Development of a Teaching Material of Integrated Study in Senior High School : Mathematical Proof of Kepler's Laws

新しい学習指導要領に基づく教育が間もなく始まるが, 多くの教師にとって'総合的な学習'をいかに扱うかは大きな課題であり, 様々な取り組みや実践が行われている。しかし, その内容は小, 中, 高で異なり得ることはもちろん, 高等学校に限っても生徒の興味・関心の違い等により, 独自の展開が求められるであろう。今回の報告は, 高等学校3年理系の物理選択者に対して, 彼らの希望を踏まえて行った'ケプラーの法則の数学的証明'であり, 極めて限定された対象者に対する毎回90分, 4回連続の講義の実践記録である

Efficacy of SGLT2 inhibitors in IgA nephropathy associated with alcoholic liver cirrhosis accompanied by nephrotic syndrome: a case report

We present a 51-year-old male patient with a history of Child-Pugh Grade B alcoholic liver cirrhosis (ALC) who developed renal impairment (serum creatinine of 2.00 mg/dL) and nephrotic syndrome (a urinary protein level of 4.35 g/gCr). The patient was diagnosed with immunoglobulin A nephropathy (IgAN) associated with ALC based on findings from comprehensive evaluations, including markedly elevated serum IgA levels (883.7 mg/dL), a kidney biopsy revealing significant IgA deposition in the para-mesangial area, and a liver diagnosis showing long-standing advanced ALC. Our treatment approach involved initiating dapagliflozin therapy, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, alongside strict alcohol abstinence. Remarkably, the patient demonstrated a dramatic reduction in proteinuria within one week of dapagliflozin administration. No hypoglycemic events were observed. This case adds valuable clinical insights into the potential therapeutic role of SGLT2 inhibitors in IgAN associated with ALC. Specifically, in cases where conventional steroid therapies may be contraindicated due to coexisting comorbidities such as diabetes or obesity, dapagliflozin emerges as a potentially efficacious alternative. Further investigations are warranted to validate these preliminary observations

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The relationship between knee muscle strength and knee biomechanics during running at 6 and 12 months after anterior cruciate ligament reconstruction

Background: Knee joint kinematics and kinetics during running recover at 12 months, not 6 months, following anterior cruciate ligament (ACL) reconstruction surgery. Knee muscle strength is a criterion used to assess an individual’s readiness to return-to-sports (RTS); however, the relationship between knee muscle strength and knee biomechanics is unclear. This study investigated the relationship between knee muscle strength and dynamic knee biomechanics during running at 6 and 12 months after ACL reconstruction surgery. Methods: Knee joint kinematics and kinetics during running were analyzed in 21 patients (10 males, 11 females) who underwent ACL reconstruction for a unilateral ACL deficiency. Kinematics and Kinetics were measured by three-dimensional motion analysis system, and Knee flexion angle was calculated using Point cluster technique and internal extension moment was calculated by the inverse dynamics method. Patients were compared to a control group matched by age, height and weight. Isokinetic knee extension and flexion strength in ACL-reconstructed patients were measured at 6 and 12 months postsurgery, by separated gender. Results: Knee flexion angle was significantly lower in ACL patients at 6 months postsurgery compared to the control group (F (2, 62)=5.78, P=0.014). There were significant lower peak knee flexion angles in male groups than female (F (1, 62)=6.33, P<0.01). Knee extension moments were significantly lower in both male and female ACL patients compared to the control group at 6 and 12 months postsurgery (F (2, 62)=12.05, P<0.01(6 months), P=0.034(12 months)), and there were significant correlations with knee extension moments and maximum torque of knee extension/flexion (P<0.05). At 12 months after surgery, knee joint kinematics in ACL patients were restored. Both peak knee angle and knee extension moment were significantly associated with maximum knee extension/flexion torque values in female patients at 12 months postsurgery. Conclusions: Dynamic knee biomechanics during running were not restored 6 and 12 months after ACL reconstruction both male and female. It is necessary to strengthen knee extension and flexion muscles to restore knee kinetics during running, especially female patients

Factors associated with 10-m walking speed in outpatients undergoing hemodialysis: a multicenter cross-sectional study

Abstract Introduction Walking ability is an important prognostic factor for patients undergoing maintenance hemodialysis (HD). Since complications such as poor nutrition, anemia, malnutrition, and inflammation in patients undergoing HD may affect walking ability, the factors affected by 10-m walking speed must be investigated. This cross-sectional study enrolled 1205 outpatients undergoing HD and measured their 10-m walking speed. Methods Lower extremity muscle strength (LES), grip strength, one-leg standing time (OLST), and short physical performance battery (SPPB) score were measured as physical functions. Age, sex, body mass index, dialysis history, comorbidities, and hematological data were collected. Results A multiple regression analysis revealed that the 10-m walking speed was significantly associated with LES, grip strength, OLST, SPPB, and % creatinine production rate, even after adjusting for corresponding variables (R 2 = 0.69, p < 0.05). Conclusion Muscle strength and muscle mass may be essential factors for the 10-m walking speed in patients undergoing HD