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1.
Surg Case Rep ; 7(1): 221, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596772

RESUMO

BACKGROUND: Metastatic neuroendocrine carcinoma has an extremely poor prognosis, and no effective second-line treatment is available. Herein, we describe a case of multiple metastases after primary resection of esophageal neuroendocrine carcinoma successfully treated with nivolumab plus radiotherapy in a short time. CASE PRESENTATION: A man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. Upper gastrointestinal endoscopy revealed a type 2 tumor spanning the endothelial cell junction to the abdominal esophagus. Histopathological examination of the biopsy confirmed a diagnosis of esophageal neuroendocrine carcinoma. The patient had no distant metastases. Thoracoscopic esophagectomy with three-field lymph node dissection was performed. Histopathological examination confirmed a diagnosis of esophageal neuroendocrine carcinoma with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. The postoperative course was good, with no complications. The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. A positron emission tomography-computed tomography scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex. The patient was diagnosed with metastatic esophageal neuroendocrine carcinoma postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a positron emission tomography-computed tomography scan showed disappearance of all lesions. A complete response was achieved. Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months. CONCLUSIONS: We experienced a case in which nivolumab in combination with radiotherapy was effective for metastatic esophageal neuroendocrine carcinoma after primary resection.

2.
Surg Case Rep ; 7(1): 200, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477988

RESUMO

BACKGROUND: Treatment options for complete rectal prolapse include over 100 procedures. In previous reports, operative rectal prolapse repair, regardless of the technique by perineal approach, was associated with high recurrence rates. However, there is no consensus on the optimal surgical procedure for relapsed rectal prolapse. CASE PRESENTATION: A 97-year-old woman was admitted to our hospital with a chief complaint of complete rectal prolapse measuring > 5 cm. The patient had a history of laparoscopic anterior suture rectopexy without sigmoid resection under general anesthesia for complete rectal prolapse one year prior. The patient's postoperative course was uneventful. However, her dementia worsened (Hasegawa's dementia scale: 5/30 points) after the first operation. Further, moderate-to-severe aortic valve stenosis was first diagnosed with heart failure 6 months after the operation. Nine months after the initial surgery, she experienced a recurrence of complete rectal prolapse measuring approximately 5 cm. Considering the coexistence of advanced age, severe dementia, and aortic valve stenosis, surgery under general anesthesia was not indicated. Perineal stapled prolapse resection in combination with the t operation was planned because of its minimal invasiveness and shortened hospital stay. The procedure was performed by a team of two surgeons in the jack knife position, under spinal anesthesia. The prolapse was cut along the long-axis direction with three linear staplers and resected along the short-axis direction with four linear staplers. The cross-section of the linear stapler was reinforced with 3-0 Vicryl sutures. After rectal resection, the Thiersch operation using 1-0 nylon thread 1 cm away from the anal verge was additionally performed. The operative time was 24 min, and intraoperative blood loss was 1 mL. The postoperative course was uneventful. Three months after the operation, no recurrence was observed, and defecation function was good with improvements of Wexner score. CONCLUSIONS: Perineal stapled prolapse resection in combination with the Thiersch operation could be a useful option for patients with relapsed rectal prolapse and with poor general condition, who are not indicated for other surgical procedures.

3.
Sci Rep ; 11(1): 18511, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531471

RESUMO

Cancer cells acquire drug resistance through the following stages: nonresistant, pre-resistant, and resistant. Although the molecular mechanism of drug resistance is well investigated, the process of drug resistance acquisition remains largely unknown. Here we elucidate the molecular mechanisms underlying the process of drug resistance acquisition by sequential analysis of gene expression patterns in tamoxifen-treated breast cancer cells. Single-cell RNA-sequencing indicates that tamoxifen-resistant cells can be subgrouped into two, one showing altered gene expression related to metabolic regulation and another showing high expression levels of adhesion-related molecules and histone-modifying enzymes. Pseudotime analysis showed a cell transition trajectory to the two resistant subgroups that stem from a shared pre-resistant state. An ordinary differential equation model based on the trajectory fitted well with the experimental results of cell growth. Based on the established model, it was predicted and experimentally validated that inhibition of transition to both resistant subtypes would prevent the appearance of tamoxifen resistance.

4.
Heart Vessels ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591159

RESUMO

Perioperative complications have been reported to be associated with a lower incidence of cancer-free survival. Perioperative atrial fibrillation (POAF) is one of occasionally observed complications in patients with malignancies who undergo noncardiac surgeries. However, the long-term clinical impact of POAF on those with malignancies have remained unknown. This was a prospective, single-center, observational study. Patients who underwent noncardiac surgeries for definitive malignancies between 2014 and 2017 were included. The primary and secondary endpoints were 3-year recurrence of malignancies and cancer death, respectively. The present study included consecutive 752 patients (mean age, 68 ± 11 years; males, 62%), and POAF was observed in 77 patients. The follow-up duration was 1037 (interquartile range, 699-1408) days. The 3-year recurrence of malignancies was observed in 239 (32%) patients (POAF, 32 [42%]; non-POAF, 207 [31%]) and 3-year mortality was 130 patients (17%). Cardiac, noncardiac, and cancer deaths were observed in 4 (0.5%), 126 (17%), and 111 (15%) patients, respectively. Multivariate Cox regression analysis demonstrated that POAF was associated with 3-year recurrence of malignancies (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.15-2.52). Landmark analysis demonstrated that POAF tended to be correlated with the incidence of 3-year cancer death (HR, 1.79; 95% CI, 0.96-3.31). In conclusion, POAF is associated with the subsequent recurrence of malignancies. The association of arrhythmia with cancer death may be revealed under longer follow-up durations.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018270 . UMIN ID: UMIN000016146.

5.
Liver Int ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34411400

RESUMO

BACKGROUND & AIMS: We recently analysed and reported the features of the micro biome under hepatitis C virus (HCV) infection, but the effect of HCV infection on bile acid (BA) metabolism in the gut-liver axis remains poorly understood. The aim of this study was to clarify the characteristics of the gut-liver axis in HCV-infected patients. METHODS: The faecal BAs composition and gut microbiota from 100 chronic hepatitis C (CHC) patients were compared with those from 23 healthy individuals. For transcriptional analysis of the liver, 22 mild CHC (fibrosis stages [F] 0-2) and 42 advanced CHC (F3-4) cases were compared with 12 healthy individuals. The findings were confirmed using chimeric mice with human hepatocytes infected with HCV HCR6. RESULTS: Chronic hepatitis C patients, even at earlier disease stages, showed BA profiles distinct from healthy individuals, in which faecal deoxycholic acid (DCA) was significantly reduced and lithocholic acid or ursodeoxycholic acid became dominant. The decrease in faecal DCA was correlated with reduction in commensal Clostridiales and increase in oral Lactobacillales. Impaired biosynthesis of cholic acid (CA) was observed as a reduction in the transcription level of cytochrome P450 8B1 (CYP8B1), a key enzyme in CA biosynthesis. The reductions in faecal DCA and liver CYP8B1 were also observed in HCV-infected chimeric mice. CONCLUSIONS: Chronic hepatitis C alters the intestinal BA profile, in association with the imbalance of BA biosynthesis, which differs from the pattern in NAFLD. These imbalances appear to drive disease progression through the gut-microbiome-liver axis.

6.
Nat Commun ; 12(1): 4821, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376672

RESUMO

Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.


Assuntos
Genoma Viral/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Leucemia-Linfoma de Células T do Adulto/genética , Análise de Célula Única/métodos , Transcriptoma/genética , Adulto , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Cultivadas , Evolução Clonal/genética , Células Clonais/metabolismo , Células Clonais/patologia , Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Humanos , Células Jurkat , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/virologia , Mutação , RNA-Seq/métodos , Receptor Notch1/genética , Receptores de Antígenos de Linfócitos T/genética , Fator de Transcrição STAT3/genética
7.
Anim Sci J ; 92(1): e13620, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34402134

RESUMO

The effect of ginkgo fruit addition on methane production potential of cattle feces and slurry was assessed in relation to other fermentation products and the microbial community. Holstein cattle fresh feces and slurry were left at 30°C for 0, 30, 60, 90, and 180 days with/without ginkgo fruit to monitor the effect on fermentation potential. With the addition of ginkgo fruit, methane production potential of feces was reduced on Day 30 and thereafter, and that of slurry was consistently reduced over the experimental period. As a general trend, ginkgo fruit addition resulted in decreased acetate and increased propionate in feces and acetate accumulation in slurry. With ginkgo fruit addition, MiSeq analyses indicated decreases in methanogen (in particular Methanocorpusculum), Ruminococcaceae, and Clostridiaceae populations and increases in Bacteroidaceae and Porphyromonadaceae populations, which essentially agreed with quantitative real-time polymerase chain reaction (qPCR) assay results. These data indicate that direct addition of ginkgo fruit to cattle excreta is useful for reducing methane emissions by altering the microbial community structure. The application of ginkgo fruit to lower methane emissions from cattle excreta is, therefore, useful in cases in which the excreta is left without special management for a long period of time.

8.
DNA Res ; 28(4)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34387305

RESUMO

The crown-of-thorns starfish (COTS) is a coral predator that is widely distributed in Indo-Pacific Oceans. A previous phylogenetic study using partial mitochondrial sequences suggested that COTS had diverged into four distinct species, but a nuclear genome-based analysis to confirm this was not conducted. To address this, COTS species nuclear genome sequences were analysed here, sequencing Northern Indian Ocean (NIO) and Red Sea (RS) species genomes for the first time, followed by a comparative analysis with the Pacific Ocean (PO) species. Phylogenetic analysis and ADMIXTURE analysis revealed clear divergences between the three COTS species. Furthermore, within the PO species, the phylogenetic position of the Hawaiian sample was further away from the other Pacific-derived samples than expected based on the mitochondrial data, suggesting that it may be a PO subspecies. The pairwise sequentially Markovian coalescent model showed that the trajectories of the population size diverged by region during the Mid-Pleistocene transition when the sea-level was dramatically decreased, strongly suggesting that the three COTS species experienced allopatric speciation. Analysis of the orthologues indicated that there were remarkable genes with species-specific positive selection in the genomes of the PO and RS species, which suggested that there may be local adaptations in the COTS species.


Assuntos
Evolução Biológica , Genoma , Filogenia , Estrelas-do-Mar/genética , Animais , Genômica , Filogeografia , Análise de Sequência de DNA
9.
Microbiol Spectr ; 9(1): e0070821, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34378948

RESUMO

Chronic inflammation is a hallmark of human immunodeficiency virus (HIV) infection and a risk factor for the development and progression of age-related comorbidities. Although HIV-associated gut dysbiosis has been suggested to be involved in sustained chronic inflammation, there remains a limited understanding of the association between gut dysbiosis and chronic inflammation during HIV infection. Here, we investigated compositional changes in the gut microbiome and its role in chronic inflammation in patients infected with HIV. We observed that the gut microbiomes of patients with low CD4 counts had reduced alpha diversity compared to those in uninfected controls. Following CD4 recovery, alpha diversity was restored, but intergroup dissimilarity of bacterial composition remained unchanged between patients and uninfected controls. Patients with HIV had higher abundance of the classes Negativicutes, Bacilli, and Coriobacteriia, as well as depletion of the class Clostridia. These relative abundances positively correlated with inflammatory cytokines and negatively correlated with anti-inflammatory cytokines. We found that gut dysbiosis accompanying HIV infection was characterized by a depletion of obligate anaerobic Clostridia and enrichment of facultative anaerobic bacteria, reflecting increased intestinal oxygen levels and intestinal permeability. Furthermore, it is likely that HIV-associated dysbiosis shifts the immunological balance toward inflammatory Th1 responses and encourages proinflammatory cytokine production. Our results suggest that gut dysbiosis contributes to sustaining chronic inflammation in patients with HIV infection despite effective antiretroviral therapy and that correcting gut dysbiosis will be effective in improving long-term outcomes in patients. IMPORTANCE Chronic inflammation is a hallmark of HIV infection and is associated with the development and progression of age-related comorbidities. Although the gastrointestinal tract is a major site of HIV replication and CD4+ T-cell depletion, the role of HIV-associated imbalance of gut microbiome in chronic inflammation is unclear. Here, we aimed to understand the causal relationship between abnormalities in the gut microbiome and chronic inflammation in patients with HIV. Our results suggest HIV-associated gut dysbiosis presents a more aerobic environment than that of healthy individuals, despite prolonged viral suppression. This dysbiosis likely results from a sustained increase in intestinal permeability, which supports sustained bacterial translocation in HIV patients, despite effective therapy. Additionally, we observed that several bacterial taxa enriched in HIV patients were associated with increased expression of inflammatory cytokines. Collectively, these results suggest that gut dysbiosis plays an important role in chronic inflammation in HIV patients.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34435630

RESUMO

CONTEXT: Nonalcoholic fatty liver disease (NAFLD) is becoming a major issue worldwide, even in children. Multiple parallel hits hypothesis has been suggested as progress of NAFLD, but the mechanism of NAFLD is not completely understood. ß-Tubulin is essential in mitoses, neuronal migration, and axon guidance during neuronal development. Pathogenic variants in the TUBB3 gene were shown to be associated with a wide spectrum of neurological abnormalities, but not accompanied with hepatic complications, such as NAFLD. CASE DESCRIPTION: A 11-year-old girl has been followed up as atypical Moebius syndrome since infancy, as she was born with bilateral ptosis, paralytic strabismus, and facial weakness. At the age of 7 years, she was diagnosed with TUBB3 E410K syndrome by whole exome sequencing. At the age of 10 years, her blood examination revealed elevated liver transaminase levels, which persisted for almost 2 years. She underwent liver biopsy, the results of which was suggestive of non-alcoholic steatohepatitis (NASH). The expression of TUBB3 was absent, but that of tyrosine hydroxylase (TH) was present in the parenchymal nerve fibers of the liver. On the other hand, in comparison with an autopsy case of NASH and a normal control, these showed co-expression of TUBB3 and TH in the liver. CONCLUSION: We report the first case of TUBB3 E410K syndrome accompanied with NASH. This case suggests that TUBB3 mutation may be associated with the pathogenesis and progression of NASH in humans.

11.
Cancer Res ; 81(19): 4926-4938, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34413060

RESUMO

Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy. SIGNIFICANCE: Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance.

12.
Anim Sci J ; 92(1): e13614, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34405934

RESUMO

The methane-mitigating potency of cashew nutshell liquid (CNSL) was evaluated by investigating gas production from batch cultures using feces from Thai native ruminants that had been incubated for different periods. Feces was obtained from four Thai native cattle and four swamp buffaloes reared under practical feeding conditions at the Kasetsart University farm, Thailand. Fecal slurry from the same farm was also included in the analysis. CNSL addition successfully suppressed the methane production potential of feces from both ruminants by shifting short chain fatty acid profiles towards propionate production. Methane mitigation continued for almost 150 days, although the degree of mitigation was more apparent from Day 0 to Day 30. Bacterial and archaeal community shifts with CNSL addition were observed in feces from both ruminants; specifically, Bacteroides increased, whereas Lachnospiraceae and Ruminococcaceae decreased in feces to which CNSL was added. Fecal slurry did not show marked changes in gas production with CNSL addition. The findings showed that the addition of CNSL to the feces of ruminants native to the Southeast Asian region can suppress methane emission. Because CNSL can be easily obtained as a byproduct of the local cashew industry in this region, its on-site application might be ideal.


Assuntos
Anacardium/química , Fezes/microbiologia , Gases/metabolismo , Microbioma Gastrointestinal/fisiologia , Metano/metabolismo , Extratos Vegetais/farmacologia , Animais , Búfalos , Bovinos , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Microbiota , Propionatos/metabolismo , Tailândia
13.
Sci Rep ; 11(1): 16694, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404894

RESUMO

The conventional approach of trephine stoma creation is associated with various limitations, including poor elevation of the sigmoid colon, misidentification of the target organs, and poor visualization of the operative field, which may require conversion to an open approach. Our study aimed to evaluate the safety, feasibility, and complications of minimally invasive colostomy with endoscopy (MICE), a new technique for trephine stoma creation. This retrospective cohort study included 14 patients. Patients diagnosed with obstructive rectal cancer or bladder and rectal disorders due to spinal cord injury or bone metastasis requiring sigmoid loop colostomy were eligible for the procedure. MICE was performed using a combination of endoscopic and fluoroscopic procedures. The primary endpoint was the technical success of MICE. Technical success using MICE was achieved in all 14 cases. The mean total operative time was 52.6 (range 32-107) min, and mean blood loss was 18.9 (range 1-50) mL. There was no incidence of conversion to open surgery. Postoperative complications included peristomal abscess formation and ischemic colitis in each case. MICE may be useful as a minimally invasive approach for trephine stoma creation that overcomes the problems of a conventional approach in high-risk patients.

14.
Cancer Res ; 81(18): 4835-4848, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34247147

RESUMO

Tumor heterogeneity underlies resistance to tyrosine kinase inhibitors (TKI) in lung cancers harboring EGFR mutations. Previous evidence suggested that subsets of preexisting resistant cells are selected by EGFR-TKI treatment, or alternatively, that diverse acquired resistance mechanisms emerge from drug-tolerant persister (DTP) cells. Many studies have used bulk tumor specimens or subcloned resistant cell lines to identify resistance mechanism. However, intratumoral heterogeneity can result in divergent responses to therapies, requiring additional approaches to reveal the complete spectrum of resistance mechanisms. Using EGFR-TKI-resistant cell models and clinical specimens, we performed single-cell RNA-seq and single-cell ATAC-seq analyses to define the transcriptional and epigenetic landscape of parental cells, DTPs, and tumor cells in a fully resistant state. In addition to AURKA, VIM, and AXL, which are all known to induce EGFR-TKI resistance, CD74 was identified as a novel gene that plays a critical role in the drug-tolerant state. In vitro and in vivo experiments demonstrated that CD74 upregulation confers resistance to the EGFR-TKI osimertinib and blocks apoptosis, enabling tumor regrowth. Overall, this study provides new insight into the mechanisms underlying resistance to EGFR-TKIs. SIGNIFICANCE: Single-cell analyses identify diverse mechanisms of resistance as well as the state of tolerant cells that give rise to resistance to EGFR tyrosine kinase inhibitors.

15.
J Am Coll Surg ; 233(3): 459-466.e6, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34265428

RESUMO

BACKGROUND: Despite the major advances in analgesic techniques, pain relief in coughing after abdominal surgery remains challenging. Cough-related pain causes postoperative respiratory complications by impairing sputum clearance; nevertheless, an effective technique to abolish it is not yet available. We devised the bilateral flank compression (BFC) maneuver, in which the flanks are compressed medially using both hands. We conducted a prospective, single-center, single arm, nonrandomized, open-label, interventional trial, to investigate whether the BFC maneuver relieves cough-related pain after abdominal surgery and examined the efficacy of this maneuver in relation to patient characteristics and surgical factors. STUDY DESIGN: Participants were patients who underwent gastroenterologic surgery (except for open inguinal hernia repair) at the Department of Surgery, Kyorin University School of Medicine. We evaluated postoperative pain, from postoperative days (PODs) 1 to 7, on coughing, with and without the BFC maneuver, using the Prince Henry pain scale. RESULTS: We finally analyzed 514 patients. On each of the first 7 PODs, the BFC maneuver significantly relieved cough-related pain, especially on POD1; (the mean pain scores [standard deviation] with and without the BFC maneuver were 0.98 [1.030] vs 1.63 [1.112] points, p < 0.0001). On each POD, more patients were free of cough-related pain with than without the BFC maneuver, with the most marked difference on POD7 (52.0% [208/400] vs 16.8% [67/400], p < 0.0001). CONCLUSIONS: The BFC maneuver relieves cough-related pain after abdominal surgery and may help prevent of postoperative pulmonary complications.

16.
J Surg Res ; 267: 350-357, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34198111

RESUMO

BACKGROUND: Surgical site infections (SSI) are one of the most frequent complications following stoma reversal (SR-SSI) and lead to multiple problems such as decreased mobility of the patients or increased hospital costs. Several risk factors for SR-SSI have been reported, but there are no risk scoring systems for predicting SR-SSI. The current study aimed to analyze the risk factors for SR-SSI and develop a scoring system. MATERIALS AND METHODS: Multivariate analysis of risk factors for SR-SSI was performed in patients who underwent elective SR and were followed-up during the first month after surgery. A logistic regression model was used to identify risk factors and construct a predictive score. RESULTS: Of the 182 patients, 53 (29.1%) developed SSI. In multivariate analysis, three variables as preoperative risk factors were associated with increased SR-SSI incidence: subcutaneous fat thickness (≥ 20 mm) (odds ratio [OR]: 8.46 [95% confidence interval (CI): 3.45-20.7], P <0.001), period from stoma creation (≤ 20 weeks) (OR: 2.88 [95% CI: 1.14-7.28], P = 0.025), and SSI after the primary operation (OR: 3.06 [95% CI: 1.19-7.90], P = 0.021). Each of these variables contributed 2,1, and 1 points to the risk score, respectively. The SR-SSI rate was 2.9%, 20.3%, 34.2%, 54.5%, and 81.8% for the scores of 0,1,2,3, and 4 points, respectively. The area under the receiver operating characteristic curve was 0.773 (95% CI: 0.703-0.844). CONCLUSIONS: A simple clinical scoring system based on three preoperative variables may be useful in predicting the risk of SR-SSI.

17.
Inflamm Regen ; 41(1): 22, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34271973

RESUMO

Even within a single type of cancer, cells of various types exist and play interrelated roles. Each of the individual cells resides in a distinct microenvironment and behaves differently. Such heterogeneity is the most cumbersome nature of cancers, which is occasionally uncountable when effective prevention or total elimination of cancers is attempted. To understand the heterogeneous nature of each cell, the use of conventional methods for the analysis of "bulk" cells is insufficient. Although some methods are high-throughput and compressive regarding the genes being detected, the obtained data would be from the cell mass, and the average of a large number of the component cells would no longer be measured. Single-cell analysis, which has developed rapidly in recent years, is causing a drastic change. Genome, transcriptome, and epigenome analyses at single-cell resolution currently target cancer cells, cancer-associated fibroblasts, endothelial cells of vessels, and circulating and infiltrating immune cells. In fact, surprisingly diverse features of clonal evolution of cancer cells, during the development of cancer or acquisition of drug resistance, accompanied by corresponding gene expression changes in the circumstantial stromal cells, appeared in recent single-cell analyses. Based on the obtained novel insights, better optimal drug selection and new drug administration sequences were started. Even a remaining concern of the single cell analyses is being addressed. Until very recently, it was impossible to obtain positional information of cells in cancer via single-cell analysis because such information is lost during preparation of single-cell suspensions. A new method, collectively called spatial transcriptome (ST) analysis, has been developed and rapidly applied to various clinical specimens. In this review, we first outline the recent achievements of single-cell cancer analysis in analyzing the molecular basis underlying the acquisition of drug resistance, particularly focusing on the latest anti-epidermal growth factor receptor tyrosine kinase inhibitor, osimertinib. Further, we review the currently available ST analysis methods and introduce our recent attempts regarding the respective topics.

18.
Nutrients ; 13(6)2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34207794

RESUMO

Because vitamin D responsive elements have been found to be located in the PD-L1 gene, vitamin D supplementation was hypothesized to regulate serum PD-L1 levels and thus alter survival time of cancer patients. A post hoc analysis of the AMATERASU randomized, double-blind, placebo-controlled trial of postoperative vitamin D3 supplementation (2000 IU/day) in 417 patients with stage I to stage III digestive tract cancer from the esophagus to the rectum was conducted. Postoperative serum PD-L1 levels were measured by ELISA and divided into quintiles (Q1-Q5). Serum samples were available for 396 (95.0%) of the original trial. Vitamin D supplementation significantly (p = 0.0008) up-regulated serum PD-L1 levels in the lowest quintile (Q1), whereas it significantly (p = 0.0001) down-regulated them in the highest quintile (Q5), and it did not either up- or down-regulate them in the middle quintiles (Q2-Q4). Significant effects of vitamin D supplementation, compared with placebo on death (HR, 0.34; 95% CI, 0.12-0.92) and relapse/death (HR, 0.37; 95% CI, 0.15-0.89) were observed in the highest quintile (Q5) of serum PD-L1, whereas significant effects were not observed in other quintiles (Pinteraction = 0.02 for death, Pinteraction = 0.04 for relapse/death). Vitamin D supplementation significantly reduced the risk of relapse/death to approximately one-third in the highest quintile of serum PD-L1.


Assuntos
Antígeno B7-H1/sangue , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Neoplasias do Sistema Digestório/mortalidade , Terapia Nutricional/mortalidade , Vitaminas/administração & dosagem , Idoso , Neoplasias do Sistema Digestório/sangue , Neoplasias do Sistema Digestório/cirurgia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Terapia Nutricional/métodos , Período Pós-Operatório , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
19.
Anim Sci J ; 92(1): e13601, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34318572

RESUMO

The rumen microbiota comprises a vast range of bacterial taxa, which may affect the production of high-quality meat in Japanese Black cattle. The aim of this study was to identify core rumen microbiota in rumen fluid samples collected from 74 Japanese Black cattle raised under different dietary conditions using 16S rRNA gene amplicon sequencing. In the rumen of fattening Japanese Black cattle, 10 bacterial taxa, showing >1% average relative abundance and >95% prevalence, irrespective of the dietary conditions and the fattening periods, were identified as the core rumen bacterial taxa, which accounted for approximately 80% of the rumen microbiota in Japanese Black cattle. Additionally, population dynamics of the core rumen bacterial taxa revealed two distinct patterns: Prevotella spp. and unclassified Bacteroidales decreased in the mid-fattening period, whereas unclassified Clostridiales, unclassified Ruminococcaceae, Ruminococcus spp., and unclassified Christensenellaceae increased during the same period. Therefore, the present study reports the wide distribution of the core rumen bacterial taxa in Japanese Black cattle, and the complementary nature of the population dynamics of these core taxa, which may ensure stable rumen fermentation during the fattening period.

20.
DNA Res ; 28(3)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34142133

RESUMO

Spinach (Spinacia oleracea) is grown as a nutritious leafy vegetable worldwide. To accelerate spinach breeding efficiency, a high-quality reference genome sequence with great completeness and continuity is needed as a basic infrastructure. Here, we used long-read and linked-read technologies to construct a de novo spinach genome assembly, designated SOL_r1.1, which was comprised of 287 scaffolds (total size: 935.7 Mb; N50 = 11.3 Mb) with a low proportion of undetermined nucleotides (Ns = 0.34%) and with high gene completeness (BUSCO complete 96.9%). A genome-wide survey of resistance gene analogues identified 695 genes encoding nucleotide-binding site domains, receptor-like protein kinases, receptor-like proteins and transmembrane-coiled coil domains. Based on a high-density double-digest restriction-site associated DNA sequencing-based linkage map, the genome assembly was anchored to six pseudomolecules representing ∼73.5% of the whole genome assembly. In addition, we used SOL_r1.1 to identify quantitative trait loci for bolting timing and fruit/seed shape, which harbour biologically plausible candidate genes, such as homologues of the FLOWERING LOCUS T and EPIDERMAL PATTERNING FACTOR-LIKE genes. The new genome assembly, SOL_r1.1, will serve as a useful resource for identifying loci associated with important agronomic traits and for developing molecular markers for spinach breeding/selection programs.


Assuntos
Frutas/genética , Genoma de Planta , Locos de Características Quantitativas , Spinacia oleracea/genética , Sequenciamento Completo do Genoma , Frutas/anatomia & histologia , Genes de Plantas , Ligação Genética , Sementes/anatomia & histologia , Sementes/genética
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