Precise Spectroscopy of the 3n and 3p Systems via the

To search for low-energy resonant structures in isospin T=3/2 three-body systems, we have performed the experiments ^{3}H(t,^{3}He)3n and ^{3}He(^{3}He,t)3p at intermediate energies. For the 3n experiment, we have newly developed a thick Ti-^{3}H target that has the largest tritium thickness among targets of this type ever made. The 3n experiment for the first time covered the momentum-transfer region as low as 15 MeV/c, which provides ideal conditions for producing fragile systems. However, in the excitation-energy spectra we obtained, we did not observe any distinct peak structures. This is in sharp contrast to tetraneutron spectra. The distributions of the 3n and 3p spectra are found to be similar, except for the displacement in energy due to Coulomb repulsion. Comparisons with theoretical calculations suggest that three-body correlations exist in the 3n and 3p systems, although not enough to produce a resonant peak.

Discovery of

The new isotope ^{39}Na, the most neutron-rich sodium nucleus observed so far, was discovered at the RIKEN Nishina Center Radioactive Isotope Beam Factory using the projectile fragmentation of an intense ^{48}Ca beam at 345 MeV/nucleon on a beryllium target. Projectile fragments were separated and identified in flight with the large-acceptance two-stage separator BigRIPS. Nine ^{39}Na events have been unambiguously observed in this work and clearly establish the particle stability of ^{39}Na. Furthermore, the lack of observation of ^{35,36}Ne isotopes in this experiment significantly improves the overall confidence that ^{34}Ne is the neutron dripline nucleus of neon. These results provide new key information to understand nuclear binding and nuclear structure under extremely neutron-rich conditions. The newly established stability of ^{39}Na has a significant impact on nuclear models and theories predicting the neutron dripline and also provides a key to understanding the nuclear shell property of ^{39}Na at the neutron number N=28, which is normally a magic number.

Coffee consumption and mortality in Japan with 18 years of follow-up: the Jichi Medical School Cohort Study.

OBJECTIVE: Coffee consumption can be expected to reduce mortality due to cardiovascular diseases and cancer. This study tested the hypothesis of an inverse association between coffee intake and all-cause mortality and mortality due to cancer, coronary heart disease, or stroke. STUDY DESIGN: Prospective cohort study. METHODS: We analyzed data from the Jichi Medical School Cohort Study, Japan, enrolling 9946 subjects (men/women: 3870/6,076, age: 19-93 years) from 12 communities. A food frequency questionnaire assessing the subjects' daily coffee consumption was used. RESULTS: During an average follow-up of 18.4 years, the total number of deaths was 2024, including 677 for cancer, 238 for coronary heart disease, and 244 for stroke. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality and cause-specific mortality due to cancer, coronary heart disease, and stroke. Overall, no significant association was shown between coffee consumption and all-cause mortality. In the cause-specific mortality analyses, stroke mortality was significantly lower in those who consumed 1-2 cups of coffee daily (HR [95% CI]: 0.63 [0.42-0.95]) than in those who do not consume coffee, and this association occurred only in men. CONCLUSION: This study showed no significant association between coffee consumption and all-cause mortality. A U-shaped association between coffee consumption and stroke mortality with a 37% lower stroke mortality, only significant in men who consume 1-2 cups of coffee daily was observed. It is necessary to examine the possibility of intervention studies to reduce stroke mortality through coffee consumption.

Discovery of

The discovery of the important neutron-rich nucleus _{20}^{60}Ca_{40} and seven others near the limits of nuclear stability is reported from the fragmentation of a 345 MeV/u ^{70}Zn projectile beam on ^{9}Be targets at the radioactive ion-beam factory of the RIKEN Nishina Center. The produced fragments were analyzed and unambiguously identified using the BigRIPS two-stage in-flight separator. The eight new neutron-rich nuclei discovered, ^{47}P, ^{49}S, ^{52}Cl, ^{54}Ar, ^{57}K, ^{59,60}Ca, and ^{62}Sc, are the most neutron-rich isotopes of the respective elements. In addition, one event consistent with ^{59}K was registered. The results are compared with the drip lines predicted by a variety of mass models and it is found that the models in best agreement with the observed limits of existence in the explored region tend to predict the even-mass Ca isotopes to be bound out to at least ^{70}Ca.

Occult fetomaternal hemorrhage in women with pathological placenta with respect to permeability.

AIM: Women with pre-eclampsia (PE), placenta previa (PP), placental abruption (PA), and placental mesenchymal dysplasia (PMD) have been described as having placental permeability dysfunction. This study was performed to determine whether occult fetomaternal hemorrhage (FMH) is common in women with such complications and in women with non-reassuring fetal status. METHODS: Forty-one antenatal and 39 postnatal blood samples were obtained from 46 women, including 11 with placental permeability dysfunction (5, 3, 2, and 1 with PE, PP, PA, and PMD, respectively) and 35 controls without such complications. To estimate the amount of fetal red blood cells, flow cytometry was performed using the fetal cell count system with two antibodies against fetal hemoglobin and carbonic anhydrase and the ß-γ system with two monoclonal antibodies against hemoglobin ß-chain and hemoglobin γ-chain. A diagnosis of FMH was made when the fraction size of the isolated cell population on scatter plots expressing fetal hemoglobin alone or hemoglobin γ-chain alone accounted for ≥0.02% of the total cell population on scatter plots. RESULTS: FMH was identified in five women, including one each with PE, PA, PP, PMD, and no complications. Thus, the prevalence rate of FMH was significantly higher in women with complications than in controls (36% [4/11] vs 2.9% [1/35], respectively, P =  0.009). The FMH occurrence rate did not differ between women with and without non-reassuring fetal status (7.7% [1/13] vs 12% [4/33], respectively, P =  1.000). CONCLUSION: The risk of fetal red blood cells trafficking into the maternal circulation may be increased in women complicated with PE, PA, PP, and PMD.

Aquagrams of raw milk for oestrus detection in dairy cows.

The purpose of this research was to develop rapid and cost-effective method for oestrus detection in dairy cows by means of near infrared spectroscopy and aquaphotomics, using raw milk from individual cows. We found that aquaphotomics approach showed consistent specific water spectral pattern of milk at the oestrus periods of the investigated Holstein cows. Characteristic changes were detected especially in foremilk collected at morning milking. They were reflected in calculated aquagrams of milk spectra where distinctive spectral pattern of oestrus showed increased light absorbance of strongly hydrogen-bonded water. Results showed that monitoring of raw milk near infrared spectra provides an opportunity for analysing hormone levels indirectly, through the changes of water spectral pattern caused by complex physiological changes related to fertile periods.

Statins inhibit tumor progression via an enhancer of zeste homolog 2-mediated epigenetic alteration in colorectal cancer.

While statin intake has been proven to reduce the risk of colorectal cancer (CRC), the mechanism of antitumor effects and clinical significance in survival benefits remain unclear. Statin-induced antiproliferative effects and its underlying mechanism were examined using six CRC cell lines. Statins except pravastatin showed antiproliferative effects (simvastatin ≥ fluvastatin > atorvastatin) even though both of simvastatin and pravastatin could activate mevalonate pathways, suggesting the statin-mediated antiproliferative effects depended on non-mevalonate pathway. Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. In the clinical setting, Statin intake (except pravastatin) displayed the downregulated EZH2 expression and inversely upregulated p27(KIP1) expression in the resected CRC by immunohistochemical staining and resulted in the significantly better prognoses both in overall survival (p = 0.02) and disease free survival (p < 0.01) compared to patients without statin intake. Statins may inhibit tumor progression via an EZH2-mediated epigenetic alteration, which results in survival benefits after resected CRC. Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer therapy by their synergistic effects in CRC.

Association between anti-U1 ribonucleoprotein antibodies and inflammatory mediators in cerebrospinal fluid of patients with neuropsychiatric systemic lupus erythematosus.

OBJECTIVE: We investigated possible associations between neurotoxic inflammatory mediators (IMs) and anti-U1RNP antibodies (Abs) in cerebrospinal fluid (CSF) of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Serum and CSF anti-U1RNP Abs were detected using an RNA-immunoprecipitation assay and CSF anti-U1RNP Ab levels were measured by ELISA. IFN-α, MCP-1 and IL-8 levels in CSF were determined by quantitative multiplex cytokine analysis. IM levels were compared among anti-U1RNP-positive and anti-U1RNP-negative NPSLE as well as other rheumatic disease controls (controls). RESULTS: Anti-U1RNP Abs were detected in serum (58%) and in CSF (18%) of 82 NPSLE patients. CSF MCP-1 levels were higher in NPSLE than in controls. CSF IFN-α level was higher in CSF anti-U1RNP Ab-positive than in -negative patients or controls. When limited to serum anti-U1RNP Ab-positive patients, however, levels of all three IMs in CSF were higher in CSF anti-U1RNP Ab-positive than in -negative patients. Anti-U1RNP Ab levels in CSF correlated with CSF MCP-1, but not IFN-α and IL-8 levels. CONCLUSIONS: CSF anti-U1RNP Ab positivity is associated with increased level of CSF IFN-α. MCP-1 levels correlated with CSF anti-U1RNP Ab levels, whereas the increased CSF MCP-1 was not specific to CSF anti-U1RNP Ab-positive NPSLE.

Hanging drop monoculture for selection of optimal antioxidants during in vitro maturation of porcine oocytes.

We analysed the effect of three antioxidants that have different functional mechanisms on the in vitro maturation (IVM) of porcine oocytes. Single oocyte monoculture using the hanging drop (HD) system has some advantages such as improving analysis efficiency brought by the smaller number of samples than the number of oocytes cultured in one drop. Direct effects of ligands on single oocytes could also be detected without considering the effects of paracrine factors from other oocytes. After 22 h of pre-culture, denuded oocytes were cultured for 22 h with 0.01 and 0.1 µg/ml of L-carnitine (LC), lactoferrin (LF) or sulforaphane (SF) in the presence/non-presence of oxidant stress induced by H2O2 supplementation to evaluate the reducing effects against oxidative stress on nuclear maturation. As a result, compared with LC and SF, LF showed effective reduction in oxidative stress at a lower concentration (0.01 µg/ml), suggesting that LF is a more effective antioxidant in porcine oocyte IVM. Additionally, LF also increased maturation rate even in culture without H2O2. Our results clearly suggest that the HD monoculture system is useful for screening the substances that affect porcine oocyte culture.

Supporting rural remote physicians to conduct a study and write a paper: experience of Clinical Research Support Team (CRST)-Jichi.

CONTEXT: Jichi Medical University (JMU) is the only medical school in Japan that is devoted solely to producing rural and remote doctors. To support research activities of its graduates, mainly young graduates under obligatory rural service, JMU established a voluntary team, Clinical Research Support Team (CRST)-Jichi. ISSUES: CRST-Jichi consists of current and past JMU faculty members; all of them are specialists of certain medical fields and many are also graduates of JMU who have completed rural service. A client who asks the CRST for advice on study design or editing a paper emails the CRST to ask for support in conducting a study. Then, core members of the CRST assign the job to a registered specialist of the corresponding topic, who becomes a 'responsible supporter' and continues to support the client until a paper has been published. During the 3 years from July 2010, 12 English papers have been published in international peer-review journals, two Japanese papers in domestic journals, and 13 studies are in progress. Ninety-one percent of clients were satisfied with the service, and eighty-two percent considered their papers would not have been published if they had not used the service. Sense of commitment, existence of JMU-graduated specialists, and quick response were reported by clients as major strengths of CRST-Jichi. LESSONS LEARNED: The experience of CRST-Jichi can potentially be transferred to not only other Japanese medical schools with rural doctor production programs, which are now rapidly increasing as part of a national policy, but also rural medical education systems in other countries.

Progression of paralysis is the most useful factor for differentiating malignant from benign intramedullary tumors.

STUDY DESIGN: Retrospective study. OBJECTIVES: The purpose of this study was to identify the clinical factors for differentiating malignant from benign intramedullary spinal cord tumors. SETTING: Niigata, Japan. METHODS: We conducted a retrospective review of charts and images. Preoperative paralysis including walking ability, urinary function, magnetic resonance imaging (MRI) findings and pathological diagnosis were evaluated in 33 consecutive cases of intramedullary spinal cord tumor, and the clinical factors that were useful for differentiating malignant from benign tumors were identified. RESULTS: Early progression of paralysis was the most valuable feature for differentiating malignant from benign tumors. Malignant tumors were suspected in only three of ten cases on the basis of MRI findings. CONCLUSION: Simple assessment of walking ability is easy to perform and is useful for predicting the pathological malignancy of intramedullary tumors of the spinal cord.

Cultural adaptation, content, and protocol of a feasibility study of school-based "Let's learn about emotions" intervention for Finnish primary school children.

Introduction: Emotional awareness and emotion regulation are crucial for cognitive and socio-emotional development in children. School-based interventions on socio-emotional skills have the potential to prevent these problems and promote well-being of children. The Japanese school-based program, Universal Unified Prevention Program for Diverse Disorders (Up2-D2), has shown preventive effects on mental health of children in Japan. The aims of this protocol paper are to describe the unique process of adapting the Up2-D2 from Eastern to Western context, and to present a feasibility study of the intervention, conducted in Finland. Methods: The cultural adaptation process started with the linguistic translation of materials, followed by the modification of language to fit the Finnish context. While the Japanese ideology was saved, some content was adapted to fit Finnish school children. Further modifications were made based on feedback from pupils and teachers. The Finnish version of the program was named "Let's learn about emotions" and consisted of 12 sessions and targeted 8- to 12-year-old pupils. A teacher education plan was established to assist Finnish teachers with the intervention, including a workshop, teachers' manual, brief introductory videos, and online support sessions. A feasibility study involving 512 4th graders in the City of Hyvinkää, South of Finland, was conducted. It assessed emotional and behavioral problems, classroom climate, bullying, loneliness, perception of school environment, knowledge of emotional awareness, and program acceptability. Discussion: The originality of this study underlies in the East-West adaptation of a cognitive behavioral therapy-based program. If promising feasibility findings are replicated in Finland, it could pave the way for further research on implementing such programs in diverse contexts and cultures, promoting coping skills, awareness, social skills and early prevention of child mental health problems. Ethics: The ethical board of the University of Turku gave ethics approval for this research. The educational board of the City of Hyvinkää accepted this study.

A case of progressive digital ischemia after early withdrawal of gemcitabine and S-1 in a patient with systemic sclerosis.

The safety of chemotherapy for patients with systemic sclerosis is unclear, and there are few published reports documenting the side effects of chemotherapy in patients with this condition. Here, we report the case of a patient with systemic sclerosis who developed severe digital ischemia during combination gemcitabine/S-1 chemotherapy for pancreatic cancer. In spite of aggressive treatment, the digital ischemia progressively worsened and gangrenous changes developed in multiple fingers and toes. In this patient, the systemic sclerosis had been well controlled, with no digital ischemic symptoms for the previous 6 years, so this progressive clinical course in spite of aggressive treatment strongly suggests that the chemotherapy triggered or aggravated the digital necrosis. To the best of our knowledge, this is only the third reported case of a patient with systemic sclerosis developing digital necrosis after gemcitabine-based chemotherapy. The incidence of digital necrosis during chemotherapy in patients with systemic sclerosis is unknown, and the mechanism by which it occurs is unclear, but the three reports published to date, including the present case, suggest that physicians should be very cautious about administering gemcitabine-based chemotherapy to patients with systemic sclerosis. Any resulting digital ischemia might be refractory to treatment and worsen progressively, even if chemotherapy is withdrawn in the early stages of digital ischemia.

Evaluation of elastin fibres in young and aged eyelids and abdominal skin using computational 3D structural analysis.

Background: Aging-related degeneration of elastic fibres causes skin wrinkles and loss of elasticity. A correlation has been reported between dermal elastic fibre degradation and wrinkles. However, the mechanism of wrinkle formation is complex and unclear. To establish methods for treating wrinkles, it is necessary to understand the aging-related morphological alterations underlying elastin fibre degradation or disappearance. Objectives: To image and analyse aging-related three-dimensional (3D) morphological alterations of elastic fibres in the eyelid and abdominal skin. Methods: Excised human eyelid and abdominal skin tissues were examined. The structure of elastic fibres in the skin tissues was examined via nuclear, tropoelastin and fibrillin-1 immunostaining. Then, 3D imaging was performed using a confocal laser microscope and tissue decolourization technology. Images were analysed using a computational method. Results: The decolourization technology made it possible to image elastin fibres in 3D, and we devised a method for analyzing the elastin fibre structure using computational methods. It was quantitatively shown that the eyelid skin has a more complex fibrous structure than the abdomen, and the fibres became curved, shortened and thickened with age. Conclusions: We provide a novel 3D analysis method for elastin fibres and report age-related alterations in elastin fibre structure in the human eyelid and abdominal skin. This method contributes to the understanding of elastin fibre degeneration in more detail than conventional methods. Applying this 3D analysis method to skin tissues will contribute to a better understanding of age-related changes in fibres and to the development of novel wrinkle treatments.

Regulation by chemokines of circulating dendritic cell precursors, and the formation of portal tract-associated lymphoid tissue, in a granulomatous liver disease.

We have studied the recruitment and roles of distinct dendritic cell (DC) precursors from the circulation into Propionibacterium acnes-induced granulomas in mouse liver. During infection, F4/80(-)B220(-)CD11c(+) DC precursors appeared in the circulation, migrated into the perisinusoidal space, and matured within newly formed granulomas. Recruited DCs later migrated to the portal area to interact with T cells in what we term "portal tract-associated lymphoid tissue" (PALT). Macrophage inflammatory protein 1alpha attracted blood DC precursors to the sinusoidal granuloma, whereas secondary lymphoid organ chemokine (SLC) attracted mature DCs to the newly identified PALT. Anti-SLC antibody diminished PALT expansion while exacerbating granuloma formation. Therefore, circulating DC precursors can migrate into a solid organ like liver, and participate in the granulomatous reaction in response to specific chemokines.

Aberrant high expression of B lymphocyte chemokine (BLC/CXCL13) by C11b+CD11c+ dendritic cells in murine lupus and preferential chemotaxis of B1 cells towards BLC.

We observed here that the expression of B lymphocyte chemokine (BLC/CXCL13) was markedly enhanced in the thymus and kidney in aged (NZB x NZW)F1 (BWF1) mice developing lupus nephritis, but not in similarly aged NZB and NZW mice. BLC-positive cells were present in the cellular infiltrates in the target organs with a reticular pattern of staining. CD11b+CD11c+ dendritic cells were increased in the thymus and spleen in aged BWF1 mice and identified as the major cell source for BLC. CD4+ T cells as well as B cells were dramatically increased in the thymus in aged BWF1 mice, whereas no increase was observed in aged NZB and NZW mice. B1/B2 ratio in the thymus was significantly higher than those in the spleen and peripheral blood in aged BWF1 mice. Interestingly, BLC showed preferential chemotactic activity for B1 cells derived from several mouse strains, including nonautoimmune mice. Cell surface CXCR5 expression on B1 cells was significantly higher than that on B2 cells. Thus, aberrant high expression of BLC by myeloid dendritic cells in the target organs in aged BWF1 mice may play a pivotal role in breaking immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus.

Abnormal expression of the genes involved in cytokine networks and mitochondrial function in systemic juvenile idiopathic arthritis identified by DNA microarray analysis.

OBJECTIVES: Systemic juvenile idiopathic arthritis (sJIA) is a rheumatic disease in childhood characterised by systemic symptoms and a relatively poor prognosis. Peripheral leukocytes are thought to play a pathological role in sJIA although the exact cause of the disease is still obscure. In this study, we aimed to clarify cellular functional abnormalities in sJIA. METHODS: We analysed the gene expression profile in peripheral leukocytes from 51 patients with sJIA, 6 patients with polyarticular type JIA (polyJIA) and 8 healthy children utilising DNA microarrays. Gene ontology analysis and network analysis were performed on the genes differentially expressed in sJIA to clarify the cellular functional abnormalities. RESULT: A total of 3491 genes were differentially expressed in patients with sJIA compared to healthy individuals. They were functionally categorised mainly into a defence response group and a metabolism group according to gene ontology, suggesting the possible abnormalities in these functions. In the defence response group, molecules predominantly constituting interferon (IFN)gamma and tumour necrosis factor (TNF) network cascades were upregulated. In the metabolism group, oxidative phosphorylation-related genes were downregulated, suggesting a mitochondrial disorder. Expression of mitochondrial DNA-encoded genes including cytochrome c oxidase subunit 1(MT-CO1) and MT-CO2 were suppressed in patients with sJIA but not in patients with polyJIA or healthy children. However, nuclear DNA-encoded cytochrome c oxidases were intact. CONCLUSION: Our findings suggest that sJIA is not only an immunological disease but also a metabolic disease involving mitochondria disorder.

The effect of Bacillus subtilis mouth rinsing in patients with periodontitis.

Bacillus subtilis is an effective probiotic product for prevention of enteric infections both in humans and animals. We hypothesized that a mouth rinse containing Bacillus subtilis should adhere to and colonize part of the oral bacteria on periodontal tissue. The rinsing ability of Extraction 300E (containing Bacillus subtilis: E-300) was compared with that of a mouth wash liquid , Neosteline Green (benzethonium chloride; NG) that is commonly used in Japan. Compared with NG rinsing, E-300 rinsing resulted in a marked change in the BANA-score. The mean BANA values (score +/- SD) over the course of the study from 0 to 30 days were 1.52 +/- 0.51 (p < or = 0.1) and 0.30 +/- 0.47 (p < or = 0.01) for E-300, and 1.56 +/- 0.51 and 0.93 +/- 0.68 for NG, respectively. Gingival Index also had improvement, while probing pocket depth and bleeding on probing showed small improvements. Mouth rinsing with E-300 significantly reduced periodontal pathogens compared with NG. These results suggest that Bacillus subtilis is an appropriate mouth rinse for patients with periodontitis.

Bronchovascular cuff formation and lung lymph flow in edema formation of anesthetized sheep.

The relationship between bronchovascular cuff formation and lung lymph flow in hydrostatic edema was evaluated. After a balloon was inserted into the left atrium to increase left atrial pressure for 5 hrs, peripheral lung tissues were resected for analysis of the wet-dry ratio and cuff formation. The degree of cuff formation was expressed as the cuff ratio (outer diameter of cuff/outer diameter of microvessel or airway) in three size categories: 80-200, 200-400, and 400-750 microm in diameter. The amount of excess lung lymph (Ex LL) for 5 hrs was calculated from the recorded data for the whole lymph flow wave. The wet-dry ratio showed a significant correlation with ALAP and lung lymph flow increased significantly (flow rate, 0.67 +/- 0.46 ml/min (mean +/- SD); Ex LL, 56.4 +/- 47.6 ml). Cuff formation was found at all levels of the bronchovascular tree, with a larger cuff ratio (> 1.3) observed at arteries and veins of 80-200 microm in diameter, but a significant correlation with Ex LL was found only for arteries of 80-200 microm. Fluid accumulation in lung interstitium first occurred at smaller extra-alveolar arteries even under mild hydrostatic pressure elevation with a significant increase in lymph flow.

[Combined surgery for ischemic cardiomyopathy].

The results of combined surgery for ischemic cardiomyopathy were reviewed focusing on the selection of operative procedures. Left ventricular volume reduction was performed in 33 patients. Hospital mortality was 17% in Dor procedure (n=24), 20% in Batista operation (n=5) and 0% in over-lapping method (n=4). Procedures should be selected according to left ventricular wall area to be excluded. Mitral valve plasty was performed in 50 patients, and early and late results of our original "papillary muscle sandwich plasty" (n=27) was superior to those of other conventional procedures (n=23). In "sandwich plasty", the papillary muscle heads of the anterior and the posterior mitral valve leaflets are approximated using tefron-pledgeted 3-0 ticron suture at the anterolateral and posteromedian commissural portions, respectively. In conclusion, active combined surgery is necessary for the treatment of ischemic cardiomyopathy.