Supplementary Material for: Anti-Caries Effect of Arginine-Containing Formulations in vivo: A Systematic Review and Meta-Analysis

<b><i>Objective:</i></b> To assess the anti-caries effect of arginine-containing formulations in vivo on caries lesions compared with fluorides or placebo. <b><i>Methods:</i></b> Randomized or quasi-randomized human clinical trials wherein arginine was delivered by any method were considered. The MEDLINE, Web of Science, EMBASE, Cochrane Library, and CBM databases were searched to identify relevant articles published up to December 2014. Grey literature was also searched. Two authors performed data extraction independently and in duplicate using data collection forms. Each included study was assessed using the Cochrane risk of bias assessment tool. <b><i>Results:</i></b> Of the 470 studies screened, 31 full articles were scrutinized and assessed for eligibility. Ten studies (n = 15,546 participants) were selected for final inclusion. The meta-analysis results (n = 7 studies) demonstrated a synergistic effect of arginine when used in conjunction with fluoride on early coronal and root caries compared with placebo or fluoride alone. No specific side effects related to arginine usage were identified. <b><i>Conclusions:</i></b> When used in combination with a calcium compound and fluoride, arginine potentially provides a superior anti-caries effect compared with matched formulations of fluoride alone. However, the level of evidence was downgraded because of risks of bias and potential publication bias. In the future, more high quality, non-industry-supported clinical studies in this research area are required before any definitive recommendations can be made

Supplementary Material for: Prognostic Value of Stress Hyperglycaemia Ratio in Young Patients with Ischaemic Stroke or Transient Ischaemic Attack

Introduction: Stress hyperglycaemia is common in stroke. Recently, the stress hyperglycaemia ratio (SHR) has been proposed as a novel marker for stress hyperglycaemia and found to be associated with adverse outcomes in many diseases. However, data regarding the impact of the SHR on ischaemic stroke, especially in young adults, are limited. Therefore, the aim of this study was to investigate whether the SHR is associated with stroke severity and adverse outcomes in young adults with ischaemic stroke or transient ischaemic attack (TIA). Methods: We retrospectively recruited patients aged 18–45 years with acute ischaemic stroke or TIA. The SHR was calculated as fasting blood glucose (FBG) divided by glycated haemoglobin. The primary and secondary outcomes were 90-day poor functional outcomes and stroke severity on admission, respectively. Multivariable logistic regression, restricted cubic spline models, and subgroup analysis were performed to validate the relationship between the SHR and ischaemic stroke or TIA in young adults. Results: A total of 687 young adults (mean age 36.9 years) were recruited. Among them, 119 (17.3%) patients had prior diabetes, and 568 (82.7%) did not. The SHR was significantly associated with stroke severity and poor functional outcome. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have moderate-to-severe stroke. The multivariable-adjusted OR (95% CI) was 1.70 (1.21–2.39) after adjusting for all potential confounders excluding FBG and 1.50 (1.03–2.17) after FBG adjustment. The restricted cubic spline showed a J-shaped association between the SHR and moderate-to-severe stroke. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have poor functional outcome at 90-day follow-up. The multivariable-adjusted OR (95% CI) was 1.95 (1.12–3.41) after adjusting for all potential confounders excluding FBG and 1.84 (1.01–3.36) after FBG adjustment. A J-shaped association was found between the SHR and poor functional outcomes at the 90-day follow-up. In the subgroup analysis, SHR was independently associated with more severe stroke (OR, 1.79, 95% CI, 1.18–2.72) and poor functional outcomes (OR, 2.11, 95% CI, 1.32–3.35) in nondiabetic patients but not in diabetic patients in multivariate logistic analysis. Despite this, the interaction effects of prior diabetes on the association between the SHR and stroke severity and poor functional outcomes did not reach statistical significance. Conclusion: The SHR is independently related to more severe stroke and an increased risk of poor functional outcomes among young adults with ischaemic stroke or TIA

Supplementary Material for: Association between Obstructive Sleep Apnea and Acute Kidney Injury in Critically Ill Patients: A Propensity-Matched Study

<p><b><i>Background/Aims:</i></b> Obstructive sleep apnea (OSA) is a known risk factor for chronic kidney disease (CKD); however, its association with acute kidney injury (AKI) is not well documented. We aimed to study whether OSA is associated with the risk of AKI in the intensive care unit (ICU) setting. <b><i>Methods:</i></b> All consecutive adult Olmsted County, MN residents who were admitted in Mayo Clinic ICUs from January 1, 2010 to December 31, 2010 were screened. Chronic and acute risk factors were collected within the first 48 h of ICU admission. Logistic regression and propensity score matching were used to examine crude and adjusted associations of OSA with AKI. <b><i>Results:</i></b> Among 1,259 enrolled ICU patients, 183 patients had a diagnosis of OSA prior to the index ICU admission. Compared with non-OSA patients, the incidence of AKI in OSA patients was more frequent (41 vs. 57%, <i>p </i>< 0.001). In univariate analysis, it was found that CKD, age, gender, Caucasian race, congestive heart failure, cerebrovascular disease, diabetes mellitus, body mass index, and OSA were associated with AKI. In the multivariate model, following adjustment for age, gender, race, and chronic and acute risk factors, OSA was found to have an independent association with AKI (OR 1.53; 95% CI 1.04-2.24; <i>p </i>= 0.031). Among 176 propensity score matched pairs, there was a significant difference in the incidence of AKI between the OSA and non-OSA groups (OR 1.54; 95% CI 1.01-2.35; <i>p</i> = 0.04). <b><i>Conclusions:</i></b> The history of OSA diagnosed by polysomnography is associated with higher risk of AKI in critically ill patients.</p

Supplementary Material for: Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

Recognition of viral pathogen-associated molecular patterns by pattern recognition receptors (PRRs) is the first step in the initiation of a host innate immune response. As a PRR, RIG-I detects either viral RNA or replication transcripts. Avoiding RIG-I recognition is a strategy employed by viruses for immune evasion. Epstein-Barr virus (EBV) infects the majority of the human population worldwide. During the latent infection period there are only a few EBV proteins expressed, whereas EBV-encoded microRNAs, such as BART microRNAs, are highly expressed. BART microRNAs regulate both EBV and the host's gene expression, modulating virus proliferation and the immune response. Here, through gene expression profiling, we found that EBV miR-BART6-3ps inhibited genes of RIG-I-like receptor signaling and the type I interferon (IFN) response. We demonstrated that miR-BART6-3p rather than other BARTs specifically suppressed RIG-I-like receptor signaling-mediated IFN-β production. RNA-seq was used to analyze the global transcriptome change upon EBV infection and miR-BART6-3p mimics transfection, which revealed that EBV infection-triggered immune response signaling can be repressed by miR-BART6-3p overexpression. Furthermore, miR-BART6-3p inhibited the EBV-triggered IFN-β response and facilitated EBV infection through targeting the 3′UTR of RIG-I mRNA. These findings provide new insights into the mechanism underlying the strategies employed by EBV to evade immune surveillance