Current models of cell-intrinsic immunity to RNA viruses centre on virus-triggered inducible antiviral responses initiated by RIG-I-like receptors or Toll-like receptors that sense ...pathogen-associated molecular patterns, and signal downstream through interferon regulatory factors (IRFs), transcription factors that induce synthesis of type I and type III interferons
. RNA viruses have evolved sophisticated strategies to disrupt these signalling pathways and evade elimination by cells, attesting to their importance
. Less attention has been paid to how IRFs maintain basal levels of protection against viruses. Here, we depleted antiviral factors linked to RIG-I-like receptor and Toll-like receptor signalling to map critical host pathways restricting positive-strand RNA virus replication in immortalized hepatocytes and identified an unexpected role for IRF1. We show that constitutively expressed IRF1 acts independently of mitochondrial antiviral signalling (MAVS) protein, IRF3 and signal transducer and activator of transcription 1 (STAT1)-dependent signalling to provide intrinsic antiviral protection in actinomycin D-treated cells. IRF1 localizes to the nucleus, where it maintains the basal transcription of a suite of antiviral genes that protect against multiple pathogenic RNA viruses, including hepatitis A and C viruses, dengue virus and Zika virus. Our findings reveal an unappreciated layer of hepatocyte-intrinsic immunity to these positive-strand RNA viruses and identify previously unrecognized antiviral effector genes.
Purpose
Validating outcome measures is a prerequisite for using administrative databases for comparative effectiveness research. Although the Japanese Diagnosis Procedure Combination database is ...widely used in surgical studies, the outcome measure for postsurgical infection has not been validated. We developed a model to identify postsurgical infections using the routinely collected Diagnosis Procedure Combination data.
Methods
We retrospectively identified inpatients who underwent surgery for gastric, colon, or liver cancer between April 2016 and March 2018 at four hospitals. Chart reviews were conducted to identify postsurgical infections. We used bootstrap analysis with backwards variable elimination to select independent variables from routinely collected diagnosis and procedure data. Selected variables were used to create a score predicting the chart review‐identified infections, and the performance of the score was tested.
Results
Among the 746 eligible patients, 96 patients (13%) had postoperative infections. Three variables were identified as predictors: diagnosis of infectious disease recorded as a complication arising after admission, addition of an intravenous antibiotic, and bacterial microscopy or culture. The prediction model had a C‐statistic of 0.885 and pseudo‐R2 of 0.358. A cut‐off of one point of the score showed a sensitivity of 92% and specificity of 72%, and a cut‐off of two points showed a sensitivity of 75% and specificity of 91%.
Conclusions
Our model using routinely collected administrative data accurately identified postoperative infections. Further external validation would lead to the application of the model for research using administrative databases.
Background
The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change the practice in Japan. However, the ...perspective of this topic among children and adults has not been investigated in detail.
Methods
We studied changes in the practice of information sharing with children with cancer at pediatric cancer centers and the perspective of cancer diagnosis disclosure to children among school children, their parents and pediatric oncologists in the last 20 years by comparing the results of questionnaire surveys conducted in 1998, 2008 and 2018.
Results
This study revealed that the performing rate has increased with the times, but the institutions actively performing for children aged 7–9 years were 36.4% even in the 2018 survey. More than 70% of children wished diagnosis disclosure if they suffer from cancer in the series of surveys, while the ratio of parents who tell cancer diagnosis to their children hovered at 34.5 to 53.7% (
p
< 0.001 in all surveys). The ratio of pediatric oncologists having the policy to perform diagnosis disclosure proactively increased from 9.3 to 60.0%, while that of parents having the same policy stayed at 5.3% even in 2018.
Conclusions
The performing rate of information sharing with children with cancer was significantly changed in the last 20 years. The opinion gaps were observed between parents and children and between parents and pediatric oncologists.
Supported anisotropic bimetallic nanocrystals are attractive owing to their potential for novel catalytic applications. Au-Pd nanocrystals are expected to have higher catalytic activity for alcohol ...oxidation than Au nanocrystals. However, only a few studies have reported the application of anisotropic Au-Pd nanocrystals as alcohol-oxidation nanocatalysts. Support materials such as Al2O3 and Fe2O3 influence the catalytic activity of spherical Au nanoparticles. Thus, optimization of the support is expected to improve the catalytic activity of anisotropic Au-Pd nanocrystals. Herein, we report the synthesis and catalytic performances of Al2O3- and Fe2O3-supported Au and Au-Pd nanoflowers. Au99-Pd1 NFs supported on Fe2O3 exhibited the highest catalytic activity for 1-phenylethyl alcohol oxidation.
Dissolving microneedles (DMs) were applied to glucose monitoring in the dermal interstitial fluid (ISF) of rats and their potential as an alternative blood glucose monitoring device was evaluated. ...Sodium chondroitin sulfate was used to prepare DM array chips, which consisted of 300 DMs/cm2. The mean length of the DMs was 475±18 µm and the mean diameter of the basement was 278±8 µm. After DMs were inserted into the skin of the hair-removed rat abdomen, a wet unwoven cloth containing 10–30 µL of water was placed on the skin and ISF was extracted. By increasing the absorbed amount of water on the unwoven cloth from 10 to 30 µL, the extracted amount of glucose increased from 1.66±0.35 µg to 2.75±0.61 µg. Increasing the adhesion time of the wet unwoven cloth to the skin from 0.1 to 5.0 min, increased the amount of ISF glucose from 1.99±0.13 µg to 5.04±0.38 µg. The relation between the amount of glucose in ISF and blood glucose concentrations was examined. With increase in the adhesion time, the coefficient of determination, r2, increased from 0.501 to 0.750. The number of DMs also affected the relationship and values of the coefficient of determinations, r2 were: 0.340 (25 DMs), 0.758 (50 DMs), 0.763 (100 DMs), 0.774 (200 DMs), and 0.762 (300 DMs). These results indicate the usefulness of DMs as an alternative blood glucose monitoring device.
•Frailty is a major concern for mortality in elderly cardiovascular patients.•Relieving frailty by cardiac rehabilitation leads to regain of physical function.•Rehabilitation time for regain of ...exercise capacity is different from that for physical function.•Optimal rehabilitation time for regain of exercise capacity needs future consideration.
The effects of cardiac rehabilitation (CR) on long-term prognosis of cardiovascular disease (CVD) are well known. However, the effect of CR on frail CVD patients has not been fully addressed.
This study consisted of 89 CVD patients with their age ≥65 years old (68 males, 75 ± 6 years), who participated in the outpatient CR program for 3 months. All the patients underwent cardiopulmonary exercise testing and the physical frailty was assessed using the Japanese Version of the Cardiovascular Health Study Standard before and after CR. Based on the assessment of frailty before CR, the patients were divided into the following two groups: frailty group (n = 23) and non-frailty group (n = 66: robust in 10 and pre-frail in 56 patients).
In the frailty group, 20 patients (87%) improved from frail status after CR, and usual walking speed, maximal grip strength, and lower extremity strength were significantly improved (1.06±0.20 vs. 1.20±0.18 m/sec, p<0.001; 21.7 ± 5.5 vs. 23.6 ± 6.3 kg, p<0.01; 0.37±0.09 vs. 0.43±0.11 kgf/kg, p = 0.001, respectively), but peak VO2 did not change after CR (15.9 ± 3.1 vs. 16.2 ± 3.8 ml/min/kg, NS). In the non-frailty group, all these parameters were significantly improved after CR (1.24±0.19 vs. 1.29±0.23 m/sec, p<0.05, 28.7 ± 7.0 vs. 30.2 ± 7.3 kg, p<0.001, 0.50±0.18 vs. 0.54±0.13 kgf/kg, p<0.05, 17.7 ± 4.7 vs 18.5 ± 4.2 ml/min/kg, p<0.01, respectively).
Short-term CR could obtain the improvement of the physical function, providing the prerequisite step for possibly following improvement of exercise capacity in elderly CVD patients with frailty. It may be inferred that longer duration of CR would be needed to obtain the improvement of exercise capacity in these patients, being the future consideration to be determined.
Cancer immunotherapy with human γδ T cells expressing Vγ2Vδ2 T cell receptor (also termed Vγ9Vδ2) has shown promise because of their ability to recognize and kill most types of tumors in a major ...histocombatibility complex (MHC) ‐unrestricted fashion that is independent of the number of tumor mutations. In clinical trials, adoptive transfer of Vγ2Vδ2 T cells has been shown to be safe and does not require preconditioning. In this report, we describe a method for preparing highly enriched human Vγ2Vδ2 T cells using the bisphosphonate prodrug, tetrakis‐pivaloyloxymethyl 2‐(thiazole‐2‐ylamino)ethylidene‐1,1‐bisphosphonate (PTA). PTA stimulated the expansion of Vγ2Vδ2 cells to purities up to 99%. These levels were consistently higher than those observed after expansion with zoledronic acid, the most commonly used stimulator for clinical trials. Cell numbers also averaged more than those obtained with zoledronic acid and the expanded Vγ2Vδ2 cells exhibited high cytotoxicity against tumor cells. The high purity of Vγ2Vδ2 cells expanded by PTA increased engraftment success in immunodeficient NOG mice. Even low levels of contaminating αβ T cells resulted in some mice with circulating human αβ T cells rather than Vγ2Vδ2 cells. Vγ2Vδ2 cells from engrafted NOG mice upregulated CD25 and secreted tumor necrosis factor‐α and interferon‐γ in response to PTA‐treated tumor cells. Thus, PTA expands Vγ2Vδ2 T cells to higher purity than zoledronic acid. The high purities allow the successful engraftment of immunodeficient mice without further purification and may speed up the development of allogeneic Vγ2Vδ2 T cell therapies derived from HLA‐matched normal donors for patients with poor autologous Vγ2Vδ2 T cell responses.
Adoptive transfer of Vγ2Vδ2 T cells for treatment of cancer patients has been shown to be safe.In this report, we describe a method for preparing large numbers of highly enriched human Vγ2Vδ2 T cells using a new bisphosphonate prodrug. When the expanded Vγ2Vδ2 cells were administered to immunodeficient mice, the cells remained circulating in the blood for more than 2 weeks and they were functionally active.
Background: Education regarding death diagnosis is not often included in the medical education. Objective: To investigate the change minds at the time of death diagnosis among residents after ...lectures based on our guidebook. Design: Uncontrolled, open-label, multi-center trial. Subjects: A total of 131 doctors undergoing their initial training were enrolled this study. Measurements: Questionnaires were administered to volunteers before and after the lecture by the clinical training instructor presented information regarding doctors’ behaviors at the death diagnosis based on our guidebook at each hospital. Results: The subjects had an average age of 27.1 years and comprised 76 men (58.0%) and 54 women (41.2%). A total of 83 subjects (63.4%) had learned how to diagnose death as medical students, and 52 subjects (39.7%) had experienced death diagnosis scenes as medical students. Among those who had difficulties related to death diagnoses, the highest number (88.4%) indicated that “I do not know what to say to the family after a death diagnosis”. Self-evaluation significantly increased after the lecture for many items concerning explanations to and considerations of the family: the effect size for “Give words of comfort and encouragement to family” increased significantly after the lecture to 0.9. Conclusions: Few of the residents felt that they had received education regarding death diagnoses; they reported difficulties with diagnosing death and responding to patients’ families. After the lecture using our guidebook, residents’ mind changed significantly for death diagnosis, suggesting that the guidebook at the time of death diagnosis may be useful.
A woman in her 50s was transported to our hospital after experiencing a road traffic crash that led to a massive haemothorax and haemorrhagic shock due to a cervical vascular injury caused by the ...seat belt. Contrast-enhanced CT of the chest showed extravascular leakage of the contrast medium from the vicinity of the right subclavicular area and fluid accumulation in the thoracic cavity. The patient was intubated, and a thoracic drainage catheter was placed. She underwent angiography and embolisation of the right costocervical trunk, right thyrocervical trunk and right suprascapular artery using a gelatine sponge and 25%
-butylcyanoacrylate-Lipiodol. She was extubated on the second day after stabilisation of the respiratory and circulatory status. In cases where the bleeding vessel is known and an emergency thoracotomy can serve as a backup, embolisation by interventional radiology should be considered the initial treatment approach.
Background
Social awareness of cancer can be changed with cancer education and proper distribution of cancer information. This study addressed the current situation and historical changes to ...children's perception of cancer.
Methods
Questionnaire surveys were conducted among healthy school children aged 10–15 years in 2008 and 2018. Knowledge of cancer was surveyed and compared with that of asthma, tuberculosis, and measles. The children were asked about their health information resources.
Results
The numbers of participants and collection rates were 438 and 63.9% in 2008, and 320 and 44.7% in 2018. Children's perception of cancer changed significantly in the last decade. The proportion of respondents answering “cancer affects children” changed from 78.3 to 89.5% (P = 0.0001), “cancer is preventable” from 42.0 to 49.7% (P = 0.0425), and “cancer is curable,” from 52.4 to 66.0% (P = 0.0003). Significantly more junior high school students answered that cancer is preventable than elementary school children in 2018 (55.9 vs 42.7%, P = 0.0028). The major resources of information on health were television, parents, and books. The proportion of children choosing the Internet significantly increased from 15.3 to 47.8% (P < 0.0001). Significantly more junior high school students selected television and the Internet than elementary school children (94.5 vs 86.9%, P = 0.0202 for television; 57.1 vs 37.9%, P = 0.0007 for the Internet).
Conclusions
The proportion of children correctly perceiving cancer information had increased in the last decade. Junior high school students better understood the information. The Internet is of increasing importance as an information resource for school children.
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