Mucoadhesion across scales: Towards the design of protein-based adhesives

Mucoadhesion is a special case of bioadhesion in which a material adheres to soft mucosal tissues. This review elucidates our current understanding of mucoadhesion across length, time, and energy scales by focusing on relevant structural features of mucus. We highlight the importance of both covalent and non-covalent interactions that can be tailored to maximize mucoadhesive interactions, particularly concerning proteinaceous mucoadhesives, which have been explored only to a limited extent so far in the literature. In particular, we highlight the importance of thiol groups, hydrophobic moieties, and charged species inherent to proteins as key levers to fine tune mucoadhesive performance. Some aspects of protein surface modification by grafting specific functional groups or coupling with polysaccharides to influence mucoadhesive performance are examined. Insights from this review offer a physicochemical roadmap to inform the development of biocompatible, protein-based mucoadhesive systems that can fulfil dual roles for both adhesion and delivery of actives, enabling the fabrication of advanced biomedical, nutritional and allied soft material technologies

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Changes in coral reef communities and an associated reef fish species, Cephalopholis cruentata (Lacépède), after 30 years on Curaçao (Netherlands Antilles)

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Some like it cold: microbial transformations of mercury in polar regions

The contamination of polar regions with mercury that is transported from lower latitudes as inorganic mercury has resulted in the accumulation of methylmercury (MeHg) in food chains, risking the health of humans and wildlife. While production of MeHg has been documented in polar marine and terrestrial environments, little is known about the responsible transformations and transport pathways and the processes that control them. We posit that as in temperate environments, microbial transformations play a key role in mercury geochemical cycling in polar regions by: (1) methylating mercury by one of four proposed pathways, some not previously described; (2) degrading MeHg by activities of mercury resistant and other bacteria; and (3) carrying out redox transformations that control the supply of the mercuric ion, the substrate of methylation reactions. Recent analyses have identified a high potential for mercury-resistant microbes that express the enzyme mercuric reductase to affect the production of gaseous elemental mercury when and where daylight is limited. The integration of microbially mediated processes in the paradigms that describe mercury geochemical cycling is therefore of high priority especially in light of concerns regarding the effect of global warming and permafrost thawing on input of MeHg to polar regions

Moving beyond binary opposition: exploring the tapestry of gender in consumer research and marketing

The last two decades have seen an exponential growth in research pertaining to gender issues in marketing and consumer research. This special issue of Marketing Theory, together with the ongoing Association for Consumer Research Gender, Marketing and Consumer Research conference series, now approaching its tenth iteration, demonstrates the continued interest in gender issues in our disciplines. Introducing the special issue, this paper’s remit is threefold: it maps the substantive and theoretical developments of gender research within our discipline; it locates this work on gender within its broader context in humanities and social science; and it introduces the reader to the four papers in this special issue. The paper concludes that gender research has moved from the margins to become a strong body of work within marketing and consumer research. That said, there remains substantive opportunity for further development, where gender and feminist research can offer new insights, critiques, theories and approaches