Effect of Nebulized BromAc on Rheology of Artificial Sputum: Relevance to Muco-Obstructive Respiratory Diseases.

Respiratory diseases such as cystic fibrosis, COPD, and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Earlier studies have shown success with BromAc as a mucolytic agent. Hence, we tested the formulation on two gelatinous airway representative sputa models, to determine whether similar efficacy exist. Sputum lodged in an endotracheal tube was treated to aerosol N-acetylcysteine, bromelain, or their combination (BromAc). After measuring the particle size of aerosolized BromAc, the apparent viscosity was measured using a capillary tube method, whilst the sputum flow was assessed using a 0.5 mL pipette. Further, the concentration of the agents in the sputa after treatment were quantified using chromogenic assays. The interaction index of the different formulations was also determined. Results indicated that the mean particle size of BromAc was suitable for aerosol delivery. Bromelain and N-acetylcysteine affected both the viscosities and pipette flow in the two sputa models. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, a correlation was found between the rheological effects and the concentration of agents in the sputa. The combination index using viscosity measurements showed synergy only with 250 µg/mL bromelain + 20 mg/mL NAC whilst flow speed showed synergy for both combinations of bromelain (125 and 250 µg/mL) with 20 mg/mL NAC. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretions.

Geopolitical shift at a time of Covid-19 and the Asian Infrastructure Investment Bank: A case study of Chinese innovation in multilateralism

How China will contribute to global governance has become a critical question in international relations, amplified by the linkages between the Covid-19 pandemic, escalating geopolitical contest and multilateralism in crisis. China has been doubling down on its authoritarian model of domestic governance while becoming more internationally assertive, including in existing and new multilateral institutions. Meanwhile, the United States appeared in recent years to be undermining the institutions, norms and rules of the liberal international order that it, itself, built. The subsequent decline in international cooperation poses grave risks to public health, economic and other forms of security. Can China cooperate with other actors to contribute public goods and stabilisation of global governance in such a deteriorating international environment? While there is a wide range of institutions in which to examine China's growing role in international governance, from United Nations bodies such as the World Health Organisation and World Trade Organisation to regional initiatives such as the Regional Comprehensive Economic Partnership, this paper examines the Asian Infrastructure Investment Bank (AIIB), an example of Chinese innovation in multilateralism. Established amidst geopolitical contest, the new institution seeks to address the Asian deficit of financing for sustainable development. The bank challenges a number of prevailing norms, including replacing the disproportionate power of the US and the advanced economies in the multilateral system with a more proportionate role for China and other developing countries;a new focus on infrastructure-led development which is built on Chinese confidence in the East Asian development model;and a shift away from the Bretton Woods practices of using financing conditions to drive liberal democratic and neo-liberal economic reforms. At the same time as representing a challenge to the traditional order, the bank exhibits – at least to date – best practices in implementation and addresses previously unmet concerns of the developing world. While it is not possible to extrapolate from only one initiative to draw comprehensive conclusions about China's likely future role in global governance, the AIIB case nonetheless suggests that, at least in some fields, China will challenge liberal norms to reform rather than revolutionise the international order.

Peritoneal Oxygenation as a Novel Technique for Extrapulmonary Ventilation; A Review and Discussion of the Literature.

The COVID-19 crisis has highlighted the difficulties that might occur when attempting to oxygenate patients who have suffered a severe pulmonary insult, including in the development of acute respiratory distress syndrome (ARDS). Traditional mechanical ventilation (MV) is effective; however, in severe cases of hypoxia, the use of rescue therapy, such as extracorporeal membrane oxygenation (ECMO), may be required but is also associated with significant complexity and complications. In this review, we describe peritoneal oxygenation; a method of oxygenation that exploits the peritoneum's gas exchange properties in a fashion that is similar to peritoneal dialysis and has shown considerable promise in animal models. We have conducted a review of the available literature and techniques, including intraperitoneal perfluorocarbons, intraperitoneal jet ventilation, a continuous low-pressure oxygen system (PEROX) and the use of phospholipid-coated oxygen microbubbles (OMBs) through peritoneal microbubble oxygenation (PMO). We conclude that peritoneal oxygenation is a promising technique that warrants further investigation and might be used in clinical settings in the future.

COVID-19 and systemic lupus erythematosus genetics: A balance between autoimmune disease risk and protection against infection.

Genome wide association studies show there is a genetic component to severe COVID-19. We find evidence that the genome-wide genetic association signal with severe COVID-19 is correlated with that of systemic lupus erythematosus (SLE), having formally tested this using genetic correlation analysis by LD score regression. To identify the shared associated loci and gain insight into the shared genetic effects, using summary level data we performed meta-analyses, a local genetic correlation analysis and fine-mapping using stepwise regression and functional annotation. This identified multiple loci shared between the two traits, some of which exert opposing effects. The locus with most evidence of shared association is TYK2, a gene critical to the type I interferon pathway, where the local genetic correlation is negative. Another shared locus is CLEC1A, where the direction of effects is aligned, that encodes a lectin involved in cell signaling, and the anti-fungal immune response. Our analyses suggest that several loci with reciprocal effects between the two traits have a role in the defense response pathway, adding to the evidence that SLE risk alleles are protective against infection.

Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19.

COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC). Both drugs present mucolytic effect and have been studied to treat COVID-19. Therefore, we sought to examine the mucolytic and anti-inflammatory effect of BromAc® in tracheal aspirate samples from critically ill COVID-19 patients requiring mechanical ventilation. METHOD: Tracheal aspirate samples from COVID-19 patients were collected following next of kin consent and mucolysis, rheometry and cytokine analysis using Luminex kit was performed. RESULTS: BromAc® displayed a robust mucolytic effect in a dose dependent manner on COVID-19 sputum ex vivo. BromAc® showed anti-inflammatory activity, reducing the action of cytokine storm, chemokines including MIP-1alpha, CXCL8, MIP-1b, MCP-1 and IP-10, and regulatory cytokines IL-5, IL-10, IL-13 IL-1Ra and total reduction for IL-9 compared to NAC alone and control. BromAc® acted on IL-6, demonstrating a reduction in G-CSF and VEGF-D at concentrations of 125 and 250 µg. CONCLUSION: These results indicate robust mucolytic and anti-inflammatory effect of BromAc® ex vivo in tracheal aspirates from critically ill COVID-19 patients, indicating its potential to be further assessed as pharmacological treatment for COVID-19.

Polarization, partisanship, and pandemic: The relationship between county-level support for Donald Trump and the spread of Covid-19 during the spring and summer of 2020.

OBJECTIVE: Republicans and Democrats have displayed widely divergent beliefs and behaviors related to COVID-19, creating the possibility that geographic areas with more Donald Trump supporters may be more likely to suffer from the disease. METHODS: I use 2016 election data, COVID-19 case and mortality data, and multilevel linear growth models with state fixed effects to estimate the relationship between county-level support for Donald Trump and the trajectory of cumulative COVID-19 cases and deaths per 100,000 county residents between March 17, 2020 and August 31, 2020. RESULTS: Counties more supportive of Trump had fewer COVID-19 cases and deaths in the early months of the pandemic. However, as the summer moved into July and August, counties less supportive of Trump stopped growth rates of COVID-19 cases and deaths, while counties more supportive of Trump saw a trajectory of increased cases and deaths in July and August. This is likely due to the widely divergent beliefs and behaviors displayed by Republicans and Democrats toward COVID-19. CONCLUSION: This study underscores the power of polarization and partisanship in the public sphere, even when it comes to a public health issue.

Study protocol for resolution of organ injury in acute pancreatitis (RESORP): an observational prospective cohort study.

INTRODUCTION: Survivors of acute pancreatitis (AP) have shorter overall survival and increased incidence of new-onset cardiovascular, respiratory, liver and renal disease, diabetes mellitus and cancer compared with the general population, but the mechanisms that explain this are yet to be elucidated. Our aim is to characterise the precise nature and extent of organ dysfunction following an episode of AP. METHODS AND ANALYSIS: This is an observational prospective cohort study in a single centre comprising a University hospital with an acute and emergency receiving unit and clinical research facility. Participants will be adult patient admitted with AP. Participants will undergo assessment at recruitment, 3 months and 3 years. At each time point, multiple biochemical and/or physiological assessments to measure cardiovascular, respiratory, liver, renal and cognitive function, diabetes mellitus and quality of life. Recruitment was from 30 November 2017 to 31 May 2020; last follow-up measurements is due on 31 May 2023. The primary outcome measure is the incidence of new-onset type 3c diabetes mellitus during follow-up. Secondary outcome measures include: quality of life analyses (SF-36, Gastrointestinal Quality of Life Index); montreal cognitive assessment; organ system physiological performance; multiomics predictors of AP severity, detection of premature cellular senescence. In a nested cohort within the main cohort, individuals may also consent to multiparameter MRI scan, echocardiography, pulmonary function testing, cardiopulmonary exercise testing and pulse-wave analysis. ETHICS AND DISSEMINATION: This study has received the following approvals: UK IRAS Number 178615; South-east Scotland Research Ethics Committee number 16/SS/0065. Results will be made available to AP survivors, caregivers, funders and other researchers. Publications will be open-access. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov Registry (NCT03342716) and ISRCTN50581876; Pre-results.

The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.

Occupational risk prevention, education and support in black, Asian and ethnic minority health worker in the COVID-19 pandemic

The onset of the COVID-19 in the UK has resulted in an inordinate amount of deaths affecting Black, Asian and Ethnic Minority (BAME) healthcare workers. The occupational risk to this group is thought to be a contributory factor, but other factors include race, genetics, medical co-morbidities, socio-economic status, and access to personal protection equipment. Why COVID-19 appears to be more deadly in BAME members remains unknown, but the UK government is investigating this now. It does appear that certain factors may worsen the disease process in BAME members, but which ones are pertinent to prevention remain to be determined, until a vaccine is available. Thus, the onus should rest on risk prevention, education, and support for all.Some of the safety strategies that may be instituted to help guide those in the workplace include education, treating potential therapeutic targets and ensuring protection in the working environment. The consideration of a compensation scheme, for families of healthcare workers that have suffered because of COVID-19, would go some way to support the recovery process.

Impact of lockdown measures implemented during the Covid-19 pandemic on the burden of trauma presentations to a regional emergency department in Kwa-Zulu Natal, South Africa.

INTRODUCTION: The Covid-19 pandemic triggered unprecedented nationwide regulations aimed primarily at slowing the spread of the virus. The objective of this study was to describe the effect of these regulations on the number and severity of trauma presentations to a regional emergency department in Kwa-Zulu Natal. METHODS: A retrospective cohort study of the triage register at Edendale Hospital Emergency Department was conducted, comparing all trauma presentations in the month of April 2020 with those from the preceding two years. The number of patients, mechanism of trauma and severity of illness were recorded and compared. RESULTS: A 47% reduction in the number of trauma cases was recorded for April 2020. The proportion of severe cases did not change. The categories showing a major decrease were motor vehicle accidents, pedestrian vehicle accidents, assault and gunshot wounds. The incidence of dog bite wounds and burns remained unchanged. CONCLUSION: This study shows that the burden of trauma presenting to the emergency department was decreased in the month of April 2020 by the regulations implemented in response to the Covid-19 pandemic.