Key Clinical Points Evaluation and Management of Severe Covid-19 Patients with severe coronavirus disease 2019 (Covid-19) may become critically ill with acute respiratory distress syndrome that typ...

https://www.nejm.org/doi/pdf/10.1056/NEJMcp2009575?articleTools=true

Severe Covid-19

Clinical pathways are optimal patient care processes that have been developed to improve the quality of care for patients. Anecdotal evidence has suggested that patients presenting to the healthcar...

Using the modified delphi method to establish clinical consensus for the diagnosis and treatment of patients with rotator cuff pathology

Proteins span an extraordinary range of shapes, sizes and functionalities. Therefore generic approaches are needed to overcome this diversity and stream-line protein analysis or application. Here we review SpyTag technology, now used in hundreds of publications or patents, and its potential for detecting and controlling protein behaviour. SpyTag forms a spontaneous and irreversible isopeptide bond upon binding its protein partner SpyCatcher, where both parts are genetically-encoded. New variants of this pair allow reaction at a rate approaching the diffusion limit, while reversible versions allow purification of SpyTagged proteins or tuned dynamic interaction inside cells. Anchoring of SpyTag-linked proteins has been established to diverse nanoparticles or surfaces, including gold, graphene and the air/water interface. SpyTag/SpyCatcher is mechanically stable, so is widely used for investigating protein folding and force sensitivity. A toolbox of scaffolds allows SpyTag-fusions to be assembled into defined multimers, from dimers to 180-mers, or unlimited 1D, 2D or 3D networks. Icosahedral multimers are being evaluated for vaccination against malaria, HIV and cancer. For enzymes, Spy technology has increased resilience, promoted substrate channelling, and assembled hydrogels for continuous flow biocatalysis. Combinatorial increase in functionality has been achieved through modular derivatisation of antibodies, light-emitting diodes or viral vectors. In living cells, SpyTag allowed imaging of protein trafficking, retargeting of CAR-T cell killing, investigation of heart contraction, and control of nucleosome position. The simple genetic encoding and rapid irreversible reaction provide diverse opportunities to enhance protein function. We describe limitations as well as future directions.

/pdf/power-to-the-protein-enhancing-and-combining-activities-5eovmn72xp.pdf

Power to the protein: enhancing and combining activities using the Spy toolbox.

Respirable aerosols ( 5 µm) precautions at other times. However, emerging evidence indicates respiratory activities may be a more important source of aerosols than clinical procedures such as tracheal intubation. We aimed to measure the size, total number and volume of all human aerosols exhaled during respiratory activities and therapies. We used a novel chamber with an optical particle counter sampling at 100 l.min-1 to count and size-fractionate close to all exhaled particles (0.5-25 µm). We compared emissions from ten healthy subjects during six respiratory activities (quiet breathing; talking; shouting; forced expiratory manoeuvres; exercise; and coughing) with three respiratory therapies (high-flow nasal oxygen and single or dual circuit non-invasive positive pressure ventilation). Activities were repeated while wearing facemasks. When compared with quiet breathing, exertional respiratory activities increased particle counts 34.6-fold during talking and 370.8-fold during coughing (p < 0.001). High-flow nasal oxygen 60 at l.min-1 increased particle counts 2.3-fold (p = 0.031) during quiet breathing. Single and dual circuit non-invasive respiratory therapy at 25/10 cm.H2 O with quiet breathing increased counts by 2.6-fold and 7.8-fold, respectively (both p < 0.001). During exertional activities, respiratory therapies and facemasks reduced emissions compared with activities alone. Respiratory activities (including exertional breathing and coughing) which mimic respiratory patterns during illness generate substantially more aerosols than non-invasive respiratory therapies, which conversely can reduce total emissions. We argue the risk of aerosol exposure is underappreciated and warrants widespread, targeted interventions.

https://associationofanaesthetists-publications.onlinelibrary.wiley.com/doi/pdf/10.1111/anae.15475

The effect of respiratory activity, non-invasive respiratory support and facemasks on aerosol generation and its relevance to COVID-19.

Aerosol generating procedures: are they of relevance for transmission of SARS-CoV-2?

In the context of covid-19, aerosol generating procedures have been highlighted as requiring a higher grade of personal protective equipment. We investigated how official guidance documents and academic publications have classified procedures in terms of whether or not they are aerosol-generating. We performed a rapid systematic review using preferred reporting items for systematic reviews and meta-analyses standards. Guidelines, policy documents and academic papers published in english or french offering guidance on aerosol-generating procedures were eligible. We systematically searched two medical databases (medline, cochrane central) and one public search engine (google) in march and april 2020. Data on how each procedure was classified by each source were extracted. We determined the level of agreement across different guidelines for each procedure group, in terms of its classification as aerosol generating, possibly aerosol-generating, or nonaerosol-generating. 128 documents met our inclusion criteria; they contained 1248 mentions of procedures that we categorised into 39 procedure groups. Procedures classified as aerosol-generating or possibly aerosol-generating by ≥90% of documents included autopsy, surgery/postmortem procedures with high-speed devices, intubation and extubation procedures, bronchoscopy, sputum induction, manual ventilation, airway suctioning, cardiopulmonary resuscitation, tracheostomy and tracheostomy procedures, non-invasive ventilation, high-flow oxygen therapy, breaking closed ventilation systems, nebulised or aerosol therapy, and high frequency oscillatory ventilation. Disagreements existed between sources on some procedure groups, including oral and dental procedures, upper gastrointestinal endoscopy, thoracic surgery and procedures, and nasopharyngeal and oropharyngeal swabbing. There is sufficient evidence of agreement across different international guidelines to classify certain procedure groups as aerosol generating. However, some clinically relevant procedures received surprisingly little mention in our source documents. To reduce dissent on the remainder, we recommend that (a) clinicians define procedures more clearly and specifically, breaking them down into their constituent components where possible; (b) researchers undertake further studies of aerosolisation during these procedures; and (c) guideline-making and policy-making bodies address a wider range of procedures.

https://bmjopenrespres.bmj.com/content/bmjresp/7/1/e000730.full.pdf

Classification of aerosol-generating procedures: a rapid systematic review.

Most UK medical schools have postponed clinical teaching because of the covid-19 pandemic, leaving students, who would usually be busy with exam preparations and clinical commitments, with time off. Some students might find a long period of unstructured study daunting. In this article, we share our thoughts and experiences on how you might use this time positively by continuing learning and professional development and helping the national efforts in dealing with covid-19 (box 1).

Box 1 
### Tips for using time positively during the covid-19 pandemic

#### Exam preparation

#### Preparing for practice

#### Career development

#### Look out for others

#### Look after yourselfRETURN TO TEXT

### Improve your learning strategies and prepare educational resources

Medicine involves lifelong learning, so find effective study strategies that work for you. With the pressures of upcoming exams and a seemingly endless amount to learn, it is tempting to rote learn topics, but this will give you only a superficial grasp of them.1 Use this time to develop more effective learning strategies that support long term knowledge retention. Strategies might include:

Following your medical school’s curriculum will ensure you cover the right topics.

You can commit …

https://www.bmj.com/content/bmj/369/bmj.m1489.full.pdf

Covid-19: how to use your time when clinical placements are postponed.

Dose-response experiments are a mainstay of receptor biology studies and can reveal valuable insights into receptor function. Such studies of receptors that bind cell surface ligands are currently limited by the difficulty in manipulating the surface density of ligands at a cell-cell interface. Here, we describe a generic cell surface ligand system that allows precise manipulation of cell surface ligand densities over several orders of magnitude. These densities are robustly quantifiable, a major advance over previous studies. We validate the system for a range of immunoreceptors, including the T-cell receptor (TCR), and show that this generic ligand stimulates via the TCR at a similar surface density as its native ligand. We also extend our work to the activation of chimeric antigen receptors. This novel system allows the effect of varying the surface density, valency, dimensions, and affinity of the ligand to be investigated. It can be readily broadened to other receptor-cell surface ligand interactions and will facilitate investigation into the activation of, and signal integration between, cell surface receptors.

/pdf/a-generic-cell-surface-ligand-system-for-studying-cell-cell-1o6txlswf2.pdf

A generic cell surface ligand system for studying cell-cell recognition.

Dose-response experiments are a mainstay of receptor biology studies and can reveal valuable insights into receptor function. Such studies of receptors that bind cell surface ligands are currently limited by the difficulty in manipulating the surface density of ligands at a cell-cell interface. Here we describe a generic cell surface ligand system that allows precise manipulation of cell surface ligand densities over several orders of magnitude. We validate the system for a range of immunoreceptors, including the T cell receptor (TCR), and show that this generic ligand stimulates via the TCR at a similar surface density as its native ligand. This system allows the effect of surface density, valency, dimensions, and affinity of the ligand to be manipulated. It can be readily extended to other receptor-cell surface ligand interactions, and will facilitate investigation into the activation of, and signal integration between, cell surface receptors.

/pdf/a-generic-cell-surface-ligand-system-for-studying-cell-cell-59e4at820o.pdf

A generic cell surface ligand system for studying cell-cell recognition

/pdf/you-re-a-girl-you-re-black-you-re-poor-dorothy-lavinia-brown-2ayawyfb6u.pdf

Susannah M Black

Papers

Classification of aerosol-generating procedures: a rapid systematic review.

Covid-19: how to use your time when clinical placements are postponed.

A generic cell surface ligand system for studying cell-cell recognition.

A generic cell surface ligand system for studying cell-cell recognition

‘You’re a girl, You’re Black, You’re poor’: Dorothy Lavinia Brown: Challenging inequality in surgery