Analysis of Technological Portfolios for CO2 stabilizations and Effects of Technological Changes

In this study, cost-effective technological options to stabilize CO2 concentrations at 550, 500, and 450 ppmv are evaluated using a world energy systems model of linear programming with a high regional resolution. This model treats technological change endogenously for wind power, photovoltaics, and fuel-cell vehicles, which are technologies of mass production and are considered to follow the “learning by doing” process. Technological changes induced by climate policies are evaluated by maintaining the technological changes at the levels of the base case wherein there is no climate policy. The results achieved through model analyses include 1) cost-effective technological portfolios, including carbon capture and storage, marginal CO2 reduction costs, and increases in energy system cost for three levels of stabilization and 2) the effect of the induced technological change on the above mentioned factors. A sensitivity analysis is conducted with respect to the learning rate.Energy systems model, Global warming, Technological portfolios, Technological changes

Idiopathic pneumoperitoneum after trauma

Intra-abdominal free gas is a finding of extra-intestinal gas in the abdominal cavity on radiography or CT, mainly suggesting gastrointestinal perforation and necessitating emergency surgery. Idiopathic pneumoperitoneum is diagnosed when there is no obvious gastrointestinal perforation, but there is presence of free gas in the abdominal cavity with an unidentifiable cause. Herein, we report a case of idiopathic pneumoperitoneum secondary to high-energy trauma following a car rollover accident. A 95-year-old man was transferred to our clinic after a car-to-car rollover accident. He had abrasions on his right upper arm and left abdomen that appeared to be the result of the accident ; however, no other apparent traumatic injuries were noted. There was no pain in the abdomen, and peritoneal irritation symptoms were also not noted. A CT scan showed fine free air. Although idiopathic pneumoperitoneum could not be ruled out, considering the patient’s background and the possibility of traumatic small bowel perforation, emergency surgery was performed. A thorough search of the abdominal cavity was performed ; however, the surgery was completed without an obvious perforation site. Idiopathic pneumoperitoneum should be considered as a differential disease in cases who have free air on abdominal CT but clinically lack obvious inflammatory reaction findings

Treatment for recurrence after esophagectomy

Background : With regard to the recurrence of esophageal cancer after surgery, the prognosis has improved with the progress of multimodal perioperative treatment. In this study, the recurrence pattern, treatment method, and prognosis of recurrent cases following esophageal cancer surgery were retrospectively examined. Materials and Methods : Three hundred seven patients with histologically proven squamous cell carcinoma, adenocarcinoma, and others were enrolled in the study. With respect to clinicopathologic factors and recurrence patterns, recurrence risk factors, recurrence period, treatment for recurrence, and prognosis were investigated. Results : Ninety two percent of all recurrent cases were observed within two years after radical esophagectomy. Locoregional recurrence, distant recurrence, and mixed recurrence were observed in 38 (35%), 56 (51%), and 16 (14%) cases, respectively. Patients with lymph node metastasis showed a significantly longer survival in comparison to those with metastasis to other organs (p = 0.0032). When analyzed using the treatment method, patients who underwent surgery (only surgery or additional postoperative chemotherapy) exhibited better survival in comparison to those who underwent other treatments. Discussion : Detailed and strict follow-up within two years are necessary in cases with deeper than muscular invasion, cases with extensive lymph node metastasis, or cases with lymphatic or vascular invasion

Flt1/VEGFR1 heterozygosity causes transient embryonic edema

Vascular endothelial growth factor-A is a major player in vascular development and a potent vascular permeability factor under physiological and pathological conditions by binding to a decoy receptor Flt1 and its primary receptor Flk1. In this study, we show that Flt1 heterozygous (Flt1+/−) mouse embryos grow up to adult without life-threatening abnormalities but exhibit a transient embryonic edema around the nuchal and back regions, which is reminiscent of increased nuchal translucency in human fetuses. Vascular permeability is enhanced and an intricate infolding of the plasma membrane and huge vesicle-like structures are seen in Flt1+/− capillary endothelial cells. Flk1 tyrosine phosphorylation is elevated in Flt1+/− embryos, but Flk1 heterozygosity does not suppress embryonic edema caused by Flt1 heterozygosity. When Flt1 mutants are crossed with Aspp1−/− mice which exhibit a transient embryonic edema with delayed formation and dysfunction of lymphatic vessels, only 5.7% of Flt1+/−; Aspp1−/− mice survive, compared to expected ratio (25%). Our results demonstrate that Flt1 heterozygosity causes a transient embryonic edema and can be a risk factor for embryonic lethality in combination with other mutations causing non-lethal vascular phenotype

Essential pre-treatment imaging examinations in patients with endoscopically-diagnosed early gastric cancer

<p>Abstract</p> <p>Background</p> <p>There have been no reports discussing which imaging procedures are truly necessary before treatment of endoscopically-diagnosed early gastric cancer (eEGC). The aim of this pilot study was to show which imaging examinations are essential to select indicated treatment or appropriate strategy in patients with eEGC.</p> <p>Methods</p> <p>In 140 consecutive patients (95 men, 45 women; age, 66.4 +/- 11.3 years [mean +/- standard deviation], range, 33-90) with eEGC which were diagnosed during two years, the pre-treatment results of ultrasonography (US) and contrast-enhanced computed tomography (CT) of the abdomen, barium enema (BE) and chest radiography (CR) were retrospectively reviewed. Useful findings that might affect indication or strategy were evaluated.</p> <p>Results</p> <p>US demonstrated useful findings in 13 of 140 patients (9.3%): biliary tract stones (n = 11) and other malignant tumors (n = 2). Only one useful finding was demonstrated on CT (pancreatic intraductal papillary mucinous tumor) but not on US (0.7%; 95% confidential interval [CI], 2.1%). BE demonstrated colorectal carcinomas in six patients and polyps in 10 patients, altering treatment strategy (11.4%; 95%CI, 6.1-16.7%). Of these, only two colorectal carcinomas were detected on CT. CR showed three relevant findings (2.1%): pulmonary carcinoma (n = 1) and cardiomegaly (n = 2). Seventy-nine patients (56%) were treated surgically and 56 patients were treated by endoscopic intervention. The remaining five patients received no treatment due to various reasons.</p> <p>Conclusions</p> <p>US, BE and CR may be essential as pre-treatment imaging examinations because they occasionally detect findings which affect treatment indication and strategy, although abdominal contrast-enhanced CT rarely provide additional information.</p

〈Cases Reports〉Successful treatment with intravenous colistin of sepsis caused by metallo-beta-lactamase-producing multidrug-resistant Pseudomonas aeruginosa in a patient with acute myeloid leukemia

[Abstract] In recent years, multidrug-resistant Pseudomonas aeruginosa (MDRP) has been detected in patients undergoing chemotherapy for hematological malignancies. MDRP can cause life-threatening infections such as sepsis and pneumonia, being a major concern for physiciansand patients. Here, we report the case of a patient with acute myeloid leukemia (AML ; FAB classification M2) who developed septic shock from MDRP infection during leukopenia induced by the first cycle of consolidation therapy, and in whom the combination of colistin administration and steroid pulse therapy promptly improved the septic shock symptoms and cleared MDRP from the blood. Although a transient nephrotoxic effect was observed, itsubsided rapidly on discontinuation of treatment. MDRP in stool samples fell to undetectable levels following oral doses of polymyxin B sulfate. The patient could continue consolidation chemotherapy and has remained in remission

A Critical Role of Fatty Acid Binding Protein 4 and 5 (FABP4/5) in the Systemic Response to Fasting

During prolonged fasting, fatty acid (FA) released from adipose tissue is a major energy source for peripheral tissues, including the heart, skeletal muscle and liver. We recently showed that FA binding protein 4 (FABP4) and FABP5, which are abundantly expressed in adipocytes and macrophages, are prominently expressed in capillary endothelial cells in the heart and skeletal muscle. In addition, mice deficient for both FABP4 and FABP5 (FABP4/5 DKO mice) exhibited defective uptake of FA with compensatory up-regulation of glucose consumption in these tissues during fasting. Here we showed that deletion of FABP4/5 resulted in a marked perturbation of metabolism in response to prolonged fasting, including hyperketotic hypoglycemia and hepatic steatosis. Blood glucose levels were reduced, whereas the levels of non-esterified FA (NEFA) and ketone bodies were markedly increased during fasting. In addition, the uptake of the 125I-BMIPP FA analogue in the DKO livers was markedly increased after fasting. Consistent with an increased influx of NEFA into the liver, DKO mice showed marked hepatic steatosis after a 48-hr fast. Although gluconeogenesis was observed shortly after fasting, the substrates for gluconeogenesis were reduced during prolonged fasting, resulting in insufficient gluconeogenesis and enhanced hypoglycemia. These metabolic responses to prolonged fasting in DKO mice were readily reversed by re-feeding. Taken together, these data strongly suggested that a maladaptive response to fasting in DKO mice occurred as a result of an increased influx of NEFA into the liver and pronounced hypoglycemia. Together with our previous study, the metabolic consequence found in the present study is likely to be attributed to an impairment of FA uptake in the heart and skeletal muscle. Thus, our data provided evidence that peripheral uptake of FA via capillary endothelial FABP4/5 is crucial for systemic metabolism and may establish FABP4/5 as potentially novel targets for the modulation of energy homeostasis

Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero

Newly identified tissue-resident vascular precursor cells are recruited into growing vessels and contribute to vasculogenesis in adult mice

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