Idiopathic combined adrenocorticotropin and growth hormone deficiency mimicking chronic fatigue syndrome

A 42-year-old man who had suffered from severe fatigue for 5 years was diagnosed as having chronic fatigue syndrome (CFS) and fibromyalgia. Endocrinological workup using combined anterior pituitary function tests showed that the patient had adrenocorticotropin hormone (ACTH) deficiency, with a normal pituitary MRI. Treatment with a physiologic dose of oral hydrocortisone replacement physically ameliorated his general fatigue. A secondary workup using a growth hormone-releasing peptide-2 test revealed that he also had growth hormone (GH) deficiency, and GH replacement therapy was started. His muscle pain and depression were improved by the therapy. Here, we present a rare case of combined deficiency of ACTH and GH in a middle-aged man with severe general fatigue. This case report aims to raise awareness of combined deficiency of ACTH and GH as a differential diagnosis of CFS and its mimics

Antibiotic literacy among Japanese medical students

Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship

Impact of the COVID-19 Pandemic on the Psychological Distress of Medical Students in Japan: Cross-sectional Survey Study

Background: The COVID-19 pandemic has negatively affected medical education. However, little data are available about medical students’ distress during the pandemic. Objective: This study aimed to provide details on how medical students have been affected by the pandemic. Methods: A cross-sectional study was conducted. A total of 717 medical students participated in the web-based survey. The survey included questions about how the participants’ mental status had changed from before to after the Japanese nationwide state of emergency (SOE). Results: Out of 717 medical students, 473 (66.0%) participated in the study. In total, 29.8% (141/473) of the students reported concerns about the shift toward online education, mostly because they thought online education would be ineffective compared with in-person learning. The participants’ subjective mental health status significantly worsened after the SOE was lifted (P Conclusions: Given our findings, the sudden shift to online education might have overwhelmed medical students. Thus, we recommend that educators inform learners that online learning is not inferior to in-person learning, which could attenuate potential depression and anxiety

Blastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats.

Murine animal models from genetically modified pluripotent stem cells (PSCs) are essential for functional genomics and biomedical research, which require germline transmission for the establishment of colonies. However, the quality of PSCs, and donor-host cell competition in chimeras often present strong barriers for germline transmission. Here, we report efficient germline transmission of recalcitrant PSCs via blastocyst complementation, a method to compensate for missing tissues or organs in genetically modified animals via blastocyst injection of PSCs. We show that blastocysts from germline-deficient Prdm14 knockout rats provide a niche for the development of gametes originating entirely from the donor PSCs without any detriment to somatic development. We demonstrate the potential of this approach by creating PSC-derived Pax2/Pax8 double mutant anephric rats, and rescuing germline transmission of a PSC carrying a mouse artificial chromosome. Furthermore, we generate mouse PSC-derived functional spermatids in rats, which provides a proof-of-principle for the generation of xenogenic gametes in vivo. We believe this approach will become a useful system for generating PSC-derived germ cells in the future

Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology

Abe, S., Kobayashi, K., Oji, A. et al. Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology. Sci Rep 7, 15189 (2017). https://doi.org/10.1038/s41598-017-15033-

Integration-Free iPS Cells Engineered Using Human Artificial Chromosome Vectors

Human artificial chromosomes (HACs) have unique characteristics as gene-delivery vectors, including episomal transmission and transfer of multiple, large transgenes. Here, we demonstrate the advantages of HAC vectors for reprogramming mouse embryonic fibroblasts (MEFs) into induced pluripotent stem (iPS) cells. Two HAC vectors (iHAC1 and iHAC2) were constructed. Both carried four reprogramming factors, and iHAC2 also encoded a p53-knockdown cassette. iHAC1 partially reprogrammed MEFs, and iHAC2 efficiently reprogrammed MEFs. Global gene expression patterns showed that the iHACs, unlike other vectors, generated relatively uniform iPS cells. Under non-selecting conditions, we established iHAC-free iPS cells by isolating cells that spontaneously lost iHAC2. Analyses of pluripotent markers, teratomas and chimeras confirmed that these iHAC-free iPS cells were pluripotent. Moreover, iHAC-free iPS cells with a re-introduced HAC encoding Herpes Simplex virus thymidine kinase were eliminated by ganciclovir treatment, indicating that the HAC safeguard system functioned in iPS cells. Thus, the HAC vector could generate uniform, integration-free iPS cells with a built-in safeguard system

Transitional Changes in Fatigue-Related Symptoms Due to Long COVID: A Single-Center Retrospective Observational Study in Japan

Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p < 0.01), dysgeusia (14% vs. 40%, ** p < 0.01) and hair loss (7% vs. 28%, ** p < 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p < 0.05), insomnia (26% vs. 13%, * p < 0.05) and cough (20% vs. 7%, ** p < 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized