In adult mammalian brain, occurrence of the synthesis of estradiol from endogenous cholesterol has been doubted because of the inability to detect dehydroepiandrosterone synthase, P45017␣. In adult male rat hippocampal formation, significant localization was demonstrated for both cytochromes P45017␣ and P450 aromatase, in pyramidal neurons in the CA1-CA3 regions, as well as in the granule cells in the dentate gyrus, by means of immunohistochemical staining of slices. Only a weak immunoreaction of these P450s was observed in astrocytes and oligodendrocytes. ImmunoGold electron microscopy revealed that P45017␣ and P450 aromatase were localized in pre-and postsynaptic compartments as well as in the endoplasmic reticulum in principal neurons. The expression of these cytochromes was further verified by using Western blot analysis and RT-PCR. Stimulation of hippocampal neurons with N-methyl-D-aspartate induced a significant net production of estradiol. Analysis of radioactive metabolites demonstrated the conversion from [ 3 H]pregnenolone to [ 3 H]estradiol through dehydroepiandrosterone and testosterone.This activity was abolished by the application of specific inhibitors of cytochrome P450s. Interestingly, estradiol was not significantly converted to other steroid metabolites. Taken together with our previous finding of a P450scc-containing neuronal system for pregnenolone synthesis, these results imply that 17␤-estradiol is synthesized by P45017␣ and P450 aromatase localized in hippocampal neurons from endogenous cholesterol. This synthesis may be regulated by a glutamate-mediated synaptic communication that evokes Ca 2؉ signals.

Background There is limited understanding of the characteristics of coronavirus disease 2019 (COVID-19) patients requiring hospitalization in Japan. Methods This study included 2638 cases enrolled from 227 health care facilities that participated in the COVID-19 Registry Japan (COVIREGI-JP). The inclusion criteria for enrollment of a case in COVIREGI-JP are both (1) a positive SARS-CoV-2 test and (2) inpatient treatment at a health care facility. Results The median age of hospitalized patients with COVID-19 was 56 years (interquartile range [IQR]: 40-71). More than half of the cases were male (58.9%, 1542/2619). Nearly 60% of the cases had close contact to confirmed or suspected cases of COVID-19. The median duration of symptoms before admission was 7 days (IQR: 4-10). The most common comorbidities were hypertension (15%, 396/2638) and diabetes without complications (14.2%, 374/2638). The number of non-severe cases (68.2%, n=1798) was twice the number of severe cases (31.8%, n=840) at admission. The respiratory support during hospitalization includes those who received no oxygen support (61.6%, 1623/2636), followed by those who received supplemental oxygen (29.9%, 788/2636), and IMV/ECMO (mechanical ventilation or extracorporeal membrane oxygenation) (8.5%, 225/2636). Overall, 66.9% (1762/2634) of patients were discharged home, while 7.5% (197/2634) died. Conclusions We identified the clinical epidemiological features of COVID-19 in hospitalized patients in Japan. When compared with existing inpatient studies in other countries, these results demonstrated less comorbidities and a trend towards lower mortality.

Highlights Close relationship is found between low serum zinc and severe states of COVID-19. Hypozincemia critically contributes to aggravation of COVID-19. Serum zinc level can be predictive factor for critical illness of COVID-19. We would recommend oral medication of zinc salts to patients with COVID-19. Abstract Objectives Because most severely ill patients with COVID-19 in our hospital showed zinc deficiency, we aimed to examine the relationship between the patient’s serum zinc level and severe cases of COVID-19. Methods Serum zinc <70 µg/dL was defined as the criterion for hypozincemia, and patients continuously with serum zinc <70 µg/dL were classified in the hypozincemia cohort. To evaluate whether hypozincemia could be a predictive factor for critical illness of COVID-19, we performed the multivariate analysis by employing logistic regression analysis. Results Prolonged hypozincemia was found to be a risk factor for a severe case of COVID-19. In evaluating the relationship between the serum zinc level and severity of patients with COVID-19 by multivariate logistic regression analysis, critical illness can be predicted through the sensitivity and false specificity of an ROC curve with an error rate of 10.3% and AUC of 94.2% by only two factors: serum zinc value ( P = 0.020) and LDH value ( P = 0.026). Conclusions Proper management of the prediction results in this study can contribute to the establishment and maintenance of a safe medical system, taking the arrival of the second wave and spread of COVID-19 in the future into consideration.