Reopening of ductus arteriosus in idiopathic premature constriction or closure of ductus arteriosus: A case series.

BACKGROUND: There is no consensus on managing pregnancy when the fetus is diagnosed with idiopathic premature constriction or closure of the ductus arteriosus (PCDA). Knowing whether the ductus reopens is valuable information for managing idiopathic PCDA. We conducted a case-series study to investigate the natural perinatal course of idiopathic PCDA and examined factors associated with ductal reopening. METHODS: We retrospectively collected information about the perinatal course and echocardiographic findings at our institution, which, on principle, does not determine delivery timing based on fetal echocardiographic results. We also examined perinatal factors related to the reopening of the ductus arteriosus. RESULTS: Thirteen cases of idiopathic PCDA were included in the analysis. The ductus reopened in 38% of cases. Among cases diagnosed in < 37 weeks of gestation, 71% reopened, which was confirmed seven days after diagnosis (interquartile range 4-7). Diagnosis earlier in gestation was associated with ductal reopening (p = 0.006). Two cases (15%) developed persistent pulmonary hypertension. No fetal hydrops or death occurred. CONCLUSIONS: The ductus is likely to reopen when prenatally diagnosed before 37 weeks gestation. There were no complications due to our pregnancy management policy. In idiopathic PCDA, especially if the prenatal diagnosis is made before 37 weeks of gestational age, continuing the pregnancy with careful monitoring of the fetus's well-being is recommended.

Osteoarthritic changes in the knees of recently retired male professional footballers: a pilot study.

Background: Knee osteoarthritis (OA) is common amongst retired male professional footballers. There is limited understanding with respect to the interplay between imaging findings, clinical presentation and patient-reported outcome measures (PROMs) in retired professional footballers with knee OA. Objectives: This pilot study aimed to evaluate the extent of radiological and clinical knee OA in a cohort of retired male professional footballers, and to explore the relationship between these findings and knee-related PROMs. Methods: Fifteen retired male professional footballers underwent knee radiographs and were surveyed on their history of clinical OA, severe knee injury and previous knee surgery. The Knee Injury and Osteoarthritis Outcome Score Physical Function Short Form (KOOS-PS) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) were used to assess health outcomes, such as level of function and pain. Results: Radiological knee OA was diagnosed in six out of 15 participants. Seven of the participants had a clinical diagnosis of knee OA. Evidence of clinical and radiological OA was present amongst four participants. Radiological knee OA and clinical OA was significantly associated with a history of severe knee injury and previous knee surgery. Low correlations (ρ<-0.40) were found between knee OA severity and knee-related PROMs. Moderate correlation (ρ=-0.65) was found between clinical knee OA and KOOS-SP. Conclusion: Clinical knee OA correlates with PROMs amongst retired professional footballers but radiological OA does not. Further studies are required to understand the relationship between imaging findings, clinical presentation and PROMs amongst retired professional footballers with knee OA.

Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation.

OBJECTIVE: Low molecular weight compounds that reduce the expression of MMP13 at the mRNA level might serve as disease-modifying osteoarthritis (OA) drugs (DMOADs). The objective of this study was to identify a candidate DMOAD that targets MMP13 expression. DESIGN: High-throughput screening was performed to identify compounds that suppress inflammatory cytokine-induced MMP13 expression. Ingenuity pathway analysis (IPA) using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to identify signaling pathways related to cytokines. MMP13 expression in chondrocytes was evaluated through RT-qPCR and western blotting analyses. Additionally, 10-week-old mice were subjected to destabilization of the medial meniscus (DMM) surgery to induce OA and were sacrificed 12 weeks post-surgery for pathological examination. OA was evaluated using the OARSI scoring system. RESULTS: Colchicine was identified as a DMOAD candidate as it inhibited inflammatory cytokine-induced MMP13 expression in vitro, and the colchicine-administered mice with DMM presented significantly lower OARSI scores (adjusted P: 0.0242, mean difference: 1.6, 95% confidence interval (CI) of difference: 0.1651-3.035) and significantly lower synovial membrane inflammation scores (adjusted P: 0.0243, mean difference: 0.6, 95% CI of difference: 0.06158-1.138) than mice with DMM. IPA further revealed that components of the Rho signaling pathways are regulated by cytokines and colchicine. IL-1ß and TNF-α activate RAC1 and SRC signals, respectively, leading to the phosphorylation of PLC-γ1 and synergistic induction of MMP13 expression. Most notably, colchicine abrogates inflammatory cytokine-induced phosphorylation of PLC-γ1, leading to the induction of MMP13 expression. CONCLUSIONS: Colchicine is a potential DMOAD candidate that inhibits MMP13 expression and consequent cartilage degradation by disrupting the SRC/RAC1-phospho-PLCγ1-Ca2+ signaling pathway.

Eriodictyon angustifolium extract, but not Eriodictyon californicum extract, reduces human hair greying.

OBJECTIVE: Yerba Santa (Eriodictyon angustifolium and Eriodictyon californicum) has been used for many years in traditional medicine. However, the effect of Yerba Santa on melanogenesis has not yet been investigated. We aimed to assess the biological effects of Yerba Santa on hair pigmentation. METHODS: Yerba Santa extracts were assessed for their cytological effects following X-ray irradiation treatment and then tested directly for the prevention of human hair greying. Ultra-performance liquid chromatography (UPLC) was utilized to identify the individual extract components. RESULTS: Eriodictyon angustifolium extract significantly increased melanin synthesis in the melanoma cell line through activation of the WNT/MITF/tyrosinase-signalling pathway. In contrast, E. californicum had no effect on melanin synthesis. E. angustifolium extract also demonstrated a protective effect against the damage induced by X-ray irradiation in human keratinocytes. Application of the extracts to subjects who had grey beards demonstrated a reduced number of grey beard hair per year specifically with the E. angustifolium extract. A significant decrease in grey head hair was also observed after application of E. angustifolium extract. Upregulation of gene expression related to melanin production and WNT signalling was observed after the application of E. angustifolium extract. Sterubin was the most abundant flavonoid detected by UPLC in E. angustifolium extract. In addition, sterubin showed the highest difference in terms of quantity, between E. angustifolium and E. californicum extract. CONCLUSION: Eriodictyon angustifolium extract, which is abundant in sterubin, may be suitable as a potential cosmetic and medical agent for the prevention and improvement of hair greying.

OBJECTIF: Yerba Santa (Eriodictyon angustifolium et Eriodictyon californicum) est utilisé depuis de nombreuses années en médecine traditionnelle. Cependant, l'effet de Yerba Santa sur la mélanogenèse n'a pas encore été étudié. Notre objectif était d'évaluer les effets biologiques de Yerba Santa sur la pigmentation des cheveux. MÉTHODES: Les extraits de Yerba Santa ont été évalués pour leurs effets cytologiques après un traitement d'irradiation aux rayons X, puis testés directement pour la prévention du grisonnement des cheveux humains. La chromatographie liquide ultra-performante (UPLC) a été utilisée pour identifier les composants d'extrait individuels. RÉSULTATS: L'extrait d'E. angustifolium a augmenté de manière significative la synthèse de mélanine dans la lignée cellulaire du mélanome par l'activation de la voie de signalisation WNT/MITF/tyrosinase. En revanche, E. californicum n'a eu aucun effet sur la synthèse de mélanine. L'extrait d'E. angustifolium a également démontré un effet protecteur contre les dommages induits par l'irradiation aux rayons X dans les kératinocytes humains. L'application des extraits à des sujets qui avaient une barbe grise a démontré un nombre réduit de poils gris par an spécifiquement avec l'extrait d'E. angustifolium. Une diminution significative des cheveux gris a également été observée après l'application d'extrait d'E. angustifolium. Une régulation à la hausse de l'expression des gènes liée à la production de mélanine et à la signalisation WNT a été observée après l'application d'extrait d'E. angustifolium. La stérubine était le flavonoïde le plus abondant détecté par UPLC dans l'extrait d'E. angustifolium. De plus, la stérubine a montré la plus grande différence en termes de quantité entre E. angustifolium et E. californicum. CONCLUSION: L'extrait d'E. angustifolium, qui est abondant en stérubine, peut convenir comme agent cosmétique et médical potentiel pour la prévention et l'amélioration du grisonnement des cheveux.

Effective countermeasures for Salmonella contamination in actual oilmeal-manufacturing plant in India.

AIMS: Salmonella contamination in the manufacturing process of an overseas oilmeal plant was investigated and countermeasures for Salmonella contamination were evaluated. METHODS AND RESULTS: Salmonella was detected from deposits and adhered materials inside the main processing equipment. Specifically high contamination was observed in the equipment associated with the meal cooler, with several Salmonella serovars being detected. A number of Salmonella serovars were also detected in the equipment of the fine powder recovery process. To prevent Salmonella contamination of oilmeal products, effective countermeasures that have been employed in Japan were implemented. By removing residues from the equipment and disinfecting the interior of the equipment, a significant decrease in the contamination rate of oilmeal products was achieved compared to before sanitation (P < 0·05). CONCLUSIONS: Effective countermeasures to control Salmonella contamination in the overseas manufacturing process of oilmeal were established. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report focusing on Salmonella countermeasures in an actual oilmeal-manufacturing plant overseas.

Factors associated with a positive willingness to practise oral health care in the future amongst oral healthcare and nursing students.

OBJECTIVES: The purpose of this study was to identify the weak points in the knowledge and attitudes of first-year oral health care and nursing students towards oral health care and to identify the factors associated with their positive willingness to practise oral health care after becoming a health professional in order to develop oral healthcare curricula. MATERIALS AND METHODS: The subjects were 88 first-year dental students (DSs), 64 dental hygiene students (DHSs) and 119 nursing students (NSs) enrolled in schools in Japan, as of April 2017. A questionnaire was distributed to subjects in each school to assess their knowledge and attitudes towards oral health care. RESULTS: Less than half knew that oral health care was also provided in cancer hospitals, hospices, acute care hospitals, maternity wards and psychiatric wards. Only 46.2% knew that oral health care was effective in the prevention of aspiration pneumonia. The level of knowledge and attitudes in NSs regarding oral health care were likely to be lowest amongst the student groups. Only NSs' high interest towards oral health care was associated with their positive willingness to practise oral health care in the future although oral health students' high perceptions and interest regarding oral health care were associated with the willingness. CONCLUSION: This study showed oral healthcare and nursing students' weak points regarding their attitudes and knowledge of oral health care at early stages. Oral health academic staff and professionals should develop effective oral healthcare curricula for oral healthcare students and help nursing staff develop a collaborative nursing oral healthcare curriculum to motivate nursing students.

Effect of the combined use of enamel matrix derivative and atelocollagen sponge scaffold on osteoblastic differentiation of mouse induced pluripotent stem cells in vitro.

BACKGROUND AND OBJECTIVE: Induced pluripotent stem cells (iPSCs) are a candidate cell source in periodontal regenerative therapy. Enamel matrix derivative (EMD) has been shown to regenerate periodontal tissues, and atelocollagen sponge (ACS) is considered a suitable scaffold or carrier for growth factors. This study aimed to investigate the effect of combined use of EMD and an ACS scaffold on cell behaviors and differentiation of mouse iPSCs (miPSCs) in vitro. MATERIAL AND METHODS: Following embryonic body formation from miPSCs, dissociated cells (miPS-EB-derived cells) were seeded onto ACS with or without EMD, and cultured in osteoblast differentiation medium. Scanning electron microscopy and histological analyses were used to assess cell morphology and infiltration within the ACS. Cell viability (metabolism) was determined using an MTS assay, and expression of mRNA of osteoblastic differentiation markers was assessed by quantitative RT -PCR. Alkaline phosphatase (ALP) staining intensity and activity were evaluated. Mineralization was assessed by von Kossa staining, and calcium content was quantitated using the methylxylenol blue method. RESULTS: By 24 hours after seeding, miPS-EB-derived cells in both the EMD and control groups had attached to and infiltrated the ACS scaffold. Scanning electron microscopy images revealed that by day 14, many cytoplasmic protrusions and extracellular deposits, suggestive of calcified matrix, were present in the EMD group. There was a time-dependent increase in cell viability up to day 3, but no difference between groups was observed at any time point. The levels expressed of ALP and osterix genes were significantly higher in the EMD group than in the control group. Expression of runt-related transcription factor 2 was increased in the EMD group compared with the control group on day 7. EMD upregulated the expression of bone sialoprotein and osteopontin on day 14, whereas expression of osteocalcin was lower at all time points. The staining intensity and activity of ALP were higher in the EMD group than in the control group. Mineralization levels and calcium contents were significantly higher in the EMD group throughout the observation period. CONCLUSION: These data suggest that combining ACS with EMD increases levels of osteoblastic differentiation and mineralization in miPS-EB-derived cells, compared with ACS used alone.

Severe musculoskeletal time-loss injuries and symptoms of common mental disorders in professional soccer: a longitudinal analysis of 12-month follow-up data.

PURPOSE: Psychological factors have shown to be predictors of injury in professional football. However, it seems that this is a two-way relationship, as severe musculoskeletal time-loss injuries have shown to be associated with the onset of symptoms of common mental disorders (CMD). There is no longitudinal study performed exploring this interaction between symptoms of CMD and injuries. The purpose of this study was to explore the interaction between severe musculoskeletal time-loss injuries and symptoms of CMD in professional football players over a 12-month period. METHODS: Players were recruited by their national players' unions in five European countries. Symptoms of CMD included in the study were related to distress, anxiety/depression, sleep disturbance and adverse alcohol use. RESULTS: A total of 384 professional football players were enrolled in the study, of whom 262 (68%) completed the 12-month follow-up period. The mean age of the participants at baseline was 27 ± 5 years, and they had played professional football for 8 ± 5 years on average. Symptoms of CMD at baseline were not associated with the onset of severe musculoskeletal time-loss injuries during the follow-up period with relative risks (and 95% CI) ranging from 0.6 (0.3-1.0) to 1.0 (0.5-2.2). In contrast, severe musculoskeletal time-loss injuries reported at baseline were associated with the onset of symptoms of CMD during the follow-up period with relative risks ranging from 1.8 (0.8-3.7) to 6.9 (4.0-11.9). CONCLUSION: No relationship was found between symptoms of CMD and the onset of severe musculoskeletal time-loss injuries. However, professional football players who suffered from severe musculoskeletal time-loss injuries are likely to develop subsequent symptoms of CMD. This study emphasizes the need for an interdisciplinary medical approach, which not only focuses on the physical but also on the mental health of professional football players. An early identification of players at risk of symptoms of CMD, such as those suffering from severe musculoskeletal injuries, creates the opportunity for an interdisciplinary clinical medical team to treat the players timely and adequately. LEVEL OF EVIDENCE: Prospective cohort study, Level II.

Nitrogen balance in patients with hemiparetic stroke during the subacute rehabilitation phase.

BACKGROUND: In highly invasive diseases, metabolism commonly changes. Hypercatabolism is frequent in acute stroke, and nitrogen balance tends to be negative. However, there has been no study describing nitrogen balance in subacute and chronic stroke patients. The present study aimed to examine nitrogen balance in the subacute and chronic phases and to identify the factors related to it. METHODS: Nitrogen balance was calculated from the collected urine of 56 patients with subacute stroke [mean (SD) 53.8 (18.4) days post-stroke] who were admitted for rehabilitation for their first-ever ischaemic or nonsurgical haemorrhagic stroke. In the first experiment, their nitrogen balance was measured during the rehabilitation phase, and factors (type, severity of hemiparesis, activities of daily living, dysphagia and malnutrition status) related to it were evaluated. The second experiment was performed to describe the time course of nitrogen balance in 31 consecutive patients, with assessments made at admission and at discharge. RESULTS: Nitrogen balance was positive in all patients in the subacute phase. A significant difference was seen in nitrogen balance between high and low fat-free mass in male patients. In the chronic phase, nitrogen balance was positive in 96% of the patients. There was no significant difference in nitrogen balance between discharge and admission. CONCLUSIONS: In the subacute and chronic phases of stroke, it was confirmed that hypercatabolism had resolved and that intensive rehabilitation is possible in the convalescent period of stroke.

Fabrication of hydroxyapatite thin films on polyetheretherketone substrates using a sputtering technique.

Hydroxyapatite (HA) thin films were coated on a polyetheretherketone (PEEK) substrate using a sputtering technique. A thin titanium (Ti) intermediate layer was formed between the HA and the PEEK surface to improve adhesion of the HA film to the PEEK substrate. The coated films were recrystallized using a hydrothermal treatment to reduce the dissolution of the HA film. The films were then characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), and a UV-Vis spectrophotometer. A pull-out test was performed to measure the film-to-substrate adhesion strength, and an immersion test was performed in ultra-pure water. In the XRD patterns of the sputtered film with the Ti intermediate layer on the PEEK substrate, small HA peaks and large Ti peaks were observed. After the hydrothermal treatment, the intensity of the HA peaks increased. The transmittance of the HA films with 5 and 10nm Ti intermediate layers was >79% and 68%, respectively, in the visible light wavelength region (400-700nm) after the hydrothermal treatment. The adhesion strength of the hydrothermally treated HA films increased with decreasing thickness of the Ti intermediate layer, and the strength reached 2.7MPa with the 5-nm-thick Ti intermediate layer. In the immersion test, the HA film with a 5-nm-thick Ti intermediate layer without hydrothermal treatment exhibited a released Ti concentration of 42.0±2.4ppb. After hydrothermal treatment, the released Ti concentration decreased to 17.3±1.1ppb.

Evaluation of the adsorptive behavior of cesium and strontium on hydroxyapatite and zeolite for decontamination of radioactive substances.

Removal of radioactive substances, such as cesium (Cs) and strontium (Sr), has become an emerging issue after the Fukushima Daiichi Nuclear Power Plant Disaster. To assess the possibility that hydroxyapatite (HA) and zeolites can be used for removal of radioactive substances, the adsorption capacities of Cs and Sr on the HA and a zeolite were investigated. The influence of Fe ions on Cs and Sr adsorption on the HA and the zeolite was also evaluated, because Fe ions are the most effective inhibitor of Cs adsorption on the zeolite.In the Cs adsorption process on the HA and the zeolite, the zeolite showed a higher adsorption ratio than the HA, and the maximum sorption capacity of the zeolite was calculated as 196 mg/g, whereas the HA showed a higher Sr adsorption ratio than the zeolite. The maximum sorption capacity of Sr on the HA was 123 mg/g. Under coexistence with Fe, Cs adsorption on the zeolite decreased with increasing Fe concentration, reaching 2.0 ± 0.8% at 0.1 M Fe concentration. In contrast, Cs adsorption on the zeolite was improved by adding the HA. In the case of coexistence of the HA, the Cs adsorption on the mixture of the HA and the zeolite was 52.4% ± 3.6 % at 0.1 M Fe concentration, although Cs adsorption on the HA alone was quite low. In the Fe adsorption processes of the HA and the zeolite, the HA exhibited a maximum sorption capacity of 256 mg/g, which was much higher than that of the zeolite (111 mg/g). The high affinity of Fe on the HA contributes to the improvement of the deteriorated Cs adsorption on the zeolite due to Fe ions.

Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer.

BACKGROUND: We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer. METHODS: Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide. RESULTS: Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml(-1) (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028). CONCLUSIONS: One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

Influence of the crystallinity of a sputtered hydroxyapatite film on its osteocompatibility.

Hydroxyapatite (HA) was coated onto titanium substrates using radio frequency sputtering, and the sputtered films were crystallized using a hydrothermal treatment at 120°C and 170°C to evaluate the influence of the crystallinity of the HA film on its osteocompatibility. The crystallite size and surface morphology of the films were observed using X-ray diffraction (XRD) and scanning electron microscopy (SEM), respectively. The alkaline phosphatase (ALP) expression, osteocalin (OCN) expression and bone formation of osteoblast cells on the films were measured to evaluate the osteocompatibility of the film.The crystallite size increased as the hydrothermal temperature increased, and the crystallite sizes of the film treated at 120°C and 170°C were 82.2±12.3 nm and 124.7±13.3 nm, respectively. Globular particles were observed in the hydrothermally treated film using SEM. The size of the particles on the film increased as the hydrothermal temperature increased, and the width of the particles on the film treated at 120°C and 170°C were approximately 120-190 nm and 300-500 nm, respectively. In the osteoblast cell culture experiments, the ALP expression, OCN expression and bone formation area on the films treated at 120°C were higher than those treated for films treated at 170°C.

Terahertz Dynamics of a Topologically Protected State: Quantum Hall Effect Plateaus near the Cyclotron Resonance of a Two-Dimensional Electron Gas.

We measure the Hall conductivity of a two-dimensional electron gas formed at a GaAs/AlGaAs heterojunction in the terahertz regime close to the cyclotron resonance frequency using highly sensitive Faraday rotation measurements. The sample is electrically gated, allowing the electron density to be changed continuously by more than a factor of 3. We observe clear plateaulike and steplike features in the Faraday rotation angle vs electron density and magnetic field (Landau-level filling factor) even at fields or frequencies very close to cyclotron resonance absorption. These features are the high frequency manifestation of quantum Hall plateaus-a signature of topologically protected edge states. We observe both odd and even filling factor plateaus and explore the temperature dependence of these plateaus. Although dynamical scaling theory begins to break down in the frequency region of our measurements, we find good agreement with theory.

The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer.

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of a restricted set of genes independently of its known effects on canonical signaling through sphingosine-1-phosphate receptors. High-fat diet (HFD) and obesity, which is now endemic, increase breast cancer risk and have been associated with worse prognosis. HFD accelerated the onset of tumors with more advanced lesions and increased triple-negative spontaneous breast tumors and HDAC activity in MMTV-PyMT transgenic mice. Oral administration of clinically relevant doses of FTY720 suppressed development, progression and aggressiveness of spontaneous breast tumors in these mice, reduced HDAC activity and strikingly reversed HFD-induced loss of estrogen and progesterone receptors in advanced carcinoma. In ERα-negative human and murine breast cancer cells, FTY720 reactivated expression of silenced ERα and sensitized them to tamoxifen. Moreover, treatment with FTY720 also re-expressed ERα and increased therapeutic sensitivity of ERα-negative syngeneic breast tumors to tamoxifen in vivo more potently than a known HDAC inhibitor. Our work suggests that a multipronged attack with FTY720 is a novel combination approach for effective treatment of both conventional hormonal therapy-resistant breast cancer and triple-negative breast cancer.

Prevalence and determinants of symptoms related to mental disorders in retired male professional footballers.

OBJECTIVE: The objective of this study was to determine the prevalence of symptoms related to mental disorders (distress, anxiety/depression, sleep disturbance, adverse alcohol behaviour, adverse smoking behaviour, adverse nutrition behaviour) among retired professional footballers, and to explore their associations with stressors i.e. determinants such as severe injury, surgery, life events and career dissatisfaction. METHOD: Cross--sectional analyses were conducted on baseline questionnaires from an ongoing prospective cohort study among retired male professional footballers. Based on validated questionnaires to assess both stressors and symptoms related to mental disorders, an electronic questionnaire was set up and distributed by players' unions in 11 countries across three continents. RESULTS: Prevalence of symptoms related to mental disorders among 219 retired professional footballers ranged from 11% for adverse smoking behaviour and 18% for distress, to 35% for anxiety/depression and 65% for adverse nutrition behaviour. Especially life events that occurred in the previous six months was positively associated with distress (OR=1.3; 95%CI 1.0--1.6), anxiety/depression (OR=1.6; 95%CI 1.2--2.1), sleeping disturbance (OR=1.3; 95%CI 1.1--1.7) and adverse nutrition behaviour (OR=1.4; 95%CI 1.0--1.8). CONCLUSIONS: A high prevalence of symptoms related to mental disorders was found among retired professional footballers, confirming a previous study in a similar study population. Relationships were established between symptoms of mental disorders and severe injuries, recently occurred life events, and career dissatisfaction.

Cancer stem-like cells of ovarian clear cell carcinoma are enriched in the ALDH-high population associated with an accelerated scavenging system in reactive oxygen species.

OBJECTIVE: In ovarian cancer cases, recurrence after chemotherapy is frequently observed, suggesting the involvement of ovarian cancer stem-like cells (CSCs). The chemoresistance of ovarian clear cell carcinomas is particularly strong in comparison to other epithelial ovarian cancer subtypes. We investigated the relationship between a CSC marker, aldehyde dehydrogenase 1 (ALDH1), and clinical prognosis using ovarian clear cell carcinoma tissue samples. Furthermore, we investigated the antioxidant mechanism by which CSCs maintain a lower reactive oxygen species (ROS) level, which provides protection from chemotherapeutic agents. METHODS: Immunohistochemical staining was performed to examine the CSC markers (CD133, CD44, ALDH1) using ovarian clear cell carcinoma tissue samples (n=81). Clear cell carcinoma cell lines (KOC-7C, OVTOKO) are separated into the ALDH-high and ALDH-low populations by ALDEFLUOR assay and fluorescence-activated cell sorting (FACS). We compared the intracellular ROS level, mRNA level of the antioxidant enzymes and Nrf2 expression of the two populations. RESULTS: High ALDH1 expression levels are related to advanced stage in clear cell carcinoma cases. ALDH1 expression significantly reduced progression free survival. Other markers are not related to clinical stage and prognosis. ALDH-high cells contained a lower ROS level than ALDH-low cells. Antioxidant enzymes were upregulated in ALDH-high cells. ALDH-high cells showed increased expression of Nrf2, a key transcriptional factor of the antioxidant system. CONCLUSIONS: ALDH-positive CSCs might have increased Nrf2-induced antioxidant scavengers, which lower ROS level relevant to chemoresistance in ovarian clear cell carcinoma.

Fabrication of hydroxyapatite thin films on zirconia using a sputtering technique.

Hydroxyapatite (HA) thin films were prepared on a zirconia (ZrO2) substrate using a sputtering technique, and the film was also coated on a titanium (Ti) substrate for comparison. The coated films were recrystallised using a hydrothermal treatment to reduce film dissolution. The films were then characterised by X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The osteocompatiblity of the films was evaluated by investigating the alkaline phosphatase (ALP) activity and the size of the bone formation area of osteoblast cells. In the XRD patterns of the as-sputtered films on the ZrO2 substrate, there are no peaks except for those from the ZrO2 substrate. After the hydrothermal treatment, HA peaks appeared in the patterns. Nanoparticles (less than 20 nm) were observed on the ZrO2 substrates in the SEM images of the as-sputtered films. After the hydrothermal treatment, particles of 20-40 nm were observed on the film, whereas the HA film on the Ti substrate was covered by a larger number of globular particles (20-60 nm). In the osteoblast cell cultures, the ALP activity and bone formation area on the HA films on both the ZrO2 and Ti substrates increased after the hydrothermal treatment of the films, and the values for the ZrO2 substrate were higher than those for the Ti substrate.

Characterization of Sr-substituted hydroxyapatite thin film by sputtering technique from mixture targets of hydroxyapatite and strontium apatite.

Sr-substituted hydroxyapatite thin films were prepared by sputtering technique from mixture targets of hydroxyapatite (HA) and strontium apatite (SrAp). The HA and SrAp powders were mixed at 0-100% Sr/(Sr+Ca) target ratios. The coated films were recrystallized by a hydrothermal treatment to reduce film dissolution. The films were then characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM) and inductively coupled plasma atomic emission spectrometry (ICP). The osteocompatiblity of the films was also evaluated by the size of the bone formation area in osteoblast cells.In the XRD patterns, peaks shifted to lower 2θ values with increasing Sr/(Sr+Ca) target ratios, which indicated Sr incorporation into the HA lattice. In the SEM observation of the hydrothermally treated films, the surface was covered with globular particles, and the size of the globular particles increased from Sr0 to Sr40, and then the size decreased from Sr60 to Sr100. The ICP analysis showed that the Sr/(Sr+Ca) film ratios were almost the same as the target ratios. In the cell culture, the bone formation area on the Sr-substituted HA films increased with increasing Sr concentration, and saturated at Sr60.