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The His-Asp phosphorelay signal transduction from histidine kinase (HK) to the response regulator (RR) is an important mechanism for adaptation to environmental changes. Aspergillus nidulans expresses 15 different HKs, which may be involved in different types of adaptations. As reactive oxygen species (ROS) are a key signal of environmental changes, some HKs might be involved in ROS generation through transcriptional regulation. Previously, we identified 3 HK (NikA, FphA, and HysA) deletion strains that showed increased ROS production during growth. We also showed that the phosphorylation function of HysA is involved in ROS generation. Here, we investigated the role of HysA in ROS production in A. nidulans cells. HysA protein was detected in both the cytosol and mitochondria by biological fractionation of the vegetative cell lysate of A. nidulans. The subcellular localization analysis by expressing the the HysA-GFP fusion protein along with MitoTracker Red staining did not clearly reveal mitochondrial localization of HysA at the conidiophore during asexual development. However, mitochondrial ROS in hysA mutant strains were detected by MitoSOX Red staining, and their excess levels possibly caused morphological changes during asexual development.The fifth wave of the coronavirus disease 2019 (COVID-19) pandemic caused by delta variant infection depleted medical resources, and the Japanese government announced glucocorticoid use for outpatients. An appropriate outpatient-glucocorticoid treatment for COVID-19 has not been established; therefore, we created treatment manuals with indications for glucocorticoid administration in a care facility adequately equipped to manage patients with mild to moderate COVID-19. Thirty-eight patients (24 males, 14 females; mean age 40.5 ± 11.8 years) were treated with glucocorticoids from August 1 to October 1, 2021 [COVID-19 staging, mild (n = 1), moderate I (n = 19), and moderate II (n = 18)]. Patients were treated with 6.6 mg/day d.i.v. or 6 mg/day p.o. dexamethasone, or 20-30 mg/day p.o. prednisolone. The median (25th-75th percentile) number of days from the date of onset to glucocorticoid administration was 8.0 days (7.0-11.25 days). While 24 patients were hospitalized, the condition of 14 improved without hospitalization. The median number of days from glucocorticoid administration to hospitalization was 1.0 day (range, 1.0-1.0 day). In the non-hospitalized patients, the median number of days of glucocorticoid administration was 5.0 days (5.0-5.25 days). The mean number of days from glucocorticoid administration to discharge from the care facility for non-hospitalized patients was 8.4 ± 3.3 days. The adverse reactions among non-hospitalized patients included insomnia (n = 1) and mild liver dysfunction (n = 3). The present method of glucocorticoid administration can be safely used for patients with COVID-19 in care facilities.Fetal growth restriction (FGR) is defined as fetuses who have failed to achieve a normal weight for gestational age. FGR is associated with adverse perinatal outcomes, including stillbirth. Pregnant women often perceive decreased fetal movements before intrauterine fetal death. Previous reports on the association between fetal movements and FGR have mainly targeted livebirths, with few focusing on stillbirths. Studying stillbirths, not livebirths, may help improve perinatal adverse outcomes. This study evaluated the association between FGR leading to stillbirth and maternal perception of decreased fetal movement. This was a population-based study reviewing all stillbirths in Shiga Prefecture, Japan for 10 years. We analyzed 219 stillbirth cases, those with versus without FGR. We then compared maternal visits to healthcare providers due to perception of decreased fetal movement between these two groups. There were 82 stillbirths with FGR, and the remaining 137 stillbirth were without FGR. Women with FGR, compared with those without, were significantly less often to visit the outpatient department due to decreased fetal movement (30%; 25/82 vs. 46%; 63/137 P = 0.034). Pregnant women have more difficulty perceiving decreased fetal movements in cases with severe FGR than in those without FGR. Healthcare providers, including midwives, may need to closely monitor FGR pregnancy in addition to instructing pregnant women to be aware of decreased fetal movement.Disruption of cancer screening programs and diagnoses of gastrointestinal cancers by the COVID-19 pandemic has been reported; however, little attention has been paid to the situation in depopulated areas with low infection rates. Akita Prefecture is one of the most depopulated areas of Japan and has the lowest COVID-19 infection rate per capita; at the same time, the prefecture has been top-ranked for mortality due to gastrointestinal cancer for years. In this population-based study in Akita Prefecture, we investigated the occurrence of gastrointestinal cancers and the number of cancer screening procedures over the five-year period of 2016-2020, employing a database from the collaborative Akita Prefecture hospital-based registration system of cancers. The occurrence of gastrointestinal cancers, especially esophago-gastric cancers, declined by 11.0% in 2020, when the COVID-19 pandemic affected the overall healthcare system, compared with the average of 2016-2019. Nonetheless, the occurrence of advanced-stage (stage IV) esophago-gastric cancers increased by 7.2% in 2020. The decrease in the gastrointestinal cancer diagnosis rate in 2020 coincided with a 30% decline in the total number of regular population-based screening programs. Under the ongoing COVID-19 pandemic, cancer screening was uniformly suspended throughout Japan. Accordingly, the COVID-19 pandemic has substantially disrupted the cancer screening system, leading to delays in diagnoses of gastrointestinal cancer, even in depopulated areas (Akita Prefecture) of Japan with a low prevalence of infection. Suspension of cancer screening procedures during an infectious disease pandemic should be thoroughly considered for each region based on the cancer incidence and infection status in that area.A Nankai Trough earthquake is highly likely to occur in near future, and perinatal medical resources and care in Kochi Prefecture may be insufficient after such an event. Therefore, we evaluated the medical and public health measures needed to prepare for caring for pregnant women in Kochi Prefecture in the aftermath of such an earthquake and the potential action plans for the prefecture. We estimated that immediately after an earthquake, approximately 30 pregnant women will require urgent medical treatment, most of whom will be in the prefectural capital, Kochi City, and perinatal medical care in Kochi City may be insufficient. Therefore, we used the projected flooding areas to divide Kochi City and its surrounding areas into 3 areas and allocated at least one Disaster Liaison for Pediatrics and Perinatal Medicine (DLPPM) to each disaster base hospital in those 3 areas. In a disaster, the DLPPMs will serve as key individuals in their respective areas and coordinate the allocation of medical care. A DLPPM will be allocated also within the Disaster Medical Response Headquarters of Kochi Prefecture and be responsible for overseeing perinatal care in the whole of Kochi Prefecture. Our study shows that estimating the number of affected pregnant women and requirement for perinatal medical care is an effective way to prepare realistic disaster measures and to enable a specific plan to be formulated for effective allocation and management of DLPPMs. We believe that our system can serve as a model in perinatal disaster medicine.Asthma and atopic dermatitis are common among schoolchildren. The Great East Japan Earthquake of 2011 caused serious damage to buildings and infrastructure as well as the total or partial collapse of many hospitals and medical clinics. The aim of this study was to examine the association between recurrence or exacerbation (recurrence/exacerbation) of asthma or atopic dermatitis at the time of disaster and allergic symptoms several years later in schoolchildren. A cross-sectional survey was conducted via a parent-administered questionnaire between 2013 and 2015 in Miyagi Prefecture, northeast Japan. We analyzed the data of 2,399 schoolchildren with a diagnosis of asthma and 2,107 with a diagnosis of atopic dermatitis. Among those who had experienced recurrence/exacerbation of their symptoms soon after the disaster, the prevalence of later wheezing and eczema was 71.2% (N = 195) and 81.9% (N = 379), respectively. Recurrence/exacerbation of allergic symptoms just after the disaster was positively associated with wheezing (odds ratio, OR 6.54, 95% confidence interval, 95% CI 4.94-8.67) and eczema (OR 8.12, 95% CI 6.25-10.55) several years later. Disasters might have long-term effects on the allergy symptoms of children. It is necessary to prepare for prevention of recurrence/exacerbation, to treat allergic symptoms, and to support children to continue their allergy treatments and daily care when a disaster strikes.Takayasu arteritis (TA) is a chronic, nonspecific inflammatory disease of large and medium-sized vessels that primarily involves the aorta and its branches. TA involving the pulmonary arteries has a prevalence ranging from 14% to 86%, which can lead to pulmonary hypertension, a progressive increase in pulmonary artery pressure, and eventually death from right heart failure. The presentation of pulmonary arteritis (PA) is very nonspecific, with a reported misdiagnosis rate of up to 60% and a diagnosis time ranging from 1 month to more than 10 years. The clinical manifestation of pleural effusion is very rare in both TA and PA cases. Based on our literature review, this is the 6 th reported case of TA with pleural effusion, and the specific mechanism of TA with pleural effusion is still unclear. The characteristics of this case and the previously reported cases are summarized in this article to improve the understanding of TA and PA and reduce the misdiagnosis rate.Clopidogrel is a pro-drug which needs two-step metabolism to produce the active thiol metabolite. This study aimed to explore an efficient method to simultaneously determine the plasma clopidogrel, 2-oxo-clopidogrel (2-Oxo-CLP), and the clopidogrel active metabolite (CAM). A high-throughput liquid chromatography tandem mass spectrometry (LC-MS/MS) was therefore developed. find more The analytes were extracted from plasma by using methyl tert-butyl ether (MTBE). Chromatographic separation was performed on a C18 column under an isocratic elution, accompanied with acetonitrile and deionized water containing 0.1% formic acid. After optimizing the condition of LC-MS/MS, a stable linearity was observed in the standard curves over the concentration ranges of 0.05 to 50.0 ng/mL for clopidogrel, 0.5 to 50.0 ng/mL for 2-Oxo-CLP, and 0.5 to 100 ng/mL for clopidogrel active metabolite derivative (CAMD). The retention time was 4.78 minutes, 3.79 minutes, 3.59 minutes, and 4.82 minutes for clopidogrel, 2-Oxo-CLP, CAMD, and internal standard, respectively. Both the relative standard deviation and the relative error were within the requirement of operating criteria. No significant degradation of clopidogrel, 2-Oxo-CLP, and CAMD occurred under different storage conditions. This method was successfully validated in 3 patients with coronary artery disease. The results showed that the current LC-MS/MS method was efficient for simultaneously detecting clopidogrel, 2-Oxo-CLP, and CAM with fine linearity, accuracy, precision, and stability.
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