The everydayness of falling: consequences and management for adults with cerebral palsy across the life course.

Purpose: To explore the cause, influences and consequences of falling for adults with cerebral palsy (CP) across their life course, and how this is managed.

Materials And Methods: We used interview data from a multimethod UK study exploring the effects of ageing with CP and healthcare across the life course. Twenty-six participants were recruited and interviewed using various digital platforms to maximise inclusive participation in the UK.

Exploring the impacts of social media and crowdsourcing on disaster resilience.

Social media and crowdsourcing (SMCS) are increasingly proving useful for addressing the effects of natural and human-made hazards. SMCS allow different stakeholders to share crucial information during disaster management processes and to strengthen community resilience through engagement and collaboration. To harvest these opportunities there is a need for better knowledge on SMCS for diverse disaster scenarios.

Uptake Rates of Three COVID-19 Vaccine Doses and Risk Factors for Incomplete Vaccination Among Patients With Inflammatory Bowel Disease Residing in Wisconsin: A Single-Center Cohort.

Introduction: Patients with inflammatory bowel disease on systemic corticosteroids may be at higher risk of adverse outcomes of COVID-19 infection, and vaccination is an essential preventive measure. Uptake of the original 2-dose COVID-19 messenger RNA (mRNA) primary vaccine series was previously high among patients with inflammatory bowel disease, while uptake of subsequent doses based on interval recommendations made by the Advisory Committee on Immunization Practice remains unknown. Herein, we evaluated uptake of 3 COVID-19 mRNA vaccine doses among patients with inflammatory bowel disease.

The impact of ageing on adults with cerebral palsy: the results of a national online survey.

Background: Cerebral palsy (CP) is one of the most common neurological disorders in children and results in lifelong physical impairments. Adults with CP have approximately the same life expectancy as their non-disabled peers, so helping them to stay healthy throughout the life course will have long-term cost benefits via reductions in hospital admissions, long-term care, and unemployment rates.

Aim: To explore how adults with CP experience ageing.

Correlation of Renal Tissue Oxygenation to Venous, Arterial, and Capillary Blood Gas Oxygen Saturation in Preterm Neonates.

Objective: The aim of the study is to assess the correlation of renal regional tissue saturation of oxygen (RrSO) measured by near-infrared spectroscopy (NIRS) in preterm neonates to venous oxygen saturation (SvO) obtained from umbilical venous catheters (UVCs), arterial oxygen saturation (SaO) obtained from umbilical artery catheters (UACs), and capillary oxygen saturation (ScO) from capillary heel blood draws.

Study Design: A secondary analysis of a prospective RrSO monitoring study in preterm neonates born <32 weeks gestational age. Neonates with any blood gas obtained during RrSO monitoring were included.

High But Inequitable COVID-19 Vaccine Uptake Among Patients with Inflammatory Bowel Disease.

Coronavirus disease 2019 (COVID-19) vaccines are recommended for all patients with inflammatory bowel disease (IBD). Patients with IBD historically have had low vaccine uptake relative to the general population. However, a recent survey suggested a rate higher than that of the general population with regard to COVID-19 vaccine intent among the IBD population.

Renal tissue oxygenation after caffeine administration in preterm neonates.

Background: Caffeine has been associated with reduced rates of acute kidney injury (AKI) in preterm neonates. The effect of caffeine on preterm neonatal renal regional saturation of oxygen (RrSO) is unknown.

Methods: RrSO was recorded continuously in neonates < 32 weeks' gestation until 7 days of age with INVOS™ neonatal near-infrared spectroscopy (NIRS) sensors.

Non-invasive continuous renal tissue oxygenation monitoring to identify preterm neonates at risk for acute kidney injury.

Background: Near-infrared spectroscopy (NIRS) is an emerging tool to identify signs of inadequate tissue oxygenation in preterm neonates with acute kidney injury (AKI). Previous studies have shown a correlation between low renal tissue oxygenation (RrSO) in the first 24 hours of age and the later development of AKI. In this prospective clinical trial, NIRS monitoring was used to identify changes in RrSO in comparison to traditional AKI markers, serum creatinine (SCr), and urine output (UOP).

Novel thienopyrimidine and thiazolopyrimidine kinase inhibitors with activity against Tie-2 in vitro and in vivo.

The SAR and improvement in potency against Tie2 of novel thienopyrimidine and thiazolopyrimidine kinase inhibitors are reported. The crystal structure of one of these compounds bound to the Tie-2 kinase domain is consistent with the SAR. These compounds have moderate potency in cellular assays of Tie-2 inhibition, good physical properties, DMPK, and show evidence of in vivo inhibition of Tie-2.

Discovery of imidazole vinyl pyrimidines as a novel class of kinase inhibitors which inhibit Tie-2 and are orally bioavailable.

Tie-2 is a receptor tyrosine kinase which is involved in angiogenesis and thereby growth of human tumours. The discovery and SAR of a novel class of imidazole-vinyl-pyrimidine kinase inhibitors, which inhibit Tie-2 in vitro is reported. Their synthesis was carried out by condensation of imidazole aldehydes with methyl pyrimidines.

Aminoimidazolylmethyluracil analogues as potent inhibitors of thymidine phosphorylase and their bioreductive nitroimidazolyl prodrugs.

Thymidine phosphorylase (TP) is an important target enzyme for cancer chemotherapy because it is expressed at high levels in the hypoxic regions of many tumors and inhibitors of TP have been shown in animal model studies to inhibit angiogenesis and metastasis, and to promote tumor cell apoptosis. The 5-halo-6-[(2'-aminoimidazol-1'-yl)methyl]uracils (3, X = Cl, Br) are very potent inhibitors of E. coli and human TP with IC(50) values of approximately 20 nM when the enzyme concentration is approximately 40 nM.

Infection and food: a factor in sudden infant death syndrome?

Despite the identification of risk factors for sudden infant death syndrome (SIDS) and decreased SIDS rates in many countries, there is still no coherent, widely accepted, mechanistic explanation for SIDS. As an extension of our work on the infectious aetiology of SIDS, we have explored the prediction that infectious agents might reach susceptible infants and babies, via particular sources of food. In this ecological study, we demonstrated significant correlations between SIDS rates and exposure to meat from some sources, and we propose that more detailed studies be carried out.

Crystal structure of human thymidine phosphorylase in complex with a small molecule inhibitor.

Human thymidine phosphorylase (HTP), also known as platelet-derived endothelial cell growth factor (PD-ECGF), is overexpressed in certain solid tumors where it is linked to poor prognosis. HTP expression is utilized for certain chemotherapeutic strategies and is also thought to play a role in tumor angiogenesis. We determined the structure of HTP bound to the small molecule inhibitor 5-chloro-6-[1-(2-iminopyrrolidinyl) methyl] uracil hydrochloride (TPI).

Synthesis of cytidine ribonucleotides by stepwise assembly of the heterocycle on a sugar phosphate.

Although various syntheses of the nucleic acid bases exist and ribose is a product of the formose reaction, no prebiotically plausible methods for attaching pyrimidine bases to ribose to give nucleosides have been described. Kinetic and thermodynamic factors are thought to mitigate against such condensation reactions in aqueous solution. This inability to produce pyrimidine nucleosides and hence nucleotides is a major stumbling block of the "RNA World" hypothesis and has led to suggestions of alternative nucleic acids as evolutionary precursors to RNA.