Acute Small Bowel Perforation Caused by Obstruction of a Novel Tag-Less AgileTM Patency Capsule

A 74-year-old man visited our hospital complaining of abdominal pain. An abdominal computed tomography scan showed multiple wall thickness of the small bowel. Capsule endoscopy was recommended for further evaluation, and patency capsule examination was performed. Eighteen hours after patency capsule ingestion, he experienced small bowel perforation with severe peritonitis caused by intestinal pressure rising because of the patency capsule trapped in his terminal ileum. An ileocolic resection was performed, including the removal of the sclerotic ileum as an emergency surgery. A pathological examination showed transmural inflammation and multiple ulcers with perforation of the small intestine, consistent with Crohn’s disease. Here, we report a rare and valuable case of novel tag-less AgileTM patency capsule (Given Imaging Ltd., Yoqneam, Israel) retention leading to small bowel perforation

Brain Metastasis from Gastrointestinal Stromal Tumor: A Case Report and Review of the Literature

Metastasis of gastrointestinal stromal tumor (GIST) into the central nervous system is extremely rare. We report a patient with synchronous GIST and brain metastasis. At disease onset, there was left hemiplegia and ptosis of the right eyelids. Resection cytology of the brain tumor was reported as metastasis of GIST. After positron emission tomography examination, another tumor in the small bowel was discovered, which suggested a small bowel GIST associated with intracranial metastasis. Immunohistochemical analysis of the intestinal tumor specimen obtained by double balloon endoscopy showed a pattern similar to the brain tumor, with the tumors subsequently identified as intracranial metastases of jejunal GIST. After surgical resection of one brain tumor, the patient underwent whole brain radiation therapy followed by treatment with imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Mutational analysis of the original intestinal tumor revealed there were no gene alterations in KIT or PDGFRα. Since the results indicated the treatment had no apparent effect on either of the tumors, and because ileus developed due to an intestinal primary tumor, the patient underwent surgical resection of the intestinal lesion. However, the patient's condition gradually worsen and she subsequently died 4 months after the initial treatment

Fabrication of high-concentration Cu-doped deuterated targets for fast ignition experiments

In high-energy-density physics, including inertial fusion energy using high-power lasers, doping tracer atoms and deuteration of target materials play an important role in diagnosis. For example, a low-concentration Cu dopant acts as an x-ray source for electron temperature detection while a deuterium dopant acts as a neutron source for fusion reaction detection. However, the simultaneous achievement of Cu doping, a deuterated polymer, mechanical toughness and chemical robustness during the fabrication process is not so simple. In this study, we report the successful fabrication of a Cu-doped deuterated target. The obtained samples were characterized by inductively coupled plasma optical emission spectrometry, differential scanning calorimetry and Fourier transform infrared spectroscopy. Simultaneous measurements of Cu K-shell x-ray emission and beam fusion neutrons were demonstrated using a petawatt laser at Osaka University.Ikeda T., Kaneyasu Y., Hosokawa H., et al. Fabrication of high-concentration Cu-doped deuterated targets for fast ignition experiments. Nuclear Fusion 63, 016010 (2023); https://doi.org/10.1088/1741-4326/aca2ba

Distribution and Effects of Nonsense Polymorphisms in Human Genes

BACKGROUND: A great amount of data has been accumulated on genetic variations in the human genome, but we still do not know much about how the genetic variations affect gene function. In particular, little is known about the distribution of nonsense polymorphisms in human genes despite their drastic effects on gene products. METHODOLOGY/PRINCIPAL FINDINGS: To detect polymorphisms affecting gene function, we analyzed all publicly available polymorphisms in a database for single nucleotide polymorphisms (dbSNP build 125) located in the exons of 36,712 known and predicted protein-coding genes that were defined in an annotation project of all human genes and transcripts (H-InvDB ver3.8). We found a total of 252,555 single nucleotide polymorphisms (SNPs) and 8,479 insertion and deletions in the representative transcripts in these genes. The SNPs located in ORFs include 40,484 synonymous and 53,754 nonsynonymous SNPs, and 1,258 SNPs that were predicted to be nonsense SNPs or read-through SNPs. We estimated the density of nonsense SNPs to be 0.85x10(-3) per site, which is lower than that of nonsynonymous SNPs (2.1x10(-3) per site). On average, nonsense SNPs were located 250 codons upstream of the original termination codon, with the substitution occurring most frequently at the first codon position. Of the nonsense SNPs, 581 were predicted to cause nonsense-mediated decay (NMD) of transcripts that would prevent translation. We found that nonsense SNPs causing NMD were more common in genes involving kinase activity and transport. The remaining 602 nonsense SNPs are predicted to produce truncated polypeptides, with an average truncation of 75 amino acids. In addition, 110 read-through SNPs at termination codons were detected. CONCLUSION/SIGNIFICANCE: Our comprehensive exploration of nonsense polymorphisms showed that nonsense SNPs exist at a lower density than nonsynonymous SNPs, suggesting that nonsense mutations have more severe effects than amino acid changes. The correspondence of nonsense SNPs to known pathological variants suggests that phenotypic effects of nonsense SNPs have been reported for only a small fraction of nonsense SNPs, and that nonsense SNPs causing NMD are more likely to be involved in phenotypic variations. These nonsense SNPs may include pathological variants that have not yet been reported. These data are available from Transcript View of H-InvDB and VarySysDB (http://h-invitational.jp/varygene/)

幼稚園教諭養成課程における「領域に関する専門的事項」に求められる授業内容に関する一考察 : 保育内容領域「人間関係」及び「環境」のモデルカリキュラムを手がかりとして

本論の目的は，幼稚園教諭養成課程において新設された「領域に関する専門的事項」において取り扱うべき内容の射程について検討することである．具体的には，保育教諭養成課程研究会が作成したモデルカリキュラムと授業モデルについて，活動内容，教育内容，及び取り扱っている内容の種別等の観点から分析した．その結果，授業モデルには，①幼児の発達に関する内容，②幼稚園外における経験や現代的特徴，諸課題，③「幼児期の終わりまでに育ってほしい姿」等が示されており，「領域に関する専門的事項」は乳児期・児童期や幼稚園外の生活も射程に含むことを明らかにした．また，「領域に関する専門的事項」と「保育内容の指導法」の教育内容の射程が，教材研究における観点から区別できることを示した．今後，より具体的に取り上げるべき内容について論考するとともに，各養成校において質の高いカリキュラム及びシラバスを作成することが肝要である

Fabrication of high-concentration Cu-doped deuterated targets for fast ignition experiments

先端科学・社会共創推進機構In high-energy-density physics, including inertial fusion energy using high-power lasers, doping tracer atoms and deuteration of target materials play an important role in diagnosis. For example, a low-concentration Cu dopant acts as an x-ray source for electron temperature detection while a deuterium dopant acts as a neutron source for fusion reaction detection. However, the simultaneous achievement of Cu doping, a deuterated polymer, mechanical toughness and chemical robustness during the fabrication process is not so simple. In this study, we report the successful fabrication of a Cu-doped deuterated target. The obtained samples were characterized by inductively coupled plasma optical emission spectrometry, differential scanning calorimetry and Fourier transform infrared spectroscopy. Simultaneous measurements of Cu K-shell x-ray emission and beam fusion neutrons were demonstrated using a petawatt laser at Osaka University

Gene expression profile of human monocytic cell infected by Leishmania (Leishmania) infantum

As leishmanioses são um conjunto de doenças causadas por parasitos de diferentes espécies do gênero Leishmania, sendo a leishmaniose visceral a causa de grande morbidade e mortalidade, principalmente, em países em desenvolvimento como o Brasil. Apesar dos inúmeros estudos focados na participação dos sistemas imunes inato e adaptativo na proteção ou desenvolvimento da doença, pouco se conhece das alterações que ocorrem na célula hospedeira no início da infecção. Ao mesmo tempo em que as células suscitam respostas que levam à eliminação do parasito, esse pode induzir alterações nos processos celulares para sua evasão, sobrevivência e proliferação. Para o entendimento desses processos propomos identificar as vias biológicas moduladas na infecção de células THP-1 por Leishmania infantum. Para isso, células monocíticas humanas THP-1 foram infectadas ou não por Leishmania infantum por 6, 10, 24, 48 e 72 h. A partir do RNA total dessas células, bibliotecas de cDNA foram obtidas e submetidas ao sequenciamento pela técnica de RNA-seq. Posteriormente, o número total de sequências por gene foi obtido por meio do alinhamento das sequências de DNA ao genoma humano de referência GRCh37 (hg19) empregando o programa CLC Genomics Workbench 7.1. Esses dados foram então utilizados na composição da matriz de dados de expressão gênica global das amostras, que serviu como base para obtenção de duas redes de co-expressão gênica utilizando o programa Weighted Gene Co-expression Network Analysis (WGCNA). As redes foram compostas pelos dados de expressão gênica global das amostras controle e infectadas dos períodos 6 h e 10 h (Rede 1) e 24 h, 48 h e 72 h (Rede 2). A partir da análise dessas redes foi possível selecionar módulos altamente correlacionados às amostras controle e infectadas nos diferentes períodos, realizar o enriquecimento funcional dos genes contidos nos módulos, como também identificar genes HGS-hub (genes hub diferencialmente expressos). O enriquecimento funcional dos genes contidos nos módulos altamente correlacionados com as amostras mostrou que as maiores mudanças no perfil de expressão gênica das células infectadas, em relação às células não infectadas, ocorreram nas primeiras 10 h de infecção e que muitos dos genes relacionados com a resposta imune são expressos nas primeiras 6 h de infecção. Já a partir de 24 h de infecção, pequenas alterações no perfil de expressão entre as células não infectadas e infectadas foram observadas. A determinação dos genes HGS-hub mostrou que dentre os processos biológicos alterados por Leishmania infantum nas células THP-1, o metabolismo de lipídios foi o que mais apresentou genes diferencialmente expressos, além da resposta imune. Esses resultados sugerem que além do sistema imune, a Leishmania infantum também é capaz de modular o metabolismo de lipídios das células THP-1 infectadas.Leishmaniasis is a group of diseases caused by parasites of different species of the genus Leishmania, with visceral leishmaniasis being the cause of great morbidity and mortality, especially in developing countries such as Brazil. Despite the numerous studies focused on the participation of innate and adaptive immune systems in the protection or development of the disease, little is known about the changes that occur in the host cell at the beginning of the infection. At the same time as the cells elicit responses that lead to the elimination of the parasite, it can induce changes in the cellular processes for their evasion, survival and proliferation. To understanding these processes, we aim to identify the biological pathways modulated in THP-1 cell infected by Leishmania infantum. For this, THP-1 human monocytic cells were infected or not by Leishmania infantum for 6, 10, 24, 48 and 72 h. Using total RNA extracted from these cells, cDNA libraries were obtained and submitted to RNA sequencing. Subsequently, the total number of sequences per gene was obtained by aligning the DNA sequences to the reference human genome GRCh37 (hg19) using CLC Genomics Workbench 7.1 software. These data were then used to compose the samples\' global gene expression data matrix, which was employed to obtain two gene co-expression networks using the Weighted Gene Co-expression Network Analysis (WGCNA) program. The networks were composed by the global gene expression data from the control and infected samples at 6 h and 10 h (Network 1) and at 24 h, 48 h and 72 h (Network 2). Analysis of these networks allowed the selection of modules highly correlated to the control and infected samples in different periods, as well as the identification of HGS-hub genes (differentially expressed hub genes). The functional enrichment of the genes showed that the major changes in the infected cells gene expression profile compared to uninfected cells occurred within 10 h of infection and the genes of the biological pathway related to the immune response are expressed in the first 6 h of infection. Starting at 24 h of infection, small changes in the gene expression profile between uninfected and infected cells were observed. The HGS-hub genes analysis showed that among the biological processes altered by Leishmania infantum in THP-1 cells, lipid metabolism was the one that presented a great number of differentially expressed genes, besides the immune response. These results suggest that in addition to the immune system, Leishmania infantum is also able to modulate THP-1 macrophages\' lipid metabolism

Cloning and expression of a single-chain fragment variable against heat-labile toxin of enterotoxigenic Escherichia coli.

O diagnóstico da infecção por ETEC é baseada na detecção dos seus principais fatores de virulência, as toxinas termo-lábil e termo-estável, através de métodos de biologia molecular ou imunossorológicos. A tecnologia de anticorpos recombinantes permite a obtenção de moléculas com baixo custo, afinidades e especificidades desejáveis, através da clonagem dos domínios variáveis das cadeias leve e pesada da imunoglobulina, fusionados a um ligante flexível que permite a correta interação entre os domínios e a preservação do sítio de ligação ao antígeno. Este estudo teve como objetivo a construção de um fragmento variável em cadeia única (scFv), a partir de hibridomas produtores de anticorpo monoclonal anti-LT, seguida da sua produção em células bacterianas. Um fragmento variável em cadeia única com 723 pb foi obtido, sendo expresso em cepa de Escherichia coli como uma proteína com peso molecular aparente de 30 kDa. Após purificação em cromatografia de afinidade a Ni2+ e renaturação, o scFvLT foi capaz de reconhecer a toxina LT por ELISA de captura e Immunodot, porém não foi capaz de reconhecer as subunidades da toxina LT, por Immunoblotting, nem de neutralizar sua atividade citopática em células adrenais Y1.Heat-labile (LT) and heat-stable (ST) toxins are the main ETEC\'s virulence factors and infection diagnosis is based on their detection by molecular biology or immunoserological methods. The advances on antibody biotechnology provide alternatives to obtain low cost antibodies with desirable affinities and specificities by cloning immunoglobulin\'s heavy and light variable domains (HV and LV) as a single-chain fusion interspaced by a flexible linker, which allowing the correct interaction between the domains and preserving the antigen-binding site. In this study we aimed the construction of a scFv upon hybridoma cells that produce an anti-LT monoclonal antibody following its bacterial production. A single-chain fragment variable with 723 bp was obtained and expressed as a protein with apparent molecular weight of 30 kDa in Escherichia coli strain. The scFvLT recombinant antibody was submitted to metal affinity chromatography and refolding and was tested by immunoenzimatic assays. Refolded scFvLT was able to recognized LT toxin by capture ELISA and Immunodot. However, scFvLT wasnt able to recognize LT toxin subunits by Immunoblotting neither neutralize its activity in Y1 adrenal cells