To uncover clinical characteristics leading to false outcome prediction of the Status Epilepticus Severity Score (STESS), a validated and broadly used clinical scoring system for outcome prediction ...in status epilepticus (SE).
From 2005 to 2016, adult patients with SE treated at the University Hospital Basel, Switzerland, were included. To assess independent associations of variables differing between patients with false and correct prediction of death (STESS ≥ 3), multivariable logistic regression models were computed using automated selection.
Among 467 patients, 12% died. The median STESS was 3 (interquartile range 2-4). Regarding prediction of death, the STESS was false-positive in 51% and false-negative in 1%. Patients surviving despite having a STESS ≥3 had less fatal etiologies, less nonconvulsive SE with coma, and lower Charlson Comorbidity Index, Simplified Acute Physiology Score II, and Acute Physiology and Chronic Health Evaluation II scores. In multivariable analyses, odds for survival were high with SE types other than nonconvulsive status with coma and low with an increasing Charlson Comorbidity Index in patients with a STESS ≥ 3 (odds ratio OR
4.23, 95% confidence interval CI 2.33-9.60; and OR
0.86, 95% CI 0.75-0.98). In patients with SE types other than nonconvulsive with coma, the STESS was mainly increased because they were frequently older than 65 years and had no seizure history.
The STESS frequently and inadequately predicts death especially in patients with SE other than nonconvulsive with coma and few comorbidities. Clinicians are urged to interpret a STESS ≥3 with caution in such patients.
Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can ...persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.
To quantify the quality of physicians' emergency first response to status epilepticus (SE) and to identify risk factors for nonadherence to treatment guidelines in a standardized simulated scenario.
...In this prospective trial, 58 physicians (of different background) of the University Hospital Basel, a Swiss academic medical care center, were confronted with a simulated SE. Primary outcomes were time to (1) airway protection, (2) supplementary oxygen, and (3) administration of antiseizure drugs (ASDs).
All physicians recognized ongoing seizures. Airways were checked by 54% and protected by 16% within a median of 3.9 minutes. Supplementary oxygen was administered by 76% with a median of 2.8 minutes. First-line ASDs were administered by 98% (benzodiazepines 97% within a median of 2.9 minutes), and second-line ASDs by 57% within 8.1 minutes. Regarding secondary outcomes, the median time to monitor blood pressure and heart rate was 1.8 (interquartile range IQR 1.3-2.6) and 2.0 (IQR 1.4-2.7) minutes, respectively. Neurologic affiliation of physicians was associated with inadequate assessments of vital signs (odds ratio OR = 0.2; 95% CI 0.04-0.93) and most frequent administration of second-line ASDs (OR = 5.0; 95% CI 1.01-25.3). Knowing treatment guidelines and subjective certainty regarding SE diagnosis were associated with frequent administration of second-line ASDs (OR = 10.4; 95% CI 1.2-88.1).
Nonadherence to SE treatment guidelines is frequent. The lack of airway assessment and protection in the simulated clinical scenario of SE may increase mortality and promote treatment refractoriness related to aspiration pneumonia. Guideline-based clinical training is urgently needed to increase the quality of SE management.
ISRCTN registry (ID ISRCTN60369617; www.isrctn.com/ISRCTN60369617).
Background and aims
To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).
Methods
We conducted an ...individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd 2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU) admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.
Results
We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2 ± 15.0 years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13–3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with a higher likelihood of ICU admission, need of MV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need of MV and ICU admission, respectively.
Conclusions
Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.
Abstract
Modified vaccinia virus Ankara (MVA) is used as a vaccine against monkeypox virus and as a viral vaccine vector. MVA-MERS-S is a vaccine candidate against Middle East respiratory syndrome ...(MERS)–associated coronavirus. Here, we report that cross-reactive monkeypox virus neutralizing antibodies were detectable in only a single study participant after the first dose of MVA-MERS-S vaccine, in 3 of 10 after the second dose, and in 10 of 10 after the third dose.
A modified vaccinia virus Ankara–based candidate vaccine against Middle East respiratory syndrome–associated coronavirus elicits monkeypox virus neutralizing antibodies after 3 doses in healthy clinical trial participants.
In the context of host-pathogen interactions, gram-negative bacterial virulence factors, such as effectors, may be transferred from bacterial to eukaryotic host cytoplasm by multicomponent Type III ...protein secretion systems (T3SSs). Central to
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) pathogenesis is the secretion of over 40 effectors by two T3SSs encoded within pathogenicity islands SPI-1 and SPI-2. These effectors manipulate miscellaneous host cellular processes, such as cytoskeleton organization and immune signaling pathways, thereby permitting host colonization and bacterial dissemination. Recent research on effector biology provided mechanistic insights for some effectors. However, for many effectors, clearly defined roles and host target repertoires—further clarifying effector interconnectivity and virulence networks—are yet to be uncovered. Here we demonstrate the utility of the recently described viral-like particle trapping technology Virotrap as an effective approach to catalog
S
. Typhimurium effector-host protein complexes (EH-PCs). Mass spectrometry-based Virotrap analysis of the novel E3 ubiquitin ligase SspH2 previously shown to be implicated in modulating actin dynamics and immune signaling, exposed known host interactors PFN1 and−2 besides several putative novel, interconnected host targets. Network analysis revealed an actin (-binding) cluster among the significantly enriched hits for SspH2, consistent with the known localization of the
S
-palmitoylated effector with actin cytoskeleton components in the host. We show that Virotrap complements the current state-of-the-art toolkit to study protein complexes and represents a valuable means to screen for effector host targets in a high-throughput manner, thereby bridging the knowledge gap between effector-host interplay and pathogenesis.
Modified vaccinia virus Ankara (MVA) is used as a vaccine against monkeypox virus (MPXV) and as a viral vaccine vector. MVA-MERS-S is a vaccine candidate against Middle East respiratory syndrome- ...associated coronavirus (MERS-CoV). Here, we report that cross-reactive MPXV nAbs were detectable in only a single subject after the first dose, 3 out of 10 after the 2nd dose, and in 10 out of 10 after the 3rd dose of MVA-MERS-S vaccine.
The 'post genomics' era has seen a surge in demand for the techniques of cell biology, to aid in interpreting the function and location of the cell's myriad proteins and macromolecules. This new ...edition of Plant Cell Biology provides a grounding in established procedures before guiding the reader through the field's most current techniques. It provides advanced undergraduates, postgraduates and research staff in the plant sciences with a uniquely comprehensive guide to this rapidly expanding discipline.
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