine the effect of endurance training on O2 saturation of Mb (SmbO2) and PmbO2 kinetics during muscle contraction. Male Wistar rats were subjected to a 4-week swimming training (Tr group; 6 days per week, 30 min × 4 sets per day) with a weight load of 2% body mass. After the training period, deoxygenated Mb kinetics during muscle contraction were measured using near-infrared spectroscopy under hemoglobin-free medium perfusion. In the Tr group, the VmO2peak significantly increased by 32%. Although the PmbO2 during muscle contraction did not affect the increased mVO2 in endurance-trained muscle, the O2 release rate from Mb increased because of the increased Mb concentration and faster decremental rate in SmbO2 at the maximal twitch tension. These results suggest that the Mb dynamics during muscle contraction are contributing factors to faster VO2 kinetics in endurance-trained muscle.

Long-term performance of a lab-scale UASB reactor treating starch wastewater was investigated under different hydraulic retention times (HRT). Successful start-up could be achieved after 15days' operation. The optimal HRT was 6h with organic loading rate (OLR) 4g COD/Ld at COD concentration 1000mg/L, attaining 81.1-98.7% total COD removal with methane production rate of 0.33L CH4/g CODremoved. Specific methane activity tests demonstrated that methane formation via H2-CO2 and acetate were the principal degradation pathways. Vertical characterizations revealed that main reactions including starch hydrolysis, acidification and methanogenesis occurred at the lower part of reactor ("main reaction zone"); comparatively, at the up converting acetate into methane predominated ("substrate-shortage zone"). Further reducing HRT to 3h caused volatile fatty acids accumulation, sludge floating and performance deterioration. Sludge floating was ascribed to the excess polysaccharides in extracellular polymeric substances (EPS). More efforts are required to overcome sludge floating-related issues., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To examine the effect of electroacupuncture (EA) on early post-rupture tendon repair in a rat model of Achilles tendon rupture using histological and mechanical evaluation., Methods: An Achilles tendon rupture model was prepared in 90 Wistar rats, which were randomly assigned to EA, manual acupuncture or control groups. Rats in the EA group received EA (pulse width 5 ms; stimulation frequency 50 Hz; stimulation strength 20 μA; stimulation time 20 min) daily from 1 day following model preparation until the day of assessment (either 7 or 10 days after model preparation), when the region of interest was sampled to assess tendon repair using in vitro methods. Total cell count and the number of cells staining positive for transforming growth factor-β1 (TGF-β1) and basic fibroblast growth factor (b-FGF) were measured. Tension tests were performed 10 days after model preparation to measure the maximum breaking strength of the repaired tendon., Results: Both the total cell count and the number of cells positive for b-FGF were significantly higher in the EA group (p<0.05). In the EA group only, immunostaining showed strong expression of TGF-β1 7 days after model preparation (p<0.05). Maximum breaking strength of the repaired tendon 10 days after model preparation was significantly higher in the EA group (p<0.01)., Conclusions: The marked increase in cell count and growth factor expression as well as increased tendon strength in the EA group suggest that EA may be a useful method for promoting tendon repair., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: In patients who underwent breast-conserving surgery, we attempted to identify the histological characteristics of margin-exposed tumor components on intraoperative frozen section examinations that were predictive of residual tumor components in additionally resected specimens., Methods: Of 1835 patients who underwent breast-conserving surgery, we identified 220 patients who had positive surgical margins determined by intraoperative frozen section examinations and who had undergone immediate additional resections. Two observers (M.K., H.T.) reviewed the slides of frozen sections and confirmed the presence of tumor components., Results: In additionally resected specimens, residual tumors were detected in 115 cases (52.3%) but not in 105 cases (47.7%). The primary tumor characteristics of extensive intraductal component (+), younger age, invasive lobular carcinoma and pathological T3 classification were significantly associated with the residual tumor components. The margin-exposed tumor components of the maximum diameter, number of positive margins and histological type were correlated with the residual tumors. Multivariate analysis showed that the maximum tumor diameter was an independent risk factor for residual tumors., Conclusions: Diagnosis of positive margins by intraoperative frozen section examinations was useful for predicting residual tumors, and three histological properties of the margin-exposed tumor components were correlated with the status of residual tumor components. Although it was impossible to clearly identify the single main factor for predicting patients for whom additional resections were not necessary, it may be possible to consider stratification of additional surgical therapy according to the characteristics of margin-exposed tumor components on intraoperative frozen section examinations., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The corpus luteum (CL) forms after ovulation and acts as a temporary endocrine gland that produces progesterone (P4), a hormone that is essential for implantation and maintenance of pregnancy in mammals. In pregnant women, human chorionic gonadotropin (hCG) secreted by the conceptus prevents luteolysis. hCG also increases the survival of cultured human luteinized granulosa cells (hLGCs). To clarify the maintenance mechanism of the human CL, we investigated the effects of hCG and P4 receptor antagonists, onapristone (OP) and RU486, on the viability of hLGCs. With the patients' consent, hLGCs were isolated from follicular aspirates for in vitro fertilization. The cells were cultured with hCG (0.1, 1, 10, 100 IU/ml), OP (10, 25, 50, 100 μM), RU486 (100 μM), P4 (1, 10, 25, 50 μM) or some combination of the four for 24 h. Cell viability was significantly increased by hCG (100 IU/ml) and significantly decreased by OP (100 μM) compared with the control. Cells treated with hCG and OP together were significantly less viable than the control and OP-treated cells. The combined treatment also significantly increased CASP3 activity and cleaved CASP3 protein expression. Furthermore, P4 addition reversed the reduction in cell viability caused by the combination of hCG and OP treatment. The overall findings suggest that hCG cooperates with P4 to increase survival of hLGCs and to induce apoptosis when P4 action supported by hCG is attenuated in the human CL.

Long-term experiments herein were conducted to investigate the effect of cefalexin (CLX) on methane production during waste activated sludge (WAS) anaerobic digestion. CLX exhibited a considerable inhibition in methane production during the initial 25 days while the negative effect attenuated subsequently and methane production recovered depending on CLX doses used (600 and 1000 mg/L). The highest methane yield reached 450 mL at 1000 mg-CLX/L after 157 days of digestion, 63.8% higher than CLX-free one. Stimulated excretion of extracellular polymeric substances (EPS) by CLX served as microbial protecting layers, creating a suitable environment for microbes' growth and fermentation. Further examination via ultraviolet visible (UV-Vis) spectra also verified the elevated slime EPS, LB-EPS and TB-EPS indicated by UV-254 in the presence of CLX. Unlike the commonly accepted adverse effect, this study demonstrated the beneficial role of CLX in methane production, providing new insights into its true environmental impacts., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We developed and successfully fabricated a plannar light source device using a phosphor screen with single-walled carbon nanotubes (SWCNTs) as field emitters in a simple diode structure composed of the cathode containing the highly purified and crystalline SWCNTs dispersed into an organic In2O3-SnO2 precursor solution and a non-ionic surfactant. The cathode was activated by scratching process with sandpaper to obtain a large field emission current with low power consumption. The nicks by scratching were treated with Fourier analysis to determine the periodicity of the surface morphology and designed with controlling the count number of sandpapers. The anode, on the other hand, was made with phosphor deliberately optimized by coverage of ITO nanoparticles and assembled together with the cathode by the new stable assembling process resulting to stand-alone flat plane-emission panel. The device in a diode structure has a low driving voltage and good brightness homogeneity in that plane. Furthermore, field emission current fluctuation, which is an important factor in comparing luminance devices too, has a good stability in a simple diode panel. The flat plane-emission device employing the highly purified and crystalline SWCNTs has the potential to provide a new approach to lighting in our life style.

The number of breast augmentation surgeries (BAS) has increased. Therefore, the number of breast cancer patients with history of BAS has also increased. In this paper, we present two cases of sentinel lymph node biopsy (SLNB) in patients with previous BAS who were diagnosed with breast cancer. The patients were augmented using different approach; the first case was augmented through transaxillary incision, whereas the second case was augmented through periareolar incision. Lymphoscintigraphy (LPG) was performed on the patients 1 day prior to operation, enabling confirmation of lymphatic flow and SLN in both patients. SLNB was successfully performed in both cases. In one patient, SLNB was performed using indocyanine green (ICG) fluorescence and the Photodynamic Eye (PDE) system. Regardless of history of BAS, ICG and PDE system showed lymphatic flow and SLN in real time. LPG and ICG fluorescence were useful methods for SLN detection in patients with previous BAS, being able to confirm lymph flow before operation. Biopsy methods using LPG and PDE system were considered useful for difficult confirmation of lymph flow after breast augmentation. This is the first report of SLNB using ICG and PDE system for patients with previous BAS.

Background: The prevalence and clinical characteristics of osteochondritis dissecans (OCD) of the humeral capitellum among adolescent baseball players are unknown., Purpose: To determine the OCD prevalence in adolescent competitive baseball players and to investigate the clinical characteristics of these patients., Study Design: Cross-sectional and case-control study; Level of evidence, 3., Methods: A total of 2433 baseball players (mean age, 14.5 ± 1.5 years) belonging to junior high school and high school baseball clubs were enrolled. Players completed a questionnaire, and the elbow of each player's throwing arm was assessed by ultrasonography. Participants with abnormal results on ultrasonography were further examined through radiographic study. The OCD lesions were classified into stages based on radiographic results, and demographic data were compared between players with and without OCD lesions., Results: Osteochondritis dissecans of the humeral capitellum was found in 82 (3.4%) elbows by ultrasonography. Players with an OCD lesion began playing baseball at an earlier age (P = .016), had a longer duration of competitive play (P = .0013), and had experienced more present (P = .0025) and past (P < .0001) elbow pain compared with players without a lesion. There were no differences between the 2 groups in the position played (P = .26). Sixty-eight patients underwent further radiographic examination for OCD (radiography, computed tomography, magnetic resonance imaging). Of these players, 10 (14.7%) were classified as having stage I OCD (radiolucent stage); 26 (38.2%), stage II (fragmentation stage); 9 (13.2%), stage III (loose body stage); 9 (13.2%), stage IV (residual stage); and 14 (23.5%), stage V (postoperative stage)., Conclusion: The prevalence of OCD of the humeral capitellum, including latent cases, was 3.4% among adolescent baseball players. Players with OCD lesions began playing baseball at earlier ages, had played for longer periods, and had experienced more elbow pain. The player's current baseball position may not be related to the existence of OCD lesions in adolescents., (© 2014 The Author(s).)

Luteolysis is characterized by a reduction in progesterone (P4) production and tissue degeneration in the corpus luteum (CL). One of major events during luteolysis is luteal cell death. Galectin-3, a ubiquitously expressed protein involved in many cellular processes, serves as an antiapoptotic and/or proapoptotic factor in various cell types. Although galectin-3 is detected in the bovine CL, its role remains unclear. The expression of galectin-3 in the bovine CL was higher at the regressed stage than at the other luteal stages. Galectin-3 was localized on luteal steroidogenic cells (LSCs). When cultured LSCs were exposed to prostaglandin F2alpha (PGF) for 48 h, the expression and secretion of galectin-3 increased. When the cultured LSCs were treated with galectin-3 for 24 h, cleaved caspase-3 expression was increased, and the cell viability was decreased, whereas P4 production did not change. Beta 1 integrin, a target protein of galectin-3, was expressed in bovine CL and possessed glycans, which galectin-3 binds. Furthermore, galectin-3 bound to glycans of luteal beta 1 integrin. The decreased cell viability of cultured LSCs by galectin-3 was suppressed by beta 1 integrin antibody. The overall findings suggest that the secreted galectin-3 stimulated by PGF plays a role in structural luteolysis by binding to beta 1 integrin., (© 2014 by the Society for the Study of Reproduction, Inc.)

Nickel complexes of a series of β-diketiminate ligands ((R)L(-), deprotonated form of 2-substituted N-[3-(phenylamino)allylidene]aniline derivatives (R)LH, R = Me, H, Br, CN, and NO2) have been synthesized and structurally characterized. One-electron oxidation of the neutral complexes [Ni(II)((R)L(-))2] by AgSbF6 or [Ru(III)(bpy)3](PF6)3 (bpy = 2,2'-bipyridine) gave the corresponding metastable cationic complexes, which exhibit an EPR spectrum due to a doublet species (S = 1/2) and a characteristic absorption band in near IR region ascribable to a ligand-to-ligand intervalence charge-transfer (LLIVCT) transition. DFT calculations have indicated that the divalent oxidation state of nickel ion (Ni(II)) is retained, whereas one of the β-diketiminate ligands is oxidized to give formally a mixed-valence complex, [Ni(II)((R)L(-))((R)L(•))](+). Thus, the doublet spin state of the oxidized cationic complex can be explained by taking account of the antiferromagnetic interaction between the high-spin nickel(II) ion (S = 1) and the organic radical (S = 1/2) of supporting ligand. A single-crystal structure of one of the cationic complexes (R = H) has been successfully determined to show that both ligands in the cationic complex are structurally equivalent. On the basis of theoretical analysis of the LLIVCT band and DFT calculations as well as the crystal structure, the mixed-valence complexes have been assigned to Robin-Day class III species, where the radical spin is equally delocalized between the two ligands to give the cationic complex, which is best described as [Ni(II)((R)L(0.5•-))2](+). One-electron reduction of the neutral complexes with decamethylcobaltocene gave the anionic complexes when the ligand has the electron-withdrawing substituent (R = CN, NO2, Br). The generated anionic complexes exhibited EPR spectra due to a doublet species (S = 1/2) but showed no LLIVCT band in the near-IR region. Thus, the reduced complexes are best described as the d(9) nickel(I) complexes supported by two anionic β-diketiminate ligands, [Ni(I)((R)L(-))2](-). This conclusion was also supported by DFT calculations. Substituent effects on the electronic structures of the three oxidation states (neutral, cationic, and anionic) of the complexes are systematically evaluated on the basis of DFT calculations.

Background: Locoregional recurrence (LRR) after mastectomy reduces the patient's quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps achieve locoregional control and reduces LRR. However, in patients with large tumors, the question of which variables affect the likelihood of LRR and the role of PMRT have been subjects of substantial controversy. This study investigated what the risk factors are for LRR and the efficacy of PMRT in this patient population., Methods: This retrospective study examined 589 cases of invasive breast carcinoma with tumors 5 cm or larger from 1998 to 2008. We divided the study population into 3 groups: patients with negative nodes, 1-3 positive nodes, and ≥4 positive nodes. The relationship between various clinicopathological variables and LRR was examined, and the relationship between LRR and PMRT was estimated., Results: During the median follow-up of 44.2 months, 38 (6.5 %) patients experienced LRR. In the multivariate analysis, independent risk factors for LRR included pectoral invasion in patients with 1-3 positive nodes, severity of lymphatic invasion, estrogen receptor-negative status, and a nodal ratio of positive/excised nodes >0.50 in patients with ≥4 positive nodes. In patients without positive nodes, none of the examined variables were significantly associated with LRR. Although patients treated with PMRT had good outcomes, there was no significant difference., Conclusions: With systemic therapy and adequate lymph node dissection, PMRT by itself was of limited value in establishing locoregional control. Due to the very low incidence of LRR observed, PMRT was not necessary for patients with large tumors without lymph node metastasis. Further examination and consensus about the indications for PMRT in patients with 1-3 metastatic nodes are needed.

We investigated whether some mucinous carcinomas (MUCs) are associated with lobular neoplasia (LN) components, and if so, whether this subset has any distinct biological properties. MUC specimens from 41 patients were stratified into pure and mixed types. The LN components adjacent to MUC lesions were examined histopathologically. We also tested immunohistochemically for E-cadherin, β-catenin, and the neuroendocrine markers chromogranin A and synaptophysin; and compared results between MUCs with and without LN. Of 41 patients with MUC, LN was detected in 12 patients (29%); LN alone was the noninvasive component in 8 patients (20%). Decreased E-cadherin and β-catenin expression in the MUC component was detected in 2 (17%) and 7 (58%) cases, respectively, of MUC with LN, compared with 0% (P = 0.080) and 21% (P = 0.018) in MUCs without LN. Neuroendocrine factors were frequently detected in MUCs with LN (42%) and without LN (52%), but tended to be less frequent in MUCs with only LN components (25%) than in other MUCs (55%; P = 0.133). MUCs associated with LN components appear to be a biologically characteristic subset that frequently shows decreased cell-cell adhesion, cell polarity molecules and lack of neuroendocrine differentiation., (© 2014 The Authors. Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Regression of the corpus luteum (CL) is characterized by a decay in progesterone (P4) production (functional luteolysis) and disappearance of luteal tissues (structural luteolysis). In mares, structural luteolysis is thought to be caused by apoptosis of luteal cells, but functional luteolysis is poorly understood. 20α-hydroxysteroid dehydrogenase (20α-HSD) catabolizes P4 into its biologically inactive form, 20α-hydroxyprogesterone (20α-OHP). In mares, aldo-keto reductase (AKR) 1C23, which is a member of the AKR superfamily, has 20α-HSD activity. To clarify whether AKR1C23 is associated with functional luteolysis in mares, we investigated the expression of AKR1C23 in the CL in different luteal phases. The luteal P4 concentration and levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) mRNA were higher in the mid luteal phase than in the late and regressed luteal phases (P<0.05), but the level of 3β-HSD protein was higher in the late luteal phase than in the regressed luteal phase (P<0.05). The luteal 20α-OHP concentration and the level of AKR1C23 mRNA were higher in the late luteal phase than in the early and mid luteal phases (P<0.05), and the level of AKR1C23 protein was also highest in the late luteal phase. Taken together, these findings suggest that metabolism of P4 by AKR1C23 is one of the processes contributing to functional luteolysis in mares.

We report a case of synchronous unilateral triple breast cancers comprising invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and Paget's disease. A 57-year-old woman with a left breast mass was referred to our hospital. Mammography revealed only an isodense area with foci of microcalcification in the lateral area of the left breast. Ultrasonography revealed 2 hypoechoic masses in the outer lower and inner upper areas, and these 2 lesions were diagnosed by core needle biopsy as ILC and IDC, respectively. Left total mastectomy with sentinel lymph node biopsies was performed. In addition to the ILC and IDC, histological examination also identified Paget's disease. Breast cancer often manifests as multiple unilateral lesions; however, it is sometimes difficult to determine whether these tumors have developed multicentrically or have multifocally invaded from an intraductal carcinoma. This case was clearly diagnosed to have occurred multicentrically because of the absence of continuity among the 3 tumors, the presence of a non-invasive component in all 3 tumors, and different histopathological findings. The synchronous unilateral development of ILCs is well known. Cases of synchronous unilateral triple or more breast cancers were reviewed, and their histopathological characteristics, including the incidence of Paget's disease, is discussed.

The aim of the present study was to investigate the interaction between ovarian steroids, interleukins and prostaglandins (PG) in equine epithelial and stromal cells in vitro. In Experiment 1, cells were exposed to IL-1α (10 ng/mL), IL-1β (10 ng/mL) or IL-6 (10 ng/mL) for 24 h and cell proliferation was determined using MTT. In Experiment 2, cells were exposed to progesterone (P4; 10(-7) M); 17-β estradiol (E2; 10(-9) M) or P4+E2 for 24 h and later medium was replaced with a fresh one treated with IL-1α, IL-1β or IL-6 (10 ng/mL, each) for 24 h. The oxytocin (OT; 10(-7) M) was used as a positive control. In Experiment 3, cells were exposed to P4 (10(-7) M), E2 (10(-9) M) or P4+E2 for 24 h and the IL receptor mRNAs transcription was determined using Real-time PCR. Prostaglandins concentration was determined using the direct enzyme immunoassay (EIA) method. Our findings reveal a functional linking between ovarian steroids and IL-stimulated PG secretion by equine endometrial cells. This interaction could be one of the mechanisms responsible for endometrial local orchestrating events during the estrous cycle and early pregnancy.

The present study aimed to assess the effect of polymorphisms in the tumor necrosis factor α (TNF-α) promoter (A/A, A/G and G/G) and exons (T/T, T/C and C/C) on immune function and reproductive performance in dairy cows. The occurrence of the first postpartum ovulation within 3 weeks in the cows with the TNF-α promoter A/G and G/G genotypes was higher than in the A/A group. Among the different TNF-α exon genotypes, the occurrence of early first postpartum ovulation was higher in the T/C and C/C genotype groups than in the T/T group. Single nucleotide polymorphisms (SNPs) in the TNF-α gene did not affect the rate of artificial insemination (AI) or duration from parturition to next conception (days open). The apoptosis rate of polymorphonuclear leukocytes (PMNs) did not differ among the TNF-α promoter genotypes, but the PMN transmigration rate was significantly higher for the A/A and A/G genotypes than for the G/G genotype. Interleukin 8 (IL-8) mRNA expression in PMNs and peripheral blood mononuclear cells (PBMCs) before culture was significantly higher for the A/A genotype compared with the G/G genotype. There were no significant differences between the genotypes in the mRNA expression of TNF-α, IL-6, IL-1β, and toll-like receptor 4 (TLR4) in PMNs and PBMCs before and 4 h after culture. IL-8 and IL-1β production by PBMCs cultured for 4 h was significantly higher for the animals with the A/A genotype than for those with the G/G genotype. On the other hand, no significant difference was observed in IL-8 and IL-1β production by PMNs among different TNF-α genotypes. Taken together, these results suggest that SNP in the TNF-α gene affects immune function and reproductive performance in dairy cows.

Background: Clinical significance of intraoperative sentinel lymph node (SLN) metastases detection using one-step nucleic acid amplification (OSNA) has not been thoroughly investigated. The aim of this study was to assess the usefulness of using a combination of OSNA and conventional histological examinations., Materials and Methods: We included 772 consecutive patients with clinical node-negative cTis-cT3 primary breast cancer who underwent SLN biopsy with intraoperative OSNA and multi-section histological examination at our institution. We estimated the concordance rate and compared SLN metastases detection rates between the two methods. We also compared non-SLN metastasis detection rate between patients who tested positive in OSNA and those who tested positive in histology., Results: Among 772 patients, SLN metastases were intraoperatively detected in 211 (26.4%) by either OSNA or histology, in 168 (21.8%) by OSNA, and in 150 (19.4%) by histology. The concordance rate between OSNA and histological examination was 89.2%, but only 123 (58.8%) patients tested positive in both OSNA and histology; 45 were positive in OSNA only and 43 were positive in histology only. SLN status as per both OSNA and histology was significantly correlated with the presence of non-SLN metastases and multivariate analysis-identified independent predictive factors of non-SLN metastases., Conclusions: Intraoperative SLN metastases detection may be more accurate with a combination of OSNA and histological examination than with OSNA or histological examination alone. By using both methods, we can reduce the risk of false negative rate in SLN biopsy, and may prevent physicians from overlooking patients with non-SLN metastases., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Potential reuse of dewatered sludge (DS) and municipal solid waste incineration (MSWI) bottom ash as components to develop controlled low-strength material (CLSM) was explored. The effects of DS:MSWI bottom ash:calcium sulfoaluminate (CS¯A) cement ratio and thermal treatment of MSWI bottom ash at 900 °C on the mechanical and microstructural properties of CLSM were intensively studied to optimize the process. Results showed DS and MSWI bottom ash could be utilized for making CLSM. The CLSM prepared with milled MSWI bottom ash gave higher unconfined compressive strength (UCS) of 2.0-6.2 MPa following 1 year of curing at 1.0:0.1:0.9 ≤ DS:MSWI bottom ash:CS¯A ≤ 1.0:0.8:0.2. However, the corresponding strengths for CLSM containing thermally treated MSWI bottom ash ranged from 0.7 to 4.6 MPa, decreasing 26-65%. The microstructural analysis by X-ray powder diffraction (XRD), Fourier transforms infrared spectroscopy (FT-IR), as well as scanning electron microscopy (SEM) combined with an energy dispersive X-ray spectroscopy (EDS) revealed that ettringite (C3A·3CS¯·H32, or AFt) crystals were the most important strength-producing constituents which grew into and filled the CLSM matrix pores. Milled MSWI bottom ash addition favored the formation of highly crystalline AFt phases and accordingly enhanced compressive strengths of CLSM specimens. In contrast, thermal treatment at 900 °C produced new phases such as gehlenite (Ca2Al2SiO7) and hydroxylapatite (Ca5(PO4)3(OH)), which deteriorated the pozzolanic activity of bottom ash and caused the strengths to decrease. Leaching tests evidenced that leachable substances from CLSM samples exhibited negligible health and environmental risks. The results of this study suggested that MSWI bottom ash can be effectively recycled together with DS in developing CLSM mixtures with restricted use of CS¯A cement., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Context: Previous research on American football injuries in Japan has focused on incidence proportion in terms of the number of injuries divided by the number of players. This is the first study to examine injury rates over several seasons., Objective: To conduct a prospective study of injuries in a Japanese Division I collegiate American football team over the 2007 through 2009 seasons., Design: Cohort study., Setting: Collegiate football team at Doshisha University, Kyoto, Japan., Patients or Other Participants: All 289 athletes who played on the collegiate Division I football team during the 2007 through 2009 seasons., Main Outcome Measure(s): A certified athletic trainer kept a daily record of all practice and game injuries. Injury rates were calculated according to season, injury type, body part, severity, and mechanism. Injuries were also analyzed according to position of player, school year, and playing experience., Results: The game injury rate (GIR; 32.7 injuries/1000 athlete-exposures) was higher than the practice injury rate (PIR; 10.9 injuries/1000 athlete-exposures) over the 3 seasons (P < .05). The PIR was higher among Japanese players than the comparable United States collegiate football injury rates (5.8-7.0 injuries/1000 athlete-exposures). Ankle and foot injuries occurred more frequently during games, whereas thigh and gluteal injuries occurred more frequently during practices., Conclusions: Our data show differences between games and practices in terms of injury rates, body parts injured, and positions of players injured. The high PIR in Japan may be due to the increased contact during practices and length of practices compared with the United States. Further research involving multiple teams is recommended to validate the trends noted in this study. The expanded data set could assist in the development of safety regulations and preventive interventions for Japanese football.