Our findings imply an involvement of inflammatory processes in the pathogenesis of PCDH19-FE and therapeutic utility for corticosteroids as an adjunctive option in acute treatment. PCDH19 is well expressed in brain microvascular endothelial cells and thus its impairment may cause BBB vulnerability, which may be ameliorated by corticosteroids. The abs-NR detected in our patients may not indicate an autoimmune pathomechanism, but may rather represent non-specific sensitization to degraded neuronal components entering the general circulation, the latter process facilitated by the BBB vulnerability.
Major facilitator superfamily domain containing 2a (Mfsd2a) is a member of the major facilitator superfamily. Mfsd2a functions as a transporter for docosahexaenoic acid and also plays a role in the unfolded protein response (UPR) upon tunicamycin (TM) exposure. UPR is involved in the pathogenesis of various human diseases. TM and thapsigargin are representative experimental reagents that induce UPR. To elucidate the detailed function of Mfsd2a in UPR in vivo, we generated Mfsd2a-deficient mice and investigated the role of Mfsd2a during UPR induced by TM or thapsigargin. Phenotypically, Mfsd2a-deficient mice were small and short-lived. No gross anatomical abnormalities in Mfsd2a-deficient mice compared with the wild-type mice were exhibited. Embryonic fibroblasts derived from Mfsd2a-null mice failed to show induction of GRP78 and DDIT3 expressions upon TM exposure but not upon Tg exposure. This phenomenon could not be overcome despite the exposure under high TM concentration. Reconstitution of Mfsd2a in Mfsd2a-null MEF showed hypersensitivity to TM. Furthermore, we examined the physiological role of Mfsd2a against TM using an in vivo mouse model. DDIT3 induction by TM was drastically attenuated in both the liver and brain of Mfsd2a-deficient mice. These results reveal that Mfsd2a plays a critical role in UPR upon TM exposure.
Ethics approvalThis study was approved by the ethics committee of the National Center for Child Health and Development (NCCHD) (#1818). Informed consent was obtained from parents of the patient for publication with images and for gene analysis.
Background
The Japanese healthcare system currently faces numerous challenges, including a super-aging society and an excessive burden on medical workers; therefore, the need for innovative solutions from healthcare ventures to tackle these issues has increased. Meanwhile, as physicians play important roles in healthcare ventures, the need for Japanese physician entrepreneurs is more important than ever. Given the lack of research examining barriers to physicians starting ventures and what skills, knowledge, and surrounding environments act as facilitators, this study aimed to identify the facilitators and barriers faced by physicians to start ventures.
Methods
Between September and November 2019 and in May 2021, qualitative interviews were conducted with 33 participants, which included eight physician entrepreneurs; two administrative officers at the Ministry of Health, Labour and Welfare and the Ministry of Economy, Trade and Industry; three faculty members at Tokyo Medical and Dental University (in-depth interviews); and 20 medical students (focus group discussions). The interviews were deductively coded based on the social ecological model. The inductive approach was applied to coding any knowledge necessary to start a business. We conducted member checking with three physician entrepreneurs and seven medical students to improve our results’ credibility.
Results
The factors influencing a physician’s decision to launch a new business include their willingness to contribute to society, the unique environment in which an individual is placed while in medical school and afterward, negative aspects of the lack of diversity in physicians’ careers, the financial stability provided by a medical license, and self-efficacy.
Conclusions
Our study revealed facilitators and barriers to physicians’ entrepreneurial ventures. Knowledge about these factors might be useful in supporting physicians to launch or become involved in healthcare ventures.
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