Tarn

BACKGROUND: Malaria is a parasitic disease that affects many of the poorest economies, resulting in approximately 241 million clinical episodes and 627,000 deaths annually. Piperaquine, when administered with dihydroartemisinin, is an effective drug against the disease. Drug concentration measurements taken on day 7 after treatment initiation have been shown to be a good predictor of therapeutic success with piperaquine. A simple capillary blood collection technique, where blood is dried onto filter paper, is especially suitable for drug studies in remote areas or resource-limited settings or when taking samples from children, toddlers, and infants...

Accurate and comprehensive peptide precursor ions are crucial to tandem mass-spectrometry-based peptide identification. An identification engine can derive great advantages from the search space reduction enabled by credible and detailed precursors. Furthermore, by considering multiple precursors per spectrum, both the number of identifications and the spectrum explainability can be substantially improved. Here, we introduce PepPre, which detects precursors by decomposing peaks into multiple isotope clusters using linear programming methods...

Human trichinellosis is a parasitic infection caused by roundworms belonging to the genus Trichinella , especially Trichinella spiralis . Early and accurate clinical diagnoses of trichinellosis are required for efficacious prognosis and treatment. Current drug therapies are limited by antiparasitic resistance, poor absorption, and an inability to kill the encapsulating muscle-stage larvae. Therefore, reliable biomarkers and drug targets for novel diagnostic approaches and anthelmintic drugs are required. In this study, metabolite profiles of T...

Parasitic roundworms cause significant sickness and mortality in animals and humans. In livestock, these nematodes have severe economic impact and result in losses in food production on a global scale. None of the currently available drugs ideally suit all treatment circumstances, and the development of drug-resistant nematode strains has become a challenge to control the infection. There is an urgent need to develop novel anthelmintic compounds. According to our previous report, N-methylbenzo[d]oxazol-2-amine (1) showed anthelmintic activity and lowest cytotoxicity...

Purpose: Pregnant women are vulnerable to Coronavirus Disease 2019 (COVID-19) complications, yet may hesitate to get vaccinated. It is important to identify racial/ethnic and other individual characteristics associated with COVID-19 vaccine acceptance in the United States during pregnancy. Methods: We searched PubMed, Embase, and Web of Science for articles published through January 2023 for keywords/terms related to immunization, COVID-19, and pregnancy, and performed a systematic review and meta-analysis to examine characteristics associated with vaccine acceptance...

INTRODUCTION: It is only in recent years that major trauma systems and networks have been operating in the UK. High-quality data is available from the Trauma Audit and Research Network (TARN) database, enabling regional analysis. Our aim was to analyse Trauma Team Activations within the Cheshire and Merseyside major trauma network and discuss the implications of these data on resource allocation, training and trauma prevention. METHODS: A retrospective analysis was performed for all patients requiring Trauma Team Activation (TTA) at a category one adult Major Trauma Centre (MTC) who were submitted to the TARN database from the 1st January 2015 to the 1st January 2020...

INTRODUCTION: The epidemiology and prognosis of the isolated traumatic brain injury (TBI) and spinal cord injury (SCI) are well studied. However, the knowledge of the impact of concurrent neurotrauma is very limited. RESEARCH QUESTIONS: To characterize the longitudinal incidence of concurrent TBI and SCI and to investigate their combined impact on clinical care and outcomes, compared to a comparative but isolated SCI or TBI. MATERIALS AND METHODS: Data from 167,793 patients in the Trauma Audit and Research Network (TARN) registry collected in England and Wales between 2008 and 2018 were analysed...

The original CRISPR Cas9 gene editing system and subsequent innovations offers unprecedented opportunities to correct severe genetic defects including those causing Primary Immunodeficiencies (PIDs). Common Variable Immunodeficiency Disorders (CVID) are the most frequent symptomatic PID in adults and children. Unlike many other PIDs, patients meeting CVID criteria do not have a definable genetic defect and cannot be considered to have an inborn error of immunity (IEI). Patients with a CVID phenotype carrying a causative mutation are deemed to have a CVID-like disorder consequent to an IEI...

Mutations of the human interferon alpha and beta receptor subunit 1 (IFNAR1) gene are associated with severe viral infections. Individuals homozygous for the Glu386∗ variant have impaired type I interferon signalling and can suffer severe illness when exposed to certain viruses and live attenuated virus vaccines. Glu386∗ heterozygotes are clinically unaffected, but can pass the variant allele to their descendants. We aimed to develop an assay that can identify IFNAR1 Glu386∗ homozygotes and heterozygotes to support urgent clinical diagnosis, and that can use dried blood spots (DBS) sent at ambient temperature to overcome geographical logistical challenges in the South Pacific region...

Approximately 10% of antimicrobials used by humans in low- and middle-income countries are estimated to be substandard or falsified. In addition to their negative impact on morbidity and mortality, they may also be important drivers of antimicrobial resistance. Despite such concerns, our understanding of this relationship remains rudimentary. Substandard and falsified medicines have the potential to either increase or decrease levels of resistance, and here we discuss a range of mechanisms that could drive these changes...

Due to the growing need to recycle plastics, new possibilities for their reuse are intensively sought. In the Asian market, waste polymers are increasingly used to modify road bitumen. This solution is beneficial in many aspects, especially in economic and ecological terms. In this work, recycled poly(ethylene terephthalate) (RPET), obtained from storage points located in Lesser Poland, was subjected to material recycling, and its properties were examined using three analyses: differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and Fourier transform infrared spectroscopy (FTIR)...

BACKGROUND: There are no pharmacokinetic data of single low dose primaquine (SLDPQ) as transmission blocking in African children with acute Plasmodium falciparum and glucose-6-phosphate dehydrogenase deficiency (G6PDd). METHODS: Primaquine pharmacokinetics of age-dosed SLDPQ (shown previously to be gametocytocidal with similar tolerability as placebo) were characterised in falciparum-infected Ugandan and Congolese children aged 6 months to 11 years, treated on admission with standard 3-day dihydroartemisinin-piperaquine or artemether-lumefantrine plus SLDPQ: 6 m-<1 y: 1...

BACKGROUND: Major incidents (MIs) are an important cause of death and disability. Triage tools are crucial to identifying priority 1 (P1) patients-those needing time-critical, life-saving interventions. Existing expert opinion-derived tools have limited evidence supporting their use. This study employs machine learning (ML) to develop and validate models for novel primary and secondary triage tools. METHODS: Adults (16+ years) from the UK Trauma Audit and Research Network (TARN) registry (January 2008-December 2017) served as surrogates for MI victims, with P1 patients identified using predefined criteria...

A molecular and functional link between neurotrophin signaling and cerebellar foliation is lacking. Here we show that constitutive knockout of two homologous genes encoding the RNA binding protein RBM4 results in foliation defects at cerebellar lobules VI-VII and delayed motor learning in mice. Moreover, the features of Rbm4 double knockout (dKO), including impaired differentiation of cerebellar granule cells and dendritic arborization of Purkinje cells, are reminiscent of neurotrophin deficiency. Loss of RBM4 indeed reduced brain-derived neurotrophic factor (BDNF)...

The majority of deaths from malaria are in young African children. Parenteral artesunate is the first-line treatment for severe falciparum malaria. Since 2015 the World Health Organization has recommended individual doses of 3 mg/kg for children weighing less than 20 kg. Recently, the US Food and Drug Administration (FDA) has challenged this recommendation, based on a simulated pediatric population, and argued for a lower dose in younger children (2.4 mg/kg). In this study, we performed population pharmacokinetic modeling of plasma concentration data from 80 children with severe falciparum malaria in the Democratic Republic of Congo who were given 2...

OBJECTIVES: Stratification approaches are vital to address clinical heterogeneity in Sjogren's syndrome (SS). We previously described that the Newcastle Sjogren's Stratification Tool (NSST) identified four distinct clinical subtypes of SS. We performed proteomic and network analysis to analyse the underlying pathobiology and highlight potential therapeutic targets for different SS subtypes. METHOD: We profiled serum proteins using O-link technology of 180 SS subjects...

Point-of-care assays have greatly increased access to diagnostic information and improved healthcare outcomes globally, especially in the case of tropical diseases in rural settings. Increased recognition of the impact of these tools and increased funding, along with advances in technology have led to a surge in development of new assays. However, many new tools fail to fulfill their intended purpose due to a lack of clinical impact, operational feasibility, and input from envisioned operators. To be successful, they must fit into existing clinical decision-making models and be designed in collaboration with end users...

INTRODUCTION: Trauma accounts for 20% of deaths in pregnant women. Injury characterisation and outcome in pregnant women following trauma is poorly described. To understand and inform optimum care of this key injury population, a study was conducted using the Trauma Audit Research Network (TARN) database. METHODS: In total, 341 pregnant and 26,774 non-pregnant female patients aged 15 to 46 years were identified for comparison from the TARN database. Mortality, cross-sectional imaging, blood product administration and EQ-5D scores were compared between the two groups...

Cycloalkanes are abundant and toxic compounds in subsurface petroleum reservoirs and their fate is important to ecosystems impacted by natural oil seeps and spills. This study focuses on the microbial metabolism of methylcyclohexane (MCH) and methylcyclopentane (MCP) in the deep Gulf of Mexico. MCH and MCP are often abundant cycloalkanes observed in petroleum and will dissolve into the water column when introduced at the seafloor via a spill or natural seep. We conducted incubations with deep Gulf of Mexico (GOM) seawater amended with MCH and MCP at four stations...

SARS-CoV-2, the virus responsible for COVID-19, has caused havoc around the world. While several COVID-19 vaccines and drugs have been authorised for use, these antiviral drugs remain beyond the reach of most low- and middle-income countries. Rapid viral evolution is reducing the efficacy of vaccines and monoclonal antibodies and contributing to deaths of some fully vaccinated persons. Others with normal immunity may have chosen not be vaccinated and remain at risk if they contract the infection. Vaccines may not protect some immunodeficient patients from SARS-CoV-2, who are also at increased risk of chronic COVID-19 infection, a dangerous stalemate between the virus and a suboptimal immune response...