Revised Cut-Off Value of Human Epididymis Protein 4 Enhances Its Use as an Ovarian Tumor Marker.

OBJECTIVES: Human epididymis protein 4 (HE4), a protein secreted by ovarian tumors, has been used as an ovarian tumor marker. This study aimed to improve the usefulness of HE4 to detect malignant ovarian tumors by reviewing the cut-off values. DESIGN: A retrospective study without intervention was conducted. PARTICIPANTS: One hundred forty-nine healthy women (premenopausal, 126; postmenopausal, 23) and 24 patients with ovarian tumors (malignant, 12; benign, 12) participated in the study. SETTING: The study used the Department of Obstetrics and Gynecology of a university hospital in Japan and the university hospital as a workplace from 2016 to 2018. METHODS: The basic performance of the HE4 assay was evaluated, and the serum HE4 levels of participants were measured. Receiver operating characteristic analysis was performed using the HE4 data of the patients. RESULTS: There were no significant differences in HE4 levels between the pre- and postmenopausal groups of healthy women. When the global cut-off values (premenopausal, 70 pmol/L; postmenopausal, 140 pmol/L) were adopted, the clinical sensitivity, specificity, positive predictive value, and negative predictive value were 41.7%, 91.7%, 83.3%, and 61.1%, respectively. Based on the results of the receiver operating characteristic analysis, we set the HE4 cut-off level at 60 pmol/L, regardless of the menopausal status. With the newly set cut-off value, the clinical sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 91.7%, 88.9%, and 73.3%, respectively. That is, the clinical sensitivity of HE4 was improved without lowering specificity. LIMITATIONS: The small number of subjects and the fact that the health status of the healthy women was evaluated based on questionnaires were limitations to the study. CONCLUSION: A clinically useful cut-off value for HE4 as an ovarian tumor marker was established regardless of the menopausal status of the women, with improved clinical sensitivity, positive predictive value, and negative predictive value without lowering specificity. Currently, different cut-off values for HE4 in pre- and postmenopausal women are used globally. The cut-off value for CA125 was the same between pre- and postmenopausal women. Therefore, with the newly established cut-off value, HE4 can be used more conveniently in a non-specialized setting, especially when it is used in combination with CA125.

[A Simulation Surgery of Valve-sparing Aortic Root Replacement Using a Three-dimensional Printed Model].

Aortic valve-sparing surgery is a delicate procedure that requires specialized skills to control aortic valve regurgitation. Therefore, simulating the surgery before performing it on a patient is good practice for inexperienced surgeons. Herein, we present our experience of a simulation surgery using a three-dimensionally printed aortic root model of a 60-year-old man with severe aortic regurgitation and aortic root enlargement. We fabricated the model using multi-slice computed tomography data. The model revealed the two pitfalls:unbalanced commissure position and lower coaptation height of the right coronary cusp. We completed the simulation surgery from the proximal suture and valve reimplantation to coronary ostial reconstructions during approximately three hours with medical staffs. In the actual operation, the aortic valve regurgitation completely disappeared by accurately reconstructing the commissure in the Valsalva graft and adjusting the height of the right coronary cusp using central plication procedure. We believe that carrying out simulations before the actual surgery improves the surgeon's confidence and the patient's outcomes.

[Application of dementia care mapping (DCM) for one year in a geriatric health services facility: Effects of developmental evaluation based on collaboration by medical and welfare staff aimed at person-centred care].

PURPOSE: This study aimed to clarify the effects of dementia care mapping (DCM) for one year in a healthcare center for older adults. DCM was conducted between September 2016 and August 2017. The care staff include nurses and caregivers in a narrow sense, medical staff, such as a physician, physical therapists, and occupational therapists worked on DCM as care staff in this study. RESULTS: There were 24 participants, with an average work experience of 7.21 (±4.74) years. In comparison to the baseline evaluation, the final assessment of self-efficacy through person-centred care showed significant improvement in 'Forecasting and Problem Solving on the Job' within 'Perceived Job Competence of Care Workers'. Six main categories of content were extracted from focus group interviews: 'Awareness,' 'Change of Elderly People under the Care of Staff throughout the Development of Mapping', 'Affirmative Feelings of Care Staff for Mapping', 'Negative Feelings for Mapping', 'Need for the Efficacy and Efficiency of the Mapping', and 'Mapping Based on the Age of the Participant and Future Prospects for Mapping'. The results of person-centred care showed that both the older patients and the staff noticed changes through the development of mapping. CONCLUSION: The developmental evaluation, based on collaboration by medical and welfare staff can improve self-efficacy through the practice of person-centred care and improves the ability to solve problems during the provision of care.

Health science students' attitudes towards healthcare teams: A comparison between two universities.

There have been few studies comparing the attitudes towards healthcare teams between different universities. This study analysed the differences in attitudes towards healthcare teams between health science students at Gunma University, Japan, which implements a comprehensive interprofessional education (IPE) programme, and Kanazawa University, a similar national university. Study populations were first- and third-year students at the Gunma University School of Health Sciences and the Kanazawa University School of Health Sciences. The present study was performed just after the IPE and multi-professional education subjects at Gunma University in the first term of the 2012 academic year. The first-year students were different cohort from the third-year students. The modified Attitudes Toward Health Care Teams Scale (ATHCTS) was used to measure attitudes towards healthcare teams. The overall mean score on the modified ATHCTS of students at Gunma University was significantly higher than that of those at Kanazawa University. In both first- and third-year students, the regression factor score of "patient-centred care" was significantly higher at Gunma University than at Kanazawa University. Based on the present study, it can be stated that IPE may foster the value of collaborative practice (CP) among health science students.

Professional identity acquisition process model in interprofessional education using structural equation modelling: 10-year initiative survey.

The mandatory interprofessional education (IPE) programme at Gunma University, Japan, was initiated in 1999. A questionnaire of 10 items to assess the students' understanding of the IPE training programme has been distributed since then, and the factor analysis of the responses revealed that it was categorised into four subscales, i.e. "professional identity", "structure and function of training facilities", "teamwork and collaboration", and "role and responsibilities", and suggested that these may take into account the development of IPE programme with clinical training. The purpose of this study was to examine the professional identity acquisition process (PIAP) model in IPE using structural equation modelling (SEM). Overall, 1,581 respondents of a possible 1,809 students from the departments of nursing, laboratory sciences, physical therapy, and occupational therapy completed the questionnaire. The SEM technique was utilised to construct a PIAP model on the relationships among four factors. The original PIAP model showed that "professional identity" was predicted by two factors, namely "role and responsibilities" and "teamwork and collaboration". These two factors were predicted by the factor "structure and function of training facilities". The same structure was observed in nursing and physical therapy students' PIAP models, but it was not completely the same in laboratory sciences and occupational therapy students' PIAP models. A parallel but not isolated curriculum on expertise unique to the profession, which may help to understand their professional identity in combination with learning the collaboration, may be necessary.

Apixaban versus Warfarin for the Prevention of Periprocedural Cerebral Thromboembolism in Atrial Fibrillation Ablation: Multicenter Prospective Randomized Study.

INTRODUCTION: Stroke can be a life-threatening complication of atrial fibrillation (AF) catheter ablation. Uninterrupted warfarin treatment contributes to minimizing the risk of stroke complications. METHODS AND RESULTS: This was a prospective, open-label, randomized, multicenter study assessing the safety and efficacy of apixaban for the prevention of cerebral thromboembolism complicating AF catheter ablation. Two hundred patients with drug-resistant AF were equally assigned to take either apixaban (5 mg or 2.5 mg twice daily) or warfarin (target international normalized ratio, 2-3) for at least 1 month before AF ablation. Neither drug regimen was interrupted throughout the operative period. Diffusion-weighted magnetic resonance imaging was performed for all patients to detect silent cerebral infarction (SCI) after the ablation. Primary outcomes were defined as the occurrence of stroke, transient ischemic attack, SCI, or major bleeding that required intervention. The secondary outcome was minor bleeding. The groups did not statistically differ in patients' backgrounds or procedural parameters. During AF ablation, the apixaban group required administration of more heparin to maintain an activated clotting time > 300 seconds than the warfarin group (apixaban, 14,000 ± 4,000 units; warfarin, 9,000 ± 3,000 units). Three primary outcome events occurred in each group (apixaban, 2 SCI and 1 major bleed; warfarin, 3 SCI, P = 1.00), and 3 and 4 secondary outcome events occurred in the apixaban and warfarin groups (P = 0.70), respectively. CONCLUSION: Apixaban has similar safety and effectiveness to warfarin for the prevention of cerebral thromboembolism during the periprocedural period of AF ablation.

A rare case: bioprosthetic tricuspid valvuloplasty dramatically improved hepatic encephalopathy.

A 51-year-old woman was diagnosed as severe stenosed tricuspid bioprosthetic valve. She had developed an encephalopathy due to elevated serum ammonia concentration caused by congestive hepatic failure. Re-tricuspid valve replacement was deemed too risky, and balloon bioprosthetic valvuloplasty was instead planned. This procedure was successfully performed using a standard mitral valvuloplasty protocol. The 30-mm INOUE-BALLOON was inflated five times. The mean pressure gradient across the bioprosthetic valve decreased from 7.8 to 3.5 mmHg, and the tricuspid valve orifice area increased from 1.09 to 3.13 cm(2), without worsening of the tricuspid valve regurgitation. Finally, her hepatic encephalopathy was dramatically improved.

Validation of microinjection methods for generating knockout mice by CRISPR/Cas-mediated genome engineering.

The CRISPR/Cas system, in which the Cas9 endonuclease and a guide RNA complementary to the target are sufficient for RNA-guided cleavage of the target DNA, is a powerful new approach recently developed for targeted gene disruption in various animal models. However, there is little verification of microinjection methods for generating knockout mice using this approach. Here, we report the verification of microinjection methods of the CRISPR/Cas system. We compared three methods for injection: (1) injection of DNA into the pronucleus, (2) injection of RNA into the pronucleus, and (3) injection of RNA into the cytoplasm. We found that injection of RNA into the cytoplasm was the most efficient method in terms of the numbers of viable blastocyst stage embryos and full-term pups generated. This method also showed the best overall knockout efficiency.

Repeated cross-sectional study of the longitudinal changes in attitudes toward interprofessional health care teams amongst undergraduate students.

The interprofessional education (IPE) program at Gunma University, Maebashi, Japan, uses a lecture style for first-year students and a training style for third-year students. To investigate the comprehensive implications of IPE, the change pattern of attitudes toward health care teams was examined longitudinally in pre-qualified students. The modified Attitudes Toward Health Care Teams Scale (mATHCTS) was used. The overall mean score of the mATHCTS improved significantly after the training-style IPE in their third year. Two individual items in the factor "quality of care delivery" decreased significantly during the first year. In contrast, two individual items in the factor "patient-centered care" increased significantly during the third year. These changes over time were confirmed by analyses using regression factor scores. There are at least two independent attitudes toward collaborative practice (CP) or IPE in response to IPE interventions: the attitude toward "value of IPE for health care providers" may response negatively to IPE in the early stages, and the attitude toward "value of IPE for health care receivers" positively in the later stages. These findings suggest that the continuation of mandatory IPE, which must be designed on the basis of students' high expectations for IPE and CP on entry, may result in profound changes in attitudes amongst participating students.

Gram-negative bacterial lipopolysaccharide stimulates activin a secretion from human amniotic epithelial cells.

Activin A is involved in inflammation. The present study was performed to clarify if lipopolysaccharide, a component of Gram-negative bacteria, stimulates activin A secretion from human amniotic epithelial cells and to determine if activin A plays a role in amnionitis. Fetal membranes were obtained during elective cesarean sections performed in full-term pregnancies of patients without systemic disease, signs of premature delivery, or fetal complications. Amniotic epithelial cells were isolated by trypsinization. The activin A concentrations in the culture media were measured by enzyme-linked immunosorbent assay, and cell proliferation was assessed by 5-bromo-2'-deoxyuridine incorporation. Amniotic epithelial cells secreted activin A in a cell density-dependent manner, and lipopolysaccharide (10 µ g/mL) enhanced the secretion at each cell density. Lipopolysaccharide (10-50 µ g/mL) also stimulated activin A secretion in a dose-dependent manner. Contrary to the effect of activin A secretion, lipopolysaccharide inhibited cell proliferation in amniotic epithelial cells. The present study suggests that lipopolysaccharide stimulation of activin A secretion may be a mechanism in the pathogenesis of amnionitis.

Attitudes toward interprofessional healthcare teams: a comparison between undergraduate students and alumni.

The goal of effective interprofessional education (IPE) is high-quality patient-care delivery and attaining a high level of patient satisfaction in clinical settings. We aimed to examine if alumni who have studied in an IPE program at a pre-licensure stage maintain a positive attitude toward collaborative practice (CP) in the postgraduate clinical experience. This paper presents a cross-sectional descriptive study which employed the modified attitudes toward health care teams scale (ATHCTS) to examine the relationship between exposure to clinical practice and the attitudes toward interprofessional healthcare teams. Results indicated that the overall mean score of alumni was significantly lower than that of undergraduate students on the modified ATHCTS. Only "team efficacy" had a significantly lower regression factor score in alumni than undergraduate students. Our findings suggest that changes in professional identity in a team may be due to contact with patients after graduation in the postgraduate clinical healthcare experience. The reduction of attitudes toward healthcare teams in the postgraduate clinical experience may be related to "team efficacy". We emphasize the need for in-service IPE for sustaining attitudes and providing a useful CP, which results in good clinical outcome.

Genome engineering of mammalian haploid embryonic stem cells using the Cas9/RNA system.

Haploid embryonic stem cells (ESCs) are useful for studying mammalian genes because disruption of only one allele can cause loss-of-function phenotypes. Here, we report the use of haploid ESCs and the CRISPR RNA-guided Cas9 nuclease gene-targeting system to manipulate mammalian genes. Co-transfection of haploid ESCs with vectors expressing Cas9 nuclease and single-guide RNAs (sgRNAs) targeting Tet1, Tet2, and Tet3 resulted in the complete disruption of all three genes and caused a loss-of-function phenotype with high efficiency (50%). Co-transfection of cells with vectors expressing Cas9 and sgRNAs targeting two loci on the same chromosome resulted in the creation of a large chromosomal deletion and a large inversion. Thus, the use of the CRISPR system in combination with haploid ESCs provides a powerful platform to manipulate the mammalian genome.

Cohesiveness and hydrodynamic properties of young drinking water biofilms.

Drinking water biofilms are complex microbial systems mainly composed of clusters of different size and age. Atomic force microscopy (AFM) measurements were performed on 4, 8 and 12 weeks old biofilms in order to quantify the mechanical detachment shear stress of the clusters, to estimate the biofilm entanglement rate ξ. This AFM approach showed that the removal of the clusters occurred generally for mechanical shear stress of about 100 kPa only for clusters volumes greater than 200 µm3. This value appears 1000 times higher than hydrodynamic shear stress technically available meaning that the cleaning of pipe surfaces by water flushing remains always incomplete. To predict hydrodynamic detachment of biofilm clusters, a theoretical model has been developed regarding the averaging of elastic and viscous stresses in the cluster and by including the entanglement rate ξ. The results highlighted a slight increase of the detachment shear stress with age and also the dependence between the posting of clusters and their volume. Indeed, the experimental values of ξ allow predicting biofilm hydrodynamic detachment with same order of magnitude than was what reported in the literature. The apparent discrepancy between the mechanical and the hydrodynamic detachment is mainly due to the fact that AFM mechanical experiments are related to the clusters local properties whereas hydrodynamic measurements reflected the global properties of the whole biofilm.

Changes in attitudes toward interprofessional health care teams and education in the first- and third-year undergraduate students.

The interprofessional education (IPE) program at Gunma University, Maebashi, Japan, implements a lecture style for the first-year students and a training style for the third-year students. Changes in the scores of modified Attitudes Toward Health Care Teams Scale (ATHCTS) and those of modified Readiness of health care students for Interprofessional Learning Scale (RIPLS) at the beginning and the end of the term were evaluated in the 2008 academic year. Two hundred and eighty-five respondents of a possible 364 completed the survey. In both the scales, the overall mean scores declined significantly after the lecture-style learning in the first-year students, while the scores improved significantly after the training-style learning in the third-year students. Exploratory factor analysis revealed that the modified ATHCTS was composed of three subscales, and the modified RIPLS two subscales. Analyses using regression factor scores revealed that the scores of "quality of care delivery" subscale in the modified ATHCTS and those of "expertise" subscale in the modified RIPLS declined significantly in the first-year students. Consequently, IPE programs may be introduced early in the undergraduate curriculum to prevent stereotyped perceptions for IPE, and comprehensive IPE curricula may result in profound changes in attitudes among participating students.

Elasticity and physico-chemical properties during drinking water biofilm formation.

Atomic force microscope techniques and multi-staining fluorescence microscopy were employed to study the steps in drinking water biofilm formation. During the formation of a conditioning layer, surface hydrophobic forces increased and the range of characteristic hydrophobic forces diversified with time, becoming progressively complex in macromolecular composition, which in return triggered irreversible cellular adhesion. AFM visualization of 1 to 8 week drinking water biofilms showed a spatially discontinuous and heterogeneous distribution comprising an extensive network of filamentous fungi in which biofilm aggregates were embedded. The elastic modulus of 40-day-old biofilms ranged from 200 to 9000 kPa, and the biofilm deposits with a height >0.5 µm had an elastic modulus <600 kPa, suggesting that the drinking water biofilms were composed of a soft top layer and a basal layer with significantly higher elastic modulus values falling in the range of fungal elasticity.

Bacterial surface appendages strongly impact nanomechanical and electrokinetic properties of Escherichia coli cells subjected to osmotic stress.

The physicochemical properties and dynamics of bacterial envelope, play a major role in bacterial activity. In this study, the morphological, nanomechanical and electrohydrodynamic properties of Escherichia coli K-12 mutant cells were thoroughly investigated as a function of bulk medium ionic strength using atomic force microscopy (AFM) and electrokinetics (electrophoresis). Bacteria were differing according to genetic alterations controlling the production of different surface appendages (short and rigid Ag43 adhesins, longer and more flexible type 1 fimbriae and F pilus). From the analysis of the spatially resolved force curves, it is shown that cells elasticity and turgor pressure are not only depending on bulk salt concentration but also on the presence/absence and nature of surface appendage. In 1 mM KNO(3), cells without appendages or cells surrounded by Ag43 exhibit large Young moduli and turgor pressures (∼700-900 kPa and ∼100-300 kPa respectively). Under similar ionic strength condition, a dramatic ∼50% to ∼70% decrease of these nanomechanical parameters was evidenced for cells with appendages. Qualitatively, such dependence of nanomechanical behavior on surface organization remains when increasing medium salt content to 100 mM, even though, quantitatively, differences are marked to a much smaller extent. Additionally, for a given surface appendage, the magnitude of the nanomechanical parameters decreases significantly when increasing bulk salt concentration. This effect is ascribed to a bacterial exoosmotic water loss resulting in a combined contraction of bacterial cytoplasm together with an electrostatically-driven shrinkage of the surface appendages. The former process is demonstrated upon AFM analysis, while the latter, inaccessible upon AFM imaging, is inferred from electrophoretic data interpreted according to advanced soft particle electrokinetic theory. Altogether, AFM and electrokinetic results clearly demonstrate the intimate relationship between structure/flexibility and charge of bacterial envelope and propensity of bacterium and surface appendages to contract under hypertonic conditions.

Prevalence of facet joint degeneration in association with intervertebral joint degeneration in a sample of organ donors.

Among the most common causes of low back pain are strain on the muscles and ligaments associated with the spine, degeneration of the intervertebral discs (IVDs), and osteoarthritis of the facet joints. It is not clear, however, how these latter two conditions are related to each other in terms of their development during a patient's lifetime. The facet joint is the sole synovial joint of the spine but because it is difficult to image its degenerative history as well as its relationship to other degenerative factors within the spine remain elusive. We compared the gross and histologic characteristics of the lumbar spine from a sample of organ donors to the integrity of their associated IVDs as assessed through magnetic resonance imaging. In our study sample, we found that facet joint degeneration was common, occurring as early as 15 years of age, while the IVD could still remain intact. Facet degeneration was more severe at the L4/5 level and progressed along with IVD degeneration with age. Because such early degenerative changes in the facet joint are somewhat surprising, degeneration of this joint should not be overlooked when assessing OA of the spine and causes of lower back pain.

Assessing chlorinated ethene degradation in a large scale contaminant plume by dual carbon-chlorine isotope analysis and quantitative PCR.

The fate of chlorinated ethenes in a large contaminant plume originating from a tetrachloroethene (PCE) source in a sandy aquifer in Denmark was investigated using novel methods including compound-specific carbon and chlorine isotope analysis and quantitative real-time polymerase chain reaction (qPCR) methods targeting Dehaloccocoides sp. and vcrA genes. Redox conditions were characterized as well based on concentrations of dissolved redox sensitive compounds and sulfur isotopes in SO(4)(2-). In the first 400 m downgradient of the source, the plume was confined to the upper 20 m of the aquifer. Further downgradient it widened in vertical direction due to diverging groundwater flow reaching a depth of up to 50 m. As the plume dipped downward and moved away from the source, O(2) and NO(3)(-) decreased to below detection levels, while dissolved Fe(2+) and SO(4)(2-) increased above detectable concentrations, likely due to pyrite oxidation as confirmed by the depleted sulfur isotope signature of SO(4)(2-). In the same zone, PCE and trichloroethene (TCE) disappeared and cis-1,2-dichloroethene (cDCE) became the dominant chlorinated ethene. PCE and TCE were likely transformed by reductive dechlorination rather than abiotic reduction by pyrite as indicated by the formation of cDCE and stable carbon isotope data. TCE and cDCE showed carbon isotope trends typical for reductive dechlorination with an initial depletion of (13)C in the daughter products followed by an enrichment of (13)C as degradation proceeded. At 1000 m downgradient of the source, cDCE was the dominant chlorinated ethene and had reached the source δ(13)C value confirming that cDCE was not affected by abiotic or biotic degradation. Further downgradient (up to 1900 m), cDCE became enriched in (13)C by up to 8 ‰ demonstrating its further transformation while vinylchloride (VC) concentrations remained low (<1 µg/L) and ethene was not observed. The correlated shift of carbon and chlorine isotope ratios of cDCE by 8 and 3.9 ‰, respectively, the detection of Dehaloccocides sp genes, and strongly reducing conditions in this zone provide strong evidence for reductive dechlorination of cDCE. The significant enrichment of (13)C in VC indicates that VC was transformed further, although the mechanism could not be determined. The transformation of cDCE was the rate limiting step as no accumulation of VC occurred. In summary, the study demonstrates that carbon-chlorine isotope analysis and qPCR combined with traditional approaches can be used to gain detailed insight into the processes that control the fate of chlorinated ethenes in large scale plumes.

[A case of non-small cell lung cancer with hemodialysis which responded to docetaxel monotherapy].

A 56-year-old man receiving hemodialysis treatment was hospitalized for examination of a mass in the right middle lobe. Chest computed tomography showed a right hilar mass shadow accompanied by pleural effusion. Non-small cell lung cancer (NSCLC) was diagnosed by cytological examination of the pleural effusion. No epidermal growth factor receptor (EGFR) mutation was found. He was treated with 6 courses of docetaxel as first-line chemotherapy. Docetaxel was administered on the same day as hemodialysis. Adverse events, including hematotoxicity, were managed safely and no delay in administration occurred. This chemotherapy resulted in a partial response. Because docetaxel is metabolized in the liver and does not affect renal function, it can be administered as a standard regimen. This suggests that docetaxel monotherapy is an efficient therapy for non-small cell lung cancer patients receiving hemodialysis.