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京都府立医科大学医学部看護学科, 京都府立医科大学附属病院看護部, 京都府立医科大学看護実践キャリア開発センター, 京都府立医科大学附属病院地域医療推進部, School of Nursing, Kyoto Prefectural University of Medicine, Department of Nursing, University Hospital Kyoto Prefectural University of Medicine, Kyoto Prefectural University of Medicine, Career Development Center for Nursing, Promotion Division of Regional Medicine, University Hospital Kyoto Prefectural University of Medicine, 本研究の目的は、「緩和ケア実践看護師養成コース（以下Aコース）」「在宅緩和ケア推進看護師養成コース（以下Bコース）」を受講した修了者とその上司への調査からプログラム評価および看護実践への活用状況を指標にしてプログラムを評価することである。【方法】平成27～31年度の間に京都府立医科大学看護実践キャリア開発センターが開催する「緩和ケアを推進する看護師教育プログラム」のAコースまたはBコースを受講した修了者25名のうち、調査時点で受講時と同じ施設・病院で就労を継続している21名（Aコース14名、Bコース7名）、とその上司21名（Aコース14名、Bコース7名）を研究対象者とした。修了生の施設・病院に質問紙を郵送し、令和3年7月～8月に無記名の自記式質問紙調査を行った。調査項目は、基本属性、カリキュラムについて、教育目標について、受講内容の適切性について、学習内容の臨床での活用について、とした。なお所属する大学の医学倫理審査委員会の承認を得て実施した（ERB-E-444）。【結果】回答者は、Aコース修了者9名、Aコース上司7名、Bコース修了者5名、Bコース上司3名であった。受講した修了者の評価においては、プログラムの内容についてAコースの8割以上が、Bコースの全員が（とても・まあまあ）適切としている。自己能力の発揮状況について、Aコースは4～6割、Bコースについては4～8割ができているとしている。 上司からの評価では、両コースとも受講した講義・演習・実習が7割程度現在の看護実践に役立っていると答えた。期待される能力については両コースとも8割以上が現在の看護活動に活きていると答えた。【結論】平成27年度から開始された「緩和ケアを推進する看護師教育プログラム」に対して、受講した修了者とその上司に，研修が有用であったかを問うたところ、受講した修了者はプログラムの内容が看護の実践で活かされていると実感していることが明らかとなった。さらに、上司は、受講した修了者が研修を踏まえた看護実践ができていると評価していることが明らかになった。修了者、上司の評価からプログラムの効果を評価することができた。

Uterine artery pseudoaneurysm (UAP) is a rare disease that causes genital bleeding during the postpartum period after cesarean section. Uterine artery embolization (UAE) is an effective procedure for UAP. UAP was unexpectedly encountered in a patient with gestational trophoblastic disease; however, this patient was conservatively managed without UAE. UAP can occur during treatment for gestational trophoblastic disease. Since asymptomatic UAP may spontaneously disappear, in the selection of conservative treatment, it is important to carefully monitor patients using transvaginal ultrasonography focusing on the size of the UAP and the speed of internal blood flow.

Background In patients with epithelial ovarian cancer, whether metastasis to para-aortic lymph nodes located cephalad to the renal veins (supra-renal PAN) should be classified as regional lymph node metastasis or distant metastasis remains controversial. This study was a preliminary retrospective evaluation of the pattern of supra-renal PAN metastasis in patients with epithelial ovarian cancer. Methods The subjects were 25 patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer who underwent systematic dissection of the para-aortic nodes, including the supra-renal PAN, and pelvic lymph nodes (PLN). Patient factors, perioperative factors, the number of dissected lymph nodes, and pathological lymph node metastasis were investigated. Results Supra-renal PAN metastasis was found in 4/25 patients (16.0%). None of the 14 patients with pT1 or pT2 disease had supra-renal PAN metastasis, while 4/11 patients (36.4%) with pT3 or ypT3 disease had such metastases. None of the patients had isolated supra-renal PAN metastasis, while patients with supra-renal PAN metastasis also had multiple metastases to the infra-renal PAN and PLN. Conclusions In patients with epithelial ovarian cancer, supra-renal PAN metastases might be considered to be distant rather than regional metastases. Further studies are needed to better define the clinical significance of supra-renal PAN metastasis.

Objectives: The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin is indicated for type 2 diabetes mellitus (T2DM). However, the long-term safety, effectiveness, and clinical relationship with ...

Administration of bevacizumab to ovarian cancer patients with distal deep vein thrombosis (DVT) is problematic because of lack of evidence about the likely outcomes. We conducted a preliminary study in ovarian cancer patients with DVT who received bevacizumab combined with a direct oral anticoagulant (DOAC). We retrospectively investigated patients with advanced or recurrent epithelial ovarian cancer and distal DVT diagnosed by ultrasonography who underwent chemotherapy containing bevacizumab (15 mg/kg every 3 weeks) combined with DOAC therapy. Bevacizumab was administered to 88 patients, including 7 patients (7.9%) receiving concomitant DOAC therapy for distal DVT. In these 7 patients, the median body mass index was 21.3 kg/m2, median D-dimer level at diagnosis of DVT was 4.3 µg/mL, and median duration of DOAC therapy was 8 months. Adverse events during DOAC therapy were grade 1 epistaxis and grade 1 hemorrhoidal bleeding in one patient each. DVT resolved in four patients and was unchanged in three patients, with no central progression or secondary thromboembolism. In ovarian cancer patients who have distal DVT, bevacizumab can possibly be administered safely when combined with a DOAC. To confirm this finding, further investigation on a larger scale will be required.

Objective Evidence concerning the safety and efficacy of indacaterol maleate in a real-life setting is limited. The objective of this post-marketing surveillance was to evaluate the real-life safety and efficacy of indacaterol maleate in Japanese patients with chronic obstructive pulmonary disease (COPD). Methods This was a 52-week post-marketing surveillance conducted between April 2012 and December 2018. The safety endpoints included the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse drug reactions (ADRs). The efficacy endpoints included the physician-reported global evaluation of treatment effectiveness (GETE), change from baseline in the COPD assessment test (CAT) results, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and %FEV1 following 4, 12, 26, and 52 weeks of indacaterol administration. Results Of the 1,846 enrolled patients, 1,726 were included in the safety and efficacy analyses. The mean age of the patients was 72.5 years old. Cough, pneumonia and COPD worsening were the most common AEs reported, while pneumonia (1.04%) was the most common SAE, and cough (1.68%) was the most common ADR. GETE showed that 69.70% of patients achieved an excellent/good/moderate response following indacaterol treatment. The CAT score decreased, and lung function parameters (FVC, FEV1 and %FEV1) improved across all the COPD stages following treatment with indacaterol. Conclusion Indacaterol showed a favorable safety and tolerability profile in Japanese patients with COPD without new safety signals observed in real-life settings. These findings demonstrated that indacaterol is an effective maintenance treatment in real-life practice for Japanese patients with COPD.

Ovarian endometriotic cysts have been identified as the possible origin of ovarian clear cell carcinoma (OCCC), so predicting or preventing future transformation is important. Early detection of clear cell carcinoma is important because it shows low sensitivity to chemotherapy and the prognosis is worse than for other histologic types. We recently treated 2 patients with OCCC. They were both young women with no family history of cancer who received long-term oral contraceptive therapy for endometriotic cysts, and the histologic diagnosis was typical clear cell carcinoma in both patients. However, in Case 1, the tumor was detected by periodic examination, tumor expression of WT1 was positive, and the stage was IA. On the other hand, Case 2 presented with fever of unknown origin, her tumor showed expression of p53, and the stage was IVB. Case 1 is alive with no evidence of disease at 38 months after surgery, while Case 2 died after 19 months despite intensive treatment. These contrasting cases suggest that we need to be aware of the risk of cancer in young women receiving long-term hormone therapy for endometriotic cysts and that OCCC may show greater heterogeneity than what has been reported previously.

This paper presents a simulation study of the control of automated venetian blinds for open-plan office spaces. It has been reported that a cut-off strategy in which the slat angle of the blind is determined to cut direct sunlight is not sufficient to avoid glare. Therefore, in this study, a glare prevention control is proposed whereby the slat angle is repeatedly altered until the glare degree is calculated to be less than the glare index limit. To predict glare degree, a metric that we developed, known as PGSV (Predicted Glare Sensation Vote), is used. To obtain PGSV, the average luminance of the window area including blind slats and the outside view seen between the slats is calculated. For electric lighting control, this study focuses on daylight reflected on the ceiling, which can reduce the required amount of light from electric lighting. The illuminance of the ceiling surface provided by light from the window areas is calculated. This electric light control integrated with blind control requires input from rooftop sensors, without need for indoor photo-sensors. It is suitable for offices using partitions that block light from the windows. The glare prevention method proposed in this paper shows greater slat angle than that in the cut-off strategy. However, it can reduce power consumption for lighting by approximately 30% in typical open-plan offices in Tokyo. Moreover, it provides 46–50% of view satisfaction, which is the percentage of working hours when the occupants are satisfied with the outside view.

Background: Vildagliptin is a dipeptidyl peptidase-4 inhibitor that reduces glycemia in patients with type 2 diabetes mellitus (T2DM). When approved in 2013, data on vildagliptin combined with >750...

Background: Vildagliptin is indicated for type 2 diabetes mellitus (T2DM); however, the onset and exacerbation of diabetic complications in Japanese T2DM patients treated with vildagliptin is unknown. Research design and methods: This 2-year post-marketing surveillance (PMS) assessed the real-world safety and efficacy of vildagliptin therapy in 19,218 Japanese T2DM patients. The relationship between the incidence of macro- and microvascular complications with patient characteristics and changes in glycemic control (HbA1c) were evaluated. Results: The incidences of macro- and microvascular diseases were 1.14% and 3.09%, respectively. Patients with HbA1c ≥8.4% had a higher odds ratio (OR) for micro- and macrovascular disease (OR: 2.02 and 1.90) compared with patients with HbA1c Conclusions: Vildagliptin elicited no increases/exacerbations of diabetic complications; this PMS suggested that the incidence of diabetic complications tends to be low in subjects with good HbA1c control.

The zebrafish (Danio rerio) has become a powerful model organism for studying developmental processes and genetic diseases. However, there remain several problems in previous rearing methods. In this study, we demonstrate a novel method for rearing zebrafish larvae by using a new first food, freshwater rotifers (Brachionus calyciflorus). Feeding experiments indicated that freshwater rotifers are suitable as the first food for newly hatched larval fish. In addition, we revisited and improved a feeding schedule from 5 to 40 days postfertilization. Our feeding method using freshwater rotifers accelerated larval growth. At 49 dpf, one pair out of 10 pairs successfully produced six fertilized eggs. At 56, 63, and 71 dpf, 6 out of the 10 pairs constantly produced normal embryos. Our method will improve the husbandry of the zebrafish.

Objective To investigate the clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) patients. Methods We retrospectively reviewed the medical records of 124 advanced EOC patients and analyzed the details of neoadjuvant chemotherapy (NACT), IDS, postoperative treatment, and prognoses. Results Following IDS, 98 patients had no gross residual disease (NGRD), 15 had residual disease sized

ObjectivesSimilar to primary debulking surgery, complete resection of all macroscopic diseases during interval debulking surgery (IDS) is the primary objective while using neoadjuvant chemotherapy followed by IDS for advanced ovarian, fallopian tube, and peritoneal cancers. However, most patients develop recurrent disease even after complete cytoreduction during IDS. This study aims to identify recurrence patterns of the ovarian, fallopian tube, and peritoneal cancers in patients who underwent complete cytoreduction during IDS.MethodsWe retrospectively reviewed data of patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who were treated at our hospital from January 1, 2005, to December 31, 2011.ResultsIn this study, 105 patients underwent neoadjuvant chemotherapy followed by IDS and achieved complete cytoreduction. The median follow-up period was 42.1 months. Recurrence was documented in 70 patients (66.7%), and 35 (33.3%) showed no evidence of disease. Peritoneal dissemination was the most common recurrence (60.0%) observed. In multivariate analysis, positive peritoneal cytology (P = 0.0003) and elevated pre-IDS serum CA125 levels (P = 0.046) were independent risk factors for recurrence.ConclusionsAfter complete cytoreduction during IDS in patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers, positive peritoneal cytology at IDS and elevated pre-IDS CA125 levels are associated with an increased risk of cancer recurrence. Positive peritoneal cytology during IDS is a particularly strong predictive factor for poor outcomes in these patients.

Women with the BRCA1/2 mutations, which cause hereditary breast and ovarian cancer (HBOC), are 35–40 times more likely to develop ovarian cancer compared with the general population. We treated a patient in whom ovarian carcinosarcoma was identified during surveillance for HBOC. She had suffered from breast cancer at ages 45 and 50. At the age of 54 years, she was diagnosed as carrying an “uncertain significant” BRCA1 variant using a genetic mutation analysis. She was referred to our department, and surveillance was performed every 3–6 months for BRCA1 pathogenic mutation carriers due to her family history. At the age of 62 years, cervical and endometrial cytology suggested a diagnosis of adenocarcinoma. At this point, the CA125 level was 19.7 and positron emission tomography/computed tomography (PET/CT) images revealed a right ovarian tumor (SUVmax, 7.41). Surgery was performed, and ovarian carcinosarcoma (pT3cN0M0) was diagnosed. Adjuvant chemotherapy consisting of paclitaxel and carboplatin was initiated. In the month during which the cancer was identified, BRCA1 variant mutation was re-designated as “suspected deleterious,” and 8 years after the initial genetic diagnosis, the causative mutation was identified. The patient has been disease-free for 4 years since surgery. This case demonstrates both the importance and difficulty of surveillance.

Objective : To assess the effects of semen characteristics on the success of intrauterine insemination (IUI). Design : A retrospective study. Settings : The Department of Obstetrics and Gynecology, Tokushima University Hospital, Japan. Patients : Between 2004 and 2008, 1,177 IUI cycles in 283 couples were studied. Intervention : IUI cycles were preceded with ovarian stimulation. Main Outcome Measure : Clinical pregnancy. Result : A total of 82 clinical pregnancies were obtained (7.0% pregnancy rate per cycle, 28.9% per case). Their subsequent outcomes of pregnancies were 18 miscarriages (21.9%), 2 ectopic pregnancies (2.4%) and 60 live births (73.2%). Of the 82 clinical pregnancies, 2 were twin pregnancies (2.4%). There was no triple or higher order multiple pregnancies. At the end of the sixth cycle, 73 clinical pregnancies had been achieved (89.0%). After diagnostic laparoscopy, the pregnancy rate per cycle for patients 35 years age was 18%, which is significantly higher than that of patients 35 years of age. Pregnancies occurred up to the fifth cycle after laparoscopy. The pregnancy rate (PR) per cycle was significantly higher in cases of sperm movement rates more than 30% (PR9.3%) and total motile sperm counts more than 10 106/ml (PR 8.2%). A study comparing the washed and unwashed cases did not reveal any differences. Conclusion : In male sub-fertility cases of sperm parameters as motility rates 30% and motile sperm concentration 10 106/ml, IUI could be a useful option for infertility treatment J. Med. Invest. 58

A critical event in tumor development is the formation of new blood vessels to provide oxygen, nutrients and growth factors to the rapidly growing cancer cells. This process of angiogenesis is complex, however, it is well established that vascular endothelial growth factor (VEGF)-mediated signaling is an important early event. Knockout mice studies have implicated the EP3 receptor in tumor development and angiogenesis; however, the signaling mechanism involved with this effect is unclear. We now show that stimulation of the EP3I isoform of the human EP3 receptor with prostaglandin E2 increases the mRNA expression of both VEGF and its cognate receptor VEGF receptor-1 (VEGFR-1). These inductions by the EP3I receptor involve the sequential activation of phosphatidylinositol 3-kinase and the extracellular signal-regulated kinases. Up-regulation of VEGF and VEGFR-1 mRNA by the human EP3I receptor has not been previously reported and further strengthen the role of this receptor in tumor-associated angiogenesis.

Orthovanadate (Na 3 VO 4 ), which acts as an inhibitor of protein tyrosine phosphatases, has a various pharmacological effects including the release of arachidonic acid (AA) from cells. We investigated roles of α-type cytosolic phospholipase A 2 (cPLA 2 α), Src family kinases (Src) and protein kinase C (PKC) in the release of AA induced by Na 3 VO 4 from a murine fibroblast cell line, L929. C12 cells, a variant of L929 that lacks expression of cPLA 2 α, were used along with a clone of C12 cells that are stably expressing cPLA 2 α (C12-cPLA 2 α cells). In the presence of a Ca 2+ ionophore (10 μM A23187), 5 and 10 mM Na 3 VO 4 synergistically stimulated AA release from L929 and C12-cPLA 2 α cells, and to a much lesser extent from control C12 cells. The release of AA by Na 3 VO 4 /A23187 was inhibited by a selective cPLA 2 α inhibitor (3 μM pyrrophenone). The release of AA by Na 3 VO 4 /A23187 was significantly inhibited by a PKC inhibitor (10 μM GF109203X), in PKC-depleted cells, by a Src inhibitor (2 μM PP2) and by an inhibitor of extracellular signal-regulated kinase 1/2 (ERK1/2) kinase (10 μM U0126). The phosphorylation of ERK1/2 was stimulated by Na 3 VO 4 , and the response was significantly decreased by inhibitors of Src, PKC and ERK1/2 kinase. Our data show that Na 3 VO 4 stimulates AA release largely via cPLA 2 α activation in Ca 2+ -dependent manner, and the cross-talk between Src and PKC and the ERK-dependent pathways are involved in Na 3 VO 4 -induced AA release from L929 cells.

Hydrogen peroxide (H(2)O(2)) stimulates the release of arachidonic acid from cells, but the signaling mechanism(s) involved remains to be elucidated. We investigated the roles of alpha-type cytosolic phospholipase A(2) (cPLA(2)alpha), Src family kinases (Src) and protein kinase C (PKC) in the release of arachidonic acid from L929 cells (a murine fibroblast cell line), C12 cells (a variant of L929 that lacks cPLA(2)alpha) and a stable clone of C12 cells expressing cPLA(2)alpha (C12-cPLA(2)alpha cells). In the presence of 10 muM A23187, 100 nM phorbol myristate acetate (PMA) and 1 mM H(2)O(2) synergistically stimulated arachidonic acid release from L929 cells and C12-cPLA(2)alpha cells, and to a much lesser extent from C12 cells. The reagents alone and co-treatment with PMA and H(2)O(2) without A23187 had marginal effects. No arachidonic acid was released by PMA/A23187 or H(2)O(2)/A23187 in CaCl(2)-free buffer and the release was inhibited by a selective cPLA(2)alpha inhibitor (3 microM pyrrophenone). Addition of 10 microM H(2)O(2), which did not stimulate arachidonic acid release with A23187, enhanced the response to PMA/A23187. The release induced by PMA/A23187 and by H(2)O(2)/A23187 was significantly inhibited by a PKC inhibitor (10 microM GF109203X) and in PKC-depleted cells, and by a Src inhibitor (2 microM PP2). The phosphorylation of extracellular signal-regulated kinase 1/2 induced by PMA/A23187 and H(2)O(2)/A23187 was significantly decreased by inhibitors of PKC and Src. These findings suggest that H(2)O(2) with Ca(2+) stimulates arachidonic acid release via cPLA(2)alpha in a Src- and PKC-dependent manner in L929 cells. The role of cross-talk between Src and PKC in arachidonic acid release is discussed.

The E1 reactions of sec - and tert -alkyl phosphates to isomeric olefins, as catalyzed by trifluoromethanesulfonic acid proceed smoothly with remarkably high regio- and diastereoselectivity in a smectic liquid crystalline phase medium, in contrast to isotropic reactions, which result in much lower selectivity.

Purpose: To compare the results of a triple procedure using either extracapsular cataract extraction (ECCE) or one of two phacoemulsification techniques combined with trabeculotomy ab externo and intraocular lens (IOL) implantation. Setting: Kyoto University Hospital, Kyoto, Japan, and Nagata Eye Hospital, Nara, Japan Methods: In this comparative study, 25 eyes with primary open-angle glaucoma had ECCE combined with trabeculotomy ab externo and IOL implantation and 22 had the same procedure using phacoemulsification instead of ECCE. Of the eyes that had phacoemulsification, 10 had a single-flap and 12 had a double-flap procedure. Results: All 22 eyes that had phacoemulsification had a postoperative IOP of 21 mm Hg or less, as did all ECCE eyes except 2. Although the self-sealing incision might have caused the higher incidence of IOP spikes in the immediate postoperative period, IOPs in the phacoemulsification groups were lower after 3 months. Results were similar in the single-flap and double-flap phacoemulsification groups. There were no significant complications. Conclusion: Cataract extraction by phacoemulsification or ECCE combined with IOL implantation and trabeculotomy ab externo is a safe, effective treatment for patients with coexisting glaucoma and cataract.

Tumor necrosis factor-α (TNFα)-induced cell death is regulated through the release of arachidonic acid (AA) by group IVA cytosolic phospholipase A2 (cPLA2α) in the murine fibroblast cell line L929. However, the signaling pathway by which TNFα activates cPLA2α remained to be solved. We examined AA release in L929 cells, in a variant of L929 (C12 cells) lacking cPLA2α, and in C12 cells transfected with cPLA2α expression vectors. In transient and stable clones of C12 cells expressing cPLA2α, Ca2+ ionophore A23187 and phorbol myristate acetate (PMA) stimulated AA release within 90 min, although no response to TNFα was observed within 6 h. These results suggest that C12 cells may lack the components necessary for TNFα-induced AA release, in addition to cPLA2α. PMA is known to stimulate AA release via phosphorylation of Ser505 in cPLA2α by activating extracellular signal-regulated kinases (ERK1/2). However, PMA-induced AA release from C12 cells expressing mutant cPLA2αS505A (mutation of Ser505 to Ala), which is not phosphorylated by ERK1/2, was similar to that from L929 cells and C12 cells expressing wild-type cPLA2α. The role of Ser505 phosphorylation in AA release induced by PMA is also discussed. Keywords:: cytosolic phospholipase A2α, tumor necrosis factor, Ca2+ ionophore, phorbol myristate acetate, L929 and C12 cells