Background: Intraoperative awareness, without explicit recall, occurs after induction of anaesthesia in approximately 10% of persons under 40 yr of age. Most anaesthetic agents minimally suppress the noradrenergic system. We hypothesised that addition of dexmedetomidine, which suppresses noradrenergic activity, may reduce encephalographic (EEG) arousal in response to tracheal intubation; such an effect would lay the foundation for future studies of dexmedetomidine in reducing intraoperative awareness.
View Article and Find Full Text PDFThe HoloFood project used a hologenomic approach to understand the impact of host-microbiota interactions on salmon and chicken production by analysing multiomic data, phenotypic characteristics, and associated metadata in response to novel feeds. The project's raw data, derived analyses, and metadata are deposited in public, open archives (BioSamples, European Nucleotide Archive, MetaboLights, and MGnify), so making use of these diverse data types may require access to multiple resources. This is especially complex where analysis pipelines produce derived outputs such as functional profiles or genome catalogues.
View Article and Find Full Text PDFWe investigated mRNA vaccines encoding a membrane-anchored receptor-binding domain (RBD), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. In naive mice, RBD-TM mRNA vaccines against SARS-CoV-2 variants induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays revealed broad neutralizing activity against a range of variant RBDs.
View Article and Find Full Text PDFRedox fluctuations within redox dynamic environments influence the redox state of natural organic matter (NOM) and its interaction with redox-active elements, such as iron. In this work, we investigate the changes in the molecular composition of NOM during redox fluctuations as well as the impact of these changes on the Fe-NOM interaction employing Suwannee River Dissolved Organic Matter (SRDOM) as a representative NOM. Characterization of SRDOM using X-ray photoelectron spectroscopy and Fourier transform infrared spectrometry showed that irreversible changes occurred following electrochemical reduction and reoxidation of SRDOM in air.
View Article and Find Full Text PDFAlthough cochlear implants (CI) successfully replace the sense of hearing, they do not restore natural hearing. Still, CI users adapt to this novel signal, reaching meaningful levels of speech recognition in clinical tests that focus on repetition of words and short sentences. However, many patients who score above average in clinical speech perception tests complain that everyday speech interactions are both difficult and cognitively draining.
View Article and Find Full Text PDFMass spectral libraries are collections of reference spectra, usually associated with specific analytes from which the spectra were generated, that are used for further downstream analysis of new spectra. There are many different formats used for encoding spectral libraries, but none have undergone a standardization process to ensure broad applicability to many applications. As part of the Human Proteome Organization Proteomics Standards Initiative (PSI), we have developed a standardized format for encoding spectral libraries, called mzSpecLib (https://psidev.
View Article and Find Full Text PDFBackground: We aimed to assess perioperative changes in fibrinogen in the cerebrospinal fluid (CSF), their association with markers of blood-brain barrier breakdown and neuroinflammation, and their association with postoperative delirium severity.
Methods: We conducted a secondary analysis of the Interventions for Postoperative Delirium-Biomarker 2 (IPOD-B2, NCT02926417) study, a prospective observational cohort study. We included 24 patients aged >21 yr undergoing aortic aneurysm repair.
Understanding the association between initial experimentation with a tobacco product and subsequent patterns of tobacco use among youth is important to informing prevention activities for youth in the US. We conducted an online survey from August to October 2017 among youth aged 13-18 years. The current analysis focused on respondents reporting initial experimentation with any tobacco product (n = 2,022).
View Article and Find Full Text PDFLentiviral vector (LVV)-mediated cell and gene therapies have the potential to cure diseases that currently require lifelong intervention. However, the requirement for plasmid transfection hinders large-scale LVV manufacture. Moreover, large-scale plasmid production, testing, and transfection contribute to operational risk and the high cost associated with this therapeutic modality.
View Article and Find Full Text PDFObjective: Patient characteristics and patterns of disease in chronic limb threatening ischaemia (CLTI) have markedly changed in recent years. Urgent specialist referral and timely revascularisation are recommended in international guidelines. UK guidelines now recommend revascularisation within five days of referral for inpatients and two weeks in outpatients.
View Article and Find Full Text PDFBackground: Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69 years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI.
Methods: For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses.
The successful use of lipid nanoparticles (LNPs) for clinical development of the COVID-19 mRNA vaccines marked a breakthrough in mRNA-LNP therapeutics. As one of the vital components of LNPs, poly(ethylene glycol)-lipid conjugates (PEG-lipids) influence particle biophysical properties and stability, as well as interactions within biological environments. Reports suggesting that anti-PEG antibodies can be detected quite commonly within the human population raise concerns that PEG content in commercial LNP products could further stimulate immune responses to PEG.
View Article and Find Full Text PDFBackground & Aims: New antiviral approaches that target multiple aspects of the HBV replication cycle to improve rates of functional cure are urgently required. HBV RNA represents a novel therapeutic target. Here, we programmed CRISPR-Cas13b endonuclease to specifically target the HBV pregenomic RNA and viral mRNAs in a novel approach to reduce HBV replication and protein expression.
View Article and Find Full Text PDFThere is interest in chaplains devoted to outpatient cancer care, informed by a growing body of research as well as recommendations of accreditors. Simultaneously, a growing share of U.S.
View Article and Find Full Text PDFObjective: The aim of our study is to better understand the genetic architecture and pathological mechanisms underlying neurodegeneration in idiopathic Parkinson's disease (iPD). We hypothesized that a fraction of iPD patients may harbor a combination of common variants in nuclear-encoded mitochondrial genes ultimately resulting in neurodegeneration.
Methods: We used mitochondria-specific polygenic risk scores (mitoPRSs) and created pathway-specific mitoPRSs using genotype data from different iPD case-control datasets worldwide, including the Luxembourg Parkinson's Study (412 iPD patients and 576 healthy controls) and COURAGE-PD cohorts (7,270 iPD cases and 6,819 healthy controls).
Carotenoids are yellow, orange, and red pigments commonly found in plants. In leaves, these molecules are essential for photosynthesis, but they also play a major role in plant growth and development. Efficiently monitoring concentrations of specific carotenoids in plant tissues could help to explain plant responses to environmental stressors, infection and disease, fertilization, and other conditions.
View Article and Find Full Text PDFLow-level radioactive wastes were disposed at the Little Forest Legacy Site (LFLS) near Sydney, Australia between 1960 and 1968. According to the disposal records, U contributes a significant portion of the inventory of actinide activity buried in the LFLS trenches. Although the presence of U in environmental samples from LFLS has been previously inferred from alpha-spectrometry measurements, it has been difficult to quantify because the U and U α-peaks are superimposed.
View Article and Find Full Text PDFThe heterogenous aetiology of Parkinson's disease is increasingly recognized; both mitochondrial and lysosomal dysfunction have been implicated. Powerful, clinically applicable tools are required to enable mechanistic stratification for future precision medicine approaches. The aim of this study was to characterize bioenergetic dysfunction in Parkinson's disease by applying a multimodal approach, combining standardized clinical assessment with midbrain and putaminal 31-phosphorus magnetic resonance spectroscopy (31P-MRS) and deep phenotyping of mitochondrial and lysosomal function in peripheral tissue in patients with recent-onset Parkinson's disease and control subjects.
View Article and Find Full Text PDFObjectives: We describe an automated transcription system that addresses many documentation problems and fits within scheduled clinical hours.
Materials And Methods: During visits, the provider listens to the patient while maintaining eye contact and making brief notes on paper. Immediately after the visit conclusion and before the next, the provider makes a short voice recording on a smartphone which is transmitted to the system.