Effects of withdrawal of life-sustaining therapy on long-term neurological outcome after cardiac arrest - A multicentre matched cohort study.

Purpose: To assess the risk of self-fulfilling prophecy from withdrawal of life-sustaining therapy (WLST) in comatose cardiac arrest patients undergoing neuroprognostication.

Methods: Post-hoc multicentre study matching adults resuscitated from out-of-hospital cardiac arrests, in WLST-permitting cohorts (TTM and TTM2), and non-WLST-permitting cohorts (KORHN and ProNeCA). We matched patients in a 1:1 ratio based on a propensity score, assessing the risk of WLST due to a presumed poor neurological prognosis and criteria predictive of poor neurological outcome, as outlined in the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) guidelines.

Prediction of good functional outcome decreases diagnostic uncertainty in unconscious survivors after out-of-hospital cardiac arrest.

Purpose: To explore modifications of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) guideline algorithm for neuroprognostication after cardiac arrest to improve its prognostic accuracy.

Methods: Post-hoc analysis of four prospective multicentre studies (TTM, TTM2, KORHN and ProNeCA). We raised the Glasgow Coma Scale motor (GCS-M) inclusion threshold at 72 h after cardiac arrest from the current GCS-M < 4 to GCS-M < 6 (all unconscious patients).

CapBuild: a cloud-native tool for adeno-associated virus capsid engineering.

Adeno-associated virus (AAV) capsid engineering is essential for advancing gene therapy but remains limited by structural complexity and computational constraints. To address these challenges, we developed CapBuild, a cloud-native web server that streamlines AAV capsid prediction, assembly and engineering. CapBuild provides two distinct workflows: a PDB-based pipeline for assembling complete capsids from structural files and a modelling pipeline that constructs capsids from protein sequences via SWISS-MODEL.

-Sulfonylphenoxazines as neuronal calcium ion channel blockers.

Neuropathic pain is a type of chronic pain, usually caused by nerve damage, that responds poorly to traditional pain therapies. The N-type calcium channel (Ca2.2) is a well-validated pharmacological target to treat this condition.

[Extracorporeal cardiopulmonary resuscitation in out-of-hospital resuscitation].

If an out-of-hospital cardiac arrest (OHCA) takes longer than 15 minutes, the chances of survival are greatly reduced. With a shockable rhythm (VF/VT), there is often a treatable underlying cause, which most often can only be treated in a hospital. The patient can be transported, and circulation can be restored in the hospital, using extracorporeal cardiopulmonary resuscitation (ECPR) to gain time to treat the underlying problem.

Hypothermic versus Normothermic Temperature Control after Cardiac Arrest.

BACKGROUND: The evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics. METHODS: An individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted.

Brain death/death by neurologic criteria determination: an update.

Purpose Of Review: Brain death, also known as death by neurologic criteria (DNC), is a well-established concept. In this article, we present a short history of the concept and give an overview of recent changes and a practical update on diagnosis and definitions of brain death/DNC. Unresolved issues will be discussed.

Data-driven platform for identifying variants of interest in COVID-19 virus.

New SARS-CoV-2 variants emerge as part of the virus' adaptation to the human host. The Health Organizations are monitoring newly emerging variants with suspected impact on disease or vaccination efficacy as Variants Being Monitored (VBM), like Delta and Omicron. Genetic changes (SNVs) compared to the Wuhan variant characterize VBMs with current emphasis on the spike protein and lineage markers.

At Least Three Doses of Leading Vaccines Essential for Neutralisation of SARS-CoV-2 Omicron Variant.

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints.

Inhibition of N-type calcium ion channels by tricyclic antidepressants - experimental and theoretical justification for their use for neuropathic pain.

A number of tricyclic antidepressants (TCAs) are commonly prescribed off-label for the treatment of neuropathic pain. The blockade of neuronal calcium ion channels is often invoked to partially explain the analgesic activity of TCAs, but there has been very limited experimental or theoretical evidence reported to support this assertion. The N-type calcium ion channel (Ca2.

"But Mouse, You Are Not Alone": On Some Severe Acute Respiratory Syndrome Coronavirus 2 Variants Infecting Mice.

In silico predictions combined with in vitro, in vivo, and in situ observations collectively suggest that mouse adaptation of the severe acute respiratory syndrome 2 virus requires an aromatic substitution in position 501 or position 498 (but not both) of the spike protein's receptor binding domain. This effect could be enhanced by mutations in positions 417, 484, and 493 (especially K417N, E484K, Q493K, and Q493R), and to a lesser extent by mutations in positions 486 and 499 (such as F486L and P499T). Such enhancements, due to more favorable binding interactions with residues on the complementary angiotensin-converting enzyme 2 interface, are, however, unlikely to sustain mouse infectivity on their own based on theoretical and experimental evidence to date.

Caregiver burden and health-related quality of life amongst caregivers of out-of-hospital cardiac arrest survivors.

Aims: To describe burden and health-related quality of life amongst caregivers of out-of-hospital cardiac arrest survivors and explore the potential association with cognitive function of the survivors. Caregivers of patients with ST-elevation myocardial infarction were used as controls.

Methods: Data were collected from the cognitive substudy of the Targeted Temperature Management-trial.

Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets.

The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These "variants-of-concern" have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively.

The Impact of Nursing Delirium Preventive Interventions in the ICU: A Multicenter Cluster-randomized Controlled Clinical Trial.

Delirium is common in critically ill patients and is associated with deleterious outcomes. Nonpharmacological interventions are recommended in current delirium guidelines, but their effects have not been unequivocally established. To determine the effects of a multicomponent nursing intervention program on delirium in the ICU.

Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein.

The 'D614G' mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation.

Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients.

Objective: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations.

[How does a doctor declare death?].

Ward doctors in regular medical departments have to be competent in declaring the death of a patient. The majority of literature on confirmation of death focuses on special circumstances, including intensive care patients and cases involving organ donation. There is no consensus regarding the procedure and criteria for declaration of death in a 'normal' patient on a medical ward.

Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial-Rationale and design.

Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted.

The structure of the PA28-20S proteasome complex from Plasmodium falciparum and implications for proteostasis.

The activity of the proteasome 20S catalytic core is regulated by protein complexes that bind to one or both ends. The PA28 regulator stimulates 20S proteasome peptidase activity in vitro, but its role in vivo remains unclear. Here, we show that genetic deletion of the PA28 regulator from Plasmodium falciparum (Pf) renders malaria parasites more sensitive to the antimalarial drug dihydroartemisinin, indicating that PA28 may play a role in protection against proteotoxic stress.