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RNA sequencing and target long-read sequencing reveal an intronic transposon insertion causing aberrant splicing
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）More than half of cases with suspected genetic disorders remain unsolved by genetic analysis using short-read sequencing such as exome sequencing (ES) and genome sequencing (GS). RNA sequencing (RNA-seq) and long-read sequencing (LRS) are useful for interpretation of candidate variants and detection of structural variants containing repeat sequences, respectively. Recently, adaptive sampling on nanopore sequencers enables target LRS more easily. Here, we present a Japanese girl with premature chromatid separation (PCS)/mosaic variegated aneuploidy (MVA) syndrome. ES detected a known pathogenic maternal heterozygous variant (c.1402-5A>G) in intron 10 of BUB1B (NM_001211.6), a known responsive gene for PCS/MVA syndrome with autosomal recessive inheritance. Minigene splicing assay revealed that almost all transcripts from the c.1402-5G allele have mis-splicing with 4-bp insertion. GS could not detect another pathogenic variant, while RNA-seq revealed abnormal reads in intron 2. To extensively explore variants in intron 2, we performed adaptive sampling and identified a paternal 3.0 kb insertion. Consensus sequence of 16 reads spanning the insertion showed that the insertion consists of Alu and SVA elements. Realignment of RNA-seq reads to the new reference sequence containing the insertion revealed that 16 reads have 5’splice site within the insertion and 3’ splice site at exon 3, demonstrating causal relationship between the insertion and aberrant splicing. In addition, immunoblotting showed severely diminished BUB1B protein level in patient derived cells. These data suggest that detection of transcriptomic abnormalities by RNA-seq can be a clue for identifying pathogenic variants, and determination of insert sequences is one of merits of LRS
Extremely Poor Post-discharge Prognosis in Aspiration Pneumonia and Its Prognostic Factors: A Retrospective Cohort Study.
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There is little evidence regarding the long-term prognosis of patients with aspiration pneumonia. This study aimed to investigate post-discharge survival time and prognostic factors in older patients hospitalized for aspiration pneumonia.
Methods
This retrospective cohort study included patients aged ≥65 years hospitalized for aspiration pneumonia and discharged alive from a tertiary care hospital in Japan between April 2009 and September 2014. Candidate prognostic factors were patient’s age, sex, body mass index (BMI), performance status, chronic conditions, CURB-65 score, serum albumin level, hematocrit concentration, nutritional pathway at discharge, and discharge location. Kaplan–Meier curves were determined, and multivariable survival analysis using Cox regression model was performed to analyze the effect of each factor on mortality.
Results
In total, 209 patients were included in this study. The median age was 85 years, 58% of the patients were males, 33% had a performance status of 4, and 34% were discharged home. Among the patients, 65% received oral intake, 23% received tube feeding, and 21% received parenteral nutrition at discharge. During the follow-up period, 77% of the patients died, and the median post-discharge survival time was 369 days. Besides male sex and low BMI, tube feeding (adjusted hazard ratio [aHR]= 1.70, 95% confidence interval [CI]:1.11–2.59) and parenteral nutrition (aHR= 4.42, 95% CI:2.57–7.60) were strongly associated with mortality.
Conclusions
Long-term prognosis of patients hospitalized for aspiration pneumonia was extremely poor. The nutritional pathway at discharge was a major prognostic factor. These results may be useful for future care and research
Is oral Streptococcus mutans with collagen-binding protein a risk factor for intracranial aneurysm rupture or formation?
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）Introduction: Streptococcus mutans (SM) with the collagen-binding protein Cnm is a unique member of the oral resident flora because it causes hemorrhagic vascular disorders. In the multicenter study, we examined the relationship between Cnm-positive SM (CP-SM) and intracranial aneurysm (IA) rupture, which remains unknown. Methods: Between May 2013 and June 2018, we collected whole saliva samples from 431 patients with ruptured IAs (RIAs) and 470 patients with unruptured IAs (UIAs). Data were collected on age, sex, smoking and drinking habits, family history of subarachnoid hemorrhage, aneurysm size, number of teeth, and comorbidities of lifestyle disease. Results: There was no difference in the positivity rate of patients with CP-SM between the patients with RIAs (17.2%) and those with UIAs (19.4%). In subanalysis, the rate of positivity for CP-SM was significantly higher in all IAs <5mm than in those ≥10mm in diameter (p=0.0304). In the entire cohort, the rate of positivity for CP-SM was lower in larger aneurysms than in smaller aneurysms (p=0.0393). Conclusions: CP-SM was not involved in the rupture of UIAs. In the subanalysis, the possibility of its involvement in the formation of vulnerable aneurysms remained
Changes in the characteristics and outcomes of COVID-19 patients from the early pandemic to the delta variant epidemic: a nationwide population-based study
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Effects of volatile anesthetics on circadian rhythm in mice: a comparative study of sevoflurane, desflurane, and isoflurane
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
In vivo illustration of altered dopaminergic and GABAergic systems in early Parkinson's disease.
Get PDF浜松医科大学博士（医学）doctoral医学系研究科thesi
Tissue oxygen saturation as an indicator of wound healing around endovascular treatment in chronic limb-threatening ischemia
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）雑誌掲載タイトル: Regional tissue oxygen saturation as an intraoperative indicator of wound healing following endovascular treatment for chronic limb-threatening ischemiadoctoral医学系研究科thesi
Development of a novel airbag system of abdominal compression for reducing respiratory motion: preliminary results in healthy volunteers
Get PDF浜松医科大学Hamamatsu University School of Medicine博士（医学）doctoral医学系研究科thesi
A case study of risk-reduced salpingo-oophorectomy at single-center (Juntendo hospital)
Get PDF遺伝性乳癌卵巣癌症候群 (HBOC) の患者にRRSO を施行した約3%にSerous tubal intraepithelial carcinoma (STIC) を、約4%にSerous tubal intraepithelial lesion (STIL) を認めることが知られている。しかし、本邦においてはRRSO後の病理結果に関しての報告は少ない。2015年8月から2022年5月までにBRCA1/2 の病的バリアントを有しRRSOを施行した35例を対象として、臨床的背景と病理学的所見を後方視的に検討した。BRCA1の病的バリアントは22例、BRCA2は13例であった。RRSO施行時年齢の中央値は50.5歳であった。そのうち3例(8.6%)でSTICを、4例(11.4%)でSTILを認めた。STIC症例は全てBRCA1の病的バリアントを有しており、STIL症例はBRCA1が3例、BRCA2が1例であった。STIC/STILを認めた症例において、再発は認めていない。本検討ではSTICとSTILの割合が既報と比較して高かった。この背景には、RRSOの保険適用などのHBOCを取り巻く問題点と課題がある。また病理結果でSTIC/STILを認めた際の術後管理には一貫した指針がなく、今後の全国的なデータの解析が必要である。It is known that about 3% of patients with Hereditary Breast and Ovarian Cancer syndrome (HBOC) who underwent riskreducing salpingo-oophorectomy (RRSO) have serous tubal intraepithelial carcinoma(STIC) and about 4% have serous tubal intraepithelial lesion(STIL). In Japan, however, there are few reports on the pathological results after RRSO. In the present study, we retrospectively reviewed the clinical background and pathological findings of 35 patients who had BRCA1/2 variants and underwent RRSO from August 2015 to May 2022. Pathological variants in BRCA1 and BRCA2 were present in 22 and 13 cases, respectively. The median age at RRSO was 50.5 years. Three (8.6%) of the patients had STIC and 4 (11.4%) had STIL. All STIC cases had pathological variants in BRCA1, and 3 STIL cases had BRCA1 and 1 had BRCA2. No recurrence was observed in patients with STIC and STIL. The proportion of STIC and STIL was higher in this study than in previous reports. This is due to issues surrounding HBOC, such as insurance coverage for RRSO. In addition, there are no consistent guideline for the postoperative management of patients with STIC/STIL in pathology results, and nationwide future analysis is needed.journal articl