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Biomodd is an artistic project with the potential for supporting transdisciplinary practices in blended virtual and in-person environments. After describing the project components, we discuss the collaborative process of idea generation and participant engagement.In this paper, we argue for the integration of collaborative art practice in transdisciplinary (TD) research to generate ideas and engage researchers and non-academic stakeholders. We draw on the virtual and in-person (hybrid) participation of members of the TD collective Space Ecologies Art and Design (SEADS) during Biomodd, an art installation that addresses global challenges in ecology, humanity, technology, and technological waste. Using survey responses, diaries, and meeting minutes, we reflect on the process, methods and ideation during Biomodd and map them to the concept of the “idea journey” discussed by Jill E. Perry-Smith and Pier Vittorio Mannucci. We find that while in-person ideation was driven by utility, materiality, and emergence, the hybrid mode provided favorable conditions for a feedback loop of expansive, individual experimentation and online sharing.

Aerosols and spatter are generated in a dental clinic during aerosol-generating procedures (AGPs) that use high-speed hand pieces. Dental healthcare providers can be at increased risk of transmission of diseases such as tuberculosis, measles and severe acute respiratory syndrome (SARS) through droplets on mucosae, inhalation of aerosols or through fomites on mucosae, which harbour micro-organisms. There are ways to mitigate and contain spatter and aerosols that may, in turn, reduce any risk of disease transmission. In addition to personal protective equipment (PPE) and aerosol-reducing devices such as high-volume suction, it has been hypothesised that the use of mouth rinse by patients before dental procedures could reduce the microbial load of aerosols that are generated during dental AGPs.To assess the effects of preprocedural mouth rinses used in dental clinics to minimise incidence of infection in dental healthcare providers and reduce or neutralise contamination in aerosols.We used standard, extensive Cochrane search methods. The latest search date was 4 February 2022.We included randomised controlled trials and excluded laboratory-based studies. Study participants were dental patients undergoing AGPs. Studies compared any preprocedural mouth rinse used to reduce contaminated aerosols versus placebo, no mouth rinse or another mouth rinse. Our primary outcome was incidence of infection of dental healthcare providers and secondary outcomes were reduction in the level of contamination of the dental operatory environment, cost, change in mouth microbiota, adverse events, and acceptability and feasibility of the intervention.Two review authors screened search results, extracted data from included studies, assessed the risk of bias in the studies and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data MAIN RESULTS: We included 17 studies with 830 participants aged 18 to 70 years. We judged three trials at high risk of bias, two at low risk and 12 at unclear risk of bias. None of the studies measured our primary outcome of the incidence of infection in dental healthcare providers. The primary outcome in the studies was reduction in the level of bacterial contamination measured in colony-forming units (CFUs) at distances of less than 2 m (intended to capture larger droplets) and 2 m or more (to capture droplet nuclei from aerosols arising from the participant's oral cavity). It is unclear what size of CFU reduction represents a clinically significant amount. There is low- to very low-certainty evidence that chlorhexidine (CHX) may reduce bacterial contamination, as measured by CFUs, compared with no rinsing or rinsing with water. There were similar results when comparing cetylpyridinium chloride (CPC) with no rinsing and when comparing CPC, essential oils/herbal mouthwashes or boric acid with water. There is very low-certainty evidence that tempered mouth rinses may provide a greater reduction in CFUs than cold mouth rinses. There is low-certainty evidence that CHX may reduce CFUs more than essential oils/herbal mouthwashes. The evidence for other head-to-head comparisons was limited and inconsistent. The studies did not provide any information on costs, change in micro-organisms in the patient's mouth or adverse events such as temporary discolouration, altered taste, allergic reaction or hypersensitivity. The studies did not assess acceptability of the intervention to patients or feasibility of implementation for dentists. AUTHORS' CONCLUSIONS: None of the included studies measured the incidence of infection among dental healthcare providers. The studies measured only reduction in level of bacterial contamination in aerosols. None of the studies evaluated viral or fungal contamination. We have only low to very low certainty for all findings. We are unable to draw conclusions regarding whether there is a role for preprocedural mouth rinses in reducing infection risk or the possible superiority of one preprocedural rinse over another. Studies are needed that measure the effect of rinses on infectious disease risk among dental healthcare providers and on contaminated aerosols at larger distances with standardised outcome measurement.

Objectives The aim of this work was to explore the expression of miR-320a level in fibromyalgia patients in comparison to healthy controls, and to clarify its impact on the severity of symptoms and the cerebral processing of pain assessed by middle latency somatosensory evoked potentials (SSEPs). Design Case-control study. Setting Rheumatology and Neurology outpatient clinics. Subjects Seventy-four fibromyalgia patients and seventy-four normal healthy controls. Methods The included patients were subjected to detailed history taking, assessment of severity of fibromyalgia symptoms using the Fibromyalgia Impact Questionnaire Revised (FIQR), assessment of pain intensity using the Neuropathic Pain Symptom Inventory (NPSI), measurement of the serum level of miR-320a in addition to of measurement peak latencies and amplitudes of middle latency SSEPs. Results Fibromyalgia patients had significantly higher micro-RNA-320a levels (0.907 ± 0.022) in comparison to controls (0.874 ± 0.015) (P-value < .001). The mean values of micro-RNA-320a levels were significantly higher in fibromyalgia patients with insomnia, chronic fatigue syndrome, persistent depressive disorder, and primary headache disorder than those without (P-value = .024, Discussion Micro-RNA-320a level is significantly upregulated in fibromyalgia patient. It has a crucial impact on the severity of symptoms but not related to the cerebral processing of pain.

ObjectiveTo explore and map the findings of prior research priority-setting initiatives related to improving the health and well-being of older adults.DesignScoping review.Data sourcesSearched MEDLINE, EMBASE, AgeLine, CINAHL and PsycINFO databases from January 2014 to 26 April 2021, and the James Lind Alliance top 10 priorities.Eligibility criteriaWe included primary studies reporting research priorities gathered from stakeholders that focused on ageing or the health of older adults (≥60 years). There were no restrictions by setting, but language was limited to English and French.Data extraction and synthesisWe used a modified Reporting Guideline for Priority Setting of Health Research (REPRISE) guideline to assess the transparency of the reported methods. Population–intervention–control–outcome (PICO) priorities were categorised according to their associated International Classification of Health Interventions (ICHI) and International Classification of Functioning (ICF) outcomes. Broad research topics were categorised thematically.ResultsSixty-four studies met our inclusion criteria. The studies gathered opinions from various stakeholder groups, including clinicians (n=56 studies) and older adults (n=35), and caregivers (n=24), with 75% of the initiatives involving multiple groups. None of the included priority-setting initiatives reported gathering opinions from stakeholders located in low-income or middle-income countries. Of the priorities extracted, 272 were identified as broad research topics, while 217 were identified as PICO priorities. PICO priorities that involved clinical outcomes (n=165 priorities) and interventions concerning health-related behaviours (n=59) were identified most often. Broad research topics on health services and systems were identified most often (n=60). Across all these included studies, the reporting of six REPRISE elements was deemed to be critically low.ConclusionFuture priority setting initiatives should focus on documenting a more detailed methodology with all initiatives eliciting opinions from caregivers and older adults to ensure priorities reflect the opinions of all key stakeholder groups.

This study investigated the anti-remodeling and anti-fibrotic and effect of quercetin (QUR) in the remote non-infarcted of rats after myocardial infarction (MI). Rats were divided as control, control + QUR, MI, and MI + QUR. MI was introduced to the rats by ligating the eft anterior descending (LAD) coronary artery. All treatments were given for 30 days, daily. QUR persevered the LV hemodynamic parameters and prevented remote myocardium damage and fibrosis. Also, QUR supressed the generation of ROS, increased the nuclear levels of Nrf2, and enhanced SOD and GSH levels in the LVs of the control and MI model rats. It also reduced angiotensin II, nuclear level/activity of the nuclear factor NF-κβ p65, and protein expression of TGF-β1, α-SMA, and total/phospho-smad3 in the LVs of both groups. Concomitantly, QUR upregulated LV smad7 and BMP7. In conclusion, QUR prevents MI-induced LV remodeling by antioxidant, anti-inflammatory, and anti-fibroticα effects mediated by ROS scavenging, suppressing NF-κβ, and stimulating Nrf-2, Smad7, and BMP7.

Context Kaempferol, a flavonoid glycoside, has many hepatoprotective effects in several animals due to its antioxidant potential. Objective This study evaluated the hepatoprotective effect of kaempferol against acetaminophen (APAP)-induced liver damage and examined whether the protection involved modulation of silent information regulator 1 (SIRT1) signalling. Materials and methods Adult male Wistar rats were classified into four groups (n = 8) and treated as follows: control + normal saline (vehicle), control + kaempferol (250 mg/kg), APAP (800 mg/kg, a single dose) and APAP + kaempferol. Kaempferol was administered for the first seven days followed by administration of APAP. The study was ended 24 h after APAP administration. Results At the histological level, kaempferol reduced liver damage in APAP-treated rats. It also reduced the hepatic levels of TNF-α (66.3%), IL-6 (38.6%) and protein levels of caspase-3 (88.2%), and attenuated the increase in circulatory serum levels of ALT (47.6%), AST (55.8%) and γ-GT (35.2%) in APAP-treated rats. In both the controls and APAP-treated rats, kaempferol significantly increased the hepatic levels of glutathione (GSH) and superoxide dismutase, suppressed MDA and reactive oxygen species (ROS) levels, increased protein levels of Bcl-2 and downregulated protein levels of Bax and cleaved Bax. Concomitantly, it reduced the expression of CYP2E1, and the activity and protein levels of SIRT1. Consequently, it decreased the acetylation of all SIRT1 targets including PARP1, p53, NF-κB, FOXO-1 and p53 that mediate antioxidant, anti-inflammatory and anti-apoptotic effects. Discussion and conclusions This study encourages the use of kaempferol in further clinical trials to treat APAP-induced hepatotoxicity.

IntroductionUncertainty is an inevitable part of healthcare and a source of confusion and challenge to decision-making. Several taxonomies of uncertainty have been developed, but mainly focus on decisions in clinical settings. Our goal was to develop a holistic model of uncertainty that can be applied to both clinical as well as public and global health scenarios.MethodsWe searched Medline, Embase, CINAHL, Scopus and Google scholar in March 2021 for literature reviews, qualitative studies and case studies related to classifications or models of uncertainty in healthcare. Empirical articles were assessed for study limitations using the Critical Appraisal Skills Programme (CASP) checklist. We synthesised the literature using a thematic analysis and developed a dynamic multilevel model of uncertainty. We sought patient input to assess relatability of the model and applied it to two case examples.ResultsWe screened 4125 studies and included 15 empirical studies, 13 literature reviews and 5 case studies. We identified 77 codes and organised these into 26 descriptive and 11 analytical themes of uncertainty. The themes identified are global, public health, healthcare system, clinical, ethical, relational, personal, knowledge exchange, epistemic, aleatoric and parameter uncertainty. The themes were included in a model, which captures the macro, meso and microlevels and the inter-relatedness of uncertainty. We successfully piloted the model on one public health example and an environmental topic. The main limitations are that the research input into our model predominantly came from North America and Europe, and that we have not yet tested the model in a real-life setting.ConclusionWe developed a model that can comprehensively capture uncertainty in public and global health scenarios. It builds on models that focus solely on clinical settings by including social and political contexts and emphasising the dynamic interplay between different areas of uncertainty.

Queen bee acid or 10-hydroxy-2-decenoic acid (10-HDA) is one of the main and unique lipid components (fatty acids) in royal jelly. Previous studies have demonstrated that 10-HDA has various pharmacological and biological activities. The present study aims to evaluate the anti-tumor effects of 10-HDA alone and combined with cyclophosphamide (CP), as an alkylating agent which widely used for the treatment of neoplastic cancers, against the Ehrlich solid tumors (EST) in mice. Methods: A total of 72 female Swiss albino mice were divided into eight groups. EST mice were treated with 10-HDA (2.5 and 5 mg/kg) alone and combined with CP (25 mg/kg) orally once a day for 2 weeks. Tumor growth inhibition, body weight, the serum level of alpha-fetoprotein (AFP) and carcinoembryonic antigen tumor (CAE), liver and kidney enzymes, tumor lipid peroxidation (LPO) and nitric oxide (NO), antioxidant enzymes (e.g. glutathione reductase (GR), glutathione peroxidase (GPx), catalase enzyme (CAT)), tumor necrosis factor alpha level (TNF-α), and the apoptosis-regulatory genes expression were assessed in tested mice. Results: the findings exhibited that treatment of EST-suffering mice with 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p &lt, 0.001) decreased the tumor volume and inhibition rate, tumor markers (AFP and CEA), serum level of liver and kidney, LPO and NO, TNF-α level, as well as the expression level of Bcl-2 in comparison with the mice in the C2 group, while 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP significantly (p &lt, 0.001) improved the level of antioxidant enzymes of GPx, CAT, and SOD and the expression level of caspase-3 and Bax genes. Conclusions: According to the results of the present investigations, 10-HDA at the doses of 2.5 and 5 mg/kg especially in combination with CP showed promising antitumor effects against EST in mice and can be recommended as a new or alternative anticancer agent against tumor, nevertheless, further investigations, particularly in clinical setting, are required to confirm these results.

Background and study aims MicroRNAs (miRNAs), small single stranded RNAs, function in the post-transcriptional regulation of gene expression and incorporated in pathogenesis of HCV related chronic liver disease. This study was designed to evaluate the significance of serum miR-21, miR-223, and miR-885-5p as biomarkers in various clinicopathological stages of HCV related chronic liver disease. Patients and methods Serum miR-21, miR-223, and miR-885-5p were quantified by quantitative RT PCR in 60 patients with HCV-related liver disease (presumably genotype 4), in addition to 25 healthy controls. HCV patients were classified into: chronic non-cirrhotic HCV (n = 15), HCV related liver cirrhosis (n = 15), and hepatocellular carcinoma (HCC) (n = 30). Results: Serum levels of miR-885-5p in cirrhotic patients ± HCC (n = 45) were significantly higher than the non-cirrhotic patients (n = 15); p = 0.007 and healthy control; p = 0.001. However, no such significance was detected between HCC and non-HCC HCV patients; p = 0.12. Serum miRNA-885-5p was able to discriminate cirrhosis ± HCC from healthy controls using ROC analysis; AUC 0.85, 87% sensitivity and 80% specificity. On the other hand, HCC patients had significantly higher serum miR-2 1evels than non-HCC patients (non-cirrhotic and cirrhotic groups, n = 30); p = 0.048 and the control group; p = 0.002. ROC could differentiate HCC from control group; AUC 0.89, 80% sensitivity, 80% specificity. Both serum bilirubin and albumin showed significant weak correlation with miRNA-885-5p (r = 0.42, p = 0.001) and (r = −0.27, p = 0.04), respectively but no such correlation was observed with serum miRNA-21. In contrast, miRNA-223 showed no significant difference across the studied groups. Conclusion Along the spectrum of HCV-related chronic liver disease, miR-885-5p could be a potential marker for advanced liver damage while miR-21 could be a helpful diagnostic marker for HCC.

Modulation of the immune inflammatory system has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN); nevertheless, many of the underlying mechanisms are still unknown. A possible role of micro-RNA 152-3p in T2DM and DN has been suggested due to its immunomodulatory effect on the innate immunity. This case control study aimed, first, to determine the possible role of micro-RNA 152-3p in the pathogenesis of T2DM and DN by evaluating its serum expression in T2DM and DN patients. Second, to assess the performance of serum micro-RNAs 16 and 24 as endogenous control in TaqMan assays of micro-RNA analysis by real time PCR in such disease. Quantification of the expression of micro-RNA 152-3p by qRT-PCR was performed using serum of 70 subjects enrolled in this study and grouped into 20 apparently healthy non-diabetic participants (control group), 15 patients with T2DM without nephropathy (DM group) and 35 diabetic patients with nephropathy (DN group). In diabetic patients with nephropathy (DN) (P0.001), or without nephropathy (DM) (P 0.004), the expression of micro-RNA 152-3p demonstrated a significant elevation in comparison to the controls. Also, the level of micro-RNA 152-3p showed a positive correlation with HbA1c and the duration of diabetes mellitus. The severity of nephropathy as evaluated by markers of renal disease progression; estimated (e)GFR and albumin/creatinine ratio (ACR) revealed a significant correlation with the level of micro-RNA 152-3p. In the same context, serum level of micro-RNA 152-3p was elevated in diabetics with advanced stage of nephropathy (macroalbuminuria) versus the rest of diabetics (without albuminuria and with microalbuminuria). Two one sided T procedure provided a strong statistical support for equivalence of both micro-RNA s 16 and 24. In conclusion, such findings may indicate a pathologic role of micro-RNA 152-3p in Type 2 diabetes mellitus and in the progression of diabetic nephropathy.

BACKGROUND AND OBJECTIVE: There is considerable actual and potential waste in research. Using evidence-based research (EBR) can ensure the value of a new study. The aim of this article, the third in a series, is to describe an EBR approach to putting research results into context.STUDY DESIGN AND SETTING: EBR is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner. In this third and final article of a series, we describe how to use the context of existing evidence to reach and present a trustworthy and useful conclusion when reporting results from a new clinical study.RESULTS: We describe a method, the EBR approach, that by using a systematic and transparent consideration of earlier similar studies when interpreting and presenting results from a new original study will ensure usefulness of the conclusion.CONCLUSION: Using an EBR approach will improve the usefulness of a clinical study by providing the context to draw more valid conclusions and explicit information about new research needs.

A range of analogue space missions has been successful in exploring the psychological impact of confinement, analysing team dynamics during long-term isolation, performing biomedical research, developing food strategies, testing space suit simulators, and investigating human-robot interactions. In this presentation, we compare three different environments that use sustainability and/or artistic practices that provide possibilities to expand and diversify the concept of analogue missions. This presentation uses a literature review and observations to identify possibilities for reciprocal learning and collaboration between currently run analogue space missions and the following three projects, in which the author team has been involved in as a participant or as a researcher: a) ecovillages, b) virtual futuristic space mission workshops called CTIM, c) a community developed art installation called Seeker. The relevance of this comparative exercise comes from the fact that all these scenarios inquire into how to create conditions for the sustenance of human and non-human life in adverse environments: disrupted terrestrial ecosystems and the life-threatening conditions of outer space. The scenarios explored by ecovillages, Seeker, and CTIM can provide complimentary perspectives and inform discussions on how to prepare for different aspects of short term or long-term future space missions.

This study investigated the hypolipidemic and antioxidant effects of the juice and water seed extracts of two pomegranate species from Saudi Arabia and Egypt, and compared them with each other as well as with ellagic acid (EA) in high-cholesterol diet (HCD) fed rats. Compared with the case in rats fed HCD alone, EA and juice or water seed extracts of both pomegranate types significantly reduced the levels of total cholesterol, triglycerides, LDL-c, and GSH, increased the level of HDL-c, increased the activity of SOD and CAT, and decreased the level of MDA in the serum of HCD-fed rats. There were more profound effects of the juice or water seed extract of both the Saudi and Egyptian pomegranates on serum HDL-c and GSH levels and the activities of SOD and CAT than those of EA. In conclusion, this study showed that water seed extracts or juice of both types of pomegranate ameliorated HCD-induced hyperlipidemia, lipid peroxidation, and changes of enzymatic and non-enzymatic antioxidants in the serum of HCD-fed rats.

Given the growing global increase in harm from alcohol and substance use, and the inadequacy of standard treatment to tackle the challenge, the use of physical activity (PA) interventions has received increased attention. The aim of this review is to identify common and cross cutting themes relating to how and why physical activity may impact on reduction of/abstinence from alcohol and other drug use to support future intervention design (including aspects of physical activity, barriers and facilitators, and elements of support which may have an impact). Twenty papers including qualitative data were included in the synthesis. A deductive coding framework was created and sought to identify biological, environmental and psycho-social barriers, facilitators and mechanisms of participants’ experience of engaging with physical activity interventions. Key themes supported in the evidence included how interventions influence use (e.g. reduced cravings, increases in bodily awareness and health and fitness, the development of positive focus and new identity, and increases in mood and quality of life); the impact of frequency, intensity, type, duration and timing of physical activity; perceived barriers and facilitators to engaging in physical activity (e.g. health and fitness, access and affordability, perceptions of others); and details of how much support and in what form best supports sustained changes in physical activity (e.g. social support and environment). Despite evidence being sparse, key barriers and facilitators pertinent to intervention design were identified. Recommendations for future research are indicated and the evidence promotes the need for individually tailored programmes of support for physical activity.

For systematic reviews of interventions, replication is defined as the reproduction of findings of previous systematic reviews looking at the same effectiveness question either by: purposefully repeating the same methods to verify one or more empirical findings; or purposefully extending or narrowing the systematic review to a broader or more focused question (eg, across broader or more focused populations, intervention types, settings, outcomes, or study designs) Although systematic reviews are often used as the basis for informing policy and practice decisions, little evidence has been published so far on whether replication of systematic reviews is worthwhile Replication of existing systematic reviews cannot be done for all topics; any unnecessary or poorly conducted replication contributes to research waste The decision to replicate a systematic review should be based on the priority of the research question; the likelihood that a replication will resolve uncertainties, controversies, or the need for additional evidence; the magnitude of the benefit or harm of implementing findings of a replication; and the opportunity cost of the replication Systematic review authors, commissioners, funders, and other users (including clinicians, patients, and representatives from policy making organisations) can use the guidance and checklist proposed here to assess the need for a replication

ObjectiveTo assess the association between the lockdowns due to COVID-19 and global online searches for toothache using Google Trends (GT).MethodsWe investigated GT online searches for the search terms “toothache” and “tooth pain”, within the past five years. The time frame for data gathering was considered as the initiation and end dates of national/regional lockdowns in each country. Relative search volumes (RSVs) for online Google Search queries in 2019 was considered as the control. We analysed data after normalising based on the Internet penetration rate. We used one-way ANOVA to identify statistical difference for RSVs between 2020 and 2016-2019 for each country. A linear regression model was used to assess whether there is a correlation between RSVs in 2020 and gross domestic production, COVID-19 deaths, dentists’ density, YLDs of oral conditions, Internet access, lockdown duration, Education Index, and dental expenditure per capita.ResultsThe results of worldwide RSVs for toothache and tooth pain also showed significantly higher values in 2020 compared to the previous four years. Of 23 included countries in our study, 16 showed significantly increased RSVs during the lockdown period compared to the same periods in the past four years. There was a statistically significant relationship between difference of RSVs means in 2020 and in 2016-2019 combined with percent of urban residency (B=-1.82; 95% CI: (-3.38, −0.26); p=0.026) and dental expenditure per capita (B=-0.42; 95% CI: (-0.80, −0.05); p=0.031) (R2=0.66).ConclusionGenerally, the interest in toothache and tooth pain has significantly increased in 2020 compared to the last four years. This could implicitly reinforce the importance of dental care, as urgent medical care worldwide. Governments’ expenditure on oral healthcare and the rate of urban residency, could be mentioned as important factors to direct general populations’ online care-seeking behaviour with regard to dental pain.

Graphical abstract, This study examined if the Fisetin against streptozotocin-induced diabetic cardiomyopathy (DC) in rats involves regulating cardiac metabolism and suppressing protein kinase R (PKR). Male rats were divided (12/groups) as control (non-diabetic), control + Fisetin, T1DM, and T1DM + Fisetin. Fisetin was administered orally at a final dose of 2.5 mg/kg for 12 weeks. In T1DM1-induced rats, Fisetin prevented heart and final body weights loss, lowered circulatory levels troponin I and creatinine kinase-MB (CK-MB), increased fasting insulin levels, and improved ventricular systolic and diastolic functions. It also preserved the structure of the cardiomyocytes and reduced oxidative stress, fibrosis, protein levels of transforming growth factor-β1 (TGF-β1), collagenase 1A, caspase-3, and the activation of JNK, p53, and p38 MAPK. In the control and diabetic rats, Fisetin attenuated fasting hyperglycaemia, the increases in glucose levels after the oral and insulin tolerance tests, and HOMA-IR. It also increased cardiac glucose oxidation by increasing the activity of private dehydrogenase (PDH), phosphofructokinase (PFK), protein levels of PPAR-α and suppressed cardiac inflammation by inhibiting NF-κB. These effects were associated with a reduction in the activity of PKR and subsequent increase in the activity of eeukaryotic initiation factor 2 (eIF2) with a parallel increase in protein levels of p67, a cellular inhibitor of PKR. In cultured cardiomyocytes, Fisetin, prevented high glucose (HG)-induced activation of PKR and reduction in p67, in a dose-dependent manner. However, the effect of Fisetin on PKR was diminished in LG and HG-treated cardiomyocytes with p67-siRNA. In conclusion, Fisetin protects against DC in rats by improving cardiac glucose metabolism and suppressing PKR.

Background Many dental procedures produce aerosols (droplets, droplet nuclei and splatter) that harbour various pathogenic micro-organisms and may pose a risk for the spread of infections between dentist and patient. The COVID-19 pandemic has led to greater concern about this risk. Objectives To assess the effectiveness of methods used during dental treatment procedures to minimize aerosol production and reduce or neutralize contamination in aerosols. Search methods Cochrane Oral Health's Information Specialist searched the following databases on 17 September 2020: Cochrane Oral Health's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (in the Cochrane Library, 2020, Issue 8), MEDLINE Ovid (from 1946); Embase Ovid (from 1980); the WHO COVID-19 Global literature on coronavirus disease; the US National Institutes of Health Trials Registry (ClinicalTrials.gov); and the Cochrane COVID-19 Study Register. We placed no restrictions on the language or date of publication. Selection criteria We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on aerosol-generating procedures (AGPs) performed by dental healthcare providers that evaluated methods to reduce contaminated aerosols in dental clinics (excluding preprocedural mouthrinses). The primary outcomes were incidence of infection in dental staff or patients, and reduction in volume and level of contaminated aerosols in the operative environment. The secondary outcomes were cost, accessibility and feasibility. Data collection and analysis Two review authors screened search results, extracted data from the included studies, assessed the risk of bias in the studies, and judged the certainty of the available evidence. We used mean differences (MDs) and 95% confidence intervals (CIs) as the effect estimate for continuous outcomes, and random-effects meta-analysis to combine data. We assessed heterogeneity. Main results We included 16 studies with 425 participants aged 5 to 69 years. Eight studies had high risk of bias; eight had unclear risk of bias. No studies measured infection. All studies measured bacterial contamination using the surrogate outcome of colony-forming units (CFU). Two studies measured contamination per volume of air sampled at different distances from the patient's mouth, and 14 studies sampled particles on agar plates at specific distances from the patient's mouth. The results presented below should be interpreted with caution as the evidence is very low certainty due to heterogeneity, risk of bias, small sample sizes and wide confidence intervals. Moreover, we do not know the 'minimal clinically important difference' in CFU. High-volume evacuator Use of a high-volume evacuator (HVE) may reduce bacterial contamination in aerosols less than one foot (~ 30 cm) from a patient's mouth (MD -47.41, 95% CI -92.76 to -2.06; 3 RCTs, 122 participants (two studies had split-mouth design); very high heterogeneity I² = 95%), but not at longer distances (MD -1.00, -2.56 to 0.56; 1 RCT, 80 participants). One split-mouth RCT (six participants) found that HVE may not be more effective than conventional dental suction (saliva ejector or low-volume evacuator) at 40 cm (MD CFU -2.30, 95% CI -5.32 to 0.72) or 150 cm (MD -2.20, 95% CI -14.01 to 9.61). Dental isolation combination system One RCT (50 participants) found that there may be no difference in CFU between a combination system (Isolite) and a saliva ejector (low-volume evacuator) during AGPs (MD -0.31, 95% CI -0.82 to 0.20) or after AGPs (MD -0.35, -0.99 to 0.29). However, an 'n of 1' design study showed that the combination system may reduce CFU compared with rubber dam plus HVE (MD -125.20, 95% CI -174.02 to -76.38) or HVE (MD -109.30, 95% CI -153.01 to -65.59). Rubber dam One split-mouth RCT (10 participants) receiving dental treatment, found that there may be a reduction in CFU with rubber dam at one-metre (MD -16.20, 95% CI -19.36 to -13.04) and two-metre distance (MD -11.70, 95% CI -15.82 to -7.58). One RCT of 47 dental students found use of rubber dam may make no difference in CFU at the forehead (MD 0.98, 95% CI -0.73 to 2.70) and occipital region of the operator (MD 0.77, 95% CI -0.46 to 2.00). One split-mouth RCT (21 participants) found that rubber dam plus HVE may reduce CFU more than cotton roll plus HVE on the patient's chest (MD -251.00, 95% CI -267.95 to -234.05) and dental unit light (MD -12.70, 95% CI -12.85 to -12.55). Air cleaning systems One split-mouth CCT (two participants) used a local stand-alone air cleaning system (ACS), which may reduce aerosol contamination during cavity preparation (MD -66.70 CFU, 95% CI -120.15 to -13.25 per cubic metre) or ultrasonic scaling (MD -32.40, 95% CI - 51.55 to -13.25). Another CCT (50 participants) found that laminar flow in the dental clinic combined with a HEPA filter may reduce contamination approximately 76 cm from the floor (MD -483.56 CFU, 95% CI -550.02 to -417.10 per cubic feet per minute per patient) and 20 cm to 30 cm from the patient's mouth (MD -319.14 CFU, 95% CI - 385.60 to -252.68). Disinfectants ‒ antimicrobial coolants Two RCTs evaluated use of antimicrobial coolants during ultrasonic scaling. Compared with distilled water, coolant containing chlorhexidine (CHX), cinnamon extract coolant or povidone iodine may reduce CFU: CHX (MD -124.00, 95% CI -135.78 to -112.22; 20 participants), povidone iodine (MD -656.45, 95% CI -672.74 to -640.16; 40 participants), cinnamon (MD -644.55, 95% CI -668.70 to -620.40; 40 participants). CHX coolant may reduce CFU more than povidone iodine (MD -59.30, 95% CI -64.16 to -54.44; 20 participants), but not more than cinnamon extract (MD -11.90, 95% CI -35.88 to 12.08; 40 participants). Authors' conclusions We found no studies that evaluated disease transmission via aerosols in a dental setting; and no evidence about viral contamination in aerosols. All of the included studies measured bacterial contamination using colony-forming units. There appeared to be some benefit from the interventions evaluated but the available evidence is very low certainty so we are unable to draw reliable conclusions. We did not find any studies on methods such as ventilation, ionization, ozonisation, UV light and fogging. Studies are needed that measure contamination in aerosols, size distribution of aerosols and infection transmission risk for respiratory diseases such as COVID-19 in dental patients and staff.

BACKGROUND AND OBJECTIVES: There is considerable actual and potential waste in research. The aim of this article is to describe how using an evidence-based research approach before conducting a study helps to ensure that the new study truly adds value.STUDY DESIGN AND SETTING: Evidence-based research is the use of prior research in a systematic and transparent way to inform a new study so that it is answering questions that matter in a valid, efficient, and accessible manner. In this second article of the evidence-based research series, we describe how to apply an evidence-based research approach before starting a new study.RESULTS: Before a new study is performed, researchers need to provide a solid justification for it using the available scientific knowledge as well as the perspectives of end users. The key method for both is to conduct a systematic review of earlier relevant studies.CONCLUSION: Describing the ideal process illuminates the challenges and opportunities offered through the suggested evidence-based research approach. A systematic and transparent approach is needed to provide justification for and to optimally design a relevant and necessary new study.