Wilsons

No abstract text is available yet for this article.

Due to its widespread use for the treatment of Type-2 diabetes, metformin is routinely detected in surface waters globally. Laboratory studies have shown that environmentally relevant concentrations of metformin can adversely affect the health of adult fish, with effects observed more frequently in males. However, the potential risk to wild fish populations has yet to be fully elucidated and remains a topic of debate. To explore whether environmentally relevant metformin exposure poses a risk to wild fish populations, the present study exposed wild fathead minnows (Pimephales promelas) to 5 or 50 μg/L metformin via 2 m diameter in-lake mesocosms deployed in a natural boreal lake in Northern Ontario at the International Institute for Sustainable Development - Experimental Lakes Area (IISD-ELA)...

Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia (CMML) at Princess Margaret Hospital, Toronto 2015-2022. Using propensity score matching, we compared transplant outcomes between two well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n=46) or fludarabine-busulfan with total body irradiation (FBT200) (n=92)...

Children and neonates are highly vulnerable to the impact of antimicrobial resistance. Substantial barriers are faced in relation to research and development of antibacterial agents for use in neonates, children, and adolescents aged yonger than 19 years, and focusing finite resources on the most appropriate agents for development and paediatric optimisation is urgently needed. In November and December, 2022, following the successes of previous similar disease-focused exercises, WHO convened the first Paediatric Drug Optimisation (PADO) exercise for antibiotics, aiming to provide a shortlist of antibiotics to be prioritised for paediatric research and development, especially for use in regions with the highest burden of disease attributable to serious bacterial infection...

RNA ligands of retinoic acid-inducible gene I (RIG-I) are a promising class of oligonucleotide therapeutic with broad potential as antiviral agents, vaccine adjuvants, and cancer immunotherapies. However, their translation has been limited by major drug delivery barriers, including poor cellular uptake, nuclease degradation, and an inability to access the cytosol where RIG-I is localized. Here we address this challenge by engineering nanoparticles that harness covalent conjugation of 5'-triphospate RNA (3pRNA) to endosome-destabilizing polymers...

G protein-coupled receptors (GPCRs) transduce the effects of many neuromodulators including dopamine, serotonin, epinephrine, acetylcholine, and opioids. The localization of synthetic or endogenous GPCR agonists impacts their action on specific neuronal pathways. In this paper, we show a series of single-protein chain integrator sensors that are highly modular and could potentially be used to determine GPCR agonist localization across the brain. We previously engineered integrator sensors for the mu- and kappa-opioid receptor agonists called M- and K-Single-chain Protein-based Opioid Transmission Indicator Tool (SPOTIT), respectively...

INTRODUCTION: There is a substantial gap in knowledge regarding how perceived stress may influence the relationship between serum-measured biomarkers for Alzheimer's disease and cognitive decline. METHODS: This study consists of 1,118 older adult participants from the Chicago Health and Aging Project (CHAP) (60% Black participants and 63% female participants). Linear mixed effects regression models were conducted to examine the role of perceived stress in the association between three blood biomarkers: total tau (t-tau), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) on global cognitive decline...

OBJECTIVE: To understand factors associated with missed academic time after concussion to improve support for patients. Our goal was to assess patient-specific predictors of total school time lost after pediatric/adolescent concussion. STUDY DESIGN: We performed a prospective cohort study of children and adolescents (8-18 years of age) seen within 14 days of concussion from seven pediatric medical centers across the United States. We collected outcomes via the Concussion Learning Assessment & School Survey (CLASS) and constructed a multivariable predictive model evaluating patient factors associated with school time loss...

A critical measure of the quality of pharmaceutical proteins is the preservation of native conformations of the active pharmaceutical ingredients. Denaturation of the active proteins in any step before administration into patients could lead to loss of potency and/or aggregation, which is associated with an increased risk of immunogenicity of the products. Interfacial stress enhances protein instability as their adsorption to the air-liquid and liquid-solid interfaces are implicated in the formation of denatured proteins and aggregates...

No abstract text is available yet for this article.

Depression and intimate partner violence (IPV) are highly related. However, it is unclear what drives this relationship: the form of violence (psychological, physical, or sexual) or its severity. In this study, we first identify patterns of combined forms and severity of violence and then estimate the effects of IPV on depression. We use the DHS and focus on Peru, a country with high IPV rates. Five classes of IPV were identified. The more intense the IPV class, the higher the effect on recent depression. However, the effect on depression tends to be smaller when levels of depression are higher...

Cytomegalovirus (CMV) retinitis is commonly associated with immunosuppression and can cause irreversible vision loss. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as an effective cancer treatment option but requires immunosuppression, thereby increasing the possibility of acquiring opportunistic infections such as CMV. We present the case of a 76-year-old female with a history of hypertension and type 2 diabetes mellitus who initially presented with shortness of breath and was diagnosed with the activated B-cell subset of diffuse large B-cell lymphoma (DLBCL)...

This opinion piece emphasies the critical role of translational research in enhancing the UK's resilience against future pandemics. The COVID-19 pandemic demonstrated the lifesaving potential of scientific innovation, including genomic tracking of SARS-CoV-2, vaccine development, data linkage, modelling, and new treatments. These advances, achieved through collaborations between academic institutions, industry, government, public health bodies, and the NHS, occurred at an unprecedented pace. However, the UK's pandemic preparedness planning, as reflected in the 2016 Exercise Cygnus report, notably lacked provision for scientific innovation...

Damage control surgery has evolved during the past 40 years. The initial cases and studies were performed at level 1 trauma centers but has now shifted to damage control at smaller hospitals. This buys time for definitive care at higher-level centers. There is a role for damage control surgery in both general surgery and trauma patients at community trauma centers. The successful implementation and completion of damage control surgery require thorough planning and a full understanding of resource limitation...

BACKGROUND: The relationship between baseline perihematomal edema (PHE) and inflammation, and their impact on survival after intracerebral hemorrhage (ICH) are not well understood. OBJECTIVE: Assess the association between baseline PHE, baseline C-reactive protein (CRP), and early death after ICH. METHODS: Analysis of pooled data from multicenter ICH registries. We included patients presenting within 24 h of symptom onset, using multifactorial linear regression model to assess the association between CRP and edema extension distance (EED), and a multifactorial Cox regression model to assess the association between CRP, PHE volume and 30-day mortality...

We present a case of anatomic repair of dextro-transposition of the great arteries (d-TGA) with ventricular septal defect (VSD) in a 55-year-old man who presented with acute heart failure. This case highlights the importance of multimodal imaging and multidisciplinary involvement in developing a comprehensive surgical and medical plan for adults with congenital heart disease. We think this is the oldest reported patient undergoing anatomic surgical repair of d-TGA with VSD.

PURPOSE: This goal of this study was to optimize spectrally selective 1 H MRS methods for large volume acquisition of low concentration metabolites with downfield resonances at 7T and 3T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD + ) and tryptophan. METHODS: Spectrally selective excitation was used to avoid magnetization transfer effects with water, and various sinc pulses were compared to a pure-phase E-BURP pulse. Localization using a single slice selective pulse was compared to voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water...

Fetal growth restriction (FGR) caused by placental insufficiency is a major contributor to neonatal morbidity and mortality. There is currently no in utero treatment for placental insufficiency or FGR. The placenta serves as the vital communication, supply, exchange, and defense organ for the developing fetus and offers an excellent opportunity for therapeutic interventions. Here we show efficacy of repeated treatments of trophoblast-specific human insulin-like 1 growth factor ( IGF1 ) gene therapy delivered in a non-viral, polymer nanoparticle to the placenta for the treatment of FGR...

Missense variants can have a range of functional impacts depending on factors such as the specific amino acid substitution and location within the gene. To interpret their deleteriousness, studies have sought to identify regions within genes that are specifically intolerant of missense variation 1-12 . Here, we leverage the patterns of rare missense variation in 125,748 individuals in the Genome Aggregation Database (gnomAD) 13 against a null mutational model to identify transcripts that display regional differences in missense constraint...

Arising as co-products of canonical gene expression, transcription-associated lincRNAs, such as promoter upstream transcripts (PROMPTs), enhancer RNAs (eRNAs), and readthrough (RT) transcripts, are often regarded as byproducts of transcription, although they may be important for the expression of nearby genes. We identified regions of nascent expression of these lincRNA in 16 human cell lines using Bru-seq techniques, and found distinctly regulated patterns of PROMPT, eRNA, and RT transcription using the diverse biochemical approaches in the ENCODE4 deeply profiled cell lines collection...