Glutamatergic Neurometabolite Levels in Bipolar Disorder: A Systematic Review and Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.

BACKGROUND: The glutamatergic system is thought to play an important role in the pathophysiology of bipolar disorder (BD). While there has been an increase in proton magnetic resonance spectroscopy studies examining this neurotransmission system, the results are inconsistent. Possible reasons for the inconsistency, including clinical features such as mood state and childhood versus adulthood age, were not addressed in previous meta-analyses. METHODS: This systematic review and meta-analysis of proton magnetic resonance spectroscopy studies of BD included 40 studies, with 1135 patients with BD and 964 healthy control (HC) subjects. RESULTS: Glutamate plus glutamine and glutamine levels in the anterior cingulate cortex of patients with BD were significantly elevated compared with those of HC subjects (standardized mean difference = 0.42, 0.48, respectively). Subgroup analyses showed that adult BD patients had significantly higher levels of glutamate plus glutamine than adult HC subjects, but this was not the case in pediatric patients. For mood states, anterior cingulate cortex glutamate plus glutamine levels were higher in patients with bipolar depression than those in HC subjects. CONCLUSIONS: Our results imply that glutamatergic dysfunction in the anterior cingulate cortex may be implicated in the pathophysiology of BD, which is most evident in adult BD patients and patients with bipolar depression.

Ethics of Treatment Decisions for Extremely Premature Newborns with Poor Prognoses: Comparison of Shared Decision Making in Norway and Japan.

Ethical debates about the life-prolonging treatment of extremely premature infants and infants with congenital abnormalities with poor prognoses have long been held. We will examine approaches in Norway and Japan as examples because Norway is a well-known welfare state. By comparing the traditional Norwegian approach, the newly proposed approach of postponed withholding (PPWH) and the Japanese approach, we will revisit shared decision making in neonatology in general, where patients (i.e., newborns) inevitably have no decision-making capacity. We argue that in shared decision making, the process is critical, and that it is important to clarify who will be the final decision-maker and whose benefits are most important. In addition, we argue that the issue of cost cannot be avoided in this current time of economic disparities in global health. Shared decision making should not be a mere formality. These are significant examples of new ethical debates to be discussed in the modern era in the neonatology field.

Over-the-Counter Drug Misuse and Dependence: Public Health Ethics' Foray into Fight against the Codeine Crisis.

Over-the-counter (OTC) drugs, such as codeine, are available as an OTC drug at common drugstores and major e-commerce platforms, despite their known propensity for causing psychological dependence and harm from overuse. Misuse of and dependence on over-the-counter drugs are serious public health issues. Possible measures include stricter regulation and control, as well as regulation of access to information and awareness activities, but their effectiveness is limited. Up-scheduling, in which OTC drugs are placed under prescription or full regulation, is expected to have a definite effect. However, up-scheduling poses public health ethical challenges. Up-scheduling restricts the freedom of consumers to purchase OTC drugs, and the economic right of manufacturers and sellers. Up-scheduling may also interfere with people's right to seek self-care through the proper use of OTC drugs. Limited up-scheduling with respect to age may be an effective way to implement up-scheduling while avoiding ethical issues. However, from a public health perspective, it is necessary to improve the information infrastructure so that prescription drug information can be shared electronically, and to strengthen measures to prevent mental health problems among young people that lead to OTC drug misuse, even after up-scheduling.

Decision-Making Capacity to Refuse Treatment at the End of Life: The Need for Recognizing Real-World Practices.

End-of-life decision making is a troublesome ethical dilemma. These decisions should be made in trustful patient-doctor relationships. We aimed to propose a balanced approach when discussing this complex issue. We categorized the research into four approaches and suggest that a multidisciplinary approach may be appropriate. We also analyzed the pitfalls of the multidisciplinary approach. Our conclusion is two-fold. First, discussions in this field should be based on real-world practice. If this is not the case, the proposal may be armchair theory, which is not effective in a clinical setting. Second, interdisciplinary researchers should not stick to their position too firmly and should listen to others. Otherwise, proposals made will be paternalistic or philosophically biased. Therefore, when philosophical collaboration is applied to the topic of clinical bioethics, it is necessary to thoroughly examine different positions and carry out careful discussions with consideration for medical care settings. Researchers must also understand what is needed for a trustful patient-doctor relationship. By making such efforts, clinical bioethics will contribute to the wellbeing of patients.

Drug Repurposing for COVID-19: Ethical Considerations and Roadmaps.

While the world rushed to develop treatments for COVID-19, some turned hopefully to drug repurposing (drug repositioning). However, little study has addressed issues of drug repurposing in emergency situations from a broader perspective, taking into account the social and ethical ramifications. When drug repurposing is employed in emergency situations, the fairness of resource distribution becomes an issue that requires careful ethical consideration.This paper examines the drug repurposing in emergency situations focusing on the fairness using Japanese cases. Ethical issues under these circumstances addressed by the authors include: maintaining the evidence level, integrity of clinical research ethics, and voluntary consent by original indication patients. In order to address these issues, they argue that rapid accumulation of ethically and scientifically valid evidence is required, as is obtaining information on resource quantity.

Chronology of COVID-19 Cases on the Diamond Princess Cruise Ship and Ethical Considerations: A Report From Japan.

The Diamond Princess cruise ship has been anchored at the Yokohama port in Japan since February 3, 2020. A total of 691 cases of the coronavirus disease 2019 (COVID-19) infection had been confirmed as of February 23. The government initially assumed that the infection was not spreading aboard and therefore indicated that any persons who either tested negative for the virus or were asymptomatic should immediately disembark. However, on February 5, the government set a 14-day health observation period because of the severity of the infection. Passengers confirmed to be free from infection began disembarking on Day 15 (February 19) of the quarantine. The effectiveness and validity of infection control, justification for the timing of inspections, and even the nature of COVID-19 itself now are all in question. The ethical considerations related to cruise ship infection control include the reasonable justification for isolation, the psychological fragility and quality of life of the isolated passengers and crew members, the procedural justice inherent in a forced quarantine, and the optimization of control measures.The international coordination framework and the global ramifications of such outbreaks should be reevaluated by the international community. Denying a ship's entry based on local politics is incompatible with global justice. Events such as these require an international response and global regulations that seek to reduce disparities.

Sacrificing the Fukushima 50 again?

BACKGROUND: In the aftermath of the 2011 Fukushima nuclear plant accident, many workers helped restore the contaminated site, exposing themselves to a highly radioactive environment. They were referred to as the 'Fukushima 50' and applauded as heroes who saved Japan. A cohort study targeting those emergency workers is, currently, underway. We object to the study on ethical grounds. METHODS: Ethical and content analyses. RESULTS: First, the low participation rate raises ethical questions about why potential participants declined. Content analyses of nuclear power plant workers' narratives from a television broadcast extracted eight recurrent themes: disposable, treated like a sacrificial pawn, taboo, fear of contamination, readiness to risk one's life, distrust and dissatisfaction with the nation's response, regret over participating and uncertainty about the future. Second, the unscientific nature of the cohort design undermines the ethical basis for conducting it. Third, public resources were allocated in a way that compromises justice. CONCLUSIONS: We urge re-considering the current Fukushima 50 research study. We also urge applying the public funds now invested in this research project to activities that would directly benefit the Fukushima 50, such as offering free lifetime healthcare and direct financial compensation.

The impact of systematic para-aortic and pelvic lymphadenectomy on survival in patients with optimally debulked ovarian cancer.

AIM: The objective of this study was to verify the impact of systematic retroperitoneal lymphadenectomy on survival in patients with ovarian cancer. MATERIAL & METHODS: During 2001­2005, clinical records of 118 patients with epithelial ovarian cancer were collected in Tokushima prefecture. From a number of hospitals, patients in one group were treated without systematic lymphadenectomy, and in another group, patients were treated with routine systematic lymphadenectomy. Clinical records were reviewed retrospectively and progression-free survival (PFS) and overall survival (OS) were compared. RESULTS: Sixty-two patients were staged as I­II according to the macroscopic findings at surgery. Forty of these patients received systematic lymphadenectomy and 22 patients did not. The 5-year OS was 100 and 80%, respectively (P = 0.07). The 5-year PFS was 94 and 71%, respectively (P = 0.04). In patients with clear cell adenocarcinoma, 3-year OS and PFS were significantly better in the lymphadenectomy group (P = 0.01, P = 0.046, respectively). The 56 patients staged as III­IV according to the macroscopic findings at surgery were optimally debulked. Twenty-eight of these patients received systematic lymphadenectomy and 28 patients did not. There is no difference in the 5-year OS (65 and 66%, respectively; P = 0.71) or the 5-year PFS (30 and 52%, respectively; P = 0.48). CONCLUSION: This study has demonstrated that the systematic lymphadenectomy had benefit only in patients with ovarian cancer macroscopically confined to the pelvis. In patients with clear cell adenocarcinoma, systematic lymphadenectomy was beneficial. To the contrary, systematic lymphadenectomy had no benefit on OS or PFS in patients with advanced ovarian cancer if optimally debulked.

Lymphangioma of the ovary accompanied by chylous ascites.

Lymphangioma of the ovary is very rare, with only 17 cases reported to date. In this report, a 43-year-old woman with lymphangioma of the ovary accompanied by chylous ascites is described. Vaginal ultrasound showed a solid cystic tumor at the right ovary accompanied by ascites. The volume of ascites was changeable. Milky fluid obtained by Douglas pouch aspiration contained numerous mature lymphocytes. She underwent right salpingo-oophorectomy. Histological examination revealed that the excised tumor from the right ovary was consistent with benign lymphangioma. This is the first case report of lymphangioma of the ovary accompanied by chylous ascites. We should discriminate such cases from other malignant tumors in order to avoid overtreatment.

Morules with optically clear nuclei in ovarian borderline endometrioid tumor.

Optically clear nuclei (OCN) have been observed in morules of some neoplasms and in some conditions unrelated to the development of the morules. We first report a case of ovarian borderline endometrioid tumor (BET) showing the morules associated with OCN. The patient was a 47-year-old premenopausal woman with a left ovarian cystic tumor, atypical endometrial hyperplasia, and elevated serum levels of FSH, LH, estradiol, and CA 125. The resected ovarian tumor measured 6 cm in diameter, and showed a papillary growth. Histologically, the ovarian tumor was consistent with BET, and the morules with OCN were scattered. Immunohistochemically, OCN were proven to be rich in biotin. An aberrant nuclear expression of beta-catenin was observed in both the tumor cells and the morular cells. Our case may suggest the possibility that the appearance of OCN with or without morules in ovarian tumors is related to endometrioid differentiation of the tumor cells, and should be recognized as a diagnostic clue of ovarian endometrioid tumors. Although female sex hormones have been reported to play a role in the occurrence of OCN, the participation of beta-catenin mutation has also been suggested.