OBJECTIVEThe aims of this study were to determine the effects of heavy metals such as manganese on nicotinamideN-methyltransferase (EC 2.1.1.1) (NNMT) activity and to consider the possibility of involvement of NNMT activation in the pathogenesis of heavy metal induced Parkinson's disease.

METHODSNNMT activity in supernatants separated from brain, liver and kidney homogenates of 5 elderly male Wistar rats by centrifugation were measured by high performance liquid chromatography system with fluorescence. NNMT activity under the conditon of 0.5 or 5.0 mM Mn(2+), Fe(2+), Cu(2+) or Cd(2+) was compared with control (no metal ion existence).

RESULTSNNMT activities in rat brain, liver and kidneys were significantly decreased by Cu(2+), and those in the liver and kidneys were significantly decreased by Cd(2+). Mn(2+) reduced NNMT activity only in the liver. Fe(2+) had no effect on NNMT activity.

CONCLUSIONSNo metal increased NNMT activity in this study, contrary to our hypothesis. Further study is needed to clarify the reason why the effects of Mn(2+) and Fe(2+) which have a high relevance to Parkinson's disease on NNMT activity differ from those of Cu(2+) and Cd(2+).

The system of the Japanese Board of Cardiovascular Surgery is changing. Since the last time, we have deliberated on the medical specialty board for U-40 column articles about the problems faced by young cardiovascular surgeons. This time, we conducted the second survey to U-40 members about the realities of becoming a board-certified cardiovascular surgeon. The results showed the circumstances and details on how to acquire the board certification. Moreover, we discussed about the current problems and future perspectives for the young cardiovascular surgeons.

Background: For enhancing nursing education, we conducted concept synthesis and empirical validation of the essential genetic/genomic nursing competencies on cancer medicine for all nurses.　Methods: First, 41 articles were reviewed to produce a prototype concept of the essential genetic/genomic nursing competencies on cancer medicine (Study A). Second, focus group interviews were conducted with 21 standard-level nurses in cancer care, genetic/genomic nursing practices were extracted, and these were synthesized into Study A results. Consequently, although two new nursing practices were generated, analysis was terminated because no new concepts were created (Study B). Lastly, two experts performed empirical validation for all subjects.　Results: The following seven concepts were identified: "Utilization of genetic/genomic information," "Prevention of cancer including family members," "Adjustment of genome-related resources," "Attitude toward diversity in individuals," "Fulfillment of basic responsibilities," "Acquisition of specific medical knowledge," and "Awareness of the contribution of genetic/genomic medicine."　Discussion: Compared with the existing genetic nursing core competencies, cancer management systems and technological reforms have led to the addition of "administration management of molecularly targeted drugs" and "harmonization with organizational and regional policies." Thus, the nursing practice behind the concept has shifted from the legally prescribed "medical treatment for injured and ill persons" to "assistance in medical care" involving family members. Others concepts included core competences of general genetic/genomic nursing similar to cancer care.

Objective: To evaluate the efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. Methods: This Phase 2 open-label, single-arm study enrolled Japanese women with homologous recombination deficiency-positive relapsed, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer who had completed 3–4 lines of therapy. The starting dose of niraparib was 300 mg administered once daily in continuous 28-day cycles until objective progressive disease, unacceptable toxicity, consent withdrawal or discontinuation. The primary endpoint, objective response rate (ORR), was assessed by the investigator using RECIST version 1.1. Safety evaluations included the incidence of treatment-emergent adverse events (TEAEs), including serious TEAEs. Results: Twenty women were enrolled and the confirmed ORR in the full analysis set (FAS) was 35.0% (7/20), consisting of 1 complete response and 6 partial responses. Disease control rate in the FAS was 90.0%. The most frequently reported TEAEs (>50%) were anemia, nausea, and platelet count decreased. One patient (5.0%) had TEAEs leading to discontinuation of niraparib whereas reductions or interruptions were reported in 14 (70.0%) and 15 (75.0%) patients, respectively. The median dose intensity (202.9 mg daily) corresponded to a relative dose intensity of 67.6%. Conclusion Efficacy and safety of niraparib in heavily pretreated Japanese women was comparable to that seen in an equivalent population of non-Japanese women. No new safety signals were identified.

No abstract available.
Carcinosarcoma*