Clinical Significance of Chest CT Scan for Previous Heavy Smoker

The patient is an 83-year-old male, who smoked 20-40 cigarettes daily during 20-75 years and quit after that. In March 2021, he revealed normal chest X-P and was explained to take chest computed tomography (CT) next year. In April 2022, chest X-P was unremarkable, but CT showed a small solid abnormal shadow in the upper left lung region nearby aortic arch and abdominal aortic aneurysm (AAA) in the upper abdomen. Almost lung cancer cases are found in current smokers or ex-smokers. Using CT, lung cancer screening shows a 20-26% decrease in cancer death. Consequently, Low-Dose CT (LDCT) for smokers would be recommended

Clinically Both Effects of Weight and Glucose Variability by Oral Semaglutide (Rybelsus) for Younger Female Patient with Type 2 Diabetes (T2D)

Background: Obesity and Type 2 Diabetes (T2D) are crucial problems worldwide. Oral semaglutide (Rybelsus) was introduced to medical practice for Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA). Case presentation: The patient is 24-year-old female with obesity (BMI 39.3 kg/m2), T2D and fatty liver. Results: She started and increased Rybelsus from 3mg, 7mg to 14mg/day each 4 weeks. She showed significant efficacy for 4 months as HbA1c 6.3% to 5.6% and weight 107kg to 103kg, without Gastrointestinal Adverse Events (GIAEs). Discussion: Rybelsus is provided just after waking up, and kept >30 min fasting period. Longer fasting time may contribute current effect

Type 2 Diabetes Mellitus with Diabetic Gastroparesis and Occasional Liver Dysfunction Treated by Low Carbohydrate Diet

Diabetes mellitus (DM) has wider neurological complications. They include upper gastrointestinal (GI) symptoms, impaired motility, impaired gastric emptying (GE) and diabetic gastroparesis (DG), which are usually found. The patient was a 64-year-old man with type 2 diabetes (T2D) for 22-years. The patient weighed 74 kg with body mass index (BMI) 23.6 kg/m2, hemoglobin A1C (HbA1c) 9.2%, ankle brachial index (ABI) 1.19/1.23, AST 25 U/L(7-38), ALT 23 U/L(4-44), GGT 48 U/L(<86), Chest X-P normal, and electrocardiogram (ECG) negative. When the patient was treated with low carbohydrate diet (LCD), a significant reduction in body weight and HbA1c was observed. Abdominal computerized tomography (CT) revealed multiple gall stone, dilated common bile duct and impaired GE, indicating DG. For endoscopic examination, much food residue was found in the stomach due to DG after 13 hours fasting. Treatment for DG was initiated by mosapride citrate hydrate. During clinical progress, occasional liver dysfunction was observed twice associated with elevation of AST 196 U/L, GGT 373 U/L and without symptoms, indicating cholestasis-type dysfunction. Some possible triggers may be involved in these episodes, such as gall stone, enlarged volume of stomach due to DG, overeating, overdrinking, and other factors. This impressive report will hopefully become a reference for developing diabetic practice and research

The Mechanism of Water Cycle System in Lake Inba-Numa Watershed:A Comparative Study of Runoff Mechanisms of Small Watersheds

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Type II NKT Cells Stimulate Diet-Induced Obesity by Mediating Adipose Tissue Inflammation, Steatohepatitis and Insulin Resistance

The progression of obesity is accompanied by a chronic inflammatory process that involves both innate and acquired immunity. Natural killer T (NKT) cells recognize lipid antigens and are also distributed in adipose tissue. To examine the involvement of NKT cells in the development of obesity, C57BL/6 mice (wild type; WT), and two NKT-cell-deficient strains, Jα18−/− mice that lack the type I subset and CD1d−/− mice that lack both the type I and II subsets, were fed a high fat diet (HFD). CD1d−/− mice gained the least body weight with the least weight in perigonadal and brown adipose tissue as well as in the liver, compared to WT or Jα18−/− mice fed an HFD. Histologically, CD1d−/− mice had significantly smaller adipocytes and developed significantly milder hepatosteatosis than WT or Jα18−/− mice. The number of NK1.1+TCRβ+ cells in adipose tissue increased when WT mice were fed an HFD and were mostly invariant Vα14Jα18-negative. CD11b+ macrophages (Mφ) were another major subset of cells in adipose tissue infiltrates, and they were divided into F4/80high and F4/80low cells. The F4/80low-Mφ subset in adipose tissue was increased in CD1d−/− mice, and this population likely played an anti-inflammatory role. Glucose intolerance and insulin resistance in CD1d−/− mice were not aggravated as in WT or Jα18−/− mice fed an HFD, likely due to a lower grade of inflammation and adiposity. Collectively, our findings provide evidence that type II NKT cells initiate inflammation in the liver and adipose tissue and exacerbate the course of obesity that leads to insulin resistance

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