'You learn to smile with your eyes', exploring the impact of enhanced personal protective equipment on primary care dental practitioners in the UK: An interpretative phenomenological study.

OBJECTIVE: The aim of the study was to explore how dental practitioners in primary care settings perceive the impact of enhanced personal protective equipment (PPE) upon patient communication and wider clinical practice. METHODS: This study utilized a qualitative approach, rooted in critical realism. An interpretative phenomenological analysis (IPA) methodology was adopted as the study method. In accordance with IPA, in-depth semi-structured interviews were conducted. Eight dental practitioners were recruited, with data analysis conducted according to the principles of IPA. RESULTS: Three themes were synthesized (related to communication and clinical practice): (1) Impaired communication and relationship building; (2) Physical impacts and required adjustments when wearing enhanced-PPE; and (3) Psychological stress of implementing enhanced-PPE. Theme one reflects changes to the dynamic of communication between patients and colleagues brought about by enhanced-PPE. Theme two describes the physical and psychological strains of providing care in enhanced-PPE and the ways through which practitioners tried to overcome these challenges. Theme three explores how the roll-out and guidance related to the use of enhanced-PPE affected clinical practice. CONCLUSIONS: Dental Practitioners described several barriers to communication as well as physical and mental stressors caused by enhanced-PPE, all of which were perceived to impact upon the quality of care provided to patients. Further research is required to develop effective interventions to mitigate the impact of enhanced-PPE upon clinical practice and to explore the long-term impact of enhanced-PPE on clinical practice, post-COVID.

Assessing Google Searches for Toothache during COVID-19 Lockdowns.

Background: Lockdowns due to the coronavirus disease 2019 (COVID-19) pandemic forced many dental offices to be closed. This study aims to investigate the association between COVID-19 imposed lockdowns and online searches for toothache using Google Trends (GT). Methods: We investigated GT online searches for the term "toothache" within the past 5 years. The time frame for data gathering was considered as the initiation and end dates of national/regional lockdowns in each country. We used 1-way analysis of variance to identify statistical differences in relative search volumes (RSVs) between 2020 and 2016-2019 for each country. Results: Overall, 16 countries were included in our analyses. Among all countries, Indonesia (n = 100), Jamaica (n = 56), Philippines (n = 56), Iran (n = 52), and Turkey (47) had the highest RSVs for toothache in the specified period. Compared with the previous 4 years, higher RSVs were seen in the world (as a whole) (2020 RSVs, 94.4; vs 2019 RSVs, 77.8 [ P < 0.001]) and 13 countries (81.3% of the included countries). Conclusion: Generally, searching for the term "toothache" showed an increase during the COVID-19 lockdowns in 2020 compared with the past 4 years. This can imply the importance of dental care as urgent medical care during public health emergencies such as COVID-19.

Bacterial protease alleviate chronic liver fibrosis induced by thioacetamide through suppression of hepatic stellate cells consequently decrease its proliferative index.

In chronic liver diseases, liver fibrosis occurs due to excessive extracellular matrix (ECM) protein accumulation. Approximately 2 million deaths occur yearly due to liver disease, while cirrhosis is the 11th most common cause of death. Therefore, newer compounds or biomolecules must be synthesized to treat chronic liver diseases. In this aspect, the present study focuses on the assessment of the anti-inflammatory and antioxidant impact of Bacterial Protease (BP) produced by a new mutant strain of bacteria (Bacillus cereus S6-3/UM90) and 4,4'-(2,5-dimethoxy-1,4-phenylene) bis (1-(3-ethoxy phenyl)-1H-1,2,3-triazole) (DPET) in the treatment of early stage of liver fibrosis induced by thioacetamide (TAA). Sixty male rats were divided into six groups, ten rats each as follows: (1) Control group, (2) BP group, (3) TAA group, (4) TAA-Silymarin (S) group, (5) TAA-BP group, and (6) TAA-DPET group. Liver fibrosis significantly elevated liver function ALT, AST, and ALP, as well as anti-inflammatory interleukin 6 (IL-6) and VEGF. The oxidative stress parameters (MDA, SOD, and NO) were significantly increased with a marked reduction in GSH. Expression of MAPK and MCP-1 was unregulated in the TAA group, with downregulation of Nrf2 was observed. TAA caused histopathological alterations associated with hepatic vacuolation and fibrosis, increasing collagen fibers and high immuno-expression of VEGF. On the other hand, treatment with BP successfully improved the severe effects of TAA on the liver and restored histological architecture. Our study concluded the protective potentials of BP for attenuating liver fibrosis and could be used as adjuvant therapy for treating hepatic fibrosis.

Research priority setting related to older adults: a scoping review to inform the Cochrane-Campbell Global Ageing Partnership work programme.

OBJECTIVE: To explore and map the findings of prior research priority-setting initiatives related to improving the health and well-being of older adults. DESIGN: Scoping review. DATA SOURCES: Searched MEDLINE, EMBASE, AgeLine, CINAHL and PsycINFO databases from January 2014 to 26 April 2021, and the James Lind Alliance top 10 priorities. ELIGIBILITY CRITERIA: We 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 SYNTHESIS: We 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. RESULTS: Sixty-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. CONCLUSION: Future 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.

Preprocedural mouth rinses for preventing transmission of infectious diseases through aerosols in dental healthcare providers.

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 4 February 2022. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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.

Developing an integrated multilevel model of uncertainty in health care: a qualitative systematic review and thematic synthesis.

INTRODUCTION: Uncertainty 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. METHODS: We 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. RESULTS: We 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. CONCLUSION: We 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.

Evidence based policy making during times of uncertainty through the lens of future policy makers: four recommendations to harmonise and guide health policy making in the future.

The Covid-19 pandemic has not only outlined the importance of using evidence in the healthcare policy making process but also the complexity that exists between policymakers and the scientific community. As a matter of fact, scientific data is just one of many other concurrent factors, including economic, social and cultural, that may provide the rationale for policy making. The pandemic has also raised citizens' awareness and represented an unprecedented moment of willingness to access and understand the evidence underpinning health policies.This commentary provides policy recommendations to improve evidence-based policy making in health, through the lens of a young generation of public policy students and future policymakers, enrolled in a 24-hour course at Sciences Po Paris entitled "Evidence-based policy-making in health: theory and practice(s)".Four out of 11 recommendations were prioritised and presented in this commentary which target both policymakers and the scientific community to make better use of evidence-based policy making in health. First, policy makers and scientists should build trusting partnerships with citizens and engage them, especially those facing our target health care issues or systems. Second, while artificial intelligence raises new opportunities in healthcare, its use in contexts of uncertainty should be addressed by policymakers in terms of liability and ethics. Third, conflicts of interest must be disclosed as much as possible and effectively managed to (re) build a trust relationship between policymakers, the scientific community and citizens, implying the need for risk management tools and cross border disclosure mechanisms. Last, well-designed and secure health information systems need to be implemented, following the FAIR (findable, accessible, interoperable and reusable) principles for health data. This will take us a step further from data to 'policy wisdom'.Overall, these recommendations identified and formulated by students highlight some key issues that need to be rethought in the health policy cycle through elements like institutional incentives, cultural changes and dialogue between policy makers and the scientific community. This input from a younger generation of students highlights the importance of making the conversation on evidence-based policy making in health accessible to all generations and backgrounds.

The Impact of Micro RNA-320a Serum Level on Severity of Symptoms and Cerebral Processing of Pain in Patients with Fibromyalgia.

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, <.001, .006, .036 respectively). There were statistically significant positive correlations between micro-RNA-320a levels, and disease duration, FIQR, and NPSI total scores (P-value <0.001, 0.003, 0.002 respectively). There were no statistically significant correlations between micro-RNA-320a levels and middle latency SSEPs. 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.

What do we know about evidence-informed priority setting processes to set population-level health-research agendas: an overview of reviews.

BACKGROUND: This overview aimed to synthesize existing systematic reviews to produce a draft framework of evidence-informed health priority setting that supports countries in identifying appropriate steps and methods when developing and implementing national research agendas. MAIN BODY: We searched Ovid MEDLINE® and the WHO Institutional Repository for Information Sharing from 2010 to 2020 for critical or systematic reviews that evaluated research priority setting exercises. We adapted the AMSTAR checklist to assess the quality of included reviews and used adapted frameworks for data extraction and analysis. The search resulted in 2395 titles, of which 31 were included. Populations included in the reviews typically involved patients, families and carers, researchers, clinicians, policymakers and research funders. The topics covered in the reviews varied from specific diseases or conditions, approaches for healthcare practice or research priority setting methods itself. All the included systematic reviews were of low or critically low quality. The studies were thematically grouped based on their main focus: identifying and engaging with stakeholders; methods; context; and health area. CONCLUSION: Our overview of reviews has reconfirmed aspects of existing frameworks, but has also identified new concepts for countries to consider while developing their national research agendas. We propose a preliminary framework for consideration that highlights four key phases: (1) preparatory, (2) priority setting, (3) follow-up phase and (4) sustainability phase, which have thirteen sub-domains to consider.

PROTOCOL: Conflict of interest issues when engaging stakeholders in health and healthcare guideline development: a systematic review.

This is the protocol for a Campbell systematic review. The overall objective of this study is to gather and summarize the existing literature on conflict of interest issues when engaging stakeholders in guideline development.

Inter-method variability of hepatitis B surface antigen quantification in a cohort of Egyptian patients with chronic hepatitis B virus.

BACKGROUND AND STUDY AIMS: Hepatitis B (HB) surface antigen (HBsAg) levels can predict clinical and treatment outcomes in chronic HB virus (HBV) infection. We aimed to compare the performance of two different assays [Elecsys® (Roche) and Architect™ (Abbott)] for HBsAg quantification and evaluate HBsAg levels in the various immune phases in a cohort of Egyptian patients with chronic HBV. PATIENTS AND METHODS: Quantitative HBsAg by Elecsys® and Architect™ assays, measurement of routine biochemical and serological markers, and transient elastography were performed in 92 patients with chronic HBV. Results of the two assays and other tests were compared. RESULTS: Ninety-two treatment-naive patients with chronic HBV, (70% males; mean age, 36.1 ± 10.5 years) were recruited from Cairo Fatemic Hospital. Patients were categorized as HBeAg positive (n = 22) and HBeAg negative (n = 70). The Architect™ and Elecsys® assays were significantly correlated (intraclass correlation coefficient: 0.913; 95% CI: 0.870-0.943; p < 0.001). However, Deming regression, Passing and Bablok, and Bland-Altman statistical analyses showed discordance among the assays. HBsAg levels by both assays were significantly higher in the HBeAg positive than patients with HBeAg-negative (p = 0.033 and 0.013, respectively). HBsAg levels in the Architect™ and Elecsys® assays were significantly higher in HBeAg-negative chronic hepatitis than in HBeAg-negative chronic infection (p = 0.002 and 0.004, respectively) CONCLUSION: Both assays for qHBsAg were found to be simple and reproducible tests that could classify patients and provide additional evidence on the natural history of HBV.

The Potential of Physical Exercise to Mitigate Radiation Damage-A Systematic Review.

There is a need to investigate new countermeasures against the detrimental effects of ionizing radiation as deep space exploration missions are on the horizon. Objective: In this systematic review, the effects of physical exercise upon ionizing radiation-induced damage were evaluated. Methods: Systematic searches were performed in Medline, Embase, Cochrane library, and the databases from space agencies. Of 2,798 publications that were screened, 22 studies contained relevant data that were further extracted and analyzed. Risk of bias of included studies was assessed. Due to the high level of heterogeneity, meta-analysis was not performed. Five outcome groups were assessed by calculating Hedges' g effect sizes and visualized using effect size plots. Results: Exercise decreased radiation-induced DNA damage, oxidative stress, and inflammation, while increasing antioxidant activity. Although the results were highly heterogeneous, there was evidence for a beneficial effect of exercise in cellular, clinical, and functional outcomes. Conclusions: Out of 72 outcomes, 68 showed a beneficial effect of physical training when exposed to ionizing radiation. As the first study to investigate a potential protective mechanism of physical exercise against radiation effects in a systematic review, the current findings may help inform medical capabilities of human spaceflight and may also be relevant for terrestrial clinical care such as radiation oncology.

Evidence-Based Research Series-Paper 2 : Using an Evidence-Based Research approach before a new study is conducted to ensure value.

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.

Evidence-Based Research Series-Paper 3: Using an Evidence-Based Research approach to place your results into context after the study is performed to ensure usefulness of the conclusion.

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.

Interventions to reduce contaminated aerosols produced during dental procedures for preventing infectious diseases.

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.

Designing clinical trials for future space missions as a pathway to changing how clinical trials are conducted on Earth.

OBJECTIVE: The project aims to build a framework for conducting clinical trials for long-term interplanetary missions to contribute to innovation in clinical trials on Earth, especially around patient involvement and ownership. METHODS: We conducted two workshops in which participants were immersed in the speculative scenario of an interplanetary mission in which health problems emerged that required medical trials to resolve. The workshops used virtual reality and live simulation to mimic a zero-gravity environment and visual perception shifts and were followed by group discussion. RESULTS: Some key aspects for the framework that emerged from the workshops included: (a) approaches to be inclusive in the management of the trial, (b) approaches to be inclusive in designing the research project (patient preference trials, n-of-1 trials, designing clinical trials to be part of a future prospective meta-analysis, etc), (c) balancing the research needs and the community needs (eg, allocation of the participants based on both research and community need), (d) ethics and partnerships (ethics and consent issues and how they relate to partnerships and relationships). CONCLUSION: In identifying some key areas that need to be incorporated in future planning of clinical trials for interplanetary missions, we also identified areas that are relevant to engaging patients in clinical trials on Earth. We will suggest using the same methodology to facilitate more in-depth discussions on specific aspects of clinical trials in aerospace medicine. The methodology can be more widely used in other areas to open new inclusive conversations around innovating research methodology.

Overexpression of Serum Micro-RNA 152-3p in Type 2 Diabetes Mellitus with a Significant Elevation in Progressive Nephropathy.

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) (P<0.001), 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.

Circulating microRNAs (miR-21, miR-223, miR-885-5p) along the clinical spectrum of HCV-related chronic liver disease in Egyptian patients.

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.