iPSC-derived type IV collagen α5-expressing kidney organoids model Alport syndrome

ヒトiPS細胞から作製した腎オルガノイドを用いたアルポート症候群病態モデルの開発. 京都大学プレスリリース. 2023-09-28.iPSC-derived kidney organoids to model a lifelong renal disease. 京都大学プレスリリース. 2023-10/17.Alport syndrome (AS) is a hereditary glomerulonephritis caused by COL4A3, COL4A4 or COL4A5 gene mutations and characterized by abnormalities of glomerular basement membranes (GBMs). Due to a lack of curative treatments, the condition proceeds to end-stage renal disease even in adolescents. Hampering drug discovery is the absence of effective in vitro methods for testing the restoration of normal GBMs. Here, we aimed to develop kidney organoid models from AS patient iPSCs for this purpose. We established iPSC-derived collagen α5(IV)-expressing kidney organoids and confirmed that kidney organoids from COL4A5 mutation-corrected iPSCs restore collagen α5(IV) protein expression. Importantly, our model recapitulates the differences in collagen composition between iPSC-derived kidney organoids from mild and severe AS cases. Furthermore, we demonstrate that a chemical chaperone, 4-phenyl butyric acid, has the potential to correct GBM abnormalities in kidney organoids showing mild AS phenotypes. This iPSC-derived kidney organoid model will contribute to drug discovery for AS

Current status of a helicopter transportation system on remote islands for patients undergoing mechanical thrombectomy

Background: Mechanical thrombectomy (MT) is standard treatment for acute ischemic stroke (AIS) with large-vessel occlusion within 6 h of symptom onset to treatment initiation (OTP). Recent trials have extended the therapeutic time window for MT to within 24 h. However, MT treatment remains low in remote areas. Nagasaki Prefecture, Japan has many inhabited islands with no neurointerventionalists. Our hospital on the mainland is a regional hub for eight island hospitals. We evaluated clinical outcomes of MT for patients with AIS on these islands versus on the mainland. Methods: During 2014–2019, we reviewed consecutive patients with AIS who received MT at our hospital. Patients comprised the Islands group and Mainland group. Patient characteristics and clinical outcomes were compared between groups. Results: We included 91 patients (Islands group: 15 patients, Mainland group: 76 patients). Seven patients (46.7%) in the Islands group versus 43 (56.6%) in the Mainland group achieved favorable outcomes. Successful recanalization was obtained in 11 patients (73.3%) on the islands and 67 (88.2%) on the mainland. The median OTP time in the Islands was 365 min. In both the Islands and Mainland groups, the OTP time and successful recanalization were associated with functional outcome. The modified Rankin Scale (mRS) score at 90 days ≤2 was obtained in two patients and mRS = 3 in four patients among eight patients with OTP time >6 h. Conclusions: Few patients with AIS on remote islands have received MT. Although patients who underwent MT on the islands had longer OTP, the clinical outcomes were acceptable. OTP time on remote islands must be shortened, as this is related to functional outcome. In some cases with successful recanalization, a favorable outcome can still be obtained even after 6 h. Even if OTP exceeds 6 h, it is desirable to appropriately select patients and actively perform MT

Evaluation of a Triage Checklist for Mild COVID-19 Outpatients in Predicting Subsequent Emergency Department Visits and Hospitalization during the Isolation Period: A Single-Center Retrospective Study

Managing mild illness in COVID-19 and predicting progression to severe disease are concerning issues. Here, we investigated the outcomes of Japanese patients with mild COVID-19, and identified triage risk factors for further hospitalization and emergency department (ED) visits at a single tertiary hospital. A triage checklist with 30 factors was used. Patients recommended for isolation were followed up for 10 days for subsequent ED visits or hospital admission. Overall, 338 patients (median age, 44.0; 45% women) visited the clinic 5.0 days (median) after symptom onset. Thirty-six patients were immediately hospitalized following triage; others were isolated. In total, 72 non-hospitalized patients visited the ED during their isolation, and 30 were hospitalized after evaluation for oxygen desaturation. The median ED visit and hospitalization durations after symptom onset were 5.0 and 8.0 days, respectively. The checklist factors associated with hospitalization during isolation were age > 50 years, body mass index > 25 kg/m2, hypertension, tachycardia with pulse rate > 100/min or blood pressure > 135 mmHg at triage, and >3-day delay in hospital visit after symptom onset. No patients died. Altogether, 80% of patients with mild COVID-19 could be safely isolated at home. Age, BMI, underlying hypertension, date after symptom onset, tachycardia, and systolic blood pressure at triage might be related to later hospitalization

Toward Capturing Scientific Evidence in Elderly Care: Efficient Extraction of Changing Facial Feature Points

To capture scientific evidence in elderly care, a user-defined facial expression sensing service was proposed in our previous study. Since the time-series data of feature values have been growing at a high rate as the measurement time increases, it may be difficult to find points of interest, especially for detecting changes from the elderly facial expression, such as many elderly people can only be shown in a micro facial expression due to facial wrinkles and aging. The purpose of this paper is to implement a method to efficiently find points of interest (PoI) from the facial feature time-series data of the elderly. In the proposed method, the concept of changing point detection into the analysis of feature values is incorporated by us, to automatically detect big fluctuations or changes in the trend in feature values and detect the moment when the subject’s facial expression changed significantly. Our key idea is to introduce the novel concept of composite feature value to achieve higher accuracy and apply change-point detection to it as well as to single feature values. Furthermore, the PoI finding results from the facial feature time-series data of young volunteers and the elderly are analyzed and evaluated. By the experiments, it is found that the proposed method is able to capture the moment of large facial movements even for people with micro facial expressions and obtain information that can be used as a clue to investigate their response to care

Block fields around Mt. Dake, Fuchu City, Hiroshima Prefecture, Japan

Block fields are newly found around the Mt. Dake near the block fields of Kui and Yano. In this paper, we described the occurrence of these block fields and weathering grade of granite. The block fields at Kui and Yano were formed on the residual hill on the Sera surfaces. On the other hand, Mt. Dake is not surrounded by small-relief surface at present. However, Mt. Dake is one of residual hill on the Sera surface, because the surface has been eroded by the Ashida river. This means that formation of the block fi eld is closely related with weathering and the formation of small-relief surface

Formation process of the Block fields at Kui and Yano

Block field is an accumulation of subrounded to subangular blocks without fine sizes over solid or weathered bedrock. The block field at Kui and Yano in the Hiroshima Prefecture has been designated as a natural monument by the Government. The formation process of it is described from a standpoint of weathering in this paper. The blocks at Kui and Yano are composed of granodiorite and are rounded with diameter of 1 meter to several meters. The block fi eld occurs at the mountain slope surrounded by the low-relief surface called the Sera surface. Weathering profi le developed in this area including the Sera surface is divided into 4 zones with depth: (I) grus; (II) small corestone in grus matrix; (III) large corestone with some intervening grus; (IV) fresh or slightly weathered granite with joints. Depth of I and II-zones is more than 30 meters. The blocks at Kui and Yano are inferred to be originally associated with corestones of the III-zone: the friable grus of the III-zone was readily washed away, whereas corestones were left in situ after exposing of the III-zone. Therefore, the formation of block fi eld was related to weathering process and formation of residual hill surrounded by the low-relief surface