Rejected

Sudden cardiac arrest is one of the leading causes of death in Europe and the whole world. Effective chest compressions and advanced airway management have been shown to improve survival rates. Supraglottic airway devices such as the laryngeal tube (LT) are a well-known strategy for patients with cardiac arrest during both Basic (BLS) and Advanced Life Support (ALS). This systematic literature review aims to summarize current data for using the LT when performing BLS and ALS.

Procedural sedation is a core skill of the emergency physician. Bolus administration of propofol is widely used in UK EDs. Titrated to an end point of sedation, it has a rapid effect but has been associated with adverse incidents. The use of a target-controlled infusion (TCI) of propofol is not routine but may reduce the incidence of adverse incidents.The primary aims of this single-arm feasibility study were patient satisfaction and to establish recruitment rates for a randomised controlled trial comparing propofol TCI to bolus administration.

Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that reduces HIV-1 infectivity by an incompletely understood mechanism. We show here that viruses differing only in the envelope glycoprotein (Env) expressed on their surface have different sensitivities to IFITM3. Measurements of the sensitivity of viruses to neutralizing antibodies showed that IFITM3 increased the sensitivity of IFITM3-sensitive viruses to PG16, which targets the V1V2 loop, suggesting that IFITM3 promotes exposure of the PG16 epitope of IFITM3-sensitive viruses. Exchanges of V1V2 loops between the Env proteins of sensitive and resistant viruses revealed that V1V2 and V3 act together to modulate viral sensitivity to IFITM3. Co-immunoprecipitation experiments showed that IFITM3 interacted with both the precursor (gp160) and cleaved (gp120) forms of Env from IFITM3-sensitive viruses, but only with the precursor (gp160) form of Env from IFITM3-resistant viruses. This finding suggests that the interaction between the Env of resistant viruses and IFITM3 was inhibited once Env had been processed in the Golgi apparatus. This hypothesis was supported by immunofluorescence experiments, which showed a strong colocalization of IFITM3 with the Env of sensitive viruses, but only weak colocalization with the Env of resistant viruses on the plasma membrane of virus-producing cells. Together, these results indicate that IFITM3 interacts with Env, inducing conformational changes that may decrease viral infectivity. This antiviral action is, nevertheless, modulated by the nature of the Env, in particular its V1V2 and V3 loops, which after maturation may be able to escape this interaction. Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that reduces HIV-1 infectivity by an incompletely understood mechanism. This study aimed to elucidate the role of the HIV-1 envelope glycoprotein (Env) in determining viral susceptibility to IFITM3. We found that viruses differing only in Env expressed on their surface had different sensitivities to IFITM3. By comparing the Env proteins of viruses that were highly sensitive or resistant to IFITM3, we obtained new insight in the mechanisms by which HIV-1 escapes this protein. We showed that IFITM3 interacts with the Env protein of sensitive viruses in virion-producing cells, inducing conformational changes that may decrease viral infectivity. However, this antiviral action is modulated by the nature of Env, particularly the V1V2 and V3 loops, which may be able to escape this interaction after processing in the Golgi.

An 11-year-old boy presented with features resembling those described in health alerts on Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), including persistent fever, haemodynamic instability and abdominal pain. Laboratory tests, including raised inflammatory markers, D-dimer, troponin and a coagulopathy, were consistent with PIMS-TS. Our patient required transfer to the paediatric intensive care unit; an echocardiography revealed left ventricular dysfunction. He was treated with intravenous immunoglobulins (Igs), corticosteroids and aspirin, with full resolution of clinical symptoms. A follow-up echocardiogram 1 month after discharge was unremarkable.Three SARS-CoV-2 PCRs on respiratory samples, taken over the initial 4-day period, were negative, as was a SARS-CoV-2 PCR on faeces 1 month after presentation; titres of IgG were clearly elevated. The negative PCRs in the presence of elevated titres of IgG suggest that the inflammatory syndrome might have developed in a late phase of COVID-19 infection when the virus was no longer detectable in the upper airway.

Botulinum toxin type A (BTX-A) was considered to be a new potential drug for neuropathic pain (NP) treatment.

The peak of the global COVID-19 pandemic has not yet been reached, and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seem to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19.

Primary cardiac neoplasms are extremely rare, with an autopsy incidence of 0.0001-0.003%. Primary cardiac sarcoma is usually derived from the right atrium and it manifests as chest pain, arrhythmia, hemoptysis, dyspnea, and fatigue. The most common target organ for metastasis of primary angiosarcoma is the lungs, but the radiological-pathological correlation has been rarely reported.

1) to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases ("comorbid-FMDs"); 2) to compare comorbid-FMDs to FMDs not overlapping with other neurological diseases ("pure FMDs").

Orthostatic intolerance (OI) is a common manifestation of autonomic dysfunction. It is characterized by light-headedness and palpitations in the upright position, with relief when supine. It can affect the quality of life. Other symptoms that may accompany OI include headache, fatigue, nausea, palpitations and abdominal pain. The prevalence and characteristics of autonomic symptoms in childhood hypersomnia disorders of childhood has not been examined, and hence were studied.

Extracellular vesicles (EVs) have been implicated mechanistically in the pathobiology of neurodegenerative disorders, including central nervous system injury. However, the role of EVs in spinal cord injury (SCI) has received limited attention to date. Moreover, technical limitations related to EV isolation and characterization methods can lead to misleading or contradictory findings. Here, we examined changes in plasma EVs after mouse SCI at multiple timepoints (1d, 3d, 7d, 14d) using complementary measurement techniques. Plasma EVs isolated by ultracentrifugation (UC) were decreased at 1d post-injury, as shown by nanoparticle tracking analysis (NTA) and paralleled an overall reduction in total plasma extracellular nanoparticles. Western blot (WB) analysis of UC-derived plasma EVs revealed increased expression of the tetraspanin exosome marker, CD81, between 1d and 7d post-injury. To substantiate these findings, we performed interferometric and fluorescence imaging of single, tetraspanin EVs captured directly from plasma with ExoView®. Consistent with WB, we observed significantly increased plasma CD81+ EV count and cargo at 1d post-injury. The majority of these tetraspanin EVs were smaller than 50nm based on interferometry and were insufficiently resolved by flow cytometry-based detection. At the injury site, there was enhanced expression of EV biogenesis proteins that were also detected in EVs directly isolated from spinal cord tissue by WB. Surface expression of tetraspanins CD9 and CD63 increased in multiple cell types at the injury site; however, astrocyte CD81 expression uniquely decreased, as demonstrated by flow cytometry. UC-isolated plasma EV microRNA cargo was also significantly altered at 1d post-injury, with changes similar to that reported in EVs released by astrocytes after inflammatory stimulation. When injected into the lateral ventricle, plasma EVs from SCI mice increased both pro- and anti-inflammatory gene as well as reactive astrocyte gene expression in brain cortex. These studies provide the first detailed characterization of plasma EV dynamics after SCI and suggest that plasma EVs may be involved in posttraumatic brain inflammation.