The Persisting Burden of Intracerebral Haemorrhage: Can Effective Treatments Be Found?

Colin Josephson, Rustam Al-Shahi Salman, and colleagues discuss the effectiveness of treatments for intracerebral haemorrhage

Increased personal protective equipment litter as a result of COVID-19 measures

Use of personal protective equipment (PPE) increased during the COVID-19 pandemic to reduce virus transmission. Here, we quantitatively analyse emergence of PPE and COVID-19-related litter over 14 months for 11 countries using the litter collection application Litterati. The proportion of masks in litter increased by &gt;80-fold as a result of COVID-19 legislation, from &lt;0.01% to &gt;0.8%. Gloves and wipes, more prevalent at ~0.2% of litter before the pandemic, doubled to 0.4%, but this has since fallen. Glove litter increased in the initial stages of the pandemic but fell after the introduction of facemask policies, whereupon there was an increase of facemask litter. National COVID-19 policy responses and international World Health Organization announcements and recommendations are a probable driver of PPE litter dynamics, especially the implementation of facemask policies. Waste management should be incorporated in designing future pandemic policies to avoid negative environmental legacies of mismanaged PPE.</p

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement1, increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively2,3. Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement4. Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2,3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury