Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.
View Article and Find Full Text PDFSafely and efficiently controlling gene expression is a long-standing goal of biomedical research, and CRISPR/Cas system can be harnessed to create powerful tools for epigenetic editing. Adeno-associated-viruses (AAVs) represent the delivery vehicle of choice for therapeutic platform. However, their small packaging capacity isn't suitable for large constructs including most CRISPR/dCas9-effector vectors.
View Article and Find Full Text PDFBackground: Every year 480 people are diagnosed with a primary brain tumour in Ireland. Brain tumours can vary in type, location, treatment, and progression but neurological impairments are a consistent feature. Such neurological disability creates significant symptom burden that can seriously impact peoples' functional ability and quality of life.
View Article and Find Full Text PDFTobacco smoking remains a leading cause of preventable death in the United States, with approximately a 5% success rate for smokers attempting to quit. High relapse rates have been linked to several genetic factors, indicating that the mechanistic relationship between genes and drugs of abuse is a valuable avenue for the development of novel smoking cessation therapies. For example, various single nucleotide polymorphisms (SNPs) in the gene for neuregulin 3 (NRG3) and its cognate receptor, the receptor tyrosine-protein kinase erbB-4 (ERBB4), have been linked to nicotine addiction.
View Article and Find Full Text PDFBackground: Implementation researchers often combine the Theoretical Domain Framework (TDF) and Consolidated Framework for Implementation Research (CFIR) in their studies. However there is some debate on the merits of using multiple frameworks-whether they contribute to results or provide superfluous analysis. Our recent research combined the TDF and CFIR to identify determinants to widespread incorporation of patient held medication lists (PHML) in healthcare practice.
View Article and Find Full Text PDFTobacco smoking remains a leading cause of preventable death in the United States, with a less than 5% success rate for smokers attempting to quit. High relapse rates have been linked to several genetic factors, indicating that the mechanistic relationship between genes and drugs of abuse is a valuable avenue for the development of novel smoking cessation therapies. For example, various single nucleotide polymorphisms (SNPs) in the gene for neuregulin 3 () and its cognate receptor, the receptor tyrosine-protein kinase erbB-4 (), have been linked to nicotine addiction.
View Article and Find Full Text PDFIntroduction: Adverse drug reactions (ADRs) can have significant negative impact on peoples' daily lives, with physical, economic, social and/or psychological effects. Patient reporting of ADRs has been facilitated by pharmacovigilance systems across Europe. However, capturing data on patients' experiences of ADRs has proved challenging.
View Article and Find Full Text PDFThere is a paucity of data on trust of service users in cervical screening. A significant controversy in Ireland's national cervical cancer screening programme emerged in 2018. The Health Service Executive (HSE) confirmed that a clinical audit had revealed that more than 200 women who developed cancer had not been told of earlier misdiagnosed smear tests.
View Article and Find Full Text PDFBackground: Effective screening can prevent cervical cancer, but many women choose not to attend their screening tests.
Objective: This study aimed to investigate behavioural influences on cervical screening participation using the Theoretical Domains Framework (TDF) and COM-B models of behaviour change.
Design: A qualitative study and semistructured phone interviews were conducted with women invited for routine screening tests within the national cervical screening programme in Ireland.
Astrocytes have become established as an important regulator of neuronal activity in the brain. Accumulating literature demonstrates that cocaine self-administration in rodent models induces structural changes within astrocytes that may influence their interaction with the surrounding neurons. Here, we provide evidence that cocaine impacts astrocytes at the functional level and alters neuronal sensitivity to astrocyte-derived glutamate.
View Article and Find Full Text PDFCalcium imaging has gained substantial popularity as a tool to profile the activity of multiple simultaneously active cells at high spatiotemporal resolution. Among the diverse approaches to processing of Ca imaging data is an often subjective decision of how to quantify baseline fluorescence or . We examine the effect of popular determination methods on the interpretation of neuronal and astrocyte activity in a single dataset of rats trained to self-administer intravenous infusions of cocaine and compare them with an -independent wavelet ridgewalking event detection approach.
View Article and Find Full Text PDFOpen cholecystectomy is a painful procedure and requires a well-rounded multimodal approach for successful postoperative analgesia. A thoracic epidural is known to provide reliable pain relief for upper abdominal surgical procedures. However, in patients for whom an epidural is contraindicated, an alternative regional technique may be sought.
View Article and Find Full Text PDFLong after surgical treatment, chronic pain continues to afflict many patients with pancreatic cancer. Multimodal pain management is the current approach to managing these complex patients. In patients with refractory pain, a celiac plexus block is a commonly used adjunct to optimize pain control.
View Article and Find Full Text PDFProteolysis is a major posttranslational regulator of biology inside and outside of cells. Broad identification of optimal cleavage sites and natural substrates of proteases is critical for drug discovery and to understand protease biology. Here, we present a method that employs two genetically encoded substrate phage display libraries coupled with next generation sequencing (SPD-NGS) that allows up to 10,000-fold deeper sequence coverage of the typical six- to eight-residue protease cleavage sites compared to state-of-the-art synthetic peptide libraries or proteomics.
View Article and Find Full Text PDFParaneoplastic neurological disorders are immune-mediated diseases understood to manifest as part of a misdirected anti-tumor immune response. Paraneoplastic neurological disorder-associated autoantibodies can assist with diagnosis and enhance our understanding of tumor-associated immune processes. We designed a comprehensive library of 49-amino-acid overlapping peptides spanning the entire human proteome, including all splicing isoforms and computationally predicted coding regions.
View Article and Find Full Text PDFObjective: The incidence of human papillomavirus-associated head and neck cancers (HPV-HNC) is increasing worldwide. Research in other clinical contexts has shown that healthcare professionals (HCPs) can find discussing HPV with patients challenging. However, limited research has been conducted in HNC.
View Article and Find Full Text PDFDysregulation of dopamine neurotransmission has been linked to the development of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). To investigate the mechanisms underlying this phenomenon, this study used an inducible HIV-1 transactivator of transcription (Tat) transgenic (iTat-tg) mouse model, which demonstrates brain-specific Tat expression induced by administration of doxycycline. We found that induction of Tat expression in the iTat-tg mice for either 7 or 14 days resulted in a decrease (∼30%) in the of [H]dopamine uptake via both the dopamine transporter (DAT) and norepinephrine transporter (NET) in the prefrontal cortex (PFC), which was comparable to the magnitude (∼35%) of the decrease in for [H]WIN 35,428 and [H]nisoxetine binding to DAT and NET, respectively.
View Article and Find Full Text PDFIntroduction: Prevalence rates of human papillomavirus positive (HPV+) head and neck cancers (HNC) have increased over the last decades. Communicating about HPV is an increasingly relevant part of HNC patient care. This systematic review was conducted to explore healthcare professionals' (HCP) views and experiences of discussing HPV with HNC patients.
View Article and Find Full Text PDFAim: To determine the use and perceived value of different information sources that patients may use to support identification of medicine side effects; to explore associations between coping styles and use of information sources.
Background: Side effects from medicines can have considerable negative impact on peoples' daily lives. As a result of an ageing UK population and attendant multi-morbidity, an increasing number of medicines are being prescribed for patients, leading to increased risk of unintended side effects.
Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF). CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan).
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