Positive feedback regulation of type I IFN genes by the IFN-inducible transcription factor IRF-7

AbstractThe interferon regulatory factor (IRF) family of transcription factors regulate the interferon (IFN) system, among which IRF-3 is involved in the virus-induced IFN-β gene expression. Here we show that another member IRF-7 is critical for the IFN-α gene induction. Unlike the IRF-3 gene, the IRF-7 gene is induced by IFNs through activation of the ISGF3 transcription factor, and IRF-7 undergoes virus-induced nuclear translocation. In cells lacking p48, an essential component of IFN stimulated gene factor 3 (ISGF3), ectopic expression of IRF-7 but not IRF-3 can rescue the deficiency to induce IFN-α genes. These results indicate that IRF-7 is a key factor in the positive feedback regulation of IFN-α/β production

Swallowing rehabilitation with nutrition therapy improves clinical outcome in patients with dysphagia at an acute care hospital

Dysphagia is associated with nutritional deficits and increased risk of aspiration pneumonia. The aim of the present study was to evaluate the impact of nutrition therapy for the patients with dysphagia at an acute care hospital. We also tried to clarify the factors which improve swallowing function in these patients. Seventy patients with dysphagia were included in the present study. Multidisciplinary nutrition support team evaluated swallowing function and nutrition status. Most patients were fed by parenteral or enteral nutrition at the time of the first round. Of these 70 patients, 36 became able to eat orally. The improvement of swallowing function was associated with higher BMI in both genders and higher AMC in men. Mortality was high in the patients with lower BMI and %AMC, suggesting importance of maintaining muscle mass. Thirteen (38.2%) of 34 patients who did not show any improvement in swallowing function died, but no patients who showed improvement died (p22 kcal/kg/day. These results suggest that it is important to maintain nutritional status to promote rehabilitation in patients with dysphagia even in an acute care hospital

miRNA Changes in retinal ganglion cells after optic nerve crush and glaucomatous damage

The purpose of this study was to characterize the miRNA profile of purified retinal ganglion cells (RGC) from healthy and diseased rat retina. Diseased retina includes those after a traumatic optic nerve crush (ONC), and after ocular hypertension/glaucoma. Rats were separated into four groups: healthy/intact, 7 days after laser-induced ocular hypertension, 2 days after traumatic ONC, and 7 days after ONC. RGC were purified from rat retina using microbeads conjugated to CD90.1/Thy1. RNA were sequenced using Next Generation Sequencing. Over 100 miRNA were identified that were significantly different in diseased retina compared to healthy retina. Considerable differences were seen in the miRNA expression of RGC 7 days after ONC, whereas after 2 days, few changes were seen. The miRNA profiles of RGC 7 days after ONC and 7 days after ocular hypertension were similar, but discrete miRNA differences were still seen. Candidate mRNA showing different levels of expression after retinal injury were manipulated in RGC cultures using mimics/AntagomiRs. Of the five candidate miRNA identified and subsequently tested for therapeutic efficacy, miR-194 inhibitor and miR-664-2 inhibitor elicited significant RGC neuroprotection, whereas miR-181a mimic and miR-181d-5p mimic elicited significant RGC neuritogenesis

Concern over radiation exposure and psychological distress among rescue workers following the Great East Japan Earthquake

<p>Abstract</p> <p>Background</p> <p>On March 11, 2011, the Great East Japan Earthquake and tsunami that followed caused severe damage along Japans northeastern coastline and to the Fukushima Daiichi nuclear power plant. To date, there are few reports specifically examining psychological distress in rescue workers in Japan. Moreover, it is unclear to what extent concern over radiation exposure has caused psychological distress to such workers deployed in the disaster area.</p> <p>Methods</p> <p>One month after the disaster, 424 of 1816 (24%) disaster medical assistance team workers deployed to the disaster area were assessed. Concern over radiation exposure was evaluated by a single self-reported question. General psychological distress was assessed with the Kessler 6 scale (K6), depressive symptoms with the Center for Epidemiologic Studies Depression Scale (CES-D), fear and sense of helplessness with the Peritraumatic Distress Inventory (PDI), and posttraumatic stress symptoms with the Impact of Event Scale-Revised (IES-R).</p> <p>Results</p> <p>Radiation exposure was a concern for 39 (9.2%) respondents. Concern over radiation exposure was significantly associated with higher scores on the K6, CES-D, PDI, and IES-R. After controlling for age, occupation, disaster operation experience, duration of time spent watching earthquake news, and past history of psychiatric illness, these associations remained significant in men, but did not remain significant in women for the CES-D and PDI scores.</p> <p>Conclusion</p> <p>The findings suggest that concern over radiation exposure was strongly associated with psychological distress. Reliable, accurate information on radiation exposure might reduce deployment-related distress in disaster rescue workers.</p

Orange Juice and Its Component, Hesperidin, Decrease the Expression of Multidrug Resistance-Associated Protein 2 in Rat Small Intestine and Liver

We investigated the effects of orange juice (OJ) or hesperidin, a component of OJ, on the pharmacokinetics of pravastatin (PRV) and the expression of both protein and mRNA of multidrug resistance-associated protein 2 (Mrp2) in the rat small intestine and liver. Eight-week-old male Sprague-Dawley rats were used in this study. OJ or a 0.079% hesperidin suspension was administered orally for 2 days. Tap water was given as a control. A single dose of PRV at 100 mg/kg p.o. was administered after 2 days of OJ, hesperidin, or tap water ingestion. The AUC, Cmax, and t1/2 values of PRV were significantly increased in OJ group. Mrp2 protein and mRNA levels in the small intestine and liver, respectively, were significantly decreased after the ingestion of OJ. The same results were obtained with hesperidin. These results suggest that the changes in PRV pharmacokinetic parameters and the decrease in Mrp2 expression caused by OJ are due to hesperidin in the juice

Distinct and Essential Roles of Transcription Factors IRF-3 and IRF-7 in Response to Viruses for IFN-α/β Gene Induction

AbstractInduction of the interferon (IFN)-α/β gene transcription in virus-infected cells is an event central to innate immunity. Mice lacking the transcription factor IRF-3 are more vulnerable to virus infection. In embryonic fibroblasts, virus-induced IFN-α/β gene expression levels are reduced and the spectrum of the IFN-α mRNA subspecies altered. Furthermore, cells additionally defective in IRF-7 expression totally fail to induce these genes in response to infections by any of the virus types tested. In these cells, a normal profile of IFN-α/β mRNA induction can be achieved by coexpressing both IRF-3 and IRF-7. These results demonstrate the essential and distinct roles of the two factors, which together ensure the transcriptional efficiency and diversity of IFN-α/β genes for the antiviral response

Randomized controlled trial for an effect of catechin-enriched green tea consumption on adiponectin and cardiovascular disease risk factors

Previous observational studies have indicated that green tea (GT) consumption is associated with reduced mortality from cerebral infarction but not with mortality from cerebral hemorrhage. Therefore, we hypothesized that GT exerts a direct antiatherosclerotic effect without any effect on hypertension. To investigate this hypothesis, we focused on adiponectin that seems to be among the several key players in atherosclerosis.The objective of this randomized controlled trial (RCT) was to assess whether the consumption of catechin-enriched GT affects serum adiponectin levels and cardiovascular disease (CVD) risk factors among apparently healthy subjects.A total of 51 individuals participated in the study. Eligible participants were randomly assigned into GT consumption groups with either high catechin (400 mg/day) or low catechin (100 mg/day). The study participants were asked to stop GT consumption for 2 weeks (washout period), following which they were to start drinking the provided GT beverages everyday for 9 weeks. The outcome measures were changes in the adiponectin levels and CVD risk factors (body weight, body mass index, waist circumference, blood pressure, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting plasma glucose, as well as aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, and high-sensitive C-reactive protein).After intervention for 9 weeks, we found no significant difference between the high- and low catechin group with respect to changes in the serum adiponectin level: 0.35 &#x00B5;g/ml (95% confidence interval (CI): &#x2212;1.03, 1.74). Also, no significant difference was observed between the high- and low catechin groups with respect to changes in any of the measured CVD risk factors.This RCT showed no significant difference between the high- and low catechin groups with respect to changes in the serum adiponectin level and any CVD risk factors

Validity and Reliability of the Japanese Version of the 12-item Self-administered World Health Organization Disability Assessment Schedule (WHODAS) 2.0 in Patients with Schizophrenia

It is necessary to assess functional impairment when treating schizophrenia. The World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) has been adopted as a measure of functional disability in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This study was a secondary analysis from a cross-sectional study of health-related behaviors among patients with schizophrenia. We examined the validity and reliability of the Japanese version of the 12-item WHODAS 2.0 when self-administered by such patients. Participants were 350 outpatients with schizophrenia from a psychiatric hospital. The standard six-factor structure of the WHODAS 2.0 showed a good fit for these participants. The Cronbach’s alpha coefficient was 0.858, showing good internal consistency. The WHODAS 2.0 showed moderate correlations with the modified Global Assessment of Functioning and Kessler 6 scales (r=−0.434 and 0.555, respectively). The results of this study show that the Japanese version of the 12-item self-administered WHODAS 2.0 has good internal consistency and convergent validity among patients with schizophrenia. Further exploration of the usefulness of WHODAS 2.0 in clinical settings is needed